Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Objective:To explore the training experiences of palliative care nurses participating in a prognosis disclosure workshop based on Kolb's experiential learning model, and to provide references for future educational programs in palliative care nursing.Methods:Using purposive sampling, 11 nurses were recruited who had participated in the "Palliative Care Competency Training Program for Nurses" in Shanghai between March and May 2025 and selected the Third Affiliated Hospital of Naval Medical University as their clinical training site. Semi-structured interviews were conducted, and data were analyzed using Colaizzi's seven-step method.Results:A total of three major themes emerged: a sense of benefit from enhanced competencies; complex emotional experiences; recommendations for course optimisation.Conclusions:Workshops based on Kolb's experiential learning model offer positive value in palliative care education. They effectively improve core competencies such as communication and empathy. However, the emotional experiences of nurses must also be considered, and multifaceted optimizations to the training design are recommended to further enhance training outcomes.

Objective:To analyze the correlation and consistency of urine protein creatinine ratio (UPCR) with 24-hour urine protein quantification (24hUTP) in patients with lupus nephritis (LN).Methods:LN patients were enrolled from the STAR cohort of Peking University First Hospital, The time period is January 1, 2007 to July 31 2024. The correlation and consistency of UPCR with 24hUTP were analyzed in overall patients and various subgroups, such as,the levels of proteinuria and multiple parameters. The correlation was analyzed using Spearman′s method. The consistency was evaluated by using Kappa test, cross tabulation consistency probability, and UPCR/24hUTP ratio.Results:A total of 261 LN patients were included in this study. Overall, UPCR was positively correlated with 24hUTP ( r=0.892, P<0.001), and the consistency between then was good ( Kappa=0.603, P<0.001). Subgroup analysis based on multiple levels including different urine volume, eGFR grading, albumin, urea nitrogen, total cholesterol, low-density lipoprotein cholesterol, SLEDAI-2K, also revealed good correlation ( r=0.747~0.951; P<0.001) and consistency ( Kappa=0.393~0.771; P<0.001). Patients were divided into subgroups according to the 24hUTP (≤ 0.5 g, >0.5 g to ≤1.0 g, >1.0 g to ≤3.5 g, and>3.5 g). The best correlation and consistency were observed in ≤ 0.5g group ( r=0.728, Kappa=0.395, P<0.001), while the correlation was average or poor in other subgroups ( r=0.16~0.46). The consistency evaluated by UPCR/24hUTP ratio showed good consistency (ratios between 0.8~1.2) in 74 patients (28.4%), however, the unsatisfactory consistency in most patients, with 128 patients (68.4%) having ratios < 0.8, indicating a significantly lower UPCR than 24hUTP, and 59 patients (31.6%) having ratios > 1.2, indicating significantly higher UPCR than 24hUTP.The cross tabulation evaluation showed that the probability of consistency was distributed in a gradient, we found the worst consistency (48.9%) in >0.5 g to ≤1.0 g group, moderate consistency (64.0%) in >1.0 g to ≤3.5 g group, and the best consistency (73.3%) in >3.5 g group. Conclusion:In LN patients, the overall correlation and consistency between UPCR and 24hUTP are good, but the degree of correlation and consistency is closely related to the total amount of proteinuria. When 24hUTP ≤ 0.5 g, UPCR can be used to replace 24hUTP, but UPCR cannot be simply equated with 24hUTP at other urinary protein levels. Detecting 24hUTP to accurately reflect the total amount of proteinuria remain necessary.

Objective:To explore the training experiences of palliative care nurses participating in a prognosis disclosure workshop based on Kolb's experiential learning model, and to provide references for future educational programs in palliative care nursing.Methods:Using purposive sampling, 11 nurses were recruited who had participated in the "Palliative Care Competency Training Program for Nurses" in Shanghai between March and May 2025 and selected the Third Affiliated Hospital of Naval Medical University as their clinical training site. Semi-structured interviews were conducted, and data were analyzed using Colaizzi's seven-step method.Results:A total of three major themes emerged: a sense of benefit from enhanced competencies; complex emotional experiences; recommendations for course optimisation.Conclusions:Workshops based on Kolb's experiential learning model offer positive value in palliative care education. They effectively improve core competencies such as communication and empathy. However, the emotional experiences of nurses must also be considered, and multifaceted optimizations to the training design are recommended to further enhance training outcomes.

This study identified the types and pathogen carrying status of fleas on the surface of sheep in some areas of southern Xinjiang,and analyzed the genetic evolution differences with respect to related pathogens.The aim was to provide a reference for the local prevention and control of fleas and insect borne infectious diseases.A total of 1 586 fleas were collected from agricultural and pas-toral areas of Tumushuke City and Hotan Prefecture.Flea species were identified on the basis of morphology and the Pulex irritans mi-tochondrial COII gene.Flea DNA was extracted,and PCR was conducted to amplify the Bartonella gltA gene;Arsenophonus,Ana-plasma,Ehrlichia,and Wolbachia 16S rRNA genes;RickettsiaOmpA,17kDa,16S rRNA genes,and Yersinia pestis 16S rDNA gene.The amplified products were sequenced,and the homology of the genes of the three detected pathogens(gltA gene of Bartonella,16S rRNA gene of Wolbachia,and Anaplasma phagocytophilum)with respect to known corresponding genes of the same pathogen in Gen-Bank was analyzed.Phylogenetic trees were constructed with the adjacency method in MEGA 11.0.According to morphological and mo-lecular biology identification results,all fleas collected in this study were Pulex irritans.PCR indicated that the target gene fragments had been added to the mitochondrial COII,BartonellagltA,Wolbachia,and autophagosomal 16S rRNA genes of human fleas,all of which were consistent with the expected fragment sizes.Target bands were not amplified from Ehrlichia,Arsenophonus,spotted fever group Rickettsia,and Yersinia pestis.According to homology and genetic evolution analysis of human flea mitochondrial COII and the corresponding genes of the above-described pathogens,the COX2 gene(ON455234.1)of human fleas in Tumushuke city and Iran ob-tained in this study showed the highest homology(99.84%).The COII gene(NC_063709.1)of human fleas in Hetan City and Hunan region showed the highest homology(100%).Our findings further confirmed that the flea species was Pulex irritans.The PCR amplifi-cation results indicated that the collected Pulex irritans carried multiple pathogens,among which Bartonella and Wolbachia had the highest infection rates,and the infection rate with Anaplasma phagocytophilum was relatively low.This study is the first to discover flea species on the surface of sheep in some areas of southern Xinjiang.Our findings preliminarily confirmed that Bartonella,Wolba-chia,and Anaplasma phagocytophilum are the main Pulex irritans pathogens.

Objective:To analyze the changes in the incidence trend of liver cancer in Taizhou of Jiangsu Province, from 2012 to 2020 and provide reference for tumor prevention and control and management.Methods:Liver cancer incidence data from 2012 to 2020 were extracted from the Taizhou Center for Disease Control and Prevention's tumor registry system. Demographic data were used to calculate the crude incidence rate, age-standardized incidence rate (ASIR), Chinese age-standardized incidence rate (CASIR; based on China's 2010 standard population), and world age-standardized incidence rate (WASIR; based on Segi's world standard population). The Joinpoint regression model was applied to identify inflection points in liver cancer incidence trends during 2012-2020, and annual percentage change (APC) with average annual percentage change (AAPC) were calculated.Results:In 2020, the crude incidence ratio (CIR) of liver cancer in Taizhou was 34.6 per 100 000, with CASIR and WASIR at 19.6 per 100 000 and 14.9 per 100 000, respectively. From 2012 to 2020, the male-to-female ratio of new liver cancer cases was 2.94∶1 (10 455 males vs. 3 559 females), with male incidence consistently higher than female. Overall liver cancer incidence in Taizhou initially increased and then decreased after 2017 (2012-2017: APC=6.4%, P=0.014; 2017-2020: APC=-9.5%, P=0.035), peaking at a CASIR of 26.2 per 100 000 in 2017. The trend in male incidence mirrored the overall pattern, rising before 2017 and declining thereafter (2012-2017: APC=6.2%, P=0.005; 2017-2020: APC=-9.0%, P=0.016). Female incidence remained relatively stable (2012-2016: APC=11.0%, P=0.054; 2016-2020: APC=-6.5%, P=0.130). Conclusions:Liver cancer incidence in Taizhou increased before 2017 and declined thereafter, with 2017 as the turning point. Amid population aging, liver cancer remains a persistent public health challenge requiring sustained attention.