A high-accuracy, low-cost blood test for Alzheimer’s disease: validating P-tau181/Aβ42 in real-world cohorts

ObjectiveTo evaluate the diagnostic performance of plasma P-tau181/Aβ42 measured via flow cytometry as a cost-effective tool for Alzheimer’s disease (AD) diagnosis.MethodsA cohort study involved 123 healthy controls, 60 AD/mild cognitive impairment (MCI) patients, 34 subcortical ischemic vascular disease (SIVD) patients, and 34 frontotemporal dementia (FTD) patients. Plasma P-tau181 and Aβ42 levels were measured using flow cytometry and cross-validated with Single-molecule Array (SIMOA). Publicly available Chinese cohort data were reanalyzed for comparative performance.ResultsThe P-tau181/Aβ42 ratio revealed significant differences between groups. A reference interval (0–0.109) achieved 96.2% diagnostic accuracy (95.0% sensitivity, 96.7% specificity) for AD versus controls, distinguishing AD from SIVD (88.3% accuracy) and FTD (86.2% accuracy). Flow cytometry-based P-tau181/Aβ42 showed 88.3% consistency with SIMOA-based P-tau217, while SIMOA-based P-tau181/Aβ42 achieved 92.3% accuracy.ConclusionFlow cytometry-based P-tau181/Aβ42 offers a cost-effective and accurate diagnostic method for AD, with performance comparable to SIMOA. This biomarker supports scalable AD screening in secondary healthcare settings, overcoming accessibility and cost barriers in resource-limited environments. This biomarker supports scalable AD screening in secondary healthcare settings, overcoming accessibility and cost barriers in resource-limited environments

Sex-specific associations of the endocrine-disrupting chemicals with serum neurofilament light chain among US adults

Objective: Endocrine-disrupting chemicals (EDCs) can interfere with endocrine function and lead to neurological damage. Neurofilament light chain (NfL) is a protein released into the blood after neuroaxonal damage, and it has become a dependable biomarker for neurological conditions. The study aimed to investigate the associations between single or combined EDCs exposure and serum NfL levels in adults. Methods: The 1372 participants included in the study were from the 2013–2014 National Health and Nutrition Examination Survey. Due to the difference in types of EDCs, participants were divided into two populations. Multiple linear regression models were used to assess the association between 32 EDCs and NfL. The least absolute shrinkage and selection operator regression model was used for EDCs selection and the weighted quantile sum (WQS) regression was used for examining the association of EDCs mixture with NfL and identify the predominant exposure. Results: Levels of urinary bisphenol S, mono(2-ethylhexyl) phthalate, dibutyl phosphate, glyphosate, and 3,5,6-trichloropyridinol were positively associated with serum NfL levels, while benzophenone-3, methylparaben, and propylparaben showed negative associations. In the WQS regression model, the changes of NfL were 0.154 (95 % CI: 0.014–0.294) and 0.164 (95 % CI: 0.033–0.296) for each quartile increase in WQS index of EDCs mixture in the two populations, respectively. Analysis of the subgroup with gender stratification suggested that the association between EDCs mixture and NfL was only significant in men. The positive mixture β was 0.219 (95 % CI: 0.056–0.380) and 0.257 (95 % CI: 0.082–0.433) in the two population, respectively. Conclusion: The study suggested a potential association between single or combined exposure to EDCs and NfL levels. High-level EDCs exposure might be associated with more severe neurological damage, particularly in men

MSCs-derived HGF alleviates senescence by inhibiting unopposed mitochondrial fusion-based elongation in post-acute kidney injury

Abstract Background The underlying mechanism of human umbilical-derived mesenchymal stem cells (hUC-MSCs) therapy for renal senescence in post-acute kidney injury (post-AKI) remains unclear. Unopposed mitochondrial fusion-based mitochondrial elongation is required for cellular senescence. This study attempted to dissect the role of hUC-MSCs therapy in modulating mitochondrial elongation-related senescence by hUC-MSCs therapy in post-AKI. Methods Initially, a unilateral renal ischemia–reperfusion (uIRI) model was established in C57 mice. Subsequently, lentivirus-transfected hUC-MSCs were given by subcapsular injection. Two weeks after transplantation, histochemical staining, and transmission electron microscopy were used to assess the efficacy of hUC-MSCs in treating renal senescence, fibrosis, and mitochondrial function. To further investigate the mitochondrial regulation of hUC-MSCs secretion, hypoxic HK-2 cells were built. Finally, antibodies of HGF and its receptor were used within the hUC-MSCs supernatant. Results Unopposed mitochondrial fusion, renal senescence, and renal interstitial fibrosis were successively identified after uIRI in mice. Then, the efficacy of hUC-MSCs after uIRI was confirmed. Subsequently, inhibiting hUC-MSCs-derived HGF significantly compromises the efficacy of hUC-MSCs and leads to ineffectively curbing mitochondrial elongation, accompanying insufficient control of elevated PKA and inhibitory phosphorylation of drp1 (Drp1pSer637). As a result, the treatment efficacy of renal senescence and fibrosis alleviation was also weakened. Furthermore, similar results were obtained with antibodies blocking HGF or cMet in hypoxic HK-2 cells treated with hUC-MSCs-condition medium for further proving. Uncurbed mitochondrial elongation induced by PKA and Drp1pSer637 was inhibited by hUC-MSCs derived HGF but reversed in the activation or overexpression of PKA. Conclusions The research concluded that hUC-MSCs-derived HGF can inhibit PKA-Drp1pSer637-mitochondrial elongation via its receptor cMet to alleviate renal senescence and fibrosis in post-AKI

Role of CIV NS1 Protein in Innate Immunity and Viral Replication

The innate immune pathway serves as the first line of defense against viral infections and plays a crucial role in the host’s immune response in clearing viruses. Prior research has indicated that the influenza A virus has developed various strategies to avoid host immune responses. Nevertheless, the role of the NS1 protein of the canine influenza virus (CIV) in the innate immune pathway remains unclear. In this study, eukaryotic plasmids of NS1, NP, PA, PB1, and PB2 were constructed, and it was found that these proteins interact with melanoma differentiation-associated gene 5 (MDA5) and antagonize the activation of IFN-β promoters by MDA5. We selected the NS1 protein for further study and found that NS1 does not affect the interaction between the viral ribonucleoprotein (RNP) subunit and MDA5, but that it downregulates the expression of the laboratory of genetics and physiology 2 (LGP2) and retinoic acid-inducible gene-I (RIG-I) receptors in the RIG-I pathway. Additionally, NS1 was found to inhibit the expression of several antiviral proteins and cytokines, including MX dynamin like GTPase 1 (MX1), 2′-5′oligoadenylate synthetase (OAS), Signal Transducers and Activators of Transcription (STAT1), tripartite motif 25 (TRIM25), interleukin-2 (IL-2), IFN, IL-8, and IL-1β. To further investigate the role of NS1, a recombinant H3N2 virus strain (rH3N2) and an NS1-null virus (rH3N2ΔNS1) were rescued using reverse-genetic technology. The rH3N2ΔNS1 virus exhibited lower viral titers compared to rH3N2, but had a stronger activation effect on the receptors LGP2 and RIG-I. Furthermore, when compared to rH3N2, rH3N2ΔNS1 exhibited a more pronounced activation of antiviral proteins such as MX1, OAS, STAT1, and TRIM25, as well as antiviral cytokines such as IL-6, IFN-β, and IL-1β. These findings suggest a new mechanism by which NS1, a nonstructural protein of CIV, facilitates innate immune signaling and provides new avenues for the development of antiviral strategies

Ming Qing Hua yan chuan cheng shi liao liang zhong : "Xian shou zong cheng" yu "Xian shou chuan deng lu" /

Zong pai wen ti shi zhong guo fo jiao fa zhan li shi guo cheng dang zhong yi ge nan jie de xian xiang, zong guan zhong guo fo jiao, jing tu yi zong neng fou cheng li zhi jin reng ran ju song fen yun, tian tai yu chan zong you yu you wan zheng de wen xian ji lu, yuan liu chuan cheng xiang dui qing xi. Zhi yu xian shou zong de li shi fa zhan, duo shu fang fu meng long zhi zi, ran er suo xing jin nian xu duo chong yao shi liao xiang ji wen shi, ming qing yi lai xian shou zong fa xi chuan cheng yuan liu ji hu ke wei yun wu kuo qing, zai ci ji chu zhi shang, xue jie dui yu zhong guo fo jiao zong pai fa zhan li shi jin cheng de ren shi yi jing da fu gai xie. "Xian shou zong cheng" yu "xian shou chuan deng lu" shi ming qing yi lai liang bu zhong yao de hua yan chuan cheng shi liao, dui ren shi xian shou zong li shi fa zhan guo cheng ti gong yi ge zhong yao xian suo.宗派問題是中國佛教發展歷史過程當中一個難解的現象,綜觀中國佛教,淨土一宗能否成立至今仍然聚訟紛紜,天台與禪宗由於有完整的文獻記錄,源流傳承相對清晰.至於賢首宗的歷史發展,多屬彷彿朦朧之姿,然而所幸近年許多重要史料相繼問世,明清以來賢首宗法系傳承源流幾乎可謂雲霧廓清,在此基礎之上,學界對於中國佛教宗派發展歷史進程的認識已經大幅改寫."賢首宗乘"與"賢首傳燈錄"是明清以來兩部重要的華嚴傳承史料,對認識賢首宗歷史發展過程提供一個重要線索.Fu lu: fo xin ci ji miao bian da shi bie feng tong gong ta ming deng san zhong.Includes index.附錄: 佛心慈濟妙辨大師別峰同公塔銘等三種Zong pai wen ti shi zhong guo fo jiao fa zhan li shi guo cheng dang zhong yi ge nan jie de xian xiang, zong guan zhong guo fo jiao, jing tu yi zong neng fou cheng li zhi jin reng ran ju song fen yun, tian tai yu chan zong you yu you wan zheng de wen xian ji lu, yuan liu chuan cheng xiang dui qing xi. Zhi yu xian shou zong de li shi fa zhan, duo shu fang fu meng long zhi zi, ran er suo xing jin nian xu duo chong yao shi liao xiang ji wen shi, ming qing yi lai xian shou zong fa xi chuan cheng yuan liu ji hu ke wei yun wu kuo qing, zai ci ji chu zhi shang, xue jie dui yu zhong guo fo jiao zong pai fa zhan li shi jin cheng de ren shi yi jing da fu gai xie. "Xian shou zong cheng" yu "xian shou chuan deng lu" shi ming qing yi lai liang bu zhong yao de hua yan chuan cheng shi liao, dui ren shi xian shou zong li shi fa zhan guo cheng ti gong yi ge zhong yao xian suo.宗派問題是中國佛教發展歷史過程當中一個難解的現象,綜觀中國佛教,淨土一宗能否成立至今仍然聚訟紛紜,天台與禪宗由於有完整的文獻記錄,源流傳承相對清晰.至於賢首宗的歷史發展,多屬彷彿朦朧之姿,然而所幸近年許多重要史料相繼問世,明清以來賢首宗法系傳承源流幾乎可謂雲霧廓清,在此基礎之上,學界對於中國佛教宗派發展歷史進程的認識已經大幅改寫."賢首宗乘"與"賢首傳燈錄"是明清以來兩部重要的華嚴傳承史料,對認識賢首宗歷史發展過程提供一個重要線索.Taiwan resource centre for Chinese studie