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Lian Chen,1,* Yu-Huan Jiang,2,* Mei-Yong Li,3 Bo Huang,3 Lei Yuan,2 Jin-Hua Wan,2 Ting-Yu Qin,2 Ting-Ting Zeng,2 Qing-Gen Chen2 1Department of Ultrasound Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China*These authors contributed equally to this studyCorrespondence: Qing-Gen Chen, Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China, Tel/Fax +86 0791-86319420, Email 272880243@qq.comPurpose: The aim of the present study was to identify more effective laboratory markers to assess the severity of corona virus disease 2019 and predict the progression of the disease by collecting more laboratory markers and variables.Patients and Methods: In this study, most risk factors, including epidemiological characteristics, blood cell counts, cytokines, and infection markers, were collected from 126 patients with COVID-19 to assess their predictive value.Results: The area under curve (AUC) of Albumin (Alb) to fibrinogen (Fib) ratio (AFR) (0.791), Lactate dehydrogenase (LDH) (0.792), myoglobin (MYO) (0.795), C-reactive protein (CRP) (0.801) and lymphocyte count (0.859) were higher than other markers to distinguish severe from non-severe patients in receiver operating characteristic (ROC) analysis. In the univariate logistic regression analysis, thirty-six out of 46 risk factors, including 34 laboratory markers, were significantly associated with increased odds of severe patients. Multivariate logistic regression analysis showed that the CD19+ lymphocyte count, MYO, LDH, and AFR were associated with increased odds of severe disease. Moreover, Lymphocyte count and AFR levels increased, LDH and CRP levels decreased during hospitalization in recovered severe patients, whereas severe lymphocytopenia and continuously increasing LDH levels were observed in deteriorated patients. AFR level increased and CRP level decreased before the disease worsened in the deteriorated patients; however, when the patients deteriorated, AFR decreased and CRP increased significantly.Conclusion: CD19+ lymphocyte count, MYO, LDH, and AFR are independent biomarkers for early identification of severe COVID-19. Lymphocyte count, AFR, LDH, and CRP levels were helpful in predicting the clinical progression of the disease.\. Keywords: Albumin to fibrinogen ratio, C-reactive protein, Lymphocyte, Coronavirus Disease 2019, Inflammation

Xiufeng Chen, Yong hong Jiang, Xiaoqin Fei, Mingjing Wang, Anqi Liu, Xuejun Li, Zhiyan Jiang Department of Pediatrics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Zhiyan Jiang, Email jiangzhiyan@shutcm.edu.cnBackground: Asthma severely interferes with people’s lives through coughing, wheezing and inflammation of the lungs. Herbacetin is a class of natural compounds that inhibit the development of inflammation. However, whether Herbacetin inhibits asthma has not been definitively studied.Methods: Lipopolysaccharides (LPS)-induced lung epithelial (BASE-2B) cells injury model was established, and then the relief of damaged BASE-2B cells with different concentrations of Herbacetin was examined. The cell counting kit (CCK8) was used to detect the effect of Herbacetin on the proliferation ability in ovalbumin (OVA)-induced asthma mice model, and Western Blot and flow cytometry were used to detect the effect of Herbacetin on the apoptosis in OVA-induced asthma mice model. Additionally, pulmonary pathology was detected by HE and Masson staining, and serum inflammatory factors were detected by alveolar lavage fluid.Results: Herbacetin reduces BESA-2B cells induced by LPS level of inflammation, and reactive oxygen species (ROS) generation, inhibits cell apoptosis, promotes cell proliferation, OVA-induced mice lung histopathology test HE staining, serum inflammatory factors show the same results. Western Blot shows that Herbacetin regulates the expression of Caspase-3, Bax, and Bcl-2. SGK1 overexpression increased the rate of apoptosis, and Herbacetin reversed this phenomenon. By silencing the expression of SGK1, it was found that Herbacetin was an inhibitor of SGK1, which could inhibit the NF-κB/p-P65 pathway in asthmatic airway inflammation.Conclusion: Herbacetin reduces pro-inflammatory cytokine levels by inhibiting the SGK1/NF-κB pathway. Our data suggest that Herbacetin has a significant anti-inflammatory effect on asthma and can be used as a potential therapeutic agent.Keywords: asthma, herbacetin, SGK1, NF-κB, anti-inflammatory

Fang-Hong Shi,1,&ast; Bin-Bin Yu,2,&ast; Long Shen,3,&ast; Li Xu,3 Yi-Hong Jiang,4 Zhi-Chun Gu,1 Hou-Wen Lin,1 Hao Li5 1Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmacy, Huangyan Hospital of Wenzhou Medical University, Taizhou First People’s Hospital, Zhejiang, People’s Republic of China; 3Department of Cardiology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Endocrinology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Clinical Research Ward, Clinical Research Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Chun Gu, Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Email guzhichun213@163.com Hao Li, Clinical Research Ward, Clinical Research Center, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email lihao19880810@hotmail.comPurpose: The aim of this study was to evaluate whether intervention by clinical pharmacists can improve blood glucose and lipid levels in diabetic patients with complex medical conditions.Methods: The retrospective database included 138 patients with diabetes who had presented with acute myocardial infarction (AMI) between January 2019 and October 2021. Blood glucose and lipid levels were measured within 12 weeks and 78 weeks of follow-up. Propensity score matching (PSM) was used to balance the confounding effects of patients’ characteristics.Results: A total of 138 eligible patients were assigned to either the intervention group (n = 47) or the usual care group (n = 91). After the intervention, there were significant improvements in blood glucose (glycosylated hemoglobin-HbA1C % from 9.0 to 8.3; fasting blood glucose-FBG mmol/L from 11.3 to 7.1; postprandial blood glucose-PBG mmol/L from 17.0 to 12.1; p < 0.001) and lipid levels (total cholesterol-TC from 4.9 to 3.5, low-density lipoprotein cholesterol-LDL-C from 3.0 to 1.8, p < 0.001, mmol/L) in both follow-up periods. The blood glucose effects were most pronounced in the PBG control rate (76.9% vs 54.0%) before PSM, while HbA1C% and PBG control rate after PSM were significantly higher in the intervention group (HbA1C% rate: 65.6% vs 38.5%; PBG rate: 79.2% vs 45.8%; p < 0.05, intervention vs non-intervention). Subgroup analysis further confirmed the improvement of blood glucose and lipid mainly in patients with higher baseline FBG (≧10mmol/L) and moderate follow-up duration (4– 12 weeks).Conclusion: The intervention of clinical pharmacists in multidisciplinary team can significantly improve blood glucose and lipid levels in complex type 2 diabetic patients, especially those with high baseline FBG and moderate follow-up durations.Keywords: blood glucose, blood lipid, clinical pharmacist’s intervention, propensity score matching, complex diabetes

Chuan-An Yi,1,&ast; Yu-Hong Jiang,1,&ast; Ye Wang,2 Yu-Xian Li,3 Shi-Chang Cai,4 Xiu-Yu Wu,4 Xiang-Shang Hu,4 Xing-Guang Wan4 1Medical Morphology Experimental Center, Hunan University of Medicine, Hunan, People’s Republic of China; 2Key Laboratory of Dong Medical Research Hunan Province, Hunan, People’s Republic of China; 3Department of Neurology, Hunan University of Medicine, Hunan, People’s Republic of China; 4Department of Anatomy, Hunan University of Medicine, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan-An YiMedical Morphology Experimental Center, Hunan University of Medicine, Huaihua, 418000, Hunan Province, People’s Republic of ChinaTel +86-18674537258Email 2271604137@qq.comXing-Guang WanDepartment of Anatomy, Hunan University of Medicine, Hunan, People’s Republic of ChinaTel +86 4752382481Email 414032018@qq.comIntroduction: The study aimed to explore the effects of treatment with black bamboo rhizome extracts on learning and memory and determine the underlying mechanisms in rats with cerebral ischaemia-reperfusion injury.Methods: Sprague-Dawley rats were randomly divided into the following four groups: control, middle cerebral artery occlusion (MCAO), low-dose drug, and high-dose drug groups. Rats underwent MCAO using a suture method before drug treatment. Then, neurological impairment was assessed using the Longa scoring method, and triphenyl tetrazolium chloride staining was used to analyse the cerebral infarction area. The Elliott formula was used to calculate water content in the brain tissue. A Morris water maze (MWM) was used to assess changes in learning and memory abilities, and Western blotting was used to detect cyclic adenosine phosphate response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of MCAO rats.Results: After treatment with black bamboo rhizome extracts, the neurological dysfunction score was lower in the drug groups than in the MCAO group, and a significant difference was observed between the high-dose drug and MCAO groups (P< 0.05). Additionally, the cerebral infarction area was significantly smaller in the drug groups than in the MCAO group (P< 0.01), and the effect was more obvious in the high-dose drug group than in the low-dose drug group. There was also a significant difference in water content between the high-dose drug and MCAO groups, and cerebral oedema was significantly reduced in the high-dose drug group (P< 0.05). In the MWM, the incubation period was significantly reduced, the number of platform crossings was significantly increased, and the search time was prolonged in the drug groups compared with those in the MCAO group (P< 0.05). Moreover, the expression of BDNF and CREB was significantly increased in the drug groups compared to that in the MCAO group, and the increase was more obvious in the high-dose group than in the low-dose group (P< 0.05).Discussion: Black bamboo rhizome extracts significantly improved cognitive dysfunction, reduced cerebral oedema, decreased the cerebral infarction area, and improved the neurological function score and learning and memory abilities in rats with cerebral ischaemia-reperfusion injury.Keywords: rhizome of black bamboo root, cerebral ischaemia-reperfusion injury, cognitive function, CREB/BDNF, mechanism of action

Ji-Feng Feng,1,2 Liang Wang,1 Xun Yang,1 You-Hua Jiang1,21Department of Thoracic Surgery, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, People’s Republic of China; 2Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang Province 310022, People’s Republic of ChinaBackground: We firstly identified a combination of lactate dehydrogenase (LDH) along with albumin (ALB), which was defined as LAR (LDH/ALB ratio). The purpose of our study here was initially to explore the prognostic role of LAR in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy.Patients and methods: A retrospective study was conducted including 346 resectable ESCC patients. Patients who received curative surgery without any neoadjuvant therapy were included in the current study. The X-tile program was performed to calculate the optimal cut-off values for LDH, ALB and LAR. The Kaplan-Meier methods, Cox regression univariate and multivariate analyses were utilized to analyze the prognostic factors for cancer-specific survival (CSS).Results: There were 76 (22.0%) women and 270 (78.0%) men in all 346 patients. The mean value for serum LDH, ALB and LAR were 180±62 U/L (range 28–473 U/L), 40.3±5.3 g/L (range 26.6–52.4 g/L) and 4.6±1.8 (range 0.64–14.97), respectively. According to the X-tile program, the optimum cut-off points were 220 (U/L), 40.5 (g/L), and 5.5 for LDH, ALB, and LAR, respectively. The 5-year CSS was 31.8%. Patients with a high level of LAR (>5.5) were associated with poor CSS (13.3% vs 38.3%, P

Fan Sun,1,* Hong-Xin Peng,2,* Qiu-Fang Gao,1 Shu-Qi Li,1 Jing Zhang,1 Qing-Gen Chen,1 Yu-Huan Jiang,1 Lei Zhang,1 Xiao-Zhong Wang,1 Hou-Qun Ying1 1Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China; 2Department of Clinical Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu, China *These authors contributed equally to this work Introduction: Inflammation and nutrition are considered as two important causes leading to the progression and poor survival of colorectal cancer (CRC). The objective of this study is to investigate the prognostic significance of preoperative albumin-to-fibrinogen ratio (AFR), fibrinogen-to-pre-albumin ratio (FPR), fibrinogen (Fib), albumin (Alb), and pre-albumin (pre-Alb) in CRC individuals. Materials and methods: In this study, 3 years’ follow-up was carried out in 702 stage I–III resected CRC patients diagnosed between January 2008 and December 2013. The optimal cutoff points and prognostic values of AFR, FPR, Fib, Alb, pre-Alb, and a novel carcinoembryonic antigen (CEA)-carbohydrate antigen 19-9 (CA199)-FPR (CCF) score were assessed by X-tile software, Kaplan–Meier curve, and Cox regression model. We established the CRC prognostic nomogram, and its predictive efficacy was determined by Harrell’s concordance index (c-index). Results: Our results showed that high FPR was obviously correlated with poor survival of CRC patients. The prognostic predictive efficacy of CCF score was superior to FPR, CEA, CA199, CEA-CA199 (CCI), and CEA-FPR (CFI) score. Moreover, stage II–III patients harboring high FPR or elevated CCF (score≥1) could benefit from adjuvant chemotherapy, rather than those with low FPR or CCF (score=0). Additionally, the c-index (0.728) of the nomogram containing CCF score was significantly higher than that (0.626) without it (p

Anna K Blakney, Emily A Krogstad, Yonghou H Jiang, Kim A WoodrowDepartment of Bioengineering, University of Washington, Seattle, Washington, USABackground: Electrospun drug-eluting fabrics have enormous potential for the delivery of physicochemically diverse drugs in combination by controlling the underlying material chemistry and fabric microarchitecture. However, the rationale for formulating drugs at high drug loading in the same or separate fibers is unknown but has important implications for product development and clinical applications.Methods: Using a production-scale free-surface electrospinning instrument, we produced electrospun nanofibers with different microscale geometries for the co-delivery of tenofovir (TFV) and levonorgestrel (LNG) – two lead drug candidates for multipurpose prevention of HIV acquisition and unintended pregnancy. We investigated the in vitro drug release of TFV and LNG combinations from composites that deliver the two drugs from the same fiber (combined fibers) or from separate fibers in a stacked or interwoven architecture. For stacked composites, we also examined the role that fabric thickness has on drug-release ­kinetics. We also measured the cytotoxicity and antiviral activity of the drugs delivered alone and in combination.Results: Herein, we report on the solution and processing parameters for the free-surface electrospinning of medical fabrics with controlled microarchitecture and high drug loading (up to 20 wt%). We observed that in vitro release of the highly water-soluble TFV, but not the water-insoluble LNG, was affected by composite microarchitecture, fabric thickness, and drug content. Finally, we showed that the drug-loaded nanofibers are noncytotoxic and that the antiviral activity of TFV is preserved through the electrospinning process and when combined with LNG.Conclusion: Electrospun fabrics with high drug loading create multicomponent systems that benefit from the independent control of the nanofibrous microarchitecture. Our findings are significant because they will inform the design and production of composite electrospun fabrics for the co-delivery of physicochemically diverse drugs that may be useful for multipurpose prevention.Keywords: co-delivery, electrospinning, antiretroviral, contraceptive, microbicide, multipurpose prevention technology

It is a long-standing dream of scientists to capture the ultra-fast dynamicsof molecular or chemical reactions in real time and to make a molecular movie.With free-electron lasers delivering extreme ultraviolet (XUV) light atunprecedented intensities, in combination with pump-probe schemes, it is nowpossible to visualize structural changes on the femtosecond time scale inphoto-excited molecules. In hydrocarbons the absorption of a single photon maytrigger the migration of a hydrogen atom within the molecule. Here, such areaction was filmed in acetylene molecules (C2H2) showing a partial migrationof one of the protons along the carbon backbone which is consistent withdynamics calculations on ab initio potential energy surfaces. Our approachopens attractive perspectives and potential applications for a large variety ofXUV-induced ultra-fast phenomena in molecules relevant to physics, chemistry,and biology.

Epidemiological and experimental data suggest that dietary fiber and fat are major determinants of colorectal cancer. However, the mechanisms by which these dietary constituents alter the incidence of colon cancer have not been elucidated. Evidence indicates that dominant gain-of-function mutations short-circuit protooncogenes and contribute to the pathogenesis of cancer. Therefore, we began to dissect the mechanisms whereby dietary fat and fiber, fed during the initiation, promotion and progression stages of colon tumorigenesis, regulate ras p21 localization, expression and mutation frequency. Male Sprague-Dawley rats (140) were provided with corn oil or fish oil and pectin or cellulose plus or minus the carcinogen azoxymethane (AOM) in a 2x2x2 factorial design and killed after 34 weeks. We have previously shown adenocarcinoma incidence in these animals to be 70.3% (52/74) for corn oil + AOM and 56.1% (37/66) for fish oil + AOM (P < 0.05). Total ras expression as well as ras membrane:cytosol ratio was 4- to 6-fold higher in colon tumors than in mucosa from AOM- or saline-injected rats. Expression of ras in the mucosal membrane fraction was 13% higher for animals fed corn oil compared with fish oil feeding (P < 0.05), which is noteworthy since ras must be localized at the plasma membrane to function. The elevated ras membrane:cytosol ratio in tumors was not due to increased farnesyl protein transferase activity or prenylation state, as nearly all detectable ras was in the prenylated form. Phosphorylated p42 and p44 mitogen activated protein kinase (ERK) expression was two-fold higher in tumor extracts compared with uninvolved mucosa from AOM- and saline-injected rats (P < 0.05). The frequency of K-ras mutations was not significantly different between the various groups, but there was a trend toward a greater incidence of mutations in tumors from corn oil fed rats (85%) compared with fish oil fed rats (58%). Our results indicate that the carcinogen-induced changes in ras expression and membrane localization are associated with the in vivo activation of the ERK pathway. In addition, suppression of tumor development by dietary n-3 polyunsaturated fatty acids may be partly due to a combined effect on colonic ras expression, membrane localization, and mutation frequency. [ABSTRACT FROM PUBLISHER]

Despite death marking the end of life, several gene expression and miRNA-mediated post-transcriptional regulation events may persist or be initiated. The silkworm (Bombyx mori) is a valuable model for exploring life processes, including death. In this study, we combined transcriptomics and miRNAomics analyses of young, old, and postmortem silkworms across the entire process after death to unravel the dynamics of gene expression and miRNA-mediated post-transcriptional regulation. In total, 171 genes exhibited sustained differential expression in postmortem silkworms compared to the pre-death state, which are primarily involved in nerve signaling, transport, and immune response. Postmortem time-specific genes were associated with cell cycle regulation, thermogenesis, immunity, and zinc ion homeostasis. We found that the down-regulated expression of 36 genes related to transcription, epigenetic modification, and homeostasis resulted in a significant shift in global gene expression patterns at 2 h post-death. We also identified five mRNA-miRNA pairs (i.e., bmo-miR-2795-mhca, 2784-achi, 2762-oa1, 277-5p-creb, and 1000-tcb1) associated with stress hormone regulation, transcription activity, and signal transduction. The roles of these pairs were validated through in vivo experiments using miRNA mimics in silkworms. The findings provide valuable insights into the intricate mechanisms underlying the transcriptional and miRNA-mediated post-transcriptional regulation events in animals after death., (© The Author(s) 2024. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Amyloid β peptide (Aβ) induces neurodegeneration in the early stage of Alzheimer's disease (AD), resulting in neuroinflammation, oxidative damage, and mitochondrial impaired function. These reactions were closely associated with the pathological changes of brain microglia. Therefore, it was crucial to investigate the precise process of neuroinflammation induced by Aβ in microglia and discover therapies to alleviate its harmful consequences. This study evaluated the toxicity detection of primary microglia generated by Aβ42 ADDL. identification of inflammatory markers, measurement of ROS, and assessment of mitochondrial energy metabolism, mitochondrial membrane potential damage and mitochondrial ROS to evaluate the reparative properties of natural small molecule compounds Gallic acid and Loganic acid on primary mouse microglia. The findings indicated that Gallic acid and Loganic acid exhibited diverse reparative effects on impaired microglia. Thus, it can be provisionally predicted that Aβ42 ADDL affects microglia and promotes modifications in the NF-кB signaling pathway. Gallic acid and Loganic acid were expected to initially restore the NF-кB signaling pathway, leading to a reduction in M1-microglia and an elevation in M2-microglia, thereby decreasing various inflammatory factors and increasing anti-inflammatory factors. The mitochondrial metabolism, mitochondrial membrane potential, and mitochondrial ROS of primary microglia were restored, leading to a reduction in neuroinflammation., Competing Interests: Declaration of competing interest The authors declare no competing interests in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Ceratocystis fimbriata is a fungal pathogen that infects sweet potato roots, producing enormous economic losses. Cyclic polyhydroxy compound quinic acid is a common metabolite synthesized in plant tissues, including sweet potato tubers, showing weak antifungal properties. Although several O-acylated quinic acid derivatives have been synthesized and found in nature and their antifungal properties have been explored, derivatives based on modification of the carboxylic acid have never been evaluated., Results: In this study, amide derivatives were synthesized via linkage of amines with the carboxylic acid moiety of quinic acid. Derivatives with high dipolar moments and a low number of rotatable bonds showed greater antifungal activities toward C. fimbriata in vitro than quinic and chlorogenic acids. Derivative 5b, which was synthesized by coupling p-aminobenzoic acid (pABA) with quinic acid, had the greatest antifungal activity. 5b showed iron(II)-chelating properties and reduced ergosterol content in C. fimbriata cells, causing irregularities in the fungal cell wall and inhibiting conidia agglutination. Application of 3 mm 5b reduced black rot symptoms in sweet potatoes by 70.1%., Conclusions: Collectively, derivatization of the carboxylic acid from quinic acid was demonstrated to be a suitable strategy to improve the antifungal properties of this compound. This study reveals a new efficient strategy for management of the sweet potato pathogen C. fimbriata. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Fresh-cut produce is often contaminated with Escherichia coli O157, posing a significant risk to public health. This study investigated the synergistic inactivation effect and underlying mechanism of ultrasound (US) combined with Zanthoxylum schinifolium essential oil nanoemulsion (ZEO-NE) against E. coli O157:H7, and explored its potential application in fresh-cut cucumbers. The results demonstrated that combined treatment of US and ZEO-NE significantly reduced the viable counts of E. coli O157:H7 compared to treatment with US or ZEO-NE alone. In particular, US (20 kHz, 345 W/cm 2 ) + ZEO-NE (1.0 mg/mL) treatment for 12 min achieved an 8.91 log colony-forming units (CFU)/mL reduction in viable counts of E. coli O157:H7. Moreover, biofilm formation assay revealed that US+EO-NE treatment significantly reduced mobility, altered surface properties, and inhibited biofilm formation of E. coli O157:H7 cells compared to single treatments. The synergistic inactivation mechanism of US+ZEO-NE treatment against E. coli O157:H7 was revealed to involve increased cell membrane permeability, resulting in leakage of nucleic acids, proteins, and LDH, AKP, and ATP, disruption of cell membrane integrity, and alterations in membrane potential. Additionally, the US+ZEO-NE treatment induced reactive oxygen species accumulation and disrupted cell morphology, ultimately leading to E. coli O157:H7 cell death. Notably, the US+EO-NE treatment also significantly reduced the E. coli O15:H7 counts in fresh-cut cucumbers compared to single treatments, without adversely affecting the quality and sensory properties of the produce during storage at 4 °C for 12 days. Overall, these findings suggest that US+EO-NE is a promising technique for bacterial inactivation, and holds potential for improving microbial safety in fresh-cut produce., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Down syndrome (DS) is a congenital disorder caused by the presence of an extra copy of all or part of chromosome 21. It is characterized by significant intellectual disability, distinct facial features, and growth and developmental challenges. The utilization of metabolomics to analyze specific metabolic markers in maternal amniotic fluid may provide innovative tools and screening methods for investigating the early pathophysiology of trisomy 21 at the functional level., Methods: Amniotic fluid samples were obtained via amniocentesis from 57 pregnancies with DS and 55 control pregnancies between 17 3/7 and 24 0/7  weeks of gestation. The targeted metabolomics focused on 34 organic acids, 17 amino acids, and 5 acylcarnitine metabolites. The untargeted metabolomics analysis concentrated on lipid profiles and included 602 metabolites that met quality control standards. Principal Component Analysis, Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), and false discovery rate (FDR) adjustments were applied. MetaboAnalystR 5.0 was used to perform the metabolic pathway analysis on the identified differential metabolites., Results: Fifty differential metabolites, including L-glutamine, eight organic acids, and 41 lipids, were significantly altered in DS based on three criteria: VIP > 1 in the OPLS-DA model, FDR-adjusted p-value < 0.05, and |log 2 FC| > log 2 (1.5) from a volcano plot of all detected metabolites. An analysis of 212 differential metabolites, selected from both targeted and untargeted approaches (VIP > 1 in the OPLS-DA model and FDR-adjusted p-value < 0.05), revealed significant changes in nine metabolic pathways. Fourteen key metabolites were identified to establish a screening model for DS, achieving an area under the curve of 1.00., Conclusions: Our results underscore the potential of metabolomics approaches in identifying concise and reliable biomarker combinations that demonstrate promising screening performance in DS., (© 2024 John Wiley & Sons Ltd.)

Background: Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). The role of minimally invasive surgery in treating locally advanced UTUC remains controversial. This study aimed to compare the outcomes of open, laparoscopic, and robotic surgeries for managing locally advanced UTUC., Methods: We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes, such as cancer-specific survival, overall survival, disease-free survival and bladder-free survival, were compared between the open, laparoscopic and robotic groups., Results: The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 2-year CSS rates of the open, laparoscopic and robotic groups were 71%, 83%, and 77% respectively (p < 0.001). The robotic group had similar outcomes to the laparoscopic group. (p = 0.061, 0.825, 0.341 for OS, CSS, DFS respectively.) More lymph node dissections were performed and more lymph nodes were harvested in the robotic group (p = 0.009)., Conclusions: Our results demonstrated that minimally invasive surgery, including laparoscopic and robotic surgery, for locally advanced UTUC resulted in oncological outcomes that are non-inferior to those of open surgery., (© 2024. The Author(s).)

Background: Patients with coronavirus disease 2019(COVID-2019) infections may still experience long-term effects, with fatigue being one of the most frequent ones. Clinical research on the long COVID in the Chinese population after infection is comparatively lacking., Objective: To collect and analyze the long-term effects of non-severe COVID-19 infection patients and to develop a model for the prediction of fatigue symptoms., Methods: 223 non-severe COVID-19 patients admitted to one designated hospital were enrolled after finish all the self-designed clinical information registration form and nine-month follow-up. We explored the frequency and symptom types of long COVID. Correlation analysis was done on the neuropsychological scale results. After cluster analysis, lasoo regression and logistic regressions, a nomogram prediction model was produced as a result of investigating the risk factors for fatigue., Results: A total of 108 (48.4%) of the 223 non-severe COVID-19 patients reported sequelae for more than 4 weeks, and of these, 35 (15.7%) had fatigue sequelae that were scale-confirmed. Other sequelae of more than 10% were brain fog ( n  = 37,16.6%), cough ( n  = 26,11.7%) and insomnia (n = 23,10.3%). A correlation between depression and fatigue was discovered following the completion of neuropsychological scale. The duration of hospitalization, the non-use of antiviral medications in treatment, IL-6 and CD16+CD56 + cell levels in blood are the main independent risk factors and predictors of fatigue sequelae in long COVID. Additionally, the neurology diseases and vaccination status may also influence the fatigue sequelae., Conclusion: Nearly half of the patients infected with COVID-19 Omicron variant complained of sequelae, and fatigue was the most common symptom, which was correlated with depression. Significant predictors of fatigue sequelae included length of hospitalization, non-use of antiviral drug, and immune-related serum markers of IL-6 and CD16+CD56 + NK cell levels. The presence of neurology diseases and a lack of vaccination could also predict the occurrence of fatigue sequelae., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Esophageal stricture is one of the complications after esophageal varices sclerotherapy injection (ESI), and the incidence rate is between 2%-10%., Aim: To explore the efficacy of self-expanding metal stent (SEMS) for the stricture after endoscopic injection with cyanoacrylate (CYA) and sclerotherapy for esophageal varices., Methods: We retrospectively analyzed the efficacy of SEMS to improve the stricture after endoscopic injection with CYA and sclerotherapy for esophageal varices in 4 patients from February 2023 to June 2023., Results: The strictures were improved in four patients after stenting. The stent was removed after two weeks because of chest pain with embedding into esophageal mucosa in one patient. The stent was removed after one month, however, the stent was reinserted because of the strictures happening again in two patients. The stent was removed after three months, however, the stent was reinserted because of the strictures happening again in one patient. The stent embedded into esophageal mucosa in three patients. There were 3 patients suffered reflux esophagitis, and the acid reflux was relieved by taking hydrotalcite. There was no other complication of esophageal perforation, bleeding from varices or infection., Conclusion: SEMS may relieve the stricture which happened after endoscopic injection with CYA and sclerotherapy for esophageal varices. However, when we should remove the stent still needs to be explored., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In recent years, the emergence and application of robotic computer-assisted implant surgery (r-CAIS) has resulted in a revolutionary shift in conventional implant diagnosis and treatment. This scoping review was performed to verify the null hypothesis that r-CAIS has a relatively high accuracy of within 1 mm, with relatively few complications and a short operative time. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR). From the 3355 publications identified in the PubMed, Scopus, Web of Science, and Google Scholar databases, 28 were finally included after a comprehensive review and analysis. The null hypothesis is partly accepted, as r-CAIS has a relatively high accuracy (coronal and apical deviation within 1 mm), and no significant adverse events or complications have been reported to date, although additional confirmatory studies are needed. However, there is insufficient evidence for a shorter surgical time, and further clinical research on this topic is required., Competing Interests: Competing interests None., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Pyrethroids (PYR) are among the most widely used insecticides in households, leading to substantial exposure. Children and adolescents, especially during growth spurts, have a reduced capacity to effectively metabolize these insecticides. The relationship between PYR exposure and asthma in these age groups remains poorly understood, highlighting the need for further research.We used data from the 2007-2014 National Health and Nutrition Examination Survey, which included 1181 children aged 6-11 years and 1258 adolescents aged 12-19 years. The concentration of the PYR metabolite 3-phenoxybenzoic acid (3-PBA) in urine was quantified using solid-phase extraction-high-performance liquid chromatography-heated electrospray ionization tandem mass spectrometry. Asthma was defined based on self-reported doctor diagnoses from the questionnaire. PYR exposure was measured using urine samples collected simultaneously with the questionnaire. We explored the association between PYR exposure and asthma using multiple logistic regression analyses, adjusting for potential confounders.Multiple logistic regression analyses revealed no significant association between PYR exposure and asthma in children and adolescent boys (all P > 0.05). In contrast, PYR exposure was significantly associated with asthma in adolescent girls aged 12-19 years. Specifically, for "ever asthma," the odds ratios (ORs) were 2.49 (95% CI = 1.03-5.97) in the second quartile of PYR exposure and 2.48 (95% CI = 1.04-5.91) in the third quartile, each in comparison to the first quartile. For "current asthma," in comparison to the first quartile, the ORs were 3.99 (95% CI = 1.55-10.26) in the second quartile of PYR exposure, 3.39 (95% CI = 1.32-8.70) in the third quartile, and 2.93 (95% CI = 1.24-6.90) in the fourth quartile.Conclusions:Our study found a significant association between PYR exposure and asthma in adolescent girls, whereas no significant association was observed in children and adolescent boys. These findings suggest potential sex and age differences in susceptibility to PYR exposure. Further research is warranted to confirm these results and elucidate the underlying mechanisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Oxytocin can regulate immunological activity directly or indirectly; however, immunological functions and mechanisms of oxytocin actions under chronic stress like cesarean delivery (CD) are poorly understood. Our study found that abnormal oxytocin production and secretion in CD rats caused atrophy of thymic tissues. Neurotoxin kainic acid microinjected into the dorsolateral supraoptic nucleus in male rats selectively reduced hypothalamic oxytocin levels, increased corticotrophin-releasing hormone and plasma interleukin-1β while reducing plasma oxytocin, thyroxine and testosterone levels and causing atrophy of immune tissues. Thus, plasma oxytocin is essential for immunological homeostasis, which involves oxytocin facilitation of thyroid hormone and sex steroid secretion., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner's (HIC) and non-Hunner's IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient's needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition.

Purpose: Dysfunctional voiding (DV) is not uncommon in women with non-neurogenic voiding dysfunction. Because of its unknown pathophysiology, effective and durable treatment is lacking. This study aimed to analyze the results of treatment and predictive factors for a successful outcome of botulinum toxin A (BoNT-A) treatment in female patients with DV., Methods: In total, 66 women with DV confirmed by a videourodynamic study (VUDS) were treated with a BoNT-A injection into the urethral sphincter once (n = 33) or several times (n = 33). VUDS was performed before (baseline) and after the BoNT-A treatment. Patients with a global response assessment of the voiding condition of 2 or 3 and a voiding efficiency (VE) of >20% than baseline were considered to have a successful outcome. The baseline demographics, VUDS parameters, and VUDS DV subtypes were compared between the successful and failed groups. Predictive factors for a successful outcome were investigated by logistic regression analyses., Results: Successful and failed outcomes were achieved in 27 (40.9%) and 39 (59.1%) women, respectively. After BoNT-A injections, the maximum flow rate (Qmax), voided volume, and VE all significantly increased, and the postvoid residual (PVR) was slightly improved. No significant difference in the number of injections and medical comorbidity was found between the groups. However, the successful group had a higher incidence of previous pelvic surgery. No significant difference in the treatment outcome was found among patients with different urethral obstruction sites. Significant improvements in Qmax, voided volume, PVR, VE, and the bladder outlet obstruction (BOO) index were noted in the successful group. A lower VE at baseline and a history of surgery were identified as predictive factors for a successful outcome of BoNT-A injections for treating DV., Conclusion: BoNT-A injections into the urethral sphincter can effectively improve VE in 40.9% of women with DV. Women with higher BOO grades and previous pelvic surgery are predicted to have a successful treatment outcome.

The treatment of non-small cell lung cancer (NSCLC) is known as a significant level of unmet medical need in spite of the progress in targeted therapy and personalized therapy. Overexpression of the Na + /K + -ATPase contributes to NSCLC progression, suggesting its potentiality in antineoplastic approaches. Epi-reevesioside F, purified from Reevesia formosana, showed potent anti-NSCLC activity through inhibiting the Na + /K + -ATPase, leading to internalization of α1- and α3-subunits in Na + /K + -ATPase and suppression of Akt-independent mTOR-p70S6K-4EBP1 axis. Epi-reevesioside F caused a synergistic amplification of apoptosis induced by gefitinib but not cisplatin, docetaxel, etoposide, paclitaxel, or vinorelbine in both NCI-H460 and A549 cells. The synergism was validated by enhanced activation of the caspase cascade. Bax cleavage, tBid formation, and downregulation of Bcl-xL and Bcl-2 contributed to the synergistic apoptosis induced by the combination treatment of epi-reevesioside F and gefitinib. The increase of membrane DR4 and DR5 levels, intracellular Ca 2+ concentrations, and active m-calpain expression were responsible for the caspase-8 activation and Bax cleavage. The increased α-tubulin acetylation and activation of MAPK (i.e., p38 MAPK, Erk, and JNK) depending on cell types contributed to the synergistic mechanism under combination treatment. These signaling pathways that converged on profound c-Myc downregulation led to synergistic apoptosis in NSCLC. In conclusion, the data suggest that epi-reevesioside F inhibits the Na + /K + -ATPase and displays potent anti-NSCLC activity. Epi-reevesioside F sensitizes gefitinib-induced apoptosis through multiple pathways that converge on c-Myc downregulation. The data support the inhibition of Na + /K + -ATPase as a switch-on mechanism to sensitize gefitinib-induced anti-NSCLC activity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The suburethral sling procedure has been widely used as the first-line treatment for female stress urinary incontinence (SUI). This study retrospectively compared the long-term surgical outcomes and complications between retropubic and transobturator suburethral sling procedures., Methods: From 2010 to 2022, a total of 533 women with SUI underwent retropubic pubovaginal sling (PVS) or transobturator tape (TOT) procedures using a synthetic polypropylene mesh with or without concomitant anterior colporrhaphy. All patients underwent preoperative videourodynamic studies, Valsalva leak point pressure (VLPP), and voiding efficiency (VE). The success rate, postoperative complications, overactive bladder symptoms, transvaginal urethrolysis, and repeat procedures were compared among different surgical procedures., Results: Among the patients, PVS was performed in 251 (47.1%) patients and with colporrhaphy in 58 (10.9%), TOT in 174 (32.6%) and with colporrhaphy in 50 (9.4%). The success rate was 87.4% in the PVS group and 75.4% in the TOT group, with or without colporrhaphy (p = 0.001). Urethrolysis was performed in 4.7% of the patients, and repeat suburethral sling procedures were performed in 8.3%. The overall success rate was significantly lower in TOT group, either with high or low VLPP, or with high or low VE. The rate of persistent OAB was significantly higher in TOT group regardless of VLPP or VE, whereas patients with VE < 90% at baseline had a significantly higher rate of postoperative dysuria., Conclusion: TOT procedures had an inferior long-term success rate than PVS procedures for female SUI. Additionally, no differences in the success rate were observed between patients with different bladder functions, high or low VLPP, and high or low VE., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Recent advancements in medicine have confirmed that brain disorders often comprise multiple subtypes of mechanisms, developmental trajectories, or severity levels. Such heterogeneity is often associated with demographic aspects (e.g., sex) or disease-related contributors (e.g., genetics). Thus, the predictive power of machine learning models used for symptom prediction varies across subjects based on such factors. To model this heterogeneity, one can assign each training sample a factor-dependent weight, which modulates the subject's contribution to the overall objective loss function. To this end, we propose to model the subject weights as a linear combination of the eigenbases of a spectral population graph that captures the similarity of factors across subjects. In doing so, the learned weights smoothly vary across the graph, highlighting sub-cohorts with high and low predictability. Our proposed sample weighting scheme is evaluated on two tasks. First, we predict initiation of heavy alcohol drinking in young adulthood from imaging and neuropsychological measures from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA). Next, we detect Dementia vs . Mild Cognitive Impairment (MCI) using imaging and demographic measurements in subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Compared to existing sample weighting schemes, our sample weights improve interpretability and highlight sub-cohorts with distinct characteristics and varying model accuracy.

Anxiety is an emotional response to a potential threat. It is characterized by worry, feelings of tension, and physical changes. Trinucleotide repeat containing adaptor 6A (TNRC6A) binds to argonaute (AGO) proteins and microRNAs to form the miRNA-induced silencing complex (miRISC), which mediates mRNA degradation, storage, and translational repression functions. However, whether TNRC6A is involved in anxiety regulation remains unknown. In this study, TNRC6A was downregulated in the prefrontal cortex (PFC) of mice exposed to acute restraint stress. Inhibition of TNRC6A in PFC induced anxious behaviour. RNA immunoprecipitation, RNA pull-down and real-time quantitative PCR revealed that TNRC6A directly binds to miR-21-3p and maintains its stability. Intriguingly, miR-21-3p was downregulated in the PFC of acute stress mice, whereas overexpression of miR-21-3p significantly reduced anxiety-like behaviour. Furthermore, miR-21-3p knockdown significantly increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in the PFC pyramidal neurons. Dual luciferase assay and western blotting confirmed that miR-21-3p binds to the 3 'UTR region of corticotropin-releasing factor (CRF) mRNA and regulates CRF and cAMP-response element binding protein (CREB) expression. These results confirm that low levels of TNRC6A in the PFC decrease the stability of miR-21-3p which promotes the up-regulation of CRF, leading to the development of anxiety-like behaviours. This research provides insight into a novel molecular mechanism by which TNRC6A regulates anxiety behaviour through the miR-21-3p/CRF signalling axis., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sensory bladder disorders encompass several distinct conditions with overlapping symptoms, which pose diagnostic challenges. This study aimed to evaluate urine biomarkers for differentiating between various sensory bladder disorders, including non-Hunner's interstitial cystitis (NHIC), detrusor overactivity (DO), hypersensitive bladder (HSB), and urodynamically normal women. A retrospective analysis of 191 women who underwent a videourodynamic study (VUDS) was conducted, with some also receiving cystoscopic hydrodistention to confirm the presence of NHIC. Participants were categorized into four groups: DO (n = 51), HSB (n = 29), NHIC (n = 81), and normal controls (n = 30). The urine levels of inflammatory and oxidative stress biomarkers were measured. The DO patients exhibited elevated IP-10 levels, while the HSB patients had decreased TAC and 8-OHdG levels. The NHIC patients showed lower IL-2 and higher TNF-α levels. A TNF-α ≥ 1.05 effectively identified NHIC, with an AUROC of 0.889, a sensitivity of 98.8%, and a specificity of 81.3%. An IP-10 ≥ 6.31 differentiated DO with an AUROC of 0.695, a sensitivity of 56.8%, and a specificity of 72.3%. An 8-OHdG ≤ 14.705 and a TAC ≤ 528.7 identified HSB with AUROCs of 0.754 and 0.844, respectively. The combination of 8-OHdG and TAC provided an AUROC of 0.853 for HSB. These findings suggest that TNF-α, IP-10, TAC, 8-OHdG, and IL-2 are promising non-invasive biomarkers for distinguishing between these conditions, which may improve diagnosis and management.

The prognostic value of central pathology review in upper urinary tract cancer (UTUC) remains inadequately addressed in existing literature. In this study, we conducted an extensive central pathology review and presented its influence on multi-center UTUC studies. We conducted a retrospective review of patients who underwent radical nephroureterectomy or segmental resection for UTUC to determine eligibility for central pathology review. In the Taiwan UTUC Collaboration cohort, 377 cases met the criteria for pathology review. We assessed agreement between pathologists using both the total percentage of agreement and simple kappa statistics. The prognostic implications of original and review pathology for various parameters were examined using the Cox regression model. This study included 209 female and 168 male participants. Pathology review revealed substantial interobserver variability in pT staging, with a particularly high rate of pT2 cases being upgraded to pT3 upon central review (17/70 pT2 stage made by local pathologists were finally confirmed as pT3 disease by the review pathologist). The local pathologist cohort identified fewer significant histological predictors in survival models compared to the review pathology cohort. Advanced pT stage, perineural invasion (PNI), and positive surgical margin were independent predictors of poorer overall survival and cancer-specific survival. PNI, lymphatic vascular invasion, and positive surgical margin were independent predictors of disease recurrence. Substantial interobserver variability in histological assessment underscores the importance of centralized pathology review for both multi-center studies and accurate post-operative management of UTUC patients. Advanced stage, perineural invasion, and margin status were significant histological predictors of oncological outcomes., (© 2024. The Author(s).)

Dysfunctional voiding (DV) is an abnormal urethral sphincter activity during voiding in neurologically normal individuals. Urethral sphincter botulinum toxin A (BoNT-A) injection has been used to treat DV, but the results have not been completely satisfactory. This study investigated the neurological characteristics of women with DV using the lower urinary tract electrophysiology (EP) study and the therapeutic efficacy of BoNT-A injection. In total, 48 women with DV and 16 women with normal voiding were included. Videourodynamic studies were conducted to diagnose DV before BoNT-A injection. EP studies, including urethral sphincter electromyography, bulbocavernosus reflex, and pudendal nerve conduction velocity, were conducted. Polyphasic motor unit action potentials suggestive of reinnervation were detected in 58.3% of patients with DV and 18.8% of controls ( p = 0.001). Significant improvement in the corrected maximum flow rate (cQmax) was observed in patients with reinnervation at 1 and 3 months after BoNT-A injections into the urethral sphincter. Urethral sphincter denervation or reinnervation activity was commonly noted in 62.5% of women with DV. Repeated BoNT-A injections into the urethral sphincter provided effective treatment in 47.9% of patients, with mild improvement in cQmax observed in patients with urethral sphincter reinnervation. However, the improvement was not superior to those without reinnervation.

Peyronie's disease (PD) is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages. In this study, we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD: transforming growth factor-β1 (TGF-β1), fibrin, sodium tetradecyl sulfate (STS) combined with TGF-β1, and polidocanol (POL) combined with TGF-β1. The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature. The STS + TGF-β1 combination resulted in both histological and morphological alterations, but with a high incidence of localized necrosis that led to animal death. The POL + TGF-β1 combination produced pathological changes and curvature comparable to STS + TGF-β1 and led to fewer complications. In conclusion, fibrin, STS + TGF-β1, and POL + TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats. The POL + TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

One of the main drivers of autism spectrum disorder is risk alleles within hundreds of genes, which may interact within shared but unknown protein complexes. Here we develop a scalable genome-editing-mediated approach to target 14 high-confidence autism risk genes within the mouse brain for proximity-based endogenous proteomics, achieving the identification of high-specificity spatial proteomes. The resulting native proximity proteomes are enriched for human genes dysregulated in the brain of autistic individuals, and reveal proximity interactions between proteins from high-confidence risk genes with those of lower-confidence that may provide new avenues to prioritize genetic risk. Importantly, the datasets are enriched for shared cellular functions and genetic interactions that may underlie the condition. We test this notion by spatial proteomics and CRISPR-based regulation of expression in two autism models, demonstrating functional interactions that modulate mechanisms of their dysregulation. Together, these results reveal native proteome networks in vivo relevant to autism, providing new inroads for understanding and manipulating the cellular drivers underpinning its etiology., (© 2024. The Author(s).)

Prader-Willi syndrome (PWS) is the prototypic genomic disorder resulting from deficiency of paternally expressed genes in the human chromosome 15q11-q13 region. The unique molecular mechanism involving epigenetic modifications renders PWS as the most attractive candidate to explore a proof-of-concept of epigenetic therapy in humans. The premise is that epigenetic modulations could reactivate the repressed PWS candidate genes from the maternal chromosome and offer therapeutic benefit. Our prior study identifies an EHMT2/G9a inhibitor, UNC0642, that reactivates the expression of PWS genes via reduction of H3K9me2. However, low brain permeability and poor oral bioavailability of UNC0642 preclude its advancement into translational studies in humans. In this study, a newly developed inhibitor, MS152, modified from the structure of UNC0642, has better brain penetration and greater potency and selectivity against EHMT2/G9a. MS152 reactivated maternally silenced PWS genes in PWS patient fibroblasts and in brain and liver tissues of PWS mouse models. Importantly, the molecular efficacy of oral administration is comparable with the intraperitoneal route. MS152 treatment in newborns ameliorates the perinatal lethality and poor growth, maintaining reactivation in a PWS mouse model at postnatal 90 days. Our findings provide strong support for MS152 as a first-in-class inhibitor to advance the epigenetic therapy of PWS in humans., Competing Interests: Declaration of interests J.J. is a cofounder and equity shareholder in Cullgen, Inc., a scientific cofounder and scientific advisory board member of Onsero Therapeutics, Inc., and a consultant for Cullgen, Inc., EpiCypher, Inc., Accent Therapeutics, Inc, and Tavotek Biotherapeutics, Inc. The Jin laboratory received research funds from Celgene Corporation, Levo Therapeutics, Inc., Cullgen, Inc., and Cullinan Oncology, Inc. Y.-H.J. is a co-founder of, has an equity interest in, is a scientific advisor to, and has an unpaid seat on the board of directors to Couragene, Inc., a biotechnology company that has licensed my intellectual property. However, Couragene did not have any direct role in this paper. J.J., Y.X., Y.-H.J., and S.W. are described in a patent application for MS1262 and MS152 as inventors, titled “G9A/GLP INHIBITORS AND METHODS OF USE” and “G9a/EHMT2 inhibitor use for Prader-Willi syndrome,” which were filed in the U.S. Patent and Trademark Office as application 63/515,010 (the “Application”)., (Copyright © 2024. Published by Elsevier Inc.)

Protein glycosylation plays a crucial role in various biological processes and is related to various diseases. Highly specific enrichment of glycopeptides before mass spectrometry detection is crucial for comprehensive glycoproteomic analysis. However, it still remains a great challenge due to the absence of affinity materials with excellent enrichment efficiency. In this work, a triazine structure linked by a -NH- bond of two-dimensional (2-D) covalent organic framework (COF) nanosheets was synthesized as an affinity adsorbent for the selective capture of glycopeptides. In particular, by introducing hydrophilic monomers via a bottom-up approach, the 2-D COF (denoted as NENP-1) nanosheets were provided with abundant amino groups and inherent hydrophilicity. Owing to the specific surface area and excessive accessible sites for hydrophilicity, the resulting NENP-1 nanosheets exhibited an outstanding glycopeptide enrichment efficiency from standard samples with a superior detection sensitivity (1 × 10 -10 M), good enrichment selectivity (1 : 800, HRP tryptic digest to BSA protein), excellent binding capacity (100 mg g -1 ), great reusability, and recovery (60.2%). Furthermore, using the NENP-1 nanosheet adsorbent, twenty-four endogenous glycopeptides in the serum of patients with gastric cancer were successfully identified by LC-MS/MS technology, which illustrates a promising prospective of hydrophilic COF nanosheets in glycoproteomics research.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3-mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We apply an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in humans and mice. We unexpectedly discover an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts are altered in Shank3-mutant mice and postmortem brain tissues from individuals with autism spectrum disorder. The enhanced SHANK3 transcriptome significantly improves the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest that both deterministic and stochastic transcription of the genome is associated with SHANK family genes., Competing Interests: Declaration of interests Y.-h.J. is a scientific co-founder of Couragene, Inc., but this study is unrelated to his role. The project was supported initially by a sponsored research project by Taysha Gene Therapies. Taysha Gene Therapies did not have any direct role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Postoperative abdominal infections are an important and heterogeneous health challenge. Many samll abdominal abscesses are resolved with antibiotics, but larger or symptomatic abscesses may require procedural management., Case Summary: A 65-year-old male patient who suffered operation for the left hepatocellular carcinoma eight months ago, came to our hospital with recurrent abdominal pain, vomit, and fever for one month. Abdominal computed tomography showed that a big low-density dumbbell-shaped mass among the liver and intestine. Colonoscopy showed a submucosal mass with a fistula at colon of liver region. Gastroscopy showed a big rupture on the submucosal mass at the descending duodenum and a fistula at the duodenal bulb. Under colonoscopy, the brown liquid and pus were drained from the mass with "special stent device". Under gastroscopy, we closed the rupture of the mass with a loop and six clips for purse stitching at the descending duodenum, and the same method as colonoscopy was used to drain the brown liquid and pus from the mass. The symptom of abdominal pain, vomit and fever were relieved after the treatment., Conclusion: The special stent device could be effectively for draining the abdominal abscess respectively from colon and duodenum., Competing Interests: Conflict-of-interest statement: All authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain. In past work, we discovered that euchromatic histone lysine N-methyltransferase-2 (EHMT2/G9a) inhibitors were capable of un-silencing PWS-associated genes by restoring their expression from the maternal chromosome. Here, in mice lacking the Ehmt2 gene, we document un-silencing of the imprinted Snrpn/Snhg14 gene on the maternal chromosome in the late embryonic and postnatal brain. Using PWS and Angelman syndrome patient derived cells with either paternal or maternal deletion of 15q11-q13, we have found that chromatin of maternal PWS-IC is closed and has compact 3D folding confirmation. We further show that a new and distinct noncoding RNA preferentially transcribed from upstream of the PWS-IC interacts with EHMT2 and forms a heterochromatin complex to silence gene expression of SNRPN in CIS on maternal chromosome. Taken together, these findings demonstrate that allele-specific recruitment of EHMT2 is required to maintain the maternal imprints. Our findings provide novel mechanistic insights and support a new model for imprinting maintenance of the PWS imprinted domain., Competing Interests: Declaration of interests Y-H.J. is a co-founder of, have an equity interest in, a scientific advisor to, and have an unpaid seat on the board of directors to Couragene, Inc., a biotechnology company that has licensed his intellectual property. However, Couragene did not have any direct role in this paper. J.J., Y.X., Y-H.J., and S.E.W. are described in a patent application for MS1262 as inventors, titled “G9A/GLP INHIBITORS AND METHODS OF USE” was filed in the United States Patent and Trademark Office as application 63/515,010 (the “Application”). S.W. is an inventor on patent applications related to the chromatin tracing technology applied for by Harvard University and Yale University.

Numerous large scale genomic studies have uncovered rare but recurrent pathogenetic variants in a significant number of genes encoding epigenetic machinery in cases with neurodevelopmental disorders (NDD) especially autism spectrum disorder (ASD). These findings provide strong support for the functional importance of epigenetic regulators in neurodevelopment. After the clinical genomics evaluation of the patients using exome sequencing, we have identified, three novel protein-truncating variants (PTVs) in the MSL2 gene (OMIM: 614802) which encodes a chromatin modifying enzyme. MSL2 modifies chromatin through both mono-ubiquitination of histone 2B on lysine 34 (K34) and acetylation of histone H4 on lysine 16 (K16). We reported first time the detailed clinical features associated with 3 MSL2 PTVs. There are 15 PTVs (13 de novo) reported from the large genomics studies (12 cases) or ClinVar (3 cases) of NDD, ASD, and developmental disorders (DD) but the specific clinical features for these cases are not described. Taken together, our descriptions of dysmorphic face and other features support the causal role of MSL2 in a likely syndromic neurodevelopmental disorder and add MSL2 to a growing list of epigenetic genes implicated in ASD., (© 2024. The Author(s).)