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文献速览

辅助脉冲染料激光治疗抗癌药物引起的甲沟炎

Lasers Surg MedPMID:40884352

背景:甲沟炎是抗癌治疗的常见副作用,尤其是表皮生长因子受体抑制剂(EGFRIs)。标准治疗往往效果有限。595nm的脉冲染料激光(PDL)疗法具有血管靶向和抗炎作用,可能是一种有效的辅助治疗方法。 目的:评估辅助性595nm PDL疗法治疗抗癌药物尤其是EGFRIs所致甲沟炎的临床疗效和安全性。 材料与方法:这项前瞻性前后对照研究纳入了10例患者的70个因抗癌药物引起的甲沟炎手指,不良事件通用术语标准(CTCAE)分级为1-2级。在进行2周标准化治疗的导入期后,参与者接受4次每周一次的595nm PDL治疗。在基线、每次就诊时以及治疗后2周评估的结果包括红斑指数(EI)、改良甲沟炎评估工具(SPOT)评分、疼痛、水肿、医生整体评估(PGA)、患者满意度和不良事件。 结果:PDL治疗使EI从1.63显著降低至1.42(p<0.001),水肿从1.67降至1.45(p<0.001)。改良SPOT评分从3.61提高到1.99(p<0.001),早期疼痛缓解明显(4.40-1.25;p<0.001)。PGA在第3周有所改善,患者满意度在第5周从0提高到100(p<0.001)。 结论:PDL辅助治疗可显著改善抗癌药物所致甲沟炎的临床体征和患者报告的结果。

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根管治疗期间的健康教育可减少抗生素的使用。

Clin Exp Pharmacol PhysiolPMID:41058266

尽管抗生素可以有效控制传染病,但过度使用抗生素会导致耐药性等问题。牙髓炎和根尖周炎是人类最常见的传染病之一。为缓解剧烈的牙痛,患者常自行服用抗生素。为了更有效地指导患者管理牙髓炎和根尖周炎,我们设计了一份根管治疗健康教育表格,并在治疗期间提供了关于抗生素使用的个性化指导。2024年1月至2025年3月,共有272名患者参与了该项目。受益于健康教育,与对照组相比,抗生素的使用比例显著降低。参与该健康教育项目的患者和医护人员对该干预措施都持积极态度。我们的经验表明,在牙髓炎和根尖周炎的治疗中应积极推广健康教育。

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肾吻合性血管瘤的病例系列及文献综述:一种常被误诊的良性肿瘤。

Curr UrolPMID:41058761

背景:肾吻合性血管瘤(RAHs)较为罕见。本研究旨在总结RAH的临床、病理及影像学特征。 材料与方法:我们回顾性分析了2014年12月至2023年12月期间在本中心接受RAH手术的14例患者。此外,我们对2009年至2023年发表的关于RAH的病例报告和病例系列进行了文献综述。 结果:肾吻合性血管瘤主要累及男性,通常为单发。超过半数的肿瘤位于肾实质内。约70.7%(65/92)的患者无症状。肿瘤平均最大直径为20 mm(范围14 - 28 mm)。共有35.2%(37/105)的患者患有终末期肾病。患有终末期肾病和RAH的患者通常更年轻,且有双侧多灶性肿瘤。然而,这些肿瘤尺寸较小。患者的籍贯和肿瘤位置是影响肿瘤大小的重要因素。在中位随访期18个月内未观察到肿瘤复发或远处转移。术后病理染色仍是诊断RAH的标准;然而,术前多参数磁共振成像提供了有价值的诊断信息。RAH在皮质髓质期通常表现为周边、不连续、结节状强化,随后在排泄期出现向心性填充强化。当观察到这些特征性磁共振成像表现时,建议进行术前超声引导下经皮活检。 结论:肾吻合性血管瘤是一种罕见的良性肾肿瘤,在影像学上常被误诊,导致潜在的过度治疗。外科医生必须精通肿瘤的鉴别诊断,以便为患者提供最佳治疗。

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Skeletal Muscle Membrane Permeability Markers Derived From P-MRS May Reflect Disease Activity in Becker Muscular Dystrophy.

NMR BiomedPMID:41058238

Replacement of muscle tissue by fat in patients with Becker muscular dystrophy (BMD), as measured by quantitative muscle MRI, has been shown to reflect disease progression, but this process is considered irreversible. To monitor treatment effects in healthy-appearing muscles, biomarkers reflecting disease activity are needed. Here, we compare several candidate biomarkers for disease activity between patients with BMD and controls: intracellular ionised magnesium ([Mg]), phosphodiesters (PDE), and weighted pH measures from phosphorus-(P)-MRS; and membrane permeability derived from the random permeable barrier model (RBPM), as applied to diffusion-tensor-(DT)-MRI data. We performed 7 T P-MRS and 3 T DT-MRI in the left lower leg of 23 participants with BMD (mean [range] age: 41.1 [18.8-66.2] years) and 14 healthy controls (mean [range] age: 43.0 [21.2-63.6] years), estimating [Mg], PDE/γ-ATP, weighted pH and RPBM permeability. Follow-up scans at 24 months were performed in a subset of these participants. Muscles in patients with BMD were regarded as likely to be 'preserved' (BMD) with fat fractions ≤ 13.5% and as 'progressing' (BMD) with 13.5% < fat fraction < 81.5%. Muscles with fat fractions ≥ 81.5% were excluded from further analyses. We observed decreased [Mg] in BMD and BMD compared to healthy controls, whereas PDE/γ-ATP and weighted pH were increased in these muscles. RBPM-measured permeability did not differ between groups. We observed no longitudinal changes in [Mg], PDE/γ-ATP or weighted pH. Only [Mg] continued to show group differences on inclusion of longitudinal data, and weighted pH demonstrated inter-muscle differences. In patients with BMD, P-MRS demonstrates reduced [Mg] and increased weighted pH in the lower leg muscles versus controls, suggesting greater membrane permeability-a potential disease activity biomarker independent of the disease phase. PDE/γ-ATP was also significantly increased in progressing and preserved muscle. Incorporating P-MRS in therapeutic trials will help to further establish its use as a response biomarker.

Deciphering the Role of Long Non-coding RNAs in Neural Differentiation and Reprogramming.

Stem Cell Rev RepPMID:40965813

Long non-coding RNAs (lncRNAs) have emerged as key regulators of neural differentiation and neurological diseases. Abundantly expressed in the central nervous system, lncRNAs play crucial roles in neural development by modulating transcriptional, epigenetic, and post-transcriptional processes. This review summarizes recent advances in understanding how lncRNAs regulate the differentiation of stem cells, including embryonic stem cells and neural stem cells, by interacting with transcription factors, chromatin regulators, and microRNAs. LncRNAs influence neurogenesis by determining the fate of neural progenitors, controlling the timing of differentiation, and balancing self-renewal. In addition to their role in neural differentiation, lncRNAs also play critical roles in various neurological diseases, such as Alzheimer's disease, Parkinson's disease, and glioblastoma, where their dysregulation contributes to neuroinflammation, synaptic dysfunction, and tumor progression. These findings highlight the potential of lncRNAs as diagnostic biomarkers and therapeutic targets for neurological disorders. Despite challenges in delivery and functional characterization, targeting disease-associated lncRNAs offers promise for regenerative medicine and precision treatments. A deeper understanding of lncRNA-mediated regulatory networks could lead to novel therapeutic strategies for neurodegenerative and neuro-oncological diseases.

中国虫草产品、地理可追溯性及真伪评估:现状、挑战与未来方向

Crit Rev BiotechnolPMID:40368579

中华虫草是一种原产于青藏高原的药用真菌和营养补充剂,因其潜在的健康益处和巨大的经济价值而备受赞誉。野生中华虫草的质量因产地不同而有所差异,导致价格相差悬殊。虽然中华虫草的人工培育成功是一项重大突破,但也带来了在市场上区分野生产品和人工培育产品的挑战。该行业面临着广泛欺诈行为引发的关键问题,如产地误标、用人工培育的虫草替代野生虫草以及假冒伪劣。本综述全面概述了市场上的中华虫草产品,包括野生和人工培育的干品、鲜品以及发酵产品。详细介绍了产地误标、替代、掺假和人工增色等欺诈行为,并概述了追踪野生中华虫草地理来源、将其与替代品区分开来以及评估真伪的方法。尽管已经开发了各种方法,但在可及性和实际应用方面仍存在很大差距。未来的工作应优先进行广泛采样,建立中华虫草及相关产品化学指纹图谱的综合数据库,并建立标准化工作流程。通过将该数据库与人工智能和高光谱成像技术相结合,有可能开发出快速、无损的中华虫草地理溯源和真伪验证方法。

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从筛查到转诊:尽管有足够的支持,但将心脏移植患者与满足社会需求的资源联系起来仍具有挑战性。

Pediatr TransplantPMID:41058021

背景:在医疗环境中,筛查社会需求已变得越来越普遍。虽然美国各地的儿科项目已在临床环境中成功实施了社会需求筛查,但将筛查结果为阳性的家庭与所需资源相连接的能力尚不完全明确。通过这项质量改进计划,我们试图全面筛查社会需求,并将所有筛查结果为阳性的家庭转介至社区资源。 方法:在美国西部的一家儿科心脏移植诊所内进行社会需求筛查。诊所团队设计了两条独立的资源转介途径:高风险需求(由社会工作者处理)和低风险需求(转介至“联合我们”组织)。感兴趣的转介结果是资源识别和资源连接,其中社会工作者途径显示出更高的有效性。 结果:在筛查的86个家庭中的28个家庭中,社会需求筛查发现了66项实际需求。团队成员无法为近一半已识别的需求(n = 30,44.8%)找到社区资源,最常见的原因是未找到资源(n = 23)。在已处理的59项需求中,诊所团队能够为24项需求的家庭连接资源。总体而言,家庭与所有已识别需求中的36.4%的资源建立了连接。 结论:社会需求筛查显示出高度的社会需求。然而,转介至资源受到两个关键障碍的阻碍——缺乏可用资源和缺乏当地项目跟进。当找到资源时,面对面支持和转介途径比远程支持更有效。

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阴茎背侧折叠术对一期尿道下裂修复结果有影响吗?

Curr UrolPMID:41058767

背景:在本研究中,我们旨在评估在保留尿道板的一期尿道下裂修复术中,背侧折叠术(DP)矫正轻至中度阴茎腹侧弯曲(VPC)的疗效。 材料与方法:我们回顾性分析了2018年1月至2021年12月期间在保留尿道板的一期尿道下裂修复术中接受DP的患者的病历。根据脱套后弯曲程度将患者分为两组:<30°(第1组)和30°至40°(第2组)。分析复发性VPC、尿道并发症和小儿阴茎感知评分。 结果:76例患者符合纳入标准:第1组59例,第2组17例。两组间复发性VPC的发生率(1.7%对5.9%;P = 0.928)和尿道并发症的发生率(32.2%对29.4%;P = 0.827)相当。共收集到29份完整的小儿阴茎感知评分问卷。在对阴茎长度的不满意方面未观察到显著差异(13.6%对14.3%;P = 0.692)。 结论:对于脱套后VPC为30°至40°的病例,背侧折叠术不会增加VPC复发率、尿道并发症发生率或对阴茎长度的不满意率。需要更大样本量的长期随访来进一步评估DP的疗效。

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鉴定KRBA2作为与肾透明细胞癌免疫浸润相关的潜在预后生物标志物。

Curr UrolPMID:41058765

背景:肾透明细胞癌(KIRC)是肾细胞癌的主要亚型。由于其进展迅速且对靶向治疗耐药,KIRC对人类健康构成重大威胁。KRBA2是KRBA家族的成员,被认为是一种转录因子。然而,关于KRBA2在KIRC中的作用的研究有限。 材料与方法:利用癌症基因组图谱数据库分析KRBA2在KIRC中的表达,并采用定量实时PCR验证临床KIRC样本和KIRC细胞系中KRBA2 mRNA的表达。通过Wilcoxon秩和检验确定KRBA2表达与临床病理特征之间的相关性。接下来,我们使用Kaplan-Meier生存分析评估KRBA2在KIRC患者中的预后价值。利用肿瘤免疫估计资源研究KRBA2表达与KIRC中免疫浸润之间的关联。 结果:我们的研究表明,KRBA2在KIRC中的表达下调,且与多种临床病理特征相关。KRBA2低表达与较差的总生存期、无进展生存期和疾病特异性生存期相关。富集分析表明,KRBA2与免疫过程和细胞周期相关;肿瘤免疫估计资源分析表明,KRBA2表达与多种免疫细胞的免疫浸润水平和免疫特征相关。 结论:这些发现表明,KRBA2可能作为一种与KIRC免疫相关的潜在预后生物标志物,有望成为KIRC诊断和治疗的靶点。

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不同来源间充质干细胞用于子宫内膜修复的比较研究:蜕膜间充质干细胞的显著优势

Stem Cell Rev RepPMID:40762881

背景:子宫内膜损伤,尤其是宫腔粘连(阿谢曼综合征),会显著损害女性生育能力。目前的治疗方法,包括宫腔镜手术、宫腔屏障和口服雌激素,疗效有限,术后妊娠率为22.2%-33.3%。间充质干细胞(MSCs)因其多向分化和组织修复能力而提供了一种有前景的替代方法。本研究比较了源自骨髓、脐带、脂肪组织和蜕膜的间充质干细胞在修复受损子宫内膜方面的疗效。 方法:使用CCK8法评估间充质干细胞的增殖情况。通过免疫荧光和蛋白质印迹法评估体外向子宫内膜上皮细胞的分化情况。在体内,使用宫腔粘连大鼠模型评估间充质干细胞输注后的子宫内膜修复情况。 结果:骨髓间充质干细胞的增殖率最高,而脂肪来源的间充质干细胞增殖率最低。蜕膜间充质干细胞在向子宫内膜上皮细胞的分化方面表现优异,且在体内修复效果最为显著。 结论:蜕膜间充质干细胞在子宫内膜修复方面显示出优异的疗效,突出了其治疗宫腔粘连的潜力。未来的研究应集中在临床验证和机制探索上。

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Effect of a single administration of FSH delivered in hyaluronic acid on oocyte competence and hormonal concentrations in Italian Mediterranean buffaloes undergoing ovarian stimulation prior to ovum pick-up.

TheriogenologyPMID:40652733

This study evaluated the effectiveness of a single intramuscular administration of follicle-stimulating hormone (FSH) dissolved in 1 % hyaluronic acid (HA) for ovarian stimulation in Italian Mediterranean buffaloes (IMB) undergoing ovum pick-up (OPU). The aim was to simplify hormonal protocols, reduce handling stress, and improve oocyte competence. In Experiment 1, multiparous IMB (n = 24) were enrolled in a crossover design comparing the standard six-dose FSH protocol (FSH-6) with a single FSH-HA injection. Transrectal ultrasonography was used to record the number and the size of follicles, in vitro embryo production to assess oocyte developmental competence, and an in-house radioimmunoassay (RIA) method to measure plasma cortisol levels. In Experiment 2, plasma FSH profile during follicular growth was evaluated in IMB (n = 12) subjected to FSH-HA, FSH-6, or no stimulation (control) protocols. The FSH-HA treatment resulted in a higher (P < 0.05) proportion of medium-sized follicles compared to FSH-6 (3.4 ± 2.7 and 2.0 ± 2.3, respectively) as well as a significantly greater number of cleaved oocytes (3.3 ± 0.4 and 2.4 ± 0.4 respectively), although the total embryo yield remained similar (30.1 ± 7.2 and 29. 2 ± 4.5, respectively). Cortisol concentrations increased after OPU in all groups, but the FSH-HA group showed a trend (P < 0.10) toward lower stress levels compared to FSH-6. In Experiment 2, FSH-HA maintained higher plasma FSH concentrations for a longer period, with peak values observed between 30 and 72 h post-administration, suggesting the importance of optimizing the timing of OPU in HA-based protocols.

Surveying planetary health curriculum: Integration in Canadian nursing education.

Nurse Educ TodayPMID:40803236

PURPOSE/AIM: Nursing students and faculty are meeting face to face with the realities of a changing climate, more frequent environmental disasters, new and emerging infectious diseases, and related social and human conditions. A movement to include Planetary Health concepts, skills and practices into nursing education competencies is building across Canada and globally. The Canadian Association for Schools of Nursing (CASN) Planetary Health Interest Group embarked on an exploration of the uptake of the Planetary Health Education Framework (PHEF) and related Planetary Health curriculum initiatives. METHODS: To better understand the integration of Planetary Health into nursing curricula and pedagogical practices across the country, the Planetary Health Interest Group conducted an online, descriptive survey with analysis in 2024. Survey items were developed alongside the Planetary Health Interest Group based on published literature on Planetary Health Concepts. This study surveyed English speaking institutions of higher education in Canada, with a view to a second phase at Francophone institutions to follow. RESULTS: A total of 17 responses (one duplicate) were received from 16 different institutions. Responses were received from institutions in seven different Canadian provinces all offering undergraduate degrees, and over half offering graduate education in nursing. All reported their schools of nursing addressed one or more Planetary Health concepts such as "Indigenous land-informed ways of knowing" or "human health impacts of exceeding planetary boundaries." Most reported varied and instructor dependent ways of addressing concepts with a desire to better integrate and standardize concepts throughout curriculum. CONCLUSIONS: Informed by these survey results the CASN Planetary Health Interest Group will set goals for integration and development of targeted resources needed to ensure that the movement of Planetary Health is implemented in nursing curricula. Extending the survey to Francophone institutions is a next step forward for the strategy. From the findings, a variety of recommendations illuminated for champions and practices to advance the Planetary Health Movement.

Single-cyst morpho-molecular identification detected an unexpected high species diversity of dinoflagellate resting cysts from the coastal seas of China.

Harmful AlgaePMID:40935529

Over the past several decades, harmful algal blooms (HABs) caused by dinoflagellates frequently occurred along the coastal waters of China, with an increasing number of emerging HAB species. Due to the vital roles played by the resting cyst in the ecology of HABs, the investigation of resting cyst diversity and distribution of dinoflagellates, those causing HABs in particular, in marine sediment is of great significance. However, it has been difficult to unambiguously identify cyst species via obtaining both morphological and molecular evidence due to a variety of technological limitations (e.g. extremely simple morphology and/or small sizes of many cyst species). Although the application of high-throughput metabarcoding analysis has greatly improved the efficiency (high throughput) and accuracy (molecular identification) of cyst identification, lacking morphological evidence makes it less convincing because the sequences obtained with this approach may be doubted to be from fragmental vegetative cells or relics of eDNA. Furthermore, insufficient sequencing depths commonly adopted in studies using this technique together with the extremely large and widely-varying genome sizes of dinoflagellates have also led to the potential oversight of those species having small cell sizes and/or relatively low abundances. In this study, we employed a single-cyst morpho-molecular method (ScPCR sequencing) to identify dinoflagellate cysts from 23 sediments collected from all four seas of China. From 702 individually picked-up, micrographed, and sequenced cysts, we identified 127 species of dinoflagellates, with 63 (49.6%) fully identified to well-described species, and 64 (50.4%) that could not be determined for their species identity due to the unavailability of reference sequences. Notably, among the 63 fully-identified species, 6 had not been reported from China before, 19 are well-documented HABs-causing species (e.g. 8 Alexandrium spp., Gymnodinium catenatum, Karenia mikimotoi), and 22 were identified for the first time from one of the four seas of China. In addition, from 44 sediment samples that were collected from the East China Sea (ECS, a "hotspot" of HABs in China) and pre-processed with the sodium polytungstate protocol to concentrate their cyst assemblages, we fully identified 61 species of dinoflagellate cysts via metabarcoding analysis, including 27 species causing HABs, 10 as new records in Chinese waters, 13 as new records in the ECS, and 10 previously unreported as cyst producers. It is noteworthy that 7 (35%) of the 20 cyst species identified via ScPCR sequencing from the ECS were not detected by the metabarcoding analysis. Contrasting to that 64 species of dinoflagellate cysts had been unequivocally identified from China by 2021, the total number of cyst species identified in this study using ScPCR sequencing demonstrated the robustness of the detection technique. This study also suggests that the species diversity of dinoflagellate cysts in Chinese marine sediments is still largely underestimated, which calls for significant advancements both in the taxonomy of dinoflagellates and cyst detection technology and effort.

从姑息治疗中社会护理和医疗保健专业人员的角度看临终讨论。

Omega (Westport)PMID:37342869

本研究描述了芬兰临终讨论的状况。开展了一项采用主题访谈的定性描述性研究。数据收集自姑息治疗科的护士、医生和社会工作者。采用了归纳性内容分析法。根据受访者(n = 33)的说法,临终讨论状况包括三大类。第一,最佳临终讨论时间包括早期临终讨论、重症不同阶段的临终讨论,以及安排临终讨论的灵活性和挑战。第二,临终讨论发起者包括医疗保健专业人员和非医疗保健专业人员。第三,社会护理和医疗保健专业人员对临终讨论的体验包括临终讨论的重要性和挑战、多专业护理背景下临终沟通技能的发展,以及多元文化护理背景下的临终沟通。考虑到多专业、多元文化和国际化的运营环境,这些结果可用于证明制定国家预立医疗照护计划(ACP)战略及系统实施该战略的必要性。

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The Co-Surgeon Model for Microsurgical Free Flaps: A Survey of Perspectives and Utility.

J Reconstr MicrosurgPMID:39993427

Reconstructive microsurgery remains a demanding field, requiring technical expertise and long operating hours. This places microsurgeons at increased risk of dissatisfaction and burnout. The co-surgeon model has been developed to mitigate these challenges. This study was designed to evaluate microsurgeon perspectives on the characteristics and impact of the co-surgeon model for microsurgical free flaps.An electronic anonymous survey was distributed via email to attending microsurgeon members of the American Society of Reconstructive Microsurgeons. The survey collected various demographic and practice-related information including Likert scale questions to assess microsurgeon perspectives on the utility of the co-surgeon model.A total of 862 microsurgeons received the survey, with 102 responses available for analysis. The average age of respondents was 46.6 (± 9.7) years. Most of the microsurgeons were male (71%) practicing in the United States (93%), with 74.5% of respondents utilizing a co-surgeon model in their practice. Bilateral breast flaps were the most common microsurgical procedure performed using a co-surgeon (85%), followed by head and neck free flaps (60%), with immediate lymphatic reconstruction being the least common (3.1%). On the day of the co-surgery case, the co-surgeon was more likely than the primary surgeon to have additional cases (68.4 and 36.4%, respectively), with the additional cases being rarely free flaps. More than 80% of microsurgeons stated that the co-surgeon model improves "very much" or "quite a bit" operative efficiency and duration, as well as surgeon well-being and career longevity.This study provides new insight into the utility of using a co-surgeon for free flap reconstruction by demonstrating that approximately 80% of microsurgeons have a positive perception of the model's impact on procedure efficiency, operative time, surgeon well-being, and career longevity. Therefore, adopting a co-surgeon model for microsurgical free flap reconstruction may be useful in reducing burnout and promoting well-being among microsurgeons.

Water-stable PEG2000-modified citric acid crosslinked β-CD MOF for efficient removal of tetracycline hydrochloride: synthesis, adsorption behavior, and mechanism.

Carbohydr ResPMID:40789270

To address the ecological and health risks associated with residual tetracycline hydrochloride (TCH) in water, a green-synthesized adsorbent composed of β-cyclodextrin (β-CD), citric acid (CA), and polyethylene glycol (PEG) was developed for the effective removal of TCH from wastewater. The synthetic parameters were optimized, and the resulting PEG-CA-β-CD MOF was characterized by FT-IR, XRD, and SE. TGA analysis indicated an increase in the thermal stability. The maximum adsorption capacity of PEG-CA-β-CD MOF for TCH was 221.6 mg/g at pH = 4. Adsorption kinetics were well-described by the Elovich equation model, while the Freundlich isothermal model accurately described the equilibrium data adsorption Thermodynamic analysis revealed that the adsorption process was endothermic and spontaneous. Furthermore, the adsorbent maintained 84 % of its initial adsorption capacity after four reuse cycles. Analysis using zeta potential, FT-IR, and XPS confirmed that the possible adsorption mechanism of TCH mainly involves electrostatic interactions, hydrogen bonding, and cavity encapsulation. Finally, simulated wastewater experiments showed that PEG-CA-β-CD MOF was able to adsorb TCH efficiently even in the presence of other pollutants. Overall, due to its green synthesis process, low cost, ease of regeneration, and multi-mechanistic adsorption capability, the PEG-CA-β-CD MOF exhibits significant potential for TCH removal in wastewater treatment.

Exposure of freshwater gastropods to chlorpyrifos and cadmium: Predictable and unpredictable responses.

Comp Biochem Physiol C Toxicol PharmacolPMID:40653130

Aquatic environments near agricultural areas are increasingly contaminated by mixtures of pesticides and heavy metals, posing a threat to non-target aquatic invertebrates. Because mixtures may induce unexpected biological responses, their study is essential for realistic environmental risk assessment. This study investigated the acute and chronic effects of the pesticide chlorpyrifos (CPF), cadmium (Cd), and their mixture on the freshwater gastropods Biomphalaria glabrata and Planorbarius corneus under controlled laboratory conditions. A panel of biochemical and cellular biomarkers was used to evaluate neurotoxicity, oxidative stress, metabolic alterations and immunotoxicity. Acute CPF exposure, alone or combined with Cd, inhibited B-esterase activity and increased TBARS, indicating neurotoxic and pro-oxidant effects. Glutathione-S-transferase (GST) and catalase (CAT) remained unaltered. Hemolymph glucose levels increased with all treatments, with a synergistic hyperglycemic response to CPF + Cd observed only in B. glabrata. Cd exposure induced hypercholesterolemia in B. glabrata and hypertriglyceridemia in both species. Hemocyte revealed enhanced reactivity in response to contaminants alone, an effect absent in the mixture. Notably, under chronic CPF + Cd exposure, a pronounced hemocyte clumping occurred, an immunotoxic response, not previously reported. These findings highlight B-esterase inhibition and lipid peroxidation as sensitive biomarkers of acute CPF exposure; while hemolymph metabolic parameters may serve as complementary indicators of acute Cd exposure. GST and TBARS levels emerged as informative indicators of chronic Cd toxicity. Notably, the contaminant mixture unpredictably suppressed or amplified only certain biological responses, particularly on immune cells. This study underscore the value of integrative biomarker approaches to better predict ecological risks associated with contaminant mixtures.

Multi-omics reveals the synergistic mechanism of polymyxin B and diethyldithiocarbamate against Pseudomonas aeruginosa.

Int J Antimicrob AgentsPMID:40617550

OBJECTIVES: Resistance to polymyxin B (PMB) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) has become a global issue. A promising approach to rescue PMB treatment failures is to repurpose non-antibiotics as adjuvants to enhance the efficacy of antibiotics against CRPA. METHODS: The in vitro effects of the PMB/DDC combination were assessed by microbroth dilution method, checkerboard microbroth dilution method, time-kill assay, biofilm formation inhibition assay, live/dead bacterial staining, and scanning electron microscopy. The in vivo efficacy of the PMB/DDC combination was evaluated in a PMB-resistant P. aeruginosa infection model. Comprehensive multi-omics analysis was performed to investigate the mechanism of the PMB/DDC combination. RESULTS: We identified that the combination of PMB and diethyldithiocarbamate (DDC) had a high synergistic effect against PMB-resistant Pseudomonas aeruginosa (P. aeruginosa) strains in vitro and significantly hindered the biofilm formation. The PMB/DDC combination was effective in treating PMB-resistant P. aeruginosa infection model in vivo, as evidenced by higher survival rates in five days and lower bacterial loads in lung tissue and liver. Comprehensive multi-omics analysis revealed that the resistance of P. aeruginosa P2550 to PMB was determined by chromosomally encoded rather than plasmid-mediated mobilized colistin resistance (MCR) clusters. The combination down-regulated the expression of the operons arnBCADTEF at 2 h, which regulate LPS modification, and the abundance of metabolites of amino sugars and nucleotide sugars related to Lipid A biosynthesis and Lipid A modification were significantly perturbed. The Gac/Rsm pathway, quorum sensing (QS) system, cAMP/Vfr signalling, and c-di-GMP signalling, which are pathways associated with biofilm formation, were significantly inhibited within the first 4 h. In addition, the PMB/DDC combination significantly disturbed metabolic pathways, including arginine biosynthesis, the tricarboxylic acid cycle (TCA), and nucleotide metabolism. Notably, PMB alone, DDC alone, and the combination disrupted membrane-associated glycerophospholipid metabolism. CONCLUSIONS: The study highlights the potential of the PMB/DDC combination for treating PMB-resistant P. aeruginosa infections and elucidates the synergistic bactericidal mechanism of the combination through multi-omics methods.

Symphony of regulated cell death: Unveiling therapeutic horizons in sarcopenia.

MetabolismPMID:40752569

Sarcopenia is a progressive musculoskeletal condition associated with aging, marked by a decline in muscle mass, strength, and performance. This condition not only compromises functional independence in older individuals but also contributes to escalating healthcare and economic burdens. Although the underlying mechanisms are complex and multifaceted, recent discoveries have emphasized the regulatory influence of multiple forms of programmed cell death-including apoptosis, ferroptosis, necroptosis, and pyroptosis-on skeletal muscle degeneration. These cell death pathways contribute to key pathological features such as muscle fiber loss, proteostasis imbalance, neuromuscular dysfunction, mitochondrial deficits, and persistent inflammation. This review synthesizes current understanding of the molecular underpinnings of regulated cell death (RCD) in sarcopenia and discusses emerging therapeutic interventions aimed at modulating these pathways. These include pharmacological agents (e.g., ferroptosis inhibitors, polyphenols), structured exercise programs (notably resistance), targeted nutritional support (e.g., amino acids, vitamin D), cell-based therapies, and gene-targeted strategies. Despite growing evidence supporting RCD as a viable therapeutic target, the interplay among different cell death modalities and the translation of mechanistic insights into clinical practice remain insufficiently understood. Advancing sarcopenia treatment will require integrated multi-omics analyses, identification of predictive biomarkers, and rigorously designed clinical studies to support personalized and effective therapeutic approaches.

Cyetpyrafen, chlorfenapyr and spirodiclofen affect the olfactory recognition of Dastarcus helophoroides by acting on DhelOBP4 and DhelOBP21.

Pestic Biochem PhysiolPMID:40915828

The pine-forest guardian Dastarcus helophoroides mainly rely on olfaction to locate its host accurately and interact socially. Odorant binding proteins of D. helophoroides play an important role in olfactory recognition and transporting odors to olfactory receptors to trigger signal transduction. However, some compounds affect olfactory recognition of D. helophoroides by binding to odorant binding proteins. In this study, DhelOBP4 and DhelOBP21, which are involved in the recognition of plant volatiles, were expressed to explore compounds that affect olfactory recognition. The affinity of 24 compounds with DhelOBP4 and DhelOBP21 was investigated by vitro fluorescence competitive binding assays. It was found that cyetpyrafen, chlorfenapyr and spirodiclofen had high affinity with DhelOBP4 and DhelOBP21. At the same time, we found that these three pesticides had a good evasive effect on the D. helophoroides and elicited EAG response in a dose-dependent manner. Besides, it was found that silencing DhelOBP4 and DhelOBP21 would affect D. helophoroides identifying these three pesticides. Through homology modeling and molecular docking, we identified key amino acid sites involved in the binding of DhelOBP4 and DhelOBP21 to these three pesticides, which might revealed their specific binding molecular interactions. This study is helpful to provide a valuable addition of OBP-pesticide interactions of D. helophoroides.

Augmented methanogenic performance in straw-manure co-digestion via micro/nano bubble-enhanced syntrophic metabolism.

Bioresour TechnolPMID:40653119

This study aimed to investigate the enhancement of methane production by comparing air-nanobubble water (air-NBW) and conventional micro-bubble aeration during the anaerobic co-digestion (AcoD) of rice straw and pig manure. Remarkably, the addition of air-NBW (T3-NBW), as the most effective gas supplementation strategy, resulted in the highest cumulative methane yield of 489.49 mL/g·VS with a minimal lag phase of 0.57 days, representing a 59.80 % increase over the control (306.49 mL/g·VS, p < 0.001). This finding aligns with the kinetic fitting data (477.85 ± 5.84 mL/g·VS), wherein the maximum methane production rate for the T3-NBW was 41.89 mL/g∙VS·d. Mechanistic insights revealed that air-NBW dramatically elevated the activity of β-glucosidase (hydrolysis) and coenzyme F (methanogenesis) by 82.72% and 133.8 %, respectively, compared to the control. These results suggested that the efficient conversion of intermediate products played a critical role in enhancing overall methane yield. Microbial community analysis identified acetotrophic methanogenesis as the dominant pathway, with Methanosaeta abundance reaching 91.66 % in NBW-amended treatments. Additionally, the co-occurrence network analysis showed that the air-NBW system promoted microbial interaction and stabilized the ecological network. Crucially, the NBW treatment exhibited the lowest expression of energy-dependent antioxidant enzyme genes (e.g., superoxide reductase, SOR), suggesting reduced oxidative stress and enhanced energy allocation toward microbial growth and methanogenic activity. By enhancing oxygen dispersion and microbial intracellular redox balance, NBW technology provides a promising approach for improving methane recovery in sustainable waste-to-energy systems.

Trends in Parallel Applications to Pediatrics Residency in the United States Between 2009-2023.

J PediatrPMID:40818806

OBJECTIVE: We analyzed the trends in application to Pediatrics residency with concurrent application to one or more other specialties (parallel applications) between 2009 and 2023. STUDY DESIGN: A retrospective analysis of custom Association of American Medical Colleges Electronic Residency Application Service data of applicants to Pediatrics residency between 2009 and 2023 was conducted. Descriptive statistics and linear regressions were used to identify trends of the percent parallel applying as well as the mean number of specialties and applications submitted. We used descriptive statistics to characterize common specialty combinations with Pediatrics. RESULTS: The present analysis examined data representing 81 138 unique Pediatrics applicants. The proportion of Pediatrics parallel applicants (65.9% vs 48.4%, P < .001) and the mean number of specialties applied to (4.1 to 3.9, P < .001) declined from 2009 to 2023. The proportion of international medical graduates (IMG) (88.9% [n = 4468] vs 76.5% [n = 1906]; B = -0.90, P < .001) parallel applying decreased while the proportion of MD applicants (17.3% [n = 370] vs 22.1% [n = 485]; B = 0.56, P = .03) parallel applying increased between 2009 and 2023. During that period, the proportion of DO (32.9% [n = 116] vs 34.0% [n = 291]; B = -0.06, P = .21) applicants parallel applying did not significantly increase. Internal medicine (66.9%) and family medicine (60.7%) were the most common specialty combinations for parallel applicants in 2023. Between 2009 and 2023, the mean applications increased for single-specialty (25.3 vs 51.0; P < .001) and parallel applicants (119.7 vs 146.3; P < .001). IMG (127.1 vs 164.6; P < .001), DO (43.5 vs 119.8; P < .001) and MD (53.4 vs 90.0; P < .001) parallel applicants all experienced significant increases in the mean number of applications submitted. CONCLUSIONS: Although fewer applicants are applying to Pediatrics, around 50% of Pediatrics applicants parallel applied with the proportion of parallel applicants decreasing among IMG applicants and increasing among medical doctor applicants. Medical schools, residency programs, and application systems should revisit residency advising and application limits to reduce the strain of parallel application on applicants and residency programs.

熊果酸:一种具有妇科和乳腺癌临床应用前景的天然五环三萜类化合物(综述)。

Oncol RepPMID:40937560
熊果酸:一种具有妇科和乳腺癌临床应用前景的天然五环三萜类化合物(综述)。

妇科癌症和乳腺癌对全球女性健康构成重大挑战。尽管在诊断和治疗方面取得了显著进展,但它们仍然是癌症相关死亡的主要原因。熊果酸(UA)是一种天然存在的五环三萜类化合物,广泛存在于植物中,因其多样的药理活性而备受关注。已经证明,UA具有一系列生物学效应,包括抗肿瘤、抗炎和抗氧化特性,在乳腺癌和妇科癌症中具有特别有前景的治疗潜力。UA通过调节多种信号通路发挥其抗癌作用,如PI3K/AKT、NF-κB和Wnt/β-连环蛋白,从而有效抑制肿瘤细胞增殖、诱导凋亡、逆转化疗耐药性并抑制癌症干细胞特性。当与顺铂和阿霉素等化疗药物联合使用时,UA不仅增强抗肿瘤疗效,还减轻与化疗相关的不良反应。本综述总结了UA在妇科和乳腺癌治疗中的最新研究进展和潜在机制,旨在为该领域的研究人员和临床医生提供有价值的见解。

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Removing constraints of 4D-STEM with a framework for event-driven acquisition and processing.

UltramicroscopyPMID:40669438

Pixelated detectors in scanning transmission electron microscopy (STEM) generate large volumes of data, often tens to hundreds of GB per scan. However, to make current advancements scalable and enable widespread adoption, it is essential to use the most efficient representation of an electron's information. Event-driven direct electron detectors, such as those based on the Timepix3 chip, offer significant potential for electron microscopy, particularly for low-dose experiments and real-time data processing. In this study, we compare sparse and dense data representations in terms of their size and computational requirements across various 4D-STEM scenarios, including high-resolution imaging and nano-beam electron diffraction. The advantages of performing 4D-STEM in an event-driven mode - such as reduced requirements in memory, bandwidth, and computational demands - can only be fully leveraged if the entire acquisition and processing pipeline is optimized to work directly with the event format, avoiding intermediate dense representations. We introduce a framework designed for acquisition and processing based on this event format, and demonstrate live processing of event-driven 4D-STEM, including analytical ptychography.

LNPs-mediated VEGF-C mRNA delivery promotes heart repair and attenuates inflammation by stimulating lymphangiogenesis post-myocardial infarction.

BiomaterialsPMID:40393374

Myocardial infarction (MI) initiates a strong inflammatory response, leading to adverse ventricular remodeling. The reconstruction of functional lymphatic networks is indispensable for relieving myocardial edema and regulating post-infarction inflammation. However, conventional protein-based therapies and viral delivery systems aimed at promoting lymphangiogenesis in the heart have shown limited therapeutic efficacy due to their inherent limitations. In this study, a lipid nanoparticle (LNP) platform encapsulating VEGF-C mRNA was developed as a novel approach to regulate gene expression and stimulate sustained lymphatic neogenesis after MI. Intramyocardial delivery of VEGF-C mRNA-loaded LNPs significantly promoted lymphangiogenesis, reduced the infiltration of inflammatory cells, and inhibited pro-inflammatory and fibrosis-associated signaling pathways. This ultimately resulted in a substantial reduction in the fibrotic area and improved functional recovery. Our findings demonstrated that VEGF-C mRNA@LNPs repair myocardial ischemic injury by facilitating immune modulation through lymphatic neogenesis, offering a promising new therapeutic strategy with strong translational potential for treating myocardial infarction.

The first report of Hematodinium perezi genotype I infection of Chinese mitten crab (Eriocheir sinensis) from the River Thames, UK.

J Invertebr PatholPMID:40818767

Hematodinium is a genus of parasitic dinoflagellates which infects marine decapods, including several which are utilised in the global commercial crustacean fishery. Histological screening of the invasive Chinese mitten crab (Eriocheir sinensis) collected from the River Thames UK in 2018 revealed infection by a parasite with features of Hematodinium spp. Molecular analysis of gill tissues from infected crabs confirmed the presence of Hematodinium spp. and more specifically, Hematodinium perezi genotype I, which has previously been reported infecting crustacean species native to the UK (Carcinus maenas and Liocarcinus depurator), including from locations from the nearby English Channel. This is the first report of Hematodinium perezi infecting Chinese mitten crabs in either its native (Asian) or invasive host range. It is proposed that the Chinese mitten crab has acquired this parasite in UK waters subsequent to its introduction several decades ago. This finding is of particular interest for the future aquaculture of this species in its native range since it may indicate susceptibility to infection with Hematodinium perezi genotype II, a parasite prevalent in other crustacean species farmed in Asia. Parasites of the Hematodinium genus have been shown to cause high prevalence infection and disease in numerous farmed and fished crustacean species from around the world and this study marks a confirmed extension of that host range and the potential for Chinese mitten crabs to acquire novel infections within their invasive ranges.

A novel C-type lectin, Nattectin-like protein, with the function of regulating AMP expression and phenoloxidase activity in Procambarus clarkii.

Fish Shellfish ImmunolPMID:40701451

As a crucial member of pattern recognition receptors (PRRs), C-type lectins (CTLs) play a pivotal role in innate immunity by recognizing pathogen-associated molecular patterns. In this study, we identified and characterized a novel CTL, Nattectin-like protein (PcNTC), from Procambarus clarkii and conducted a comprehensive functional analysis. PcNTC possesses a carbohydrate recognition domain and a signal peptide. The open reading frame of PcNTC spans 570 bp and encodes a protein consisting of 189 amino acids. Quantitative polymerase chain reaction analysis revealed the ubiquitous expression of PcNTC across various crayfish tissues, with the highest expression observed in hemocytes. Following Aeromonas hydrophila challenge, the relative expression level of PcNTC in hemocytes and gills was considerably up-regulated. Enzyme-linked immunosorbent assay showed that the recombinant PcNTC (rPcNTC) can bind to polysaccharides (lipopolysaccharide and peptidoglycan). Bacterial agglutination assay revealed that rPcNTC can bind to Gram-positive (Staphylococcus aureus, Bacillus subtilis, and Bacillus thuringiensis) and Gram-negative bacteria (Escherichia coli, Vibrio parahaemolyticus, and A. hydrophila). However, the agglutination test results indicated that rPcNTC only exhibited agglutination activity against S. aureus. RNA interference experiments revealed that knockdown of PcNTC resulted in substantial decreases in the transcription levels of immune-related genes (Relish and Dorsal) and antimicrobial peptides (ALF5, ALF6, ALF8, ALF9, CRU1, CRU2, CRU3, CRU4, and Lys-i1) in hemocytes and gills. In addition, the prophenoloxidase gene expression (ppo1 and ppo2) and activity of phenoloxidase decreased considerably in the PcNTC-dsRNA group. Importantly, PcNTC knockdown substantially reduced the survival rate of P. clarkii after A. hydrophila challenge. Collectively, these findings indicate that PcNTC, functioning as a PRR, is integral to the antibacterial defense mechanisms of P. clarkii and plays a crucial role in the immune regulatory system.

PcSRB cooperates with TLR2 and promotes phagocytosis and antimicrobial peptides expression.

Fish Shellfish ImmunolPMID:40789354

Class B scavenger receptors (SRBs) are type III transmembrane proteins that participate in immune responses. However, the antibacterial mechanisms of SRBs in invertebrates have not yet been revealed. In this study, we analyzed the antibacterial activity of SRB in Procambarus clarkii (crayfish). The expression of PcSRB was upregulated after the Aeromonas hydrophila and Staphylococcus aureus challenge. A bacterial binding assay showed that PcSRB could bind to several bacteria. PcSRB can bind to polysaccharides, such as lipopolysaccharides, lipoteichoic acid, and peptidoglycan. After PcSRB interference, the survival rate of crayfish significantly decreased during the bacterial challenge. The bacterial cleaning efficiency of crayfish was also impaired by PcSRB interference. Further exploration showed that PcSRB promoted the phagocytosis of A. hydrophila by hemocytes. The expression levels of several antimicrobial peptides (AMPs) were also detected. The mRNA levels of Crustin1, Crustin2, LYZ, and SWD were down-regulated after PcSRB knockdown. In addition, PcSRB binds to TLR2, rather than to TLR4, and influences AMPs expression. Therefore, PcSRB cooperates with TLR2 to facilitate bacterial elimination by promoting hemocyte phagocytosis and AMPs expression.

Protective role of orphan G protein-coupled receptor GPR35 in the pathogenesis of colitis through regulating epithelial barrier function and immune responses.

J Pharmacol SciPMID:40983462

BACKGROUND AND OBJECTIVE: GPR35 is involved in the pathogenesis of colitis. However, because GPR35 is expressed in colonic epithelial and inflammatory/immune cells, its precise protective mechanisms remain unclear. We investigated the role of GPR35 in colitis, especially its relation to epithelial barrier function and inflammatory/immune responses. METHODS: We performed GPR35 knockout (KO) in a dextran sodium sulfate (DSS)-induced murine colitis model and elucidated the role of GPR35 through various experiments, including histological analysis, intestinal permeability, immunohistochemical staining, RT-qPCR, and western blotting. RESULTS: GPR35KO mice exhibited significantly exacerbated DSS-induced colitis, accompanied by upregulation of cytokines, compared with wild-type (WT) mice. An investigation using bone marrow (BM)-chimeric mice revealed that GPR35KO, which is expressed in both hematopoietic and non-hematopoietic cells, contributed to this exacerbation. GPR35KO mice showed significantly increased intestinal permeability compared with WT mice under normal conditions. Although no differences were observed in goblet cell number or epithelial proliferation between WT and GPR35KO mice, the expression levels of intercellular junction proteins were significantly lower in the normal colons of GPR35KO mice. Lipopolysaccharide-stimulated cytokine expression was significantly enhanced in BM-derived macrophages obtained from GPR35KO mice compared with WT mice. CONCLUSIONS: GPR35 contributes to colonic protection by regulating epithelial barrier function and inflammatory/immune responses.

RNAi bioassays targeting bursicon reveal potential targets for pest control of Henosepilachna vigintioctopunctata.

Pestic Biochem PhysiolPMID:40915839

Henosepilachna vigintioctopunctata represents a significant economic pest, typically controlled through the use of chemical insecticides. The introduction of RNA interference (RNAi) technology has opened new avenues for biopesticide development, leading to the identification of various genes that are crucial for the growth and development of insects. However, the efficient screening of target genes in H. vigintioctopunctata remains limited. The present study provides a detailed investigation into the functional role of the neuropeptide Bursicon in H. vigintioctopunctata. The analysis of spatial distribution and developmental profiles demonstrated that two primary Bursicon subunits, HvBurs-α and HvBurs-β, exhibited specific expression patterns in the central nervous system, particularly peaking during the first-instar larval stage. Targeted RNAi of these genes led to a dramatic reduction in mRNA levels, resulting in reduced pupation and eclosion rates, along with nearly complete malformation, particularly concerning wing development. Experiments involving RNAi on second- and fourth-instar larvae showed significant reductions in the size of both elytra and hindwings in the adult forms, with the hindwings suffering severe shrinkage and lacking the ability to extend. Additionally, the combination of dsRNA treatment with chemical insecticides like avermectin or beta-cypermethrin increased larval mortality and adversely affected pupation and eclosion rates. Importantly, the application of dsRNA aimed at HvBurs-α and HvBurs-β did not adversely affect the predatory lady beetle Harmonia axyridis, suggesting a promising safety profile. Altogether, these findings underscore the critical role of Bursicon in wing development in H. vigintioctopunctata and highlight its potential as a promising target for RNAi-based biopesticide strategies, providing a novel and environmentally friendly approach to managing pest populations and their migratory behaviors.

High fat diet and low dose-rotenone exposure exacerbate Parkinson's disease like pathology through gut-brain axis disruption.

Exp NeurolPMID:40691983

Parkinson's disease (PD) affects millions worldwide. In recent years, the role of the gut-brain axis and gut microbiome alterations in neurodegenerative diseases has gained significant attention. Lifestyle and environment factors play a crucial role in shaping the overall health. Herein, we investigated whether obesity induced by high-fat diet (HFD) combined with low-dose rotenone (5 mg/kg; orally, twice a day) exacerbates PD-like pathology. Our findings reveal non-motor symptoms of PD alongside gut inflammation, α-synuclein (α-syn) accumulation, and dysbiosis, possibly mediated by transient receptor potential vanilloid 1 (TRPV1) channel. In the brain, we observed the characteristic α-syn pathology in the substantia nigra (SN) and the striatum. Finally, we observe neuroinflammation including astrogliosis, microgliosis and increased expression of TRPV1 channel in the SN and striatum possibly hinting to PD like pathological features. The in-vitro findings in N2a and C6 glial cell lines hint towards possible co-relation of increased TRPV1 in response to lipotoxicity and rotenone exposure which was recovered when treated with TRPV1 antagonist; Capsazepine. In summary, we propose that HFD along with low dose rotenone poses a risk for neuronal health; exaggerating the neuroinflammatory states.

Design and modeling of Cf-252 -based neutron irradiator for NAA: MCNP6 simulations of dose rate and neutron fluxes.

Appl Radiat IsotPMID:40578121

This paper presents a new design and modeling of a rapid, multiple sample Cf-252 irradiator for neutron activation analysis (NAA) to replace research reactor irradiations, with a particular focus on safety analysis associated with neutron and gamma dose rates in areas typically occupied by individuals. The study utilizes the Monte Carlo N-Particle (MCNP6) simulation code to assess three different configurations aimed at optimizing safety and operational efficiency. ACf source emitting 5.77 × 10 neutrons per second is considered. Simulations were conducted to determine optimal shielding configurations that comply with established radiation exposure limits. Ricorad™, a borated polyethylene material known for its exceptional neutron shielding performance due to its high hydrogen concentration, was specifically utilized for efficient and lightweight shielding. Additionally, the study examines the distribution of neutron flux around the Cf source to ensure optimal sample placement for As activation - a key output of planned activation studies. Furthermore, the paper examines practical irradiation applications at this sample position by estimating the measurement time needed to achieve 2000 counts for the As peak at 559.101 keV in a sample of coal fly ash using a high-purity germanium detector. The overarching goal of this work is to ensure safe and efficient utilization of aCf-based neutron irradiator for NAA, emphasizing the importance of radiation safety while minimizing space requirements and enabling accurate and reliable measurements.

五味子合剂通过VDAC1/Grp75/IPR介导的线粒体相关内质网膜稳定及凋亡-自噬调节减轻糖尿病肾病

PhytomedicinePMID:40857962

背景:糖尿病肾病(DKD)是终末期肾病的主要病因,其发病机制与线粒体功能障碍介导的肾小管损伤有关。线粒体相关膜(MAMs)在糖尿病肾小管损伤中协调细胞凋亡和自噬。虽然五味子合剂(SM)具有肾脏保护作用,但其通过维持MAMs完整性来对抗高血糖诱导的肾小管细胞死亡和纤维化的机制仍不清楚。 目的:本研究探讨SM是否通过在高糖(HG)条件下恢复MAMs完整性来减轻肾纤维化,从而调节肾小管细胞凋亡和自噬。 方法:通过高脂/高糖饮食和链脲佐菌素注射诱导Sprague-Dawley大鼠发生DKD,随后用SM(1.5/3/6 g/kg/d)进行12周治疗。评估肾功能、损伤标志物和组织病理学。通过免疫组化定位、蛋白质印迹定量和TUNEL检测对细胞凋亡、自噬和纤维化进行表征。通过超微结构和分子分析评估线粒体-内质网(ER)相互作用和MAMs完整性。在体外,通过慢病毒介导的MAMs完整性操作验证了SM的保护机制。通过超高效液相色谱/串联质谱(UPLC-MS/MS)对SM的血清成分进行表征。 结果:在DKD大鼠中,SM治疗恢复了线粒体-内质网超微结构和偶联,MAMs锚定蛋白相互作用增强证明了这一点。SM剂量依赖性地改善肾功能,减轻肾小管细胞凋亡,恢复HG损伤的自噬,并减轻纤维化。在HG刺激的HK-2细胞中,SM同样挽救了线粒体-内质网的接近度并抑制了纤维化标志物。慢病毒模型进一步证实,SM通过维持MAMs完整性减轻肾小管损伤。UPLC-MS/MS鉴定了SM的主要血清成分(如五味子丙素);本研究未评估它们各自的生物活性。 结论:SM通过MAMs完整性,经VDAC1-Grp75-IPR轴治疗DKD,调节HG刺激的肾小管细胞凋亡和自噬,改善线粒体功能,并抑制纤维化进展。

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NMR Approaches to Study Drug-Surfactant Interactions: Insights From NOE, Relaxometry and Diffusometry.

Magn Reson ChemPMID:40855742

Characterising drug-binding mechanisms, structural changes and dynamics at atomic resolution remains a challenge due to the dynamic and heterogeneous nature of surfactant supramolecular assemblies. In this context, nuclear magnetic resonance (NMR) is uniquely suited to overcome these complexities by offering precise information on binding, structure, dynamics and transport in native-like conditions. NMR spectroscopy, leveraging the nuclear Overhauser effect (NOE), spin-relaxometry and translational self-diffusometry, offers atomistic-level insights into drug-surfactant interactions. NOE measurements reveal spatial proximities between drug and surfactant molecules, while relaxometry captures local dynamics and facilitates the estimation of rotational correlation times for both free and bound drug species. Diffusometry probes global translational motion and geometric features, enabling quantification of the bound drug fraction (p) and partition coefficient (K), both of which are pertinent to pharmaceutical and chromatographic contexts. Together, these NMR approaches provide an integrated view of structure, dynamics and transport, which is critical for understanding the physicochemical behaviour of drug-surfactant systems. This mini-review summarizes key solution-state NMR techniques, supported by theoretical models and selected applications, for incisive characterisation of these interactions.

Effect of riding experience and HMI on users' trust and riding comfort in fully driverless autonomous vehicles: An on-road study.

Appl ErgonPMID:40526986

The wide adoption of autonomous vehicles (AVs) or robot taxis relies on technological advancements and public acceptance, which can be influenced by users' trust in AVs and comfort during rides. Among the influential factors of riding comfort, motion sickness (MS) has attracted lots of attention in previous research, and both trust and MS have been found to be associated with human-machine interface (HMI) designs in AVs. However, previous research on trust and MS in AVs predominantly utilized driving simulations or "Wizard of Oz" methods, which failed to introduce risk and realistic vehicle motions, potentially introducing bias to conclusions. For the first time, our study investigated the impact of displaying the dynamic path trajectories of AVs on passengers' perceptions of system transparency, trust, and MS in a commercially running AV. The results from 16 participants and 32 rides revealed limited effects of the dynamic path trajectory on trust, and a discernible but statistically non-significant trend in MS alleviation. Further, we found that the initial riding experience was more important in trust enhancement than subsequent rides. These results provide insights into future HMI design in robot taxis and suggest directions for future research in trust enhancement and MS alleviation in AVs.

Autophagy induced by Porphyromonas gingivalis aggravates esophageal squamous cell carcinoma via YAP/TAZ-miR-21-5p axis.

Cell SignalPMID:40623656

Porphyromonas gingivalis (P. gingivalis), a keystone pathogen in adult periodontitis, is linked to an increased risk of many cancers. Although autophagy stimulated by P. gingivalis in ESCC has been reported, the molecular mechanisms and functional roles of autophagy in P. gingivalis-related ESCC progression are still unclear. P. gingivalis infection promoted the malignant progression of ESCC through autophagy, as demonstrated in both in vitro and in vivo studies. Once P. gingivalis invaded cancer cells, it induced the dephosphorylation and nuclear accumulation of YAP/TAZ, which are the effectors of Hippo pathway. In a TEAD-dependent manner, YAP/TAZ activated the miR-21-5p/RASA1/ERK signaling pathway to enhance autophagy-mediated tumor-promoting roles in the proliferation, migration, and invasion of ESCC. Additionally, P. gingivalis infection was correlated with higher levels of miR-21-5p, YAP/TAZ, and LC3, all of which were associated with shorter overall survival of patients with ESCC. Taken together, our findings reveal that the YAP/TAZ-miR-21-5p-ERK axis plays a crucial role in the P. gingivalis-infected subtype of ESCC, suggesting P. gingivalis and the autophagy pathway as promising therapeutic targets for ESCC treatment.

Enhancing the extraction of C-phycocyanin and water-soluble metabolites from Arthrospira platensis using pulsed electric field technology.

J BiotechnolPMID:40783084

Pulsed Electric Fields (PEF) technique has emerged as a promising approach to extract molecules of interest from different biological material. The present study aimed at optimizing the extraction of C-phycocyanin (C-PC) and other water-soluble biomolecules from Arthrospira platensis cyanobacterium by adjusting PEF process parameters. At a field strength of 5 kV/cm, specific energies comprised between 2.1 and 41.1 MJ/kg were applied to the PEF treatment chamber containing an aqueous solution with 1.11 g/kg of A. platensis. Experimental results showed that extraction efficiency including C-PC yield and quality are strongly influenced by PEF specific energy. The application of 20.5 MJ/kg generated a C-PC yield of 84 mg/g with purity of 0.52 (A/A) and selectivity of 3.10 (A/A), whereas only 56 % of the cells were disintegrated. Higher specific energies of 30.8 MJ/kg improved the disruption of A. platensis cells (85 %) and the C-PC extraction yield (115 mg/g) but at the expense of extracts quality. This study highlights the importance of finding a compromise between PEF energy requirements and extraction performances, which can have significant impact on the overall economic viability of A. platensis downstream processes.

斑秃患者的免疫介导性疾病:系统评价与荟萃分析

Int J DermatolPMID:40603702

斑秃(AA)是一种非瘢痕性、器官特异性自身免疫性疾病,其特征为脱发。新出现的证据表明,斑秃常与其他免疫介导的疾病共存,但这些关联的强度和一致性仍不明确。本荟萃分析旨在系统评估斑秃患者免疫介导的合并症的患病率和风险,重点关注皮肤病学、内分泌学、胃肠道和全身性免疫介导的疾病。在Medline、科学网和谷歌学术上对2000年1月至2024年7月发表的研究进行了全面的文献检索。纳入报告斑秃患者免疫介导合并症且有足够数据计算比值比(OR)的病例对照研究。18项研究符合纳入标准,涵盖462945例斑秃患者和11488192例健康对照。数据提取遵循系统评价和荟萃分析的首选报告项目(PRISMA)指南,并使用纽卡斯尔-渥太华量表评估研究质量。荟萃分析采用随机效应模型进行。分析显示,斑秃患者合并免疫介导疾病的几率显著增加,包括特应性皮炎(OR 2.63)、自身免疫性甲状腺炎(OR 1.57)、炎症性肠病(OR 1.20)、系统性红斑狼疮(OR 3.28)和白癜风(OR 6.61)。这些合并症的患病率从多发性硬化症的0.34%到特应性疾病的38.65%不等。这些发现证实斑秃与多种免疫介导疾病的风险增加有关。特别是与白癜风、系统性红斑狼疮和自身免疫性甲状腺炎的紧密联系,凸显了对斑秃患者进行全面筛查和跨学科管理的必要性。

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气候变化对亚洲人畜共患病出现和演变的影响。

Zoonoses Public HealthPMID:40888029

随着亚洲气候在全球变暖影响下发生变化,已知人畜共患病的发病率和空间分布将会演变,并且由于更多地接触目前仅存在于野生动物中的生物,预计将会出现新的人畜共患病。为了评估与不同传播方式和生物维持机制相关的风险,提供了一个分类系统,将疾病分为九个亚型。所有被认为具有全球重要性的动物疾病和人畜共患病都可以被归类为一个亚型,或者在少数情况下,可归类为多个流行病学上不同的亚型。在每个亚型中,针对具有人畜共患病重要性的选定疾病,提供了有关气候因素影响的现有证据,以说明这些疾病未来可能的演变以及不同疾病目前可用证据的程度。概述了可能影响亚洲新型人畜共患病原体出现的因素。在气候变化影响下,可用于分析、预测和评估疾病发生可能变化的方法范围迅速扩大;介绍了目前可用的工具类型。这些方法需要纳入亚洲的监测和应对策略,并概述了实现这一目标的方法。

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感到担忧的原因?英国马匹粪便中蛔虫卵阳性计数比例不断上升(2007 - 2023年)。

Equine Vet JPMID:39840839

背景:驱虫抗性(AR)威胁着马寄生虫的有效控制。自2007年以来,英国实验室进行的粪便蠕虫卵计数检测(FWECT)的季度数据总结已出现在《马季度疾病监测报告》(EQDSR)中,但此前尚未进行评估。 目的:评估英国实验室使用的圆线虫FWECT方法和阈值。调查2007年至2023年期间与实验室季度FWECT阳性率相关的因素。 研究设计:实验室调查和实验室汇总数据分析。 方法:在2018年第三季度和2023年第四季度对实验室进行了调查。使用多重混合效应线性回归分析了2007年至2023年期间各实验室每季度报告的粪便蠕虫卵计数检测阳性比例(PTP),评估了FWECT阈值、年份季度和连续年份组的有序类别在实验室层面的随机效应和固定效应变量。 结果:2018年有10个实验室做出回应,2023年有13个实验室做出回应。样本通常在每克0至<100个虫卵(epg)和≥200 epg时报告为阳性。对1190份EQDSR提交数据的回归建模证实,相对于1级基线(0至<100 epg),阈值≥100至<300 epg(2级:-12.0%,p = 0.03)、≥300 epg(3级:-第十八条 (4))时,PTP显著降低。-18.0%,p = 0.03)以及未指定阈值时(4级:-12.2%,p = 0.0)。各年份季度之间的PTP没有明显的季节性变化。总体而言,在控制实验室间差异和FWECT阈值后,仍有证据表明,相对于基线(2007 - 2009年),研究期间PTP呈显著上升趋势。2010 - 2011年PTP上升了6.9%(p < 0.001),2012 - 2013年上升了10.1%(p < 0.001),2014 - 2015年上升了14.1%(p < 0.001),2016 - 2017年上升了16.0%(p < 0.001),2018 - 2019年上升了15.6%(p < 0.001),2020 - 2021年上升了17.第一章 (3))。主要局限性:调查回复有限,大多数实验室的FWECT阈值未知。 结论:在控制实验室和FWECT阈值后,FWECT汇总数据有力地证明,2007年至2023年期间英国马匹的虫卵计数呈上升趋势。 1%(p < 0.001),2022 - 2023年上升了18.9%(p < 0.001)。

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小儿肝移植中肝动脉和胆道并发症的最小化与管理

Pediatr TransplantPMID:41063373

小儿肝移植(PLT)是一项技术要求很高的手术,肝动脉(HA)和胆道重建是影响手术结果的关键因素。本综述总结了目前在小儿肝移植中减少和处理肝动脉及胆道并发症的策略,强调了手术技术、显微外科精度以及术中决策对移植物和患者存活的影响。关键考虑因素包括使用放大镜或手术显微镜放大、个性化抗凝方案以及对肝动脉血栓形成和胆道狭窄等并发症的针对性处理。本文还强调了介入放射学不断演变的作用以及胆道重建的创新方法,强调了多学科护理对优化长期结果的重要性。

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不同加工方法对糙米粉糕点品质特性的影响及控制研究

J Sci Food AgricPMID:40797056

背景:为提高糙米饭糕的口感和风味品质,采用了多种加工方法,包括内部酶发芽改性、挤压、米糠稳定化、外源酶水解和回填。本研究旨在比较不同改性处理的糙米饭糕的质地、挥发性风味物质、味道变化和内部质地结构,从而阐明这些处理对糙米饭糕整体品质的影响。 结果:挤压和酶水解后,糙米粉的特性粘度和崩解值降低,而回复值和糊化温度显著升高。这导致米粉的热稳定性有显著提高。傅里叶变换红外光谱分析表明,改性处理改变了纤维素和淀粉的结构,增加了亲水基团-OH,并增强了糙米的蒸煮性能。与未处理的糙米相比,发芽、挤压结合酶水解显著改变了糙米饭糕的淀粉和纤维素结构。在20°衍射角下,稻花香和小站919糙米饭糕的相对结晶度分别从33.06%提高到41.43%和从23.47%提高到24.95%。 结论:发芽处理有效改善了糙米饭糕的风味品质和回复特性。对经酶水解处理的米糠进行挤压并回填到糙米饭糕中,显著增强了其质地和孔隙结构。结合这两种加工方法有可能全面提高糙米饭糕的品质特性。©2025化学工业协会。

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商业重要鱿鱼品种中的线虫感染:分布模式与食品安全问题

Zoonoses Public HealthPMID:40276962

引言:头足类动物是全球重要的渔业资源,在海洋食物链中扮演着关键角色,既是捕食者又是猎物,同时还是包括异尖科人畜共患线虫在内的蛔虫类传播的转续宿主。本研究旨在评估来自四个不同粮农组织区域、在意大利市场销售的四种鱿鱼中,人畜共患寄生虫的存在情况、组织分布及种类构成。 方法:在四个粮农组织区域共捕获238份鱿鱼样本,分别为艾氏枪乌贼、科氏枪乌贼、细纹枪乌贼和大西洋武装乌贼,并采用目视检查和紫外线按压法进行检测。收集到的幼虫通过形态学和分子学方法进行鉴定。 结果:在22.3%的鱿鱼中检测到线虫第三期幼虫(艾氏枪乌贼为18.8%,科氏枪乌贼为18.3%,细纹枪乌贼为48.8%,大西洋武装乌贼为23%),通过形态学和分子分析鉴定出简单异尖线虫、佩氏异尖线虫、宫脂属线虫和叶形蛔线虫。事实证明,紫外线按压法比目视检查更为有效。此外,由于对鞭尾蛔科物种,特别是叶形蛔线虫缺乏分子数据,使得分类学分类变得复杂,这凸显了结合形态学和遗传学方法的综合分类学方法的必要性。 结论:鉴于生的和未煮熟的头足类动物消费量不断增加,这些发现凸显了监测人畜共患寄生虫以及改进分子技术以加强食品安全法规并将消费者健康风险降至最低的重要性。

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基于感官分析结合液相色谱-紫外法对辣味休闲食品的辛辣味特征进行研究

J Sci Food AgricPMID:40605784

背景:辛辣味是影响消费者对辣味休闲食品(SLF)偏好和接受度的关键感官属性。在本研究中,我们使用15厘米线性感官量表和带紫外检测的液相色谱法评估了26种市售SLF的感官辛辣味和辣椒素含量。使用心理物理学方法进一步建立了感知辛辣味与辣椒素浓度之间的关系模型。 结果:样品的辛辣味评级范围广泛,从“微辣”到“极辣”。史蒂文斯幂定律有效地描述了三类SLF(肉类休闲食品(MLF)、谷物类休闲食品(GLF)和蔬菜类休闲食品(VLF))中辣椒素含量与感官强度之间的关系,决定系数(R)分别为0.924、0.955和0.917。每类食品都表现出不同的幂定律常数(k)和指数(n),表明食品基质组成会调节辛辣味的感知。值得注意的是,对于同等辣椒素水平,感知到的辛辣味顺序为VLF>MLF>GLF。使用独立的SLF样品验证了所推导模型的预测准确性,证实了其稳健性和适用性。 结论:本研究提出了一个用于定量表征SLF中辛辣味的心理物理学框架,为辣味食品行业的产品开发和感官评价提供了一种新工具。©2025化学工业协会。

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Compr Rev Food Sci Food SafPMID:41063486

细胞肉是一项创新技术的成果,该技术通过在可控的实验室环境中培养动物细胞来促进肉类生产。这一过程减少了传统畜牧业对环境的负面影响,并创造了优化营养成分的可能性,这对消费者健康可能产生积极影响。包括饱和脂肪酸和不饱和脂肪酸在内的脂质概况是该分析的主要组成部分,强调了它们在与健康相关背景下的重要性。理论上认为,培养肉可以富含对健康有益的脂肪酸,如omega-3,同时饱和脂肪含量降低,这可能对公众健康产生积极影响。除了营养潜力外,本文还探讨了影响消费者对培养肉接受度的因素,强调了透明生产过程以及有效的教育和沟通策略的重要性。尽管有潜在益处,但全面实施这项技术需要克服技术、经济和社会挑战,并对其安全性和健康影响进行进一步研究。

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