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Hang Lin,1,2 Cui Zhou,1 Kai-Hang Yu,3 Yi-Shuai Lin,1 Ling-Bo Wang,1 Ying Zhang,1 Shi-Xing Liu,1 Wen-Ya Xu,1 Yao Sun,1 Tie-Li Zhou,1 Jian-Ming Cao,4 Jian-Zhong Ye1 1Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2School of the First Clinical Medical Sciences, Wenhzou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 3Pathology Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Tie-Li Zhou; Jian-Zhong Ye, Department of Clinical Laboratory, Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, 325000, People’s Republic of China, Email wyztli@163.com; jzye89@163.comObjective: Acinetobacter baumannii is a hazardous bacterium that causes hospital-acquired nosocomial infections, and the advent of multidrug-resistant A. baumannii (MDR-AB) strains is concerning. Novel antibacterial therapeutic strategies must be developed. The biological effects of glabridin on MDR-AB were investigated in this study.Methods: The minimum inhibitory concentrations (MICs) of glabridin against eight clinical MDR-AB strains were determined using the broth microdilution technique. Crystal violet staining was used to assess biofilm development, which has significant contribution to bacterial resistance. Swarming motility was measured according to surface growth zone of MDR-AB on LB agar medium. qRT-PCR was used to evaluate the expression of quorum sensing genes abaI and abaR. Glabridin and routinely used therapeutic antimicrobial agents were tested for synergistic action using the checkerboard method.Results: According to our findings, glabridin suppressed MDR-AB growth at high doses (512– 1024 μg/mL). The 1/4 MIC of glabridin significantly decreased MDR-AB biofilm formation by 19.98% (P < 0.05), inhibited MDR-AB motility by 44.27% (P < 0.05), whereas the 1/2 MIC of glabridin dramatically reduced MDR-AB biofilm development by 27.43% (P < 0.01), suppressed MDR-AB motility by 50.64% (P < 0.05). Mechanistically, glabridin substantially downregulated the expression of quorum sensing-related genes abaI and abaR by up to 39.12% (P < 0.001) and 25.19% (P < 0.01), respectively. However, no synergistic effect between glabridin and antibacterial drugs was found.Conclusion: Glabridin might be a quorum sensing inhibitor that inhibits MDR-AB biofilm development and swarming motility.Keywords: Acinetobacter baumannii, multidrug-resistance, glabridin, quorum sensing

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Dementia has a long prodromal stage with various pathophysiological manifestations; however, the progression of pre-diagnostic changes remains unclear. We aimed to determine the evolutional trajectories of multiple-domain clinical assessments and health conditions up to 15 years before the diagnosis of dementia., Methods: Data was extracted from the UK-Biobank, a longitudinal cohort that recruited over 500,000 participants from March 2006 to October 2010. Each demented subject was matched with 10 healthy controls. We performed logistic regressions on 400 predictors covering a comprehensive range of clinical assessments or health conditions. Their evolutional trajectories were quantified using adjusted odds ratios (ORs) and FDR-corrected p-values under consecutive timeframes preceding the diagnosis of dementia., Findings: During a median follow-up of 13.7 [Interquartile range, IQR 12.9-14.2] years until July 2022, 7620 subjects were diagnosed with dementia. In general, upon approaching the diagnosis, demented subjects witnessed worse functional assessments and a higher prevalence of health conditions. Associations up to 15 years preceding the diagnosis comprised declined physical strength (hand grip strength, OR 0.65 [0.63-0.67]), lung dysfunction (peak expiratory flow, OR 0.78 [0.76-0.81]) and kidney dysfunction (cystatin C, OR 1.13 [1.11-1.16]), comorbidities of coronary heart disease (OR 1.78 [1.67-1.91]), stroke (OR 2.34 [2.1-1.37]), diabetes (OR 2.03 [1.89-2.18]) and a series of mental disorders. Cognitive functions in multiple tests also demonstrate decline over a decade before the diagnosis. Inadequate activity (3-5 year, overall time of activity, OR 0.82 [0.73-0.92]), drowsiness (3-5 year, sleep duration, OR 1.13 [1.04-1.24]) and weight loss (0-5 year, weight, OR 0.9 [0.83-0.98]) only exhibited associations within five years before the diagnosis. In addition, serum biomarkers of enriched endocrine, dysregulations of ketones, deficiency of brand-chain amino acids and polyunsaturated fatty acids were found in a similar prodromal time window and can be witnessed as the last pre-symptomatic conditions before the diagnosis., Interpretation: Our findings present a comprehensive temporal-diagnostic landscape preceding incident dementia, which could improve selection for preventive and early disease-modifying treatment trials., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Proteomic alterations preceding the onset of depression offer valuable insights into its development and potential interventions. Leveraging data from 46,165 UK Biobank participants and 2920 plasma proteins profiled at baseline, we conducted a longitudinal analysis with a median follow-up of 14.5 years to explore the relationship between plasma proteins and incident depression. Linear regression was then used to assess associations between depression-related proteins and brain structures, genetic factors, and stress-related events. Our analysis identified 157 proteins associated with incident depression (P <1.71 × 10 -5 ), including novel associations with proteins such as GAST, PLAUR, LRRN1, BCAN, and ITGA11. Notably, higher expression levels of GDF15 (P = 6.18 × 10 -26 ) and PLAUR (P = 2.88 × 10 -14 ) were linked to an increased risk of depression, whereas higher levels of LRRN1 (P = 4.28 × 10 -11 ) and ITGA11 (P = 3.68 × 10 -9 ) were associated with a decreased risk. Dysregulation of the 157 proteins is correlated with brain regions implicated in depression, including the hippocampus and middle temporal gyrus. Additionally, these protein alterations were strongly correlated with stress-related events, including self-harm events, adult, and childhood trauma. Biological pathway enrichment analysis highlighted the critical roles of the immune response. EGFR and TNF emerged as key proteins in the protein-protein interaction network. BTN3A2, newly linked to incident depression (P = 4.35 × 10 -10 ), was confirmed as a causal factor through Mendelian randomization analysis. In summary, our research identified the proteomic signatures associated with the onset of depression, highlighting its potential for early intervention and tailored therapeutic avenues., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Background: Recent evidences highlight the potential impact of outdoor Light at Night (LAN) on executive function. However, few studies have investigated the association between outdoor LAN exposure and executive function., Methods: We employed data from 48,502 Chinese children aged 5-12 years in a cross-sectional study conducted in Guangdong province during 2020-2021, to examine the association between outdoor LAN and executive function assessed using the validated parent-completed Behavior Rating Inventory of Executive Function. We assessed children's outdoor LAN exposure using the night-time satellite images based on the residential addresses. We used generalized linear mixed models to estimate the association between outdoor LAN exposure and executive function scores and executive dysfunction., Results: After adjusting for potential covariates, higher quintiles of outdoor LAN exposure were associated with poorer executive function. Compared to the lowest quintile (Q1), all higher quintiles of exposure showed a significant increased global executive composite (GEC) score with β (95% confidence intervals, CI) of 0.58 (0.28, 0.88) in Q2, 0.59 (0.28, 0.9) in Q3, 0.85 (0.54, 1.16) in Q4, and 0.76 (0.43, 1.09) in Q5. Higher quintiles of exposure were also associated with higher risks for GEC dysfunction with odd ratios (ORs) (95% CI) of 1.34 (1.18, 1.52) in Q2, 1.40 (1.24, 1.59) in Q3, 1.40 (1.23, 1.59) in Q4, and 1.39 (1.22, 1.58) in Q5. And stronger associations were observed in children aged 10-12 years., Conclusions: Our study suggested that high outdoor LAN exposure was associated with poor executive function in children. These findings suggested that future studies should determine whether interventions to reduce outdoor LAN exposure can have a positive effect on executive function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

The research aims to study the therapeutic impact of HEK293-XPack-Olig2 cell-derived exosomes on remyelination of the corpus callosum in a cuprizone-induced demyelinating disease model. A lentiviral vector expressing Olig2 was constructed using XPack technology. The highly abundant Olig2 exosomes (ExoOs) were isolated by centrifugation for subsequent experiments. Western blot, nanoparticle tracking analysis (NTA), and electron microscopy showed no significant difference in particle size and morphology between Exos and ExoOs, and a high level of Olig2 expression could be detected in ExoOs, indicating that exosome modification by XPack technology was successful. The Black Gold/Fluromyelin staining analysis showed that the ExoOs group significantly reduced the demyelination area in the corpus callosum compared to the PBS and Exos groups. Additionally, the PDGFRα/APC staining of the demyelinating region revealed an increase in APC + oligodendrocytes and a decrease in PDGFRα + oligodendrocyte progenitor cells (OPCs) in the ExoOs group. Furthermore, there was evident myelin regeneration in the demyelinated areas after ExoOs treatment, with better g-ratio and a higher number of intact myelin compared to the other treatment groups. The level of Sox10 expression in the brain tissue of the ExoOs group were higher compared to those of the PBS and Exos groups. The demyelination process can be significantly slowed down by the XPack-modified exosomes, the differentiation of OPCs promoted, and myelin regeneration accelerated under pathological conditions. This process is presumed to be achieved by changing the expression level of intracellular differentiation-related genes after exosomes transport Olig2 enriched into oligodendrocyte progenitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetS) is a significant public health problem and presents an escalating clinical challenge globally. To combat this problem effectively, urgent measures including identify some modifiable environmental factors are necessary. Outdoor artificial light at night (LAN) exposure garnered much attention due to its impact on circadian rhythms and metabolic process. However, epidemiological evidence on the association between outdoor LAN exposure and MetS remains limited. To determine the relationship between outdoor LAN exposure and MetS, 15,477 adults participated the 33 Communities Chinese Health Study (33CCHS) in 2009 were evaluated. Annual levels of outdoor LAN exposure at participants' residential addresses were assessed using satellite data from the Defense Meteorological Satellite Program (DMSP) Operational Linescan System (OLS). Generalized linear mixed effect models were utilized to assess the association of LAN exposure with MetS and its components, including elevated waist circumference (WC), triglycerides (TG), blood pressure (BP), fasting blood glucose (FBG), and reduced high-density lipoprotein cholesterol (HDL-C). Effect modification by various social demographic and behavior factors was also examined. Overall, 4701 (30.37 %) participants were defined as MetS. The LAN exposure ranged from 6.03 to 175.00 nW/cm 2 /sr. The adjusted odds ratio (OR) of MetS each quartile increment of LAN exposure were 1.43 (95 % CI: 1.21-1.69), 1.44 (95 % CI: 1.19-1.74) and 1.52 (95 % CI: 1.11-2.08), respectively from Q2-Q4. Similar adverse associations were also found for the components of MetS, especially for elevated BP, TG and FBG. Interaction analyses indicated that the above associations were stronger in participants without habitual exercise compared with those with habitual exercise (e.g. OR were 1.52 [95 % CI: 1.28-1.82] vs. 1.27 [95 % CI, 1.04-1.55], P -interaction  = 0.042 for MetS). These findings suggest that long-term exposure to LAN can have a significant deleterious effect on MetS, potentially making LAN an important modifiable environmental factor to target in future preventive strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Low-dimensional lead halide materials have proved to be intrinsically stable semiconductor materials. However, the development of one-dimensional (1D) perovskites or perovskitoids with both robust water stability and high optoelectronic performance still faces significant challenges. Here, we report a new class of 1D (TzBIPY)Pb 2 X 6 (X = Cl, Br, I) perovskitoids featuring a π-conjugated diamine cation (TzBIPY = 2,5-di(pyridin-4-yl)thiazolo[5,4-d]thiazole). The TzBIPY 2+ cation with delocalized electrons directly contributes to the electronic structure and hence reduces the band gap. Especially, the Br-based material exhibits enhanced carrier separation and transport capacity, benefiting from the improved electronic conjugation together with a type II intramolecular heterojunction between conjugated organic cations and Pb-X octahedra. The (TzBIPY)Pb 2 Br 6 photodetector exhibits an impressive photocurrent on/off ratio of 8.1 × 10 5 , which is much superior to the previous three-dimensional (3D) perovskite benchmark. Additionally, the π-conjugated cations serve as dense protective shields for vulnerable Pb-X inorganic lattice against being attacked by water, thus demonstrating exceptional stability even immersed in water for over 3000 h., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the potential role of autophagy-related genes in MS diseases by using bioinformatics combined with machine learning methods. Finally, we obtained 9 autophagy genes with the highest correlation with MS, and further changes in these autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of great significance for the further exploration of autophagy-related genes in demyelinating diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Demyelinating diseases are often caused by a variety of triggers, including immune responses, viral infections, malnutrition, hypoxia, or genetic factors, all of which result in the loss of myelin in the nervous system. The accumulation of myelin debris at the lesion site leads to neuroinflammation and inhibits remyelination; therefore, it is crucial to promptly remove the myelin debris. Initially, Fc and complement receptors on cellular surfaces were the primary clearance receptors responsible for removing myelin debris. However, subsequent studies have unveiled the involvement of additional receptors, including Mac-2, TAM receptors, and the low-density lipoprotein receptor-related protein 1, in facilitating the removal process. In addition to microglia and macrophages, which serve as the primary effector cells in the disease phase, a variety of other cell types such as astrocytes, Schwann cells, and vascular endothelial cells have been demonstrated to engage in the phagocytosis of myelin debris. Furthermore, we have concluded that oligodendrocyte precursor cells, as myelination precursor cells, also exhibit this phagocytic capability. Moreover, our research group has innovatively identified the low-density lipoprotein receptor as a potential phagocytic receptor for myelin debris. In this article, we discuss the functional processes of various phagocytes in demyelinating diseases. We also highlight the alterations in signaling pathways triggered by phagocytosis, and provide a comprehensive overview of the various phagocytic receptors involved. Such insights are invaluable for pinpointing potential therapeutic strategies for the treatment of demyelinating diseases by targeting phagocytosis., (© 2024 Wiley Periodicals LLC.)

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas., Competing Interests: Declaration of interests T.M.Y. is a co-founder, stockholder, and member of the board of directors of DESTROKE, Inc., an early stage start-up developing mobile technology for automated clinical stroke detection. J.L.J. has received consulting fees from Scorpion Therapeutics and Volastra Therapeutics. L.C.C. is a founder and member of the board of directors of Agios Pharmaceuticals and is a founder of Petra Pharmaceuticals. L.C.C. is an inventor on patents (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment. L.C.C. is a co-founder and shareholder in Faeth Therapeutics. P.W. is a statistical consultant for Sema4. M.G.C. receives research support from Merck, Orbus Therapeutics, and NeoimmuneTech Inc, and royalties from UpToDate., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: Clinical diagnostic value of circ-ARHGER28 in breast cancer (BC), and the biological functions of circ-ARHGER28 on the proliferation and apoptosis of MCF-7 cells were investigated., Materials and Methods: Human circRNA microarray was performed to analyze the expression of circRNAs in BC patients. RT-qPCR combined with bioinformatics analysis was applied to verify the candidate circRNAs in BC tissues and peripheral blood samples. Circ-ARHGER28 was chosen as the candidate gene for further research. The clinical diagnostic value and biological functions of circ-ARHGER28 were analyzed. The overexpression and negative control vector of circ-ARHGER28 were constructed and transfected to MCF-7 cells. The CCK 8 assay and clone formation experiments were applied to detect the cell proliferative and migratory abilities. Flow cytometry was used to analyze cell apoptosis and cell cycle distribution. RT-qPCR and Western blot were performed to detect apoptosis and expression of PI3K/AKT/mTOR-associated genes and proteins., Results: Overexpression of circ-ARHGER28 inhibited the proliferation, colony formation and migration of MCF-7 cells, while increasing the population of the cells in the G 2 /M phase and the apoptotic rate. Apoptosis associated genes and proteins were significantly increased, whereas gene and protein expression of PI3K, AKT and mTOR were decreased in the cells., Conclusion: Circular RNA ARHGER28 exhibits promising diagnostic value for BC. Circ-ARHGER28 inhibited MCF-7 cell proliferation and increased the apoptotic rate. The function of circ-ARHGER28 was associated with the PI3K/AKT/mTOR signaling pathway. Circ-ARHGER28 could be an ideal biomarker for BC diagnosis and a novel target for BC therapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Multiple sclerosis (MS) is a class of autoimmune diseases mainly caused by the immune system attacking the myelin sheath of the axons in the nervous system. Although the pathogenesis of MS is complex, studies have shown that dendritic cells (DCs) play a vital role in the pathogenesis of MS. Quercetin (QU) has a unique advantage in clinical application, especially for treating autoimmune diseases. However, the mechanism of QU in the treatment of experimental autoimmune encephalomyelitis (EAE) remains unclear. In this study, we explore the potential role of QU in EAE. Finally, we find that QU has anti-inflammatory activities and neural protective effects in EAE. The experimental results suggest that the cellular basis for QU's function is to inhibit the activation of DCs while modulating the Th17 cell differentiation in the co-culture system. Further, QU may target STAT4 to inhibit its activation in DCs. This work will be of great significance for the future development and utilization of QU., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Demyelination is a proper syndrome in plenty of central nervous system (CNS) diseases, which is the main obstacle to recovery and still lacks an effective treatment. To overcome the limitations of the brain-blood barrier on drug permeability, we modified an exosome secreted by neural stem cells (NSCs), which had transfected with lentivirus armed with platelet-derived growth factors A (PDGFA)-ligand. Through the in vivo and in vitro exosomes targeting test, the migration ability to the lesion areas and OPCs significantly improved after ligand modification. Furthermore, the targeted exosomes loaded with 3,5, 30-L-triiodothyronine (T3) have a critical myelination ability in CNS development, administrated to the cuprizone animal model treatment. The data shows that the novel drug vector loaded with T3 significantly promotes remyelination compared with T3 alone. At the same time, it improved the CNS microenvironment by reducing astrogliosis, inhibiting pro-inflammatory microglia, and alleviating axon damage. This investigation provides a straightforward strategy to produce a targeting exosome and indicates a possible therapeutic manner for demyelinating disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 μM (P<0.01) and 40 μM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 μM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P&lt;0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P&lt;0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P&lt;0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P&lt;0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

Wood-rotting fungi are organisms that can decompose wood substrates and extract nutrients from them to support their growth. They play a crucial role in the material cycle of forest ecosystems. The genus Pluteus plays a significant role in wood decomposition. In this study, the morphology and molecular systematics of the sect. Celluloderma of the genus Pluteus were carried out. Pluteusbrunneodiscus was identified as a new species, along with the discovery of two new records, P.cystidiosus and P.chrysophlebius , and a common species, P.romellii . Pluteusbrunneodiscus is characterized by the brown center of the pileus that transitions to white towards the margins, with the surface cracking to form irregular granules. It is typically found in Populus forests growing on decomposing twigs or wood chips. Line drawings, color photographs, and phylogenetic analyses of related species within the genus Pluteus accompany the descriptions of these four species. The analyses are based on ITS + TEF1-α sequence data. Finally, a key for the twenty species within the sect. Celluloderma of the genus Pluteus , which has been documented in China, is provided., Competing Interests: The authors have declared that no competing interests exist., (Zheng-Xiang Qi, Ke-Qing Qian, Lei Yue, Li-Bo Wang, Di-Zhe Guo, Dong-Mei Wu, Neng Gao, Bo Zhang, Yu Li.)

Cardiovascular diseases (CVDs) become a major public health concern. Evidence concerning the effects of outdoor artificial light at night (ALAN) on CVD in adults is scarce. We aimed to investigate the extent to which outdoor ALAN could affect the risk of CVD over a exposure range. Data from the China Health and Retirement Longitudinal Study, a population-based longitudinal study, launched in 2011-2012 and follow up till 2018, covering 28 provinces, autonomous regions and municipalities across mainland China. This study included 14,097 adults aged ≥45 years. Outdoor ALAN exposure (in nanowatts per centimeters squared per steradian) within 500 m of each participant's baseline residence was obtained from satellite image data. CVD was defined from medical diagnosis. The population was divided into three groups based on outdoor ALAN exposure from low to high. Cox regression model was used to estimate the association between outdoor ALAN exposure and incident CVD with hazard ratios (HRs) and 95 % confidence intervals (CIs). The mean (SD) age of the cohort was 57.6 (9.1) years old and 49.3 % were males. Outdoor ALAN exposure of study participants ranged from 0.02 to 39.79 nW/cm 2 /sr. During 83,033 person-years of follow-up, 2190 (15.5 %) cases of CVD were identified. Both low (HR: 1.21; 95 % CI: 1.02-1.43) and high (HR: 1.23; 95 % CI: 1.04-1.46) levels of outdoor ALAN exposure group were associated with higher risk of CVD compared with intermediate levels of outdoor ALAN exposure group. Body mass index was a significant effect modifier in the association between outdoor ALAN and risk of CVD, with stronger effects among those who was overweight or obese. The findings of this study suggest that low and high outdoor ALAN exposure were associated with a higher risk for CVD. More attention should be given to the cardiovascular effects associated with outdoor ALAN exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Demyelination is a pathological feature commonly observed in various central nervous system diseases. It is characterized by the aggregation of oligodendrocyte progenitor cells (OPCs) in the lesion area, which face difficulties in differentiating into mature oligodendrocytes (OLGs). The differentiation of OPCs requires the presence of Sox10, but its expression decreases under pathological conditions. Therefore, we propose a therapeutic strategy to regulate OPCs differentiation and achieve myelin repair by endogenously loading Sox10 into exosomes. To accomplish this, we generated a lentivirus-armed Sox10 that could anchor to the inner surface of the exosome membrane. We then infected HEK293 cells to obtain exosomes with high expression of Sox10 (exosomes-Sox10, ExoSs). In vitro, experiments confirmed that both Exos and ExoSs can be uptaken by OPCs, but only ExoSs exhibit a pro-differentiation effect on OPCs. In vivo, we administered PBS, Exos, and ExoSs to cuprizone-induced demyelinating mice. The results demonstrated that ExoSs can regulate the differentiation of PDGFRα + OPCs into APC + OLGs and reduce myelin damage in the corpus callosum region of the mouse brain compared to other groups. Further testing suggests that Sox10 may have a reparative effect on the myelin sheath by enhancing the expression of MBP, possibly facilitated by the exosome delivery of the protein into the lesion. This endogenously loaded technology holds promise as a strategy for protein-based drugs in the treatment of demyelinating diseases., Competing Interests: Declaration of Competing Interest We confirm this manuscript is original and has not been published before. We confirm that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted. The authors declare that they have no conflicts of interest to this work., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Previous studies have linked exposure to light at night (LAN) with various health outcomes, but evidence is limited for the LAN-obesity association. Thestudy analysed data from 24,845 participants of the 33 Communities Chinese Health Study and obesity (BMI ≥28 kg/m 2 ) was defined according to the Working Group on Obesity in China. The Global Radiance Calibrated Nighttime Lights data were used to estimate participants' LAN exposure. The mixed-effect regression models examined the LAN-BMI and LAN-obesity association. We found that higher LAN exposure was significantly associated with greater BMI and higher risk of obesity. Changes of BMI and the odds ratios (ORs) of obesity and 95% confidence intervals (CIs) for 2 nd , 3 rd , and 4 th against the 1 st quartile of LAN exposure were 0.363 (0.208, 0.519), 0.364 (0.211, 0.516) and 0.217 (0.051, 0.383); 1.228 (1.099, 1.371), 1.356 (1.196, 1.538) and 1.269 (1.124, 1.433), respectively. Age and regular exercise showed significant modification effects on the LAN-obesity association.

Demyelination and failure of remyelination in the central nervous system (CNS) characterize a number of neurological disorders. Spontaneous remyelination in demyelinating diseases is limited, as oligodendrocyte precursor cells (OPCs), which are often present in demyelinated lesions in abundance, mostly fail to differentiate into oligodendrocytes, the myelinating cells in the CNS. In addition to OPCs, the lesions are assembled numbers of activated resident microglia/infiltrated macrophages; however, the mechanisms and potential role of interactions between the microglia/macrophages and OPCs are poorly understood. Here, we generated a transcriptional profile of exosomes from activated microglia, and found that miR-615-5p was elevated. miR-615-5p bound to 3'UTR of myelin regulator factor (MYRF), a crucial myelination transcription factor expressed in oligodendrocyte lineage cells. Mechanistically, exosomes from activated microglia transferred miR-615-5p to OPCs, which directly bound to MYRF and inhibited OPC maturation. Furthermore, an effect of AAV expressing miR-615-5p sponge in microglia was tested in experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ)-induced demyelination model, the classical mouse models of multiple sclerosis. miR-615-5p sponge effectively alleviated disease progression and promoted remyelination. This study identifies miR-615-5p/MYRF as a new target for the therapy of demyelinating diseases., (© 2024. The Author(s).)

Developing a single-domain assay to identify individuals at high risk of future events is a priority for multi-disease and mortality prevention. By training a neural network, we developed a disease/mortality-specific proteomic risk score (ProRS) based on 1461 Olink plasma proteins measured in 52,006 UK Biobank participants. This integrative score markedly stratified the risk for 45 common conditions, including infectious, hematological, endocrine, psychiatric, neurological, sensory, circulatory, respiratory, digestive, cutaneous, musculoskeletal, and genitourinary diseases, cancers, and mortality. The discriminations witnessed high accuracies achieved by ProRS for 10 endpoints (e.g., cancer, dementia, and death), with C-indexes exceeding 0.80. Notably, ProRS produced much better or equivalent predictive performance than established clinical indicators for almost all endpoints. Incorporating clinical predictors with ProRS enhanced predictive power for most endpoints, but this combination only exhibited limited improvement when compared to ProRS alone. Some proteins, e.g., GDF15, exhibited important discriminative values for various diseases. We also showed that the good discriminative performance observed could be largely translated into practical clinical utility. Taken together, proteomic profiles may serve as a replacement for complex laboratory tests or clinical measures to refine the comprehensive risk assessments of multiple diseases and mortalities simultaneously. Our models were internally validated in the UK Biobank; thus, further independent external validations are necessary to confirm our findings before application in clinical settings., (© 2023. The Author(s).)

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-β-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Hyperhomocysteinemia (HHcy) is considered to be an independent risk factor for cardiovascular diseases, but the molecular mechanisms underlying its pathogenesis are not fully understood. Endothelial dysfunction is a key initiating factor in the pathogenesis of atherosclerosis, which is commonly observed in almost all HHcy-induced vascular diseases. HHcy promotes oxidative stress, inhibits nitric oxide production, suppresses hydrogen sulfide signaling pathway, promotes endothelial mesenchymal transition, activates coagulation pathways, and promotes protein N-homocysteination and cellular hypomethylation, all of which can cause endothelial dysfunction. This article reviews the specific links between HHcy and endothelial dysfunction, and highlights recent evidence that endothelial mesenchymal transition contributes to HHcy-induced vascular damage, with a hope to provide new ideas for the clinical treatment of HHcy-related vascular diseases.

Objective: To evaluate the correlation between clinical characteristics and radionuclide salivagram findings in infants with congenital laryngeal developmental anomalies, and determine the clinical characteristics that could predict the positive results of radionuclide salivagram., Methods: 151 hospitalized infants with congenital laryngeal developmental anomalies were retrospectively included to assess the correlation between positive radionuclide salivagram results and clinical features, and a multivariate logistic regression model was constructed to identify significant correlates that jointly predict positive radionuclide salivagram results., Results: Positive radionuclide salivagram results were significantly associated with fever, neurological diseases, congenital syndromes, and positive pathogenetic test results in univariate analysis. Positive radionuclide salivagram were significantly associated with fever (odds ratio [OR] = 3.494; 95% confidence interval [CI] 1.414-8.630; P = 0.007), neurological diseases (OR = 3.296; 95% CI 1.335-8.138; P = 0.010), and congenital syndromes (OR = 5.069, 95% CI 1.696-15.154; P = 0.004) in a multivariable logistic regression analysis., Conclusion: Fever, concurrent neurological diseases, and concurrent congenital syndromes were discovered as clinical factors that could predict positive radionuclide salivagram results and salivary aspiration should be highly suspected in infants with these clinical factors of congenital laryngeal developmental anomalies., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT., (© 2023 Wiley Periodicals LLC.)

Post-translational modifications (PTMs) play key roles in regulating cell signaling and physiology in both normal and cancer cells. Advances in mass spectrometry enable high-throughput, accurate, and sensitive measurement of PTM levels to better understand their role, prevalence, and crosstalk. Here, we analyze the largest collection of proteogenomics data from 1,110 patients with PTM profiles across 11 cancer types (10 from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium [CPTAC]). Our study reveals pan-cancer patterns of changes in protein acetylation and phosphorylation involved in hallmark cancer processes. These patterns revealed subsets of tumors, from different cancer types, including those with dysregulated DNA repair driven by phosphorylation, altered metabolic regulation associated with immune response driven by acetylation, affected kinase specificity by crosstalk between acetylation and phosphorylation, and modified histone regulation. Overall, this resource highlights the rich biology governed by PTMs and exposes potential new therapeutic avenues., Competing Interests: Declaration of interests Y.G. is a consultant for Oriel Research Therapeutics. T.M.Y. is a co-founder, stockholder, and on the board of directors of DESTROKE, Inc., an early-stage start-up developing mobile technology for automated clinical stroke detection. J.L.J. has received consulting fees from Scorpion Therapeutics and Volastra Therapeutics. Y.E.M. is a consultant for ForseeGenomics and is also an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, and MSIDetect. N.J.H. is a consultant for MorphoSys. F.A. is an inventor on a patent application related to SignatureAnalyzer-GPU and has been an employee of Illumina, Inc., since 8 November 2021. L.C.C. is a founder and member of the board of directors of Agios Pharmaceuticals and is a founder of Petra Pharmaceuticals. L.C.C. is an inventor on patents (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment. L.C.C. is a co-founder and shareholder in Faeth Therapeutics. G.G. receives research funds from IBM, Pharmacyclics, and Ultima Genomics, and is also an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, POLYSOLVER, SignatureAnalyzer-GPU, MSIDetect, and MinimuMM-Seq. He is also a founder, consultant, and privately held equity in Scorpion Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying their significant cis-effects and distal trans-effects quantified at the RNA, protein, and phosphoprotein levels. Salient observations include the association of point mutations and copy-number alterations with the rewiring of protein interaction networks, and notably, most cancer genes converge toward similar molecular states denoted by sequence-based kinase activity profiles. A correlation between predicted neoantigen burden and measured T cell infiltration suggests potential vulnerabilities for immunotherapies. Patterns of cancer hallmarks vary by polygenic protein abundance ranging from uniform to heterogeneous. Overall, our work demonstrates the value of comprehensive proteogenomics in understanding the functional states of oncogenic drivers and their links to cancer development, surpassing the limitations of studying individual cancer types., Competing Interests: Declaration of interests Y.G. is a consultant for Oriel Research Therapeutics. T.M.Y. is a co-founder, stockholder, and member of the board of directors of DESTROKE, Inc., an early-stage start-up developing mobile technology for automated clinical stroke detection. J.L.J. has received consulting fees from Scorpion Therapeutics and Volastra Therapeutics. F.A. is an inventor on a patent application related to SignatureAnalyzer-GPU and has been an employee of Illumina, Inc., since 8 November 2021. L.C.C. is a founder and member of the board of directors of Agios Pharmaceuticals and is a founder of Petra Pharmaceuticals. L.C.C. is an inventor on patents (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment. L.C.C. is a co-founder and shareholder in Faeth Therapeutics. G.G. receives research funds from IBM, Pharmacyclics, and Ultima Genomics and is also an inventor on patent applications filed by the Broad Institute related to MSMuTect, MSMutSig, POLYSOLVER, SignatureAnalyzer-GPU, MSIDetect, and MinimuMM-Seq. G.G. is also a founder, consultant, and privately held equity in Scorpion Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic pain causes both physical suffering and comorbid mental symptoms such as anhedonia. However, the neural circuits and molecular mechanisms underlying these maladaptive behaviors remain elusive. Here using a mouse model, we report a pathway from vesicular glutamate transporter 3 neurons in the dorsal raphe nucleus to dopamine neurons in the ventral tegmental area (VGluT3 DRN →DA VTA ) wherein population-level activity in response to innocuous mechanical stimuli and sucrose consumption is inhibited by chronic neuropathic pain. Mechanistically, neuropathic pain dampens VGluT3 DRN  → DA VTA glutamatergic transmission and DA VTA neural excitability. VGluT3 DRN  → DA VTA activation alleviates neuropathic pain and comorbid anhedonia-like behavior (CAB) by releasing glutamate, which subsequently promotes DA release in the nucleus accumbens medial shell (NAcMed) and produces analgesic and anti-anhedonia effects via D2 and D1 receptors, respectively. In addition, VGluT3 DRN  → DA VTA inhibition produces pain-like reflexive hypersensitivity and anhedonia-like behavior in intact mice. These findings reveal a crucial role for VGluT3 DRN  → DA VTA  → D2/D1 NAcMed pathway in establishing and modulating chronic pain and CAB., (© 2023. Springer Nature Limited.)

Porcine sapelovirus (PSV) is a ubiquitous virus in farmed pigs that is associated with SMEDI syndrome, polioencephalomyelitis, and diarrhea. However, there are few reports on the prevalence and molecular characterization of PSV in Fujian Province, Southern China. In this study, the prevalence of PSV and a poetical combinative strain PSV2020 were characterized using real-time PCR, sequencing, and bioinformatics analysis. As a result, an overall sample prevalence of 30.8% was detected in 260 fecal samples, and a farm prevalence of 76.7% was observed in 30 Fujian pig farms, from 2020 to 2022. Noteably, a high rate of PSV was found in sucking pigs. Bioinformatics analysis showed that the full-length genome of PSV2020 was 7550 bp, and the genetic evolution of its ORF region was closest to the G1 subgroup, which was isolated from Asia and America; the similarity of nucleotides and amino acids to other PSVs was 59.5~88.7% and 51.7~97.0%, respectively. However, VP1 genetic evolution analysis showed a distinct phylogenetic topology from the ORF region; PSV2020 VP1 was closer to the DIAPD5469-10 strain isolated from Italy than strains isolated from Asia and America, which comprise the G1 subgroup based on the ORF region. Amino acid discrepancy analysis illustrated that the PSV2020 VP1 gene inserted twelve additional nucleotides, corresponding to four additional amino acids (STAE) at positions 898-902 AAs. Moreover, a potential recombination signal was observed in the 2A coding region, near the 3' end of VP1, owing to recombination analysis. Additionally, 3D genetic evolutionary analysis showed that all reference strains demonstrated, to some degree, regional conservation. These results suggested that PSV was highly prevalent in Fujian pig farms, and PSV2020, a PSV-1 genotype strain, showed gene diversity and recombination in evolutionary progress. This study also laid a scientific foundation for the investigation of PSV epidemiology, molecular genetic characteristics, and vaccine development.

The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) investigates tumors from a proteogenomic perspective, creating rich multi-omics datasets connecting genomic aberrations to cancer phenotypes. To facilitate pan-cancer investigations, we have generated harmonized genomic, transcriptomic, proteomic, and clinical data for >1000 tumors in 10 cohorts to create a cohesive and powerful dataset for scientific discovery. We outline efforts by the CPTAC pan-cancer working group in data harmonization, data dissemination, and computational resources for aiding biological discoveries. We also discuss challenges for multi-omics data integration and analysis, specifically the unique challenges of working with both nucleotide sequencing and mass spectrometry proteomics data., Competing Interests: Declaration of interests F.A. is an inventor on a patent application related to SignatureAnalyzer-GPU filed by the Broad Institute and is an employee and shareholder of Illumina Inc. since 8 November 2021., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We previously showed that death-associated protein kinase 1 (DAPK1) expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease. In addition, depression is a risk factor for developing Alzheimer's disease, as well as an early clinical manifestation of Alzheimer's disease. Meanwhile, cognitive dysfunction is a distinctive feature of major depressive disorder. Therefore, DAPK1 may be related to cognitive dysfunction in major depressive disorder. In this study, we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic, mild, unpredictable stressors. We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area, and tau was hyperphosphorylated at Thr231, Ser262, and Ser396 in these mice. Furthermore, DAPK1 shifted from axonal expression to overexpression on the cell membrane. Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction. These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder., Competing Interests: None

Objective: To evaluate the value of nasal nitric oxide (nNO) measurement as a diagnostic tool for Chinese patients with primary ciliary dyskinesia (PCD). Methods: This study is a retrospective study. The patients were recruited from those who were admitted to the respiratory Department of Respiratory Medicine, Children's Hospital of Fudan University from March 2018 to September 2022. Children with PCD were included as the PCD group, and children with situs inversus or ambiguus, cystic fibrosis (CF), bronchiectasis, chronic suppurative lung disease and asthma were included as the PCD symptom-similar group. Children who visited the Department of Child health Care and urology in the same hospital from December 2022 to January 2023 were selected as nNO normal control group. nNO was measured during plateau exhalation against resistance in three groups. Mann-Whitney U test was used to analyze the nNO data. The receiver operating characteristic of nNO value for the diagnosis of PCD was plotted and, the area under the curve and Youden index was calculated to find the best cut-off value. Results: nNO was measured in 40 patients with PCD group, 75 PCD symptom-similar group (including 23 cases of situs inversus or ambiguus, 8 cases of CF, 26 cases of bronchiectasis or chronic suppurative lung disease, 18 cases of asthma), and 55 nNO normal controls group. The age of the three groups was respectively 9.7 (6.7,13.4), 9.3 (7.0,13.0) and 9.9 (7.3,13.0) years old. nNO values were significantly lower in children with PCD than in PCD symptom-similar group and nNO normal controls (12 (9,19) vs. 182 (121,222), 209 (165,261) nl/min, U =143.00, 2.00, both P <0.001). In the PCD symptom-similar group, situs inversus or ambiguus, CF, bronchiectasis or chronic suppurative lung disease and asthma were significantly higher than children with PCD (185 (123,218), 97 (52, 132), 154 (31, 202), 266 (202,414) vs. 12 (9,19) nl/min, U =1.00, 9.00, 133.00, 0, all P <0.001). A cut-off value of 84 nl/min could provide the best sensitivity (0.98) and specificity (0.92) with an area under the curve of 0.97 (95% CI 0.95-1.00, P <0.001). Conclusions: nNO value can draw a distinction between patients with PCD and others. A cut-off value of 84 nl/min is recommended for children with PCD.

Background: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown., Objective: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis., Methods: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot., Results: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway., Conclusion: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Metschnikowia bicuspidata is a pathogenic yesst that can cause disease in many different economic aquatic animal species. In recent years, there was a new disease outbreak in ridgetail white prawn (Exopalaemon carinicauda) in coastal areas of Jiangsu Province China that was referred to as zombie disease by local farmers. The pathogen was first isolated and identified as M. bicuspidata. Although the pathogenicity and pathogenesis of this pathogen in other animals have been reported in some previous studies, research on its molecular mechanisms is still very limited. Therefore, a genome-wide study is necessary to better understand the physiological and pathogenic mechanisms of M. bicuspidata., Result: In this study, we obtained a pathogenic strain, MQ2101, of M. bicuspidata from diseased E. carinicauda and sequenced its whole genome. The size of the whole genome was 15.98 Mb, and it was assembled into 5 scaffolds. The genome contained 3934 coding genes, among which 3899 genes with biological functions were annotated in multiple underlying databases. In KOG database, 2627 genes were annotated, which were categorized into 25 classes including general function prediction only, posttranslational modification, protein turnover, chaperones, and signal transduction mechanisms. In KEGG database, 2493 genes were annotated, which were categorized into five classes, including cellular processes, environmental information processing, genetic information processing, metabolism and organismal systems. In GO database, 2893 genes were annotated, which were mainly classified in cell, cell part, cellular processes and metabolic processes. There were 1055 genes annotated in the PHI database, accounting for 26.81% of the total genome, among which 5 genes were directly related to pathogenicity (identity ≥ 50%), including hsp90, PacC, and PHO84. There were also some genes related to the activity of the yeast itself that could be targeted by antiyeast drugs. Analysis based on the DFVF database showed that strain MQ2101 contained 235 potential virulence genes. BLAST searches in the CAZy database showed that strain MQ2101 may have a more complex carbohydrate metabolism system than other yeasts of the same family. In addition, two gene clusters and 168 putative secretory proteins were predicted in strain MQ2101, and functional analysis showed that some of the secretory proteins may be directly involved in the pathogenesis of the strain. Gene family analysis with five other yeasts revealed that strain MQ2101 has 245 unique gene families, including 274 genes involved in pathogenicity that could serve as potential targets., Conclusion: Genome-wide analysis elucidated the pathogenicity-associated genes of M. bicuspidate while also revealing a complex metabolic mechanism and providing putative targets of action for the development of antiyeast drugs for this pathogen. The obtained whole-genome sequencing data provide an important theoretical basis for transcriptomic, proteomic and metabolic studies of M. bicuspidata and lay a foundation for defining its specific mechanism of host infestation., (© 2023. The Author(s).)

Due to the indiscriminate abuse of pesticides and antibiotics has caused serious threats to the environment and human and animal bodies, the detection of antibiotics and pesticides has attracted widespread attention in recent years. Herein, a novel 2D Cd (II)-MOF, [Cd(L) 0.5 (1,2-bimb)] (Cd-L-1,2-bimb), [H 4 L = 1, 1'-ethylbiphenyl -3, 3', 5, 5'- tetracarboxylic acid, 1, 2-bimb = 1, 2-bis[(1H-imidazol-1-yl) methyl] benzene] is synthesized. Cd-L-1,2-bimb has excellent stability in different organic solvents and in the range of pH 1.1-12.5. Cd-L-1,2-bimb exhibits high selectivity, high sensitivity, and fast luminescent response to pesticides [pyrimethanil (PTH, LOD = 2.2 μM) and abamectin benzoate (AMB, LOD = 2.39 μM)] and antibiotic contaminants tetracycline (TET, LOD = 0.13 μM). Cd-L-1,2-bimb displays discriminative fluorescence when detecting AMB and PTH, and is an implication logic gate. Finally, the possible detection mechanism of Cd-L-1,2-bimb toward different pollutants is also further investigated. This MOF-based multifunctional sensor opens up new prospects for environmental monitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Metastasis of osteosarcoma is an important adverse factor affecting patients' survival, and cancer stemness is the crucial cause of distant metastasis. Capsaicin, the main component of pepper, has been proven in our previous work to inhibit osteosarcoma proliferation and enhance its drug sensitivity to cisplatin at low concentrations. This study aims to further explore the anti-osteosarcoma effect of capsaicin at low concentrations (100[Formula: see text][Formula: see text]M, 24[Formula: see text]h) on stemness and metastasis. The stemness of human osteosarcoma (HOS) cells was decreased significantly by capsaicin treatment. Additionally, the capsaicin treatment's inhibition of cancer stem cells (CSCs) was dose-dependent on both sphere formation and sphere size. Meanwhile, capsaicin inhibited invasion and migration, which might be associated with 25 metastasis-related genes. SOX2 and EZH2 were the most two relevant stemness factors for capsaicin's dose-dependent inhibition of osteosarcoma. The mRNAsi score of HOS stemness inhibited by capsaicin was strongly correlated with most metastasis-related genes of osteosarcoma. Capsaicin downregulated six metastasis-promoting genes and up-regulated three metastasis-inhibiting genes, which significantly affected the overall survival and/or disease-free survival of patients. In addition, the CSC re-adhesion scratch assay demonstrated that capsaicin inhibited the migration ability of osteosarcoma by inhibiting its stemness. Overall, capsaicin exerts a significant inhibitory effect on the stemness expression and metastatic ability of osteosarcoma. Moreover, it can inhibit the migratory ability of osteosarcoma by suppressing its stemness via downregulating SOX2 and EZH2 . Therefore, capsaicin is expected to be a potential drug against osteosarcoma metastasis due to its ability to inhibit cancer stemness.