Search

Qing-Yu Xiao,1 Ren-Ling Wang,2 Hai-Jun Wu,1 Wen-Bin Kuang,3 Wei-Wei Meng,4 Zhen Cheng5 1Department of Blood Transfusion, Shenzhen Baoan Shiyan People’s Hospital, Shenzhen, 518108, China; 2Department of Oncology, Kaiping Central Hospital, Jiangmen City, Guangdong Province, 529399, People’s Republic of China; 3Department of Laboratory, Longhua District Central Hospital, Shenzhen, 518110, People’s Republic of China; 4Department of Laboratory, Shenzhen Baoan Shiyan People’s Hospital, Shenzhen, 518108, China; 5Guantian Community Healthcare Center, Shenzhen Baoan Shiyan People’s Hospital, Shenzhen, Guangdong province, 518100, People’s Republic of ChinaCorrespondence: Zhen Cheng, Guantian Community Healthcare Center, Shenzhen Baoan Shiyan People’s Hospital, About 50 Meters South of hkc Huike Industrial Park, Dezheng Road, Baoan District, Shenzhen, Guangdong province, 518100, People’s Republic of China, Tel +86 13632854050, Email cheng_3003_zhen@163.comObjective: To probe into the influence of Helicobacter pylori (Hp) infection on glucose metabolism, lipid metabolism, and inflammatory cytokines in patients with nonalcoholic fatty liver disease (MASLD).Methods: A total of 140 MASLD patients admitted to our Hospital between June 2020 and May 2021 were selected as the research objects. Based on the presence or absence of Hp infection, they were divided into the study group (73 cases with infection) and control group (67 cases without infection). Glucose metabolism indicators [fasting blood glucose (FBG), 2-hour postprandial glucose (2hPG), fasting insulin (FINS), glycated hemoglobin (HbAlc)], lipid metabolism indicators [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory indicators [interleukin-37 (IL-37), interleukin-18 (IL-18)] were measured and compared between the two groups.Results: In terms of glucose metabolism indicators, the study group exhibited higher levels of FBG (5.84± 0.49 vs 5.40± 0.51, t=2.535, P=0.012), 2hPG (7.26± 1.30 vs 6.50± 1.53, t=3.321, P< 0.001), and FINS (11.13± 4.13 vs 9.12± 3.72, t=3.224, P< 0.001), and Insulin resistance index (HOMA-IR) (2.97± 0.35 VS 2.13± 0.54, t=3.761, P< 0.001) and a lower level of HbAlc (5.25± 0.56 vs 6.12± 0.57, t=5.473, P< 0.001) compared to the control group. Regarding lipid metabolism indicators, the study group exhibited higher levels of TC (5.64± 1.49 vs 5.01± 1.32, t=3.332, P< 0.001), TG (1.89± 0.34 vs 1.32± 0.43, t=3.411, P< 0.001), and LDL-C (3.31± 0.43 vs 2.12± 0.29, t=4.142, P< 0.001), and a lower level of HDL-C (1.45± 0.21 vs 1.78± 0.42, t=4.347, P< 0.001) compared to the control group. As for the inflammatory indicators, the study group exhibited higher levels of IL-37 (45.56± 6.02 vs 34.02± 3.28, t=9.332, P< 0.001) and IL-18 (73.57± 5.82 vs 60.34± 4.84, t=10.141, P< 0.001) compared to the control group.Conclusion: It is crucial to place appropriate emphasis on the impact of Hp infection on the glucose metabolism, lipid metabolism, and inflammatory response in MASLD patients, warranting careful consideration during the treatment of these patients.Keywords: Helicobacter pylori, infection, nonalcoholic fatty liver disease, glucose metabolism, lipid metabolism, inflammatory indicators

Xue-Jiao Wang,1 Jun Zhang,1 Shu-Qing Wang,1 Wei-Ren Xu,2 Xian-Chao Cheng,1 Run-Ling Wang1 1Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, People’s Republic of China Abstract: The thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARγ) agonists are restricted in clinical use as antidiabetic agents because of side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of these side effects. Multitargeted PPARα/γ/δ pan agonist development is the hot topic in the antidiabetic drug research field. In order to identify PPARα/γ/δ pan agonists, a compound database was established by core hopping of rosiglitazone, which was then docked into a PPARα/γ/δ active site to screen out a number of candidate compounds with a higher docking score and better interaction with the active site. Further, absorption, distribution, metabolism, excretion, and toxicity prediction was done to give eight compounds. Molecular dynamics simulation of the representative Cpd#1 showed more favorable binding conformation for PPARs receptor than the original ligand. Cpd#1 could act as a PPARα/γ/δ pan agonist for novel antidiabetic drug research. Keywords: PPARs, diabetes, docking, molecular dynamics simulation, ADMET

Xin Jin1,2,* Tian-Hua Yan,3,* Lan Yan,1 Qian Li,4 Rui-Lian Wang,1 Zhen-Lin Hu,1 Yuan-Ying Jiang,1 Qing-Yan Sun,1 Yong-Bing Cao1 1School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2School of Pharmacy, FuJian University of Traditional Chinese Medicine, Fuzhou, People's Republic of China; 3Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China; 4Diakite Biological Technology Co., Ltd, Shanghai, People's Republic of China *These authors contributed equally to this work Abstract: A series of novel derivatives of phenyl-substituted berberine triazolyls has been designed and synthesized via copper-catalyzed azide-alkyne cycloaddition click chemistry in an attempt to develop antitumor agents. All of the compounds were evaluated for anticancer activity against a panel of three human cancer cell lines, including MCF-7 (breast), SW-1990 (pancreatic), and SMMC-7721 (liver) and the noncancerous human umbilical vein endothelial cell (HUVEC) cell lines. The results indicated that most of the compounds displayed notable anticancer activities against the MCF-7 cells compared with berberine. Among these derivatives, compound 16 showed the most potent inhibitory activity against the SW-1990 and SMMC-7721 cell lines, with half-maximal inhibitory concentration (IC50) values of 8.54±1.97 µM and 11.87±1.83 µM, respectively. Compound 36 exhibited the most potent inhibitory activity against the MCF-7 cell line, with an IC50 value of 12.57±1.96 µM. Compound 16 and compound 36 exhibited low cytotoxicity in the HUVEC cell line, with IC50 values of 25.49±3.24 µM and 30.47±3.47 µM. Furthermore, compounds 14, 15, 16, 17, 18, 32, and 36 exhibited much better selectivity than berberine toward the normal cell line HUVEC. Keywords: berberine, anticancer, click chemistry, structure–activity relationship

Lei Liu,1 Ying Ma,2 Run-Ling Wang,2 Wei-Ren Xu,3 Shu-Qing Wang,2,5 Kuo-Chen Chou4,5 1PET/CT Center, General Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of China; 3Tianjin Institute of Pharmaceutical Research (TIPR), Tianjin, People’s Republic of China; 4Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah, Saudi Arabia; 5Gordon Life Science Institute, Belmont, MA, USA Abstract: The high prevalence of type 2 diabetes mellitus in the world as well as the increasing reports about the adverse side effects of the existing diabetes treatment drugs have made developing new and effective drugs against the disease a very high priority. In this study, we report ten novel compounds found by targeting peroxisome proliferator-activated receptors (PPARs) using virtual screening and core hopping approaches. PPARs have drawn increasing attention for developing novel drugs to treat diabetes due to their unique functions in regulating glucose, lipid, and cholesterol metabolism. The reported compounds are featured with dual functions, and hence belong to the category of dual agonists. Compared with the single PPAR agonists, the dual PPAR agonists, formed by combining the lipid benefit of PPARα agonists (such as fibrates) and the glycemic advantages of the PPARγ agonists (such as thiazolidinediones), are much more powerful in treating diabetes because they can enhance metabolic effects while minimizing the side effects. This was observed in the studies on molecular dynamics simulations, as well as on absorption, distribution, metabolism, and excretion, that these novel dual agonists not only possessed the same function as ragaglitazar (an investigational drug developed by Novo Nordisk for treating type 2 diabetes) did in activating PPARα and PPARγ, but they also had more favorable conformation for binding to the two receptors. Moreover, the residues involved in forming the binding pockets of PPARα and PPARγ among the top ten compounds are explicitly presented, and this will be very useful for the in-depth conduction of mutagenesis experiments. It is anticipated that the ten compounds may become potential drug candidates, or at the very least, the findings reported here may stimulate new strategies or provide useful insights for designing new and more powerful dual-agonist drugs for treating type 2 diabetes. Keywords: diabetes, PPAR-alpha, PPAR-gamma, dual-agonist drug, core hopping, molecular docking, ADME, binding pocket

Objective: Measurement of biomarkers is a potential approach to early prediction of the risk of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of pro-atrial natriuretic peptide (pro-ANP) and pro-adrenomedullin (pro-ADM) levels in a cohort of medical intensive care patients and to compare it with that of other known biomarkers and physiological scores.Methods: Blood samples of 51 consecutive critically ill patients admitted to the intensive care unit and 53 age-matched healthy control people were evaluated in this prospective study. The prognostic value of pro-ANP and pro-ADM levels was compared with that of acute physiology and chronic health evaluation (APACHE) II scores and various biomarkers such as C-reactive protein, interleukin-6 and procalcitonin. Pro-ANP and pro-ADM were detected by a new sandwich immunoassay.Results: On admission, 25 patients had systemic inflammatory response syndrome (SIRS), 12 sepsis, 9 severe sepsis and 5 septic shock. At that time, the median levels (ng/ml) of pro-ANP and pro-ADM were 87.22 and 0.34 respectively in patients with SIRS, 1533.30 and 2.23 in those with sepsis, 1098.73 and 4.57 in those with severe sepsis, and 1933.94 and 8.21 in those with septic shock. With the increasing severity of disease, the levels of pro-ANP and pro-ADM were gradually increased. On admission, the circulating levels of pro-ANP and pro-ADM in patients with sepsis, severe sepsis, or septic shock were significantly higher in non-survivors than in survivors (P less than 0.05). In a receiver operating characteristic curve analysis for the survival of patients with sepsis, the areas under the curve (AUCs) for pro-ANP and pro-ADM were 0.89 and 0.87 respectively, which was similar to the AUCs for procalcitonin and APACHE II scores.Conclusion: Pro-ANP and pro-ADM are valuable biomarkers for prediction of severity of septic patients. [ABSTRACT FROM AUTHOR]

Background and Purpose: Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses., Methods: Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses., Results: In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16-1.31) and 1.3 (95% CI: 1.19-1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes., Conclusions: Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

The neuromorphic vision system that utilizes spikes as information carriers is crucial for the formation of spiking neural networks. Here, we present a bioinspired flexible artificial spiking photoreceptor (ASP), which is realized by using a single VO 2 Mott memristor that can simultaneously sense and encode the stimulus light into spikes. The ASP has high spike-encoded photosensitivity and ultrawide photosensing range (405-808 nm) with good endurance (>7 × 10 7 ) and high flexibility (bending radius ∼5 mm). Then, we put forward an all-spike electronic retina architecture that comprises one layer of ASPs and one layer of artificial optical nerves (AONs) to process the spike information. Each AON consists of a single Mott memristor connected in series with a neuro-transistor that is a multiple-input floating-gate MOS transistor. Simulation results demonstrate that the all-spike electronic retina can successfully segment images with high Shannon entropy, thus laying the foundation for the development of a spike-based neuromorphic vision system.

Background: Climate change, with increasing temperatures, poses a health threat to patients on maintenance hemodialysis (MHD). Seasonal variations in body composition have been documented in this population. We hypothesized that climate warming could further exacerbate these effects. In this study we investigated the impact of climate warming on the body composition of MHD patients residing in subtropical Taiwan. Methods: This longitudinal observational study enrolled MHD patients in subtropical northern Taiwan. We assessed monthly blood pressure (BP), laboratory data, and body composition via bioimpedance spectroscopy over a three-year period. Generalized estimating equation (GEE) was employed to analyze the seasonal and annual variations in these parameters. Additionally, we explored associations between climatic variables and body composition parameters. Results: Forty patients completed the study. BP, laboratory values, and body composition exhibited significant seasonal variations. Compared with those in winter, participants had greater relative overhydration (OH) in spring, summer, and fall. Warmer months were associated with a higher lean tissue index (LTI) and a lower fat tissue index (FTI). Notably, summers across the study years showed a further increase in relative OH and FTI, accompanied by a decrease in LTI. While BP and most laboratory parameters remained stable throughout the study period, sodium and potassium levels displayed annual variations. GEE analysis revealed positive associations between rising ambient temperature and increased fluid overload, fat mass, and decreased muscle mass. Conclusions: Our findings demonstrate that climate warming is associated with variations in the body composition of MHD patients residing in a subtropical climate. These changes can have implications in MHD patients due to their heightened vulnerability to environmental changes. Further research is needed across diverse geographic regions to develop optimal care strategies in a warming world., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA., (© 2024 The Author(s). The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: Persistent inflammation over time can cause gradual harm to the body. Molecular hydrogen has the potential to specifically counteract reactive oxygen species (ROS), reduce disease severity, and enhance overall health. Investigations of the anti-inflammatory and antioxidant properties of oral solid hydrogen capsules (OSHCs) are currently limited, prompting our examination of the beneficial effects of OSHCs. Subsequently, we conducted a clinical study to assess the impact of OSHCs supplementation on individuals with chronic inflammation. Materials and methods: Initially, we evaluated the oxidative reduction potential (ORP) properties of the OSHCs solution by comparing it to hydrogen-rich water (HRW) and calcium hydride (CaH 2 ) treated water. In our outpatient department, stable patients with chronic illnesses who were treated with varying doses of OSHCs were randomized into low-, medium-, and high-dose groups for 4 weeks. Primary outcomes included changes in the serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) concentrations after four weeks of OSHCs consumption. Secondary outcomes included changes in the Brief Fatigue Inventory-Taiwan (BFI-T) fatigue scale, Control Status Scale for Diabetes (CSSD70) scores, and Disease Activity Score 28 (DAS28). Results: Compared to HRW and CaH 2 , OSHCs demonstrated a prolonged reduction in ORP for 60 minutes in vitro and enabled a regulated release of hydrogen over 24 hours. A total of 30 participants, with 10 in each dosage (low/medium/high) group, completed the study. The average ESR120 significantly decreased from the first week to the fourth week, with a noticeable dose effect (low-dose group, p = 0.494; high-dose group, p = 0.016). Overall, the average CRP concentration showed a distinct decreasing trend after four weeks of OSHCs administration (w0 vs. w4, p = 0.077). The average DAS28 score demonstrated a significant decrease following OSHCs treatment. Furthermore, there were improvements in the BFI-T and CSSD70 scores. Conclusion: OSHCs supplementation may exert anti-inflammatory and antioxidant effects on individuals with chronic inflammation. However, further clinical studies could be investigated to explore the potential therapeutic effects of OSHCs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Infectious diseases, such as COVID-19, are high-risk factors for delirium. However, the implementation of nonpharmacological interventions faces major challenges during an infectious disease pandemic., Aims: To evaluate the effect of the nurse-led Hospital Elder Life Program (NL-HELP) on delirium reduction among delirious patients with COVID-19., Design: A single-blind randomized clinical trial., Methods: This study recruited 122 delirious patients with COVID-19 from internal medicine wards at West China Hospital in China between January 30 and March 31, 2023. Participants were randomized to the NL-HELP group (n = 62) or the usual care group (n = 60). Patients in the intervention group received the NL-HELP protocol three times daily for 7 days. Patients in the control group received usual care. The primary outcome was the absence/presence of delirium during the intervention period measured by the 3-min Diagnostic Confusion Assessment Method., Results: Fewer patients remained delirious in the NL-HELP group than in the control group. There were significantly more delirium-free days in the NL-HELP group than in the usual care group. There were no statistically significant differences between the two groups in terms of delirium severity, length of hospital stay, delirium at 30 days after discharge, 30-day readmission, 30-day mortality, physical function or quality of life., Conclusions: This study demonstrated that NL-HELP could reduce the presence of delirium in delirious patients. No effect was observed in terms of shortening the length of hospital stay, reducing 30-day mortality, or improving quality of life., Impact: NL-HELP may be effective in reducing the presence of delirium in delirious patients. Further research is needed to determine whether the NL-HELP can improve patient outcomes (e.g. mortality and quality of life) in a larger study., Patient or Public Contribution: Caregivers of delirious patients were invited to provide intervention strategies to prevent or abate delirium, including environmental management, orientation communications and identification of alert signs., Trial Registration: This study was prospectively registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/) Identifier: ChiCTR2300067874., (© 2024 John Wiley & Sons Ltd.)

Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC 30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses., Competing Interests: Declaration of interests MAS receives grants from the US National Institutes of Health within the scope of this work and grants and contracts from the US Department of Veterans Affairs, US Food and Drug Administration, and Janssen Research and Development outside the scope of this work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: We previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models., Methods: ATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na + -K + -ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson's disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish., Results: Cells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na + -K + -ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson's disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio., Conclusion: This study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na + /K + -ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish., Competing Interests: 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 © 2024 Ruan, Zou, Liao, Ji, Wang, Zhang, Zhang, Gao, Chen, Yu, Wei, Li, Li, Lin, Luo and Lin.)

Objective: To investigate the expression of histone demethylase, Jumonji domain-containing protein 3 (JMJD3), in inflammatory periodontal tissues and its potential mechanism for the regulation of periodontitis. Methods: The results of single-cell sequencing of periodontal tissues published in the Gene Expression Omnibus (GEO) database in 2022 were analyzed. Nine gingival samples each from healthy and inflamed periodontal patients were collected during periodontal surgery or tooth extractions for immunohistochemical staining and real-time fluorescence quantitative PCR (RT-qPCR). Mice periodontitis models were constructed, and the experimental groups were: healthy control+saline group, silk ligation+saline group, silk ligation+GSK-J4(inhibitor of JMJD3) group. Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (Pg) (Pg-LPS) was used to mimic the periodontal inflammatory microenvironment. The macrophages were treated with small interfering RNA (siRNA) targeting Jmjd3 and the JMJD3 inhibitor GSK-J4. siRNA transfection experiments were grouped into the following: the NC group (negative control sequence transfection group), the siRNA-Jmjd3 group, the NC+LPS group, siRNA-Jmjd3+LPS group. Inhibitor experiments were grouped as dimethyl sulfoxide (DMSO) group, GSK-J4 group, DMSO+LPS group, GSK-J4+LPS group. Western blotting and immunofluorescence staining were used to explore the effects of JMJD3 on macrophage polarization and periodontal inflammation in the in vivo and in vitro settings. Results: RT-qPCR results showed that JMJD3 expression in gingival tissues of periodontitis patients (1.97±0.91) was significantly higher than that in healthy gingival tissues (1.00±0.33) ( t =2.45, P =0.048). RT-qPCR results of in vitro experiments showed that either siRNA knockdown of JMJD3 or inhibition of JMJD3 using GSK-J4 promoted M1 polarization and inhibited M2 polarization in macrophages under inflammatory environment: the expression of arginase I (Arg 1) in the NC+LPS group (0.90±0.06) was significantly higher than that in the siRNA-Jmjd3+LPS group (0.61±0.11) ( P <0.01); the expression of interleukin (Il)-6, Il-1β, and tumor necrosis factor alpha (Tnf-α) in the NC+LPS group (8.50±0.16, 5.56±0.20, 3.44±0.16) were significantly lower than those in the siRNA-Jmjd3+LPS group (14.63±0.48, 8.55±0.10, 11.72±0.16) (P<0.01). The expression of Arg-1, Ym1, Il-10 in the DMSO+LPS group (0.82±0.01, 0.35±0.16, 1.47±0.11) were significantly higher (P<0.01) than the GSK-J4+LPS group (0.55±0.03, 0.22±0.21, 0.51±0.11); the expression of Il-6, Il-1β, and Tnf-α in the DMSO+LPS group (2.03±0.13, 3.63±0.14, 4.06±0.03) were significantly lower than the GSK-J4+LPS group (2.69±0.16, 15.04±1.15, 4.36±0.10) (P<0.01). The results of the in vivo experiments revealed that inhibition of JMJD3 exacerbated bone loss in experimental periodontitis mice, increased macrophage M1 polarization, and decreased M2 polarization in inflamed periodontal tissues. The buccal cemento-enamel junction (CEJ)-alveolar bone crest (ABC), palatal CEJ-ABC, as well as the ratio of M1/M2 type macrophages were significantly lower in the silk ligation+saline group [(0.26±0.03), (0.24±0.01) mm, 0.35±0.10) than in the silk ligation+GSK-J4 group [(0.34±0.04), (0.30±0.05) mm, 2.50±0.58) ( t =3.65, P =0.006; t =2.67, P =0.049; t =7.31, P =0.004; respectively). Conclusions: Single-cell sequencing as well as the in vitro and in vivo experiments verified that JMJD3 expression was upregulated in periodontitis periodontal tissues. JMJD3 may exert a protective role in periodontitis by regulating macrophage polarization, thereby inhibiting alveolar bone destruction associated with the periodontitis.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes., Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses., Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba ., Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca 2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology., Competing Interests: 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 © 2024 Li, Kang, Zhang, Su, Bi, Wang, Xing and Sun.)

Herlyn-Werner-Wunderlich (HWW) syndrome is characterized by obstructed hemivagina and ipsilateral renal anomaly, a rare congenital anomaly of the genitourinary tract, resulting from malformations of the renal tract associated with Müllerian duct anomalies. The initial symptoms of HWW frequently present after menarche and may be nonspecific, leading to a delayed diagnosis. We presented a 19-year-old female with 3-year hematuria and abdominal pain. The final diagnosis of HWW syndrome with a rare vesicovaginal fistula was made. The treatment of HWW syndrome typically involves surgical intervention. The primary treatment is resection or removal of the obstructed vaginal septum. The patient underwent excision of vaginal septum and vaginal reconstruction via hysteroscopy, as well as repair of the vesicovaginal fistula. The patient improved well after surgery and fully recovered without sequelae after 3 months. In addition, unilateral renal agenesis is one of congenital abnormalities of the kidney and urinary tract, which are the most frequent cause of chronic kidney disease (CKD) in children. This report describes a patient of HWW syndrome with rarely combined vesicovaginal fistula, and highlights the importance of early recognition and management to prevent associated complications.

Numerous high-performance nanotechnologies have been developed, but their practical applications are largely restricted by the nanomaterials' low stabilities and high operation complexity in aqueous substrates. Herein, we develop a simple and high-reliability hydrogel-based nanotechnology based on the in situ formation of Au nanoparticles in molybdenum disulfide (MoS 2 )-doped agarose (MoS 2 /AG) hydrogels for electrophoresis-integrated microplate protein recognition. After the incubation of MoS 2 /AG hydrogels in HAuCl 4 solutions, MoS 2 nanosheets spontaneously reduce Au ions, and the hydrogels are remarkably stained with the color of as-synthetic plasmonic Au hybrid nanomaterials (Au staining). Proteins can precisely mediate the morphologies and optical properties of Au/MoS 2 heterostructures in the hydrogels. Consequently, Au staining-based protein recognition is exhibited, and hydrogels ensure the comparable stabilities and sensitivities of protein analysis. In comparison to the fluorescence imaging and dye staining, enhanced sensitivity and recognition performances of proteins are implemented by Au staining. In Au staining, exfoliated MoS 2 semiconductors directly guide the oriented growth of plasmonic Au nanostructures in the presence of formaldehyde, showing environment-friendly features. The Au-stained hydrogels merge the synthesis and recognition applications of plasmonic Au nanomaterials. Significantly, the one-step incubation of the electrophoretic hydrogels leads to high simplicity of operation, largely challenging those multiple-step Ag staining routes which were performed with high complexity and formaldehyde toxicity. Due to its toxic-free, simple, and sensitive merits, the Au staining integrated with electrophoresis-based separation and microplate-based high-throughput measurements exhibits highly promising and improved practicality of those developing nanotechnologies and largely facilitates in-depth understanding of biological information.

Background: Drug-induced liver injury (DILI) is one of the most common adverse events of medication use, and its incidence is increasing. However, early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests., Aim: To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools., Methods: Saliva samples from 31 DILI patients and 35 healthy controls (HCs) were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry. Subsequent analyses, including partial least squares-discriminant analysis modeling, t tests and weighted metabolite coexpression network analysis (WMCNA), were conducted to identify key differentially expressed metabolites (DEMs) and metabolite sets. Furthermore, we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction. The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves., Results: We found 247 differentially expressed salivary metabolites between the DILI group and the HC group. Using WMCNA, we identified a set of 8 DEMs closely related to liver injury for further prediction testing. Interestingly, the distinct separation of DILI patients and HCs was achieved with five metabolites, namely, 12-hydroxydodecanoic acid, 3-hydroxydecanoic acid, tetradecanedioic acid, hypoxanthine, and inosine (area under the curve: 0.733-1)., Conclusion: Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients. Our study may provide a potentially feasible and noninvasive diagnostic method for DILI, but further validation is needed., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: There is no reliable means to evaluate the immune status of liver transplant recipients. We proposed a novel score model, namely Mingdao immune cell analysis and Mingdao immune score system, to quantify the immunity., Methods: Data from those who underwent a single liver transplant between January 2017 and June 2020 at Beijing Chaoyang Hospital, were collected. In addition, healthy volunteers were also enrolled. The score model was based on the immune cell populations determined by flow cytometry., Results: There were a total of 376 healthy controls with 376 tests and 148 liver transplant recipients with 284 tests in this study. Evaluated by Mingdao immune cell analysis and Mingdao immune score system, the mean scores of healthy controls were near zero suggesting a balanced immune system. In contrast, the mean scores of liver transplant recipients were negative both before and after surgery indicating a compromised immune system. When liver transplant recipients were given a reduced or routine first dose according to their preoperative score, they had similar recovery of liver function. Moreover, liver transplant recipients with increased scores ≥ 5 were associated with elevated aspartate transaminase and alanine amiotransferase. Finally, on multivariate analysis the score model was the only significant independent risk factor for clinical acute rejection (P = 0.021; Odds ratio, 0.913; 95% confidence interval, 0.845-0.987)., Conclusion: The novel score model could be used as an indicator to reflect immunity and to regulate immunosuppressants in liver transplant recipients after surgery., Competing Interests: None., (AJTR Copyright © 2024.)

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM&#95;007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal., (© 2024. The Author(s).)

Aerobic granular sludge is one of the most promising biological wastewater treatment technologies, yet maintaining its stability is still a challenge for its application, and predicting the state of the granules is essential in addressing this issue. This study explored the potential of dynamic texture entropy, derived from settling images, as a predictive tool for the state of granular sludge. Three processes, traditional thickening, often overlooked clarification, and innovative particle sorting, were used to capture the complexity and diversity of granules. It was found that rapid sorting during settling indicates stable granules, which helps to identify the state of granules. Furthermore, a relationship between sorting time and granule heterogeneity was identified, helping to adjust selection pressure. Features of the dynamic texture entropy well correlated with the respirogram, i.e., R 2 were 0.86 and 0.91 for the specific endogenous respiration rate (SOUR e ) and the specific quasi-endogenous respiration rate (SOUR q ), respectively, providing a biologically based approach for monitoring the state of granules. The classification accuracy of models using features of dynamic texture entropy as an input was greater than 0.90, significantly higher than the input of conventional features, demonstrating the significant advantage of this approach. These findings contributed to developing robust monitoring tools that facilitate the maintenance of stable granular sludge operations., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: To analyze the correlation between the prostate necrosis rate at 1-month after prostatic artery embolization (PAE) and the clinical efficacy at 1-year after PAE, and to explore potential predictors of clinical success after PAE for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH)., Methods: The prostate magnetic resonance imaging data at 1-month after PAE were imported into 3D Slicer software for calculating the prostate necrosis rate and thus analyzing the relationship between the prostate necrosis rate at 1-month after PAE and the efficacy score ratio at 1-year after PAE. The 151 patients with PAE technical success were divided into a clinical success group (n = 126) and a clinical failure group (n = 25). Independent predictors of clinical success after PAE were analyzed by multifactorial logistic regression, and the predictive performance of each factor was evaluated by applying the receiver operating characteristic curve and the area under the curve (AUC)., Results: There was a linear negative correlation between the prostate necrosis rate at 1-month after PAE and the efficacy score ratio at 1-year after surgery (P < 0.001). In the clinical success group, both the initial prostate volume (PV) and the prostate necrosis rate at 1-month after PAE were significantly higher than in the clinical failure group (P < 0.001), and acute urinary retention (AUR) and adenomatous-dominant BPH were also associated with clinical success (P < 0.05). Multifactorial logistic regression analysis revealed that larger initial PV, a higher prostate necrosis rate at 1-month after surgery, and AUR were independent predictors of clinical success after PAE. The AUC values for these three indicators and their combination were 0.720, 0.928, 0.599, and 0.951, respectively, in which the prostate necrosis rate at 1-month after PAE demonstrating a high predictive value., Conclusion: The higher the prostate necrosis rate at 1-month after PAE, the better the clinical efficacy at 1-year after PAE is likely to be, and the prostate necrosis rate at 1-month after PAE is expected to become a predictor of clinical success after PAE., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To explore the neuroprotective effects of ARA290 and the role of β-common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO)., Methods: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot., Results: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR., Conclusion: ARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objective: Chronic kidney disease (CKD) is one of the most common diseases worldwide. The increasing prevalence and incidence of CKD have contributed to the critical problem of high medical costs. Due to stressful environments, aircrew members may have a high risk of renal dysfunction. A better strategy to prevent CKD progression in Air Force personnel would be to diagnosis CKD at an early stage. Since few studies have been conducted in Taiwan to examine the long-term trends in early CKD in Air Force aircrew members, this study is highly important. We investigated the prevalence of CKD and established a predictive model of disease variation among aircrew members., Materials and Methods: In this retrospective study, we included all subjects who had received physical examinations at a military hospital from 2004 to 2010 and who could be tracked for four years. The Abbreviated Modification of Diet in Renal Disease Formula (aMDRD) was used to estimate the glomerular filtration rate (GFR) and was combined with the National Kidney Foundation/ Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) to identify CKD patients., Results: A total of 212 aircrew members were assessed. The results showed that the prevalence of CKD was 3.8%, 9.4%, 9.0%, and 9.4% in each of the four years. According to the logistic regression analysis, abnormal urobilinogen levels, ketones, and white blood cell (WBC) counts in urine and a positive urine occult blood test increased the risk of CKD. A positive urine occult blood test can be used to predict the future risk of CKD. Moreover, the generalized estimating equation (GEE) model showed that a greater risk of CKD with increased examination time, age and seniority had a negative effect. In conclusion, abnormal urobilinogen levels, ketones, and urine WBC counts in urine as well as a positive urine occult blood test might serve as independent predictors for CKD., Conclusion: In the future, we can focus not only on annual physical examinations but also on simple and accurate examinations, such as urine occult blood testing, to determine the risk of CKD and prevent its progression in our aircrew members.

Interoception, the ability to precisely and timely sense internal body signals, is critical for life. The interoceptive system monitors a large variety of mechanical, chemical, hormonal, and pathological cues using specialized organ cells, organ innervating neurons, and brain sensory neurons. It is important for maintaining body homeostasis, providing motivational drives, and regulating autonomic, cognitive, and behavioral functions. However, compared to external sensory systems, our knowledge about how diverse body signals are coded at a system level is quite limited. In this review, we focus on the unique features of interoceptive signals and the organization of the interoceptive system, with the goal of better understanding the coding logic of interoception.

Background: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune disease characterized by skin or osteoarticular damage. SAPHO syndrome is often misdiagnosed or missed diagnosis due to lack of overall understanding of the disease by clinicians., Purpose: To analyze the clinical symptoms and imaging features of six Han patients with SAPHO syndrome in order to provide reference for doctors to diagnose SAPHO syndrome., Material and Methods: This study retrospectively analyzed the clinical data of six Han patients with SAPHO syndrome., Results: All six Han patients with SAPHO syndrome had severe acne or pustulosis of the hands and feet, and all of them had osteoarticular damage, including five cases involving the sternoclavicular joint. Some patients showed a specific and typical "bull's head" sign on 99m Tc-labeled methylene diphosphonate bone imaging. Among the six patients recruited, there was one thoracic vertebra, one cervical vertebra, one sacroiliac joint, and one peripheral joint involvement. Two patients had limited activity due to severe osteoarticular damage., Conclusion: Due to the atypical clinical symptoms of SAPHO syndrome, most patients will experience a tortuous and long diagnostic process, while a correct understanding and timely intervention of SAPHO syndrome are essential to improve the prognosis of patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aerobic Granular Sludge (AGS) technology is a promising solution for wastewater treatment due to its structure and high biomass retention capacity. However, the stability of AGS is still a challenge for widespread use. This study investigated the relationships among granule stability, granule diameter, biomass retention capacity, and denitrification efficiency. The results showed that granule diameter did not necessarily indicate granule stability, nor was it associated with biomass retention capacity. For mature granules, promoting simultaneous nitrification and denitrification rather than anoxic denitrification was found to improve granule stability. The deterioration of clarification capacity caused by increased anoxic denitrification at high nitrate concentration was not indicated by diameters or the commonly used SVI 5 /SVI 30 . Therefore, ensuring coordination between diameter and denitrification control is crucial for the stability of AGS. These results provide a basis for further research and development of efficient and user-friendly methods for monitoring granular stability., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dendrobium huoshanense is a famous edible and medicinal herb, and polysaccharides are the main bioactive component in it. In this study, response surface methodology (RSM) combined with a Box-Behnken design (BBD) was used to optimize the enzyme-assisted extraction (EAE), ultrasound-microwave-assisted extraction (UMAE), and hot water extraction (HWE) conditions and obtain the polysaccharides named DHP-E, DHP-UM, and DHP-H. The effects of different extraction methods on the physicochemical properties, structure characteristics, and bioactivity of polysaccharides were compared. The differential thermogravimetric curves indicated that DHP-E showed a broader temperature range during thermal degradation compared with DHP-UM and DHP-H. The SEM results showed that DHP-E displayed an irregular granular structure, but DHP-UM and DHP-H were sponge-like. The results of absolute molecular weight indicated that polysaccharides with higher molecular weight detected in DHP-H and DHP-UM did not appear in DHP-E due to enzymatic degradation. The monosaccharide composition showed that DHPs were all composed of Man, Glc, and Gal but with different proportions. Finally, the glycosidic bond types, which have a significant effect on bioactivity, were decoded with methylation analysis. The results showed that DHPs contained four glycosidic bond types, including Glc p -(1→, →4)-Man p -(1→, →4)-Glc p -(1→, and →4,6)-Man p -(1→ with different ratios. Furthermore, DHP-E exhibited better DPPH and ABTS radical scavenging activities. These findings could provide scientific foundations for selecting appropriate extraction methods to obtain desired bioactivities for applications in the pharmaceutical and functional food industries.

Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) is one of the most destructive insect pests owned strong resistance to different insecticides. Indoxacarb as a novel oxadiazine insecticide becomes the main pesticide against S. litura. DIMBOA [2,4-dihydroxy-7-methoxy-2 H-1,4-benz-oxazin-3(4 H)-one] is involved in important chemical defense processes in corn plants. However, the insects' adaptation mechanism to insecticides when exposed to defensive allelochemicals in their host plants remains unclear. Here, we assessed multi-resistance, and resistance mechanisms based on S. litura life history traits. After 18 generations of selection, indoxacarb resistance was increased by 61.95-fold (Ind-Sel) and 86.06-fold (Dim-Sel) as compared to the Lab-Sus. Also, DIMBOA-pretreated larvae developed high resistance to beta-cypermethrin, chlorpyrifos, phoxim, chlorantraniliprole, and emamectin benzoate. Meanwhile, indoxacarb (LC 50 ) was applied to detect its impact on thirty-eight detoxification-related genes expression. The transcripts of SlituCOE073, SlituCOE009, SlituCOE074, and SlituCOE111 as well as SlGSTs5, SlGSTu1, and SlGSTe13 were considerably raised in the Ind-Sel strain. Among the twenty-three P450s, CYP6AE68, CYP321B1, CYP6B50, CYP9A39, CYP4L10, and CYP4S9v1 transcripts denoted significantly higher levels in the Ind-Sel strain, suggesting that CarEs, GSTs and P450s genes may be engaged in indoxacarb resistance. These outcomes further highlighted the importance of detoxification enzymes for S. litura gene expression and their role in responses to insecticides and pest management approaches., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the level of psychological distress among Chinese children and adolescents and analyze its lifestyle influencing factors. Methods: Data were obtained from the 2019 Chinese National Survey on Students' Constitution and Health. A lotal of 120 285 Han Chinese children and adolescents aged 9-18 years with complete information on the psychological distress scale and lifestyle factors were selected, including 58 432 boys and 61 853 girls. The Kessler Psychological Distress Scale (K10) measured psychological distress, and lifestyles such as physical activity, sedentary behavior, diet, and sleep were also investigated. K10 scores of different genders were compared using the t -test, and the levels of psychological distress were compared using the χ 2 test. Logistic regression was used to analyze lifestyle risk factors associated with high psychological distress, and multiple linear regression was used to find the relationship between K10 scores and lifestyle scores. Results: The average K10 score for Han Chinese children and adolescents aged 9-18 years was 21.25±7.35, with girls (21.43±7.35) scoring higher than boys (21.06±7.36), the difference was statistically significant ( t =8.72, P <0.001). The rate of high psychological distress was 29.81%, with girls (31.08%) reporting higher rates than boys (28.46%), the difference was statistically significant ( χ 2 =98.54, P <0.001). 56.10% of children and adolescents have unhealthy lifestyles, with girls (58.77%) reporting higher rates than boys (53.27%), the difference was statistically significant ( χ 2 =368.53, P <0.001). Except for insufficient outdoor activities for girls ( P =0.128), lifestyles such as insufficient physical activity, insufficient muscle-and-bone exercises, long screen time, not eating breakfast, eggs and dairy products every day, drinking sugary beverages once or more per day, and not having enough sleep are all risk factors for high psychological distress (all P <0.001). For every additional healthy lifestyle score, the K10 score decreased by 0.98 [ β =-0.98 (95% CI : -1.01- -0.95)] points ( P <0.001). K10 scores in each region negatively correlate with lifestyle scores (all P <0.001). Among them, the K10 score in the eastern region showed the slightest decrease as the lifestyle score increased, while the western region showed the most decrease. Conclusions: The prevalence of psychological distress and unhealthy lifestyle in Chinese children and adolescents are high and interrelated. Compared those with healthy lifestyles, children and adolescents with unhealthy lifestyles are at greater risk of high psychological distress. Therefore, promoting healthy lifestyles for children and adolescents may be one of the important ways to improve their mental health.

Objective: To analyze the association between exposure to ambient PM 2.5 and its components [sulfate (SO 4 2- ), nitrate (NO 3 - ), ammonium (NH 4 + ), organic matter (OM), and black carbon (BC)] and psychological distress among school children and adolescents aged 9 to 18 years in China. Methods: Based on data from the 2019 Chinese National Survey on Students' Constitution and Health, 130 808 children and adolescents aged 9 to 18 years were included. Scoring and determination of higher psychological distress were based on the Kessler Psychological Distress Scale (K10), and annual average exposure data for air pollution were matched by survey location and time. We used a restricted cubic spline approach based on logistic regression to fit the associations between PM 2.5 , SO 4 2- , NO 3 - , NH 4 + , organic matter, black carbon concentrations, and psychological distress. Logistic regression models were used to analyse different age, gender, BMI and physical activity subgroups to estimate the association between exposure to high levels of pollution and high levels of psychological distress in different subgroups. Results: The proportion of children and adolescents with high levels of psychological distress in China was 30.4%, with girls being higher than boys at 31.6% and 29.1%, respectively ( P <0.05). A non-linear positive association existed between exposure to PM 2.5 , SO 4 2- , NO 3 - and organic matter concentrations and higher psychological distress. As PM 2.5 , NO 3 - , NH 4 + , organic matter, and black carbon concentrations continued to rise, the increase in the risk of higher psychological distress slowed, while SO 4 2- showed little change in the OR of psychological distress at lower concentrations but continued to rise at higher concentrations. PM 2.5 and its components were statistically associated with psychological distress in the physically inactive group but not in the physically active group. The association between high levels of pollutants and high psychological distress was stronger among students aged 9 to 12 years compared with students aged 13 to 15 years and 16 to 18 years. Conclusions: The ambient pollutant PM 2.5 and its components are associated with psychological distress in children and adolescents aged 9 to 18 years in China. High pollutant exposure is a risk factor for high psychological distress among physically inactive children and adolescents, and there are age differences in the association between PM 2.5 and components and psychological distress.

Objective: To analyze the association between overweight and obesity, psychological distress, and the influence of physical exercise among Chinese children and adolescents. Methods: The study used data from the 2019 Chinese National Survey on Students' Constitution and Health. A total of 95 280 Han Chinese children and adolescents aged 13 to 18 years were included in the study based on complete information on overweight and obesity, psychological distress assessment, and physical exercise variables. The Kessler Psychological Distress Scale was used to measure their psychological distress, with scores above 25 indicating high psychological distress. The BMI group of the adolescents was evaluated according to the Chinese standard "WS/T 586-2018 Screening for Overweight and Obesity in School-age Children and Adolescents", including underweight, normal weight, overweight, and obesity. The individual's BMI Z-score (BMIZ) was evaluated using the WHO standard and divided into ten groups based on the population percentile distribution. The survey collected the subjects' average daily physical exercise time and divided them into two groups: less than 1 hour and greater than or equal to 1 hour. Logistic regression analysis was used to analyze the relationship between overweight and obesity and high psychological distress among children and adolescents and the differences in association between different physical exercise groups. Results: The detection rates of overweight and obesity among Han Chinese children and adolescents aged 13 to 18 years in 2019 were 14.5%, and 7.6%, respectively. The rate of high psychological distress was 37.6%, and the rate of average daily physical exercise time exceeding 1 hour was 17.1%. Using the population with a BMIZ P 10 below as a reference, the association strength between high psychological distress and the population gradually increased, with an OR (95% CI ) value of 1.08 (1.02-1.14), 1.09 (1.02-1.14), 1.10 (1.03-1.16), and 1.16 (1.09-1.23) for BMIZ in the P 60 -, P 70 -, P 80 -, > P 90 groups. Compared to normal weight, both overweight and obesity were positively associated with high psychological distress in children and adolescents, with obesity showing a more significant correlation, while underweight was negatively associated with high psychological distress. The detection rates of high psychological distress in normal weight, underweight, overweight, and obese groups were 37.6%, 37.0%, 38.2%, and 38.7%, respectively, with an OR (95% CI ) value of 0.93 (0.88-0.98) for the underweight group and 1.05 (1.01-1.10) and 1.13 (1.07-1.19) for the overweight and obese groups, respectively. The positive correlation between BMIZ, overweight, and obesity with high psychological distress was significant only in adolescents who exercised less than 1 hour per day on average. Conclusions: Chinese children and adolescents face the problem of obesity and high psychological distress, with a positive correlation between these two problems. Physical activity may moderate the association between obesity and psychological distress in children and adolescents. Adequate physical exercise may offset the potential high psychological distress caused by obesity in children and adolescents. Thus, strengthening physical exercise among children and adolescents reduces the risks of both obesity and psychological health problems effectively.

Objective: To investigate protective effect of Cordyceps sinensis (CS) through autophagy-associated adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in acute kidney injury (AKI)-induced acute lung injury (ALI)., Methods: Forty-eight male Sprague-Dawley rats were divided into 4 groups according to a random number table, including the normal saline (NS)-treated sham group (sham group), NS-treated ischemia reperfusion injury (IRI) group (IRI group), and low- (5 g/kg·d) and high-dose (10 g/kg·d) CS-treated IRI groups (CS1 and CS2 groups), 12 rats in each group. Nephrectomy of the right kidney was performed on the IRI rat model that was subjected to 60 min of left renal pedicle occlusion followed by 12, 24, 48, and 72 h of reperfusion. The wet-to-dry (W/D) ratio of lung, levels of serum creatinine (Scr), blood urea nitrogen (BUN), inflammatory cytokines such as interleukin- β and tumor necrosis factor- α, and biomarkers of oxidative stress such as superoxide dismutase, malonaldehyde (MDA) and myeloperoxidase (MPO), were assayed. Histological examinations were conducted to determine damage of tissues in the kidney and lung. The protein expressions of light chain 3 II/light chain 3 I (LC3-II/LC3-I), uncoordinated-51-like kinase 1 (ULK1), P62, AMPK and mTOR were measured by Western blot and immunohistochemistry, respectively., Results: The renal IRI induced pulmonary injury following AKI, resulting in significant increases in W/D ratio of lung, and the levels of Scr, BUN, inflammatory cytokines, MDA and MPO (P<0.01); all of these were reduced in the CS groups (P<0.05 or P<0.01). Compared with the IRI groups, the expression levels of P62 and mTOR were significantly lower (P<0.05 or P<0.01), while those of LC3-II/LC3-I, ULK1, and AMPK were significantly higher in the CS2 group (P<0.05 or P<0.01)., Conclusion: CS had a potential in treating lung injury following renal IRI through activation of the autophagy-related AMPK/mTOR signaling pathway in AKI-induced ALI., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Sphenoid sinusitis is a rare disease associated with life-threatening complications that can be avoided with early recognition and timely treatment. Here, we present a case of a woman in her 80s admitted for symptomatic anaemia likely secondary to a gastrointestinal bleed with left cranial nerve (CN) VI palsy incidentally discovered on physical examination. CT and MRI were suggestive of chronic left sphenoid sinusitis with possible involvement of the left cavernous sinus. Surgical treatment was deferred due to high cardiac risk for perioperative mortality and recent ischaemic stroke. Despite antibiotic treatment, the patient's CN VI palsy remained unchanged. This report contributes to the current understanding of sphenoid sinusitis by presenting a complex case of chronic sphenoid sinusitis in which urgent surgical intervention was deferred due to the patient's multiple comorbidities. Furthermore, it highlighted the importance of the CN examination and imaging modalities in diagnosing sphenoid sinusitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Different kinds of poisonous mushrooms contain different toxic components. Acute liver injury caused by amanita mushroom is the main cause of death from poisonous mushroom poisoning in China. Consumption of poisonous mushrooms has an incubation period, there is a false recovery period in the clinical process, and the early performance is slight and does not attract enough attention from doctors, and it is easy to miss the treatment opportunity. The clinical characteristics, treatment and identification of mushrooms containing amanita in 4 patients were analyzed in order to improve clinicians' understanding of the diagnosis and treatment of mushroom poisoning and early species identification.

A reliable animal model is essential for ischemic stroke research. The implications of the external carotid artery (ECA) transection or common carotid artery (CCA) ligation have been described. Thus, a modified animal model, the CCA-repair model, has been established, and studies have shown that the CCA-repair model has potential advantages over the CCA-ligation model. However, whether the CCA-repair model is superior to the ECA-ligation model remains unclear. Sixty male C57BL/6 mice were randomly assigned to establish the CCA-repair ( n  = 34) or ECA-ligation ( n  = 26) models. Cerebral blood flow before middle cerebral artery occlusion (MCAO), immediately after MCAO and reperfusion were monitored and the operation duration, postoperative body weight, and food intake within 7 days, and the number of intraoperative and postoperative deaths within 7 days were recorded in the two models. Modified neurological severity scores and Bederson (0-5) scores were used to evaluate postoperative neurological function deficits on Days 1/3/5/7. 2,3,5-Triphenyltetrazolium chloride staining was used to quantify lesion volume on Day 7 after the operation. We found the establishment of the CCA-repair model required a longer total operation duration ( p  = 0.0175), especially the operation duration of reperfusion ( p  < 0.0001). However, there was no significant difference in body weight and food intake development, lesion volume and intragroup variability, neurological function deficits, mortality, and survival probability between the two groups. The CCA-repair model has no significant advantage over the ECA-ligation model. The ECA-ligation model is still a better choice for focal cerebral ischemia., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Ibrain published by Affiliated Hospital of Zunyi Medical University (AHZMU) and Wiley‐VCH GmbH.)

Introduction: MicroRNAs (miRNAs), a type of non-coding RNA, have been demonstrated to be essential posttranscriptional modulators in oral diseases and inflammatory responses. However, the specific role of miR-27a-5p in periodontitis requires further investigation. In this study, we used both cellular and animal models to determine how miR-27a-5p affects the pathogenesis of periodontitis and its associated biological functions., Methods: Quantitative real-time polymerase chain reaction and western blotting were used to analyze the expression of cytokines, phosphatase and tensin homolog deleted on chromosome ten (PTEN), and miR-27a-5p transcription. Investigation of alveolar bone resorption and inflammation of the periodontium in ligature-induced periodontitis in mice was performed using micro-computed tomography (micro-CT), hematoxylin-eosin (HE) staining, and tartrate-resistant acid phosphatase (TRAP) staining. The binding of miR-27a-5p and PTEN was predicted using the TargetScan database and experimentally confirmed using dual luciferase reporter gene assays., Results: The inflamed gingiva showed lower levels of miR-27a-5p. Macrophages from miR-27a-5p -/- mice produced much higher quantities of pro-inflammatory cytokines owing to the stimulation of Porphyromonas gingivalis lipopolysaccharide, and miR-27a-5p -/- mice with ligature-induced periodontitis also exhibited more severe alveolar bone resorption and damage to the periodontium. Target validation assays identified PTEN as a direct target of bona. Blocking PTEN expression partially reduced inflammation, both in vitro and in vivo., Conclusions: miR-27a-5p alleviated the inflammatory response in periodontitis by targeting PTEN., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Methods: Gene expression profiles and apoptosis-related data were downloaded from the Gene Expression Omnibus and Molecular Signature databases, respectively. Apoptosis-related differentially expressed mRNAs (DEGs) and miRNAs (DEMs) from blood samples between the schizophrenia and healthy control individuals were screened. A diagnostic model was developed using the data from univariate and least absolute shrinkage and selection operator (LASSO) regression analyses, followed by validation using the GSE38485 dataset. Cases were divided into low-risk (LR) and high-risk (HR) groups based on the risk score of the model, and differences in immune gene sets and pathways between these two groups were compared. Finally, a ceRNA network was constructed by integrating long non-coding RNAs (lncRNAs), DEMs, and DEGs., Results: A diagnostic model containing 15 apoptosis-related genes was developed and its diagnostic efficiency was found to be robust. The HR group was correlated with higher immune scores of chemokines, cytokines, and interleukins; it was also significantly involved in pathways such as pancreatic beta cells and early estrogen response. A ceRNA network composed of 2 lncRNAs, 14 miRNAs, and 5 mRNAs was established., Conclusions: The established model is a potential tool to improve the diagnostic efficiency of patients with schizophrenia, and the nodes included in the ceRNA network might serve as biomarkers and therapeutic targets for schizophrenia., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Zi-long Ma et al.)

Background: Transcranial Doppler flow velocity is used to monitor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Generally, blood flow velocities appear inversely related to the square of vessel diameter representing local fluid dynamics. However, studies of flow velocity-diameter relationships are few, and may identify vessels for which diameter changes are better correlated with Doppler velocity. We therefore studied a large retrospective cohort with concurrent transcranial Doppler velocities and angiographic vessel diameters., Methods: This is a single-site, retrospective, cohort study of adult patients with aneurysmal subarachnoid hemorrhage, approved by the UT Southwestern Medical Center Institutional Review Board. Study inclusion required transcranial Doppler measurements within 1.1, R 2 >0.9). Furthermore, velocity and diameter changed (P<0.033) consistent with the signature time course of cerebral vasospasm., Conclusions: These results suggest that middle cerebral artery velocity-diameter relationships are most influenced by local fluid dynamics, which supports these vessels as preferred endpoints in Doppler detection of cerebral vasospasm. Other vessels showed less influence of local fluid dynamics, pointing to greater role of factors outside the local vessel segment in determining flow velocity., Competing Interests: Declaration of Competing Interest None related to this study. Dr. McDonagh has research funding from Lungpacer Medical Inc. and Sedana Medical Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)