A novel neuroprotective method against ischemic stroke by accelerating the drainage of brain interstitial fluid.

Ischemic stroke is a leading cause of death and disability worldwide. Inflammatory response after stroke determines the outcome of ischemic injury. A recent study has reported an efficient method, epidural arterial implantation (EAI), for accelerating interstitial fluid (ISF) drainage, which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space (ECS). In this study, the method of EAI was modified (m-EAI) to control its function of accelerating the ISF drainage at different time points following ischemic attack. The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion (tMCAO) rat model. The results demonstrated the accumulation of IL-1ß, IL-6, and TNF-α was significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats, accompanied with decreased infarct volume and improved neurological function. This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS. Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.

Influences of noise reduction on speech intelligibility, listening effort, and sound quality among adults with severe to profound hearing loss.

Introduction: Noise reduction (NR) algorithms have been integrated into modern digital hearing aids to reduce noise annoyance and enhance speech intelligibility. This study aimed to evaluate the influences of a novel hearing aid NR algorithm on individuals with severe-to-profound hearing loss. Methods: Twenty-five participants with severe-to-profound bilateral sensorineural hearing loss underwent three tests (speech intelligibility, listening effort, and subjective sound quality in noise) to investigate the influences of NR. All three tests were performed under three NR strength levels (Off, Moderate, and Strong) for both speech in noise program (SpiN) and speech in loud noise program (SpiLN), comprising six different hearing aid conditions. Results: NR activation significantly reduced listening effort. Subjective sound quality assessments also exhibited benefits of activated NR in terms of noise suppression, listening comfort, satisfaction, and speech clarity. Discussion: Individuals with severe-to-profound hearing loss still experienced advantages from NR technology in both listening effort measure and subjective sound quality assessments. Importantly, these benefits did not adversely affect speech intelligibility.

Osteoarthritis, osteoarthritis treatment and risk of incident dementia: a prospective cohort study based on UK Biobank.

BACKGROUND: We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. METHODS: We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. RESULTS: During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039-1.199) and AD (HR: 1.127; 95% CI: 1.013-1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652-0.854) and surgery group (HR: 0.841; 95% CI: 0.736-0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. CONCLUSIONS: Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia.

Integration of Gut Mycobiota and Oxidative Stress to Decipher the Roles of C-Type Lectin Receptors in Inflammatory Bowel Diseases.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of inflammatory bowel disease (IBD) with rapidly increased incidence worldwide. Although multiple factors contribute to the occurrence and progression of IBD, the role of intestinal fungal species (gut mycobiota) in regulating the severity of these conditions has been increasingly recognized. C-type lectin receptors (CLRs) on hematopoietic cells, including Dectin-1, Dectin-2, Dectin-3, Mincle and DC-SIGN, are a group of pattern recognition receptors (PRRs) that primarily recognize fungi and mediate defense responses, such as oxidative stress. Recent studies have demonstrated the indispensable role of CLRs in protecting the colon from intestinal inflammation and mucosal damage. METHODS AND RESULTS: This review provides a comprehensive overview of the role of CLRs in the pathogenesis of IBD. Given the significant impact of mycobiota and oxidative stress in IBD, this review also discusses recent advancements in understanding how these factors exacerbate or ameliorate IBD. Furthermore, the latest developments in CLR-guided IBD therapy are examined to highlight the modulation of CLRs in fungal recognition and oxidative burst during the IBD process. CONCLUSION: This review emphasizes the importance of CLRs in IBD, offering new perspectives on the etiology and therapeutic approaches for this disease.

Ischemic core volume is associated with hemorrhagic transformation post endovascular thrombectomy.

INTRODUCTION: Symtomatic hemorrhagic transformation(sHT) was defined as any intracerebral hemorrhage that combined with clinical deterioration. While recent studies showed low rates of sHT in large core ischemic strokes treated with endovascular thrombectomy (EVT), the specific impact of core size on overall hemorrhagic transformation (HT) remains unclear. We aim to investigate the relationship between ischemic core size and development of HT post thrombectomy. METHODS: This prospective study enrolled acute ischemic stroke (AIS) patients with anterior large vessel occlusion undergoing EVT who had baseline MRI from 2017-2019. Pre-EVT Arterial Spin Labeling (ASL) and Diffusion-Weighted Imaging (DWI) scans were performed for volume calculations. Primary outcome was HT assessed within 72 hours post EVT. Multivariable logistic regression was used to analyze the associations between baseline DWI and ASL volumes and HT occurrence. Discriminative ability for HT was compared using receiver operating curve analysis (c-statistic). RESULTS: We included 101 patients (median age: 64 [IQR 56-74] years, baseline NIHSS 13 [IQR 9-16]). Median DWI and ASL volume were 21.0 ml [IQR 8.3-47.2] and 105ml [59.5-172.9], respectively. 36.8% recieved intravenous thrombolysis before EVT. HT occurred in 36.6% of patients, including 16.8% with sHT. Baseline DWI volume was independently associated with HT (OR=1.030, 95% CI 1.008 to 1.053, P=0.009), while ASL volume wasn't statistically significant(P=0.330). The DWI model was superior to ASL model in predicting HT within 72 hours (c-statistic, 0.787).Neither DWI (P=0.149) nor ASL volume (P=0.834) effectively indicated sHT. CONCLUSIONS: DWI-based ischemic core volume correlates significantly with HT within 72 hours post successful thrombectomy. This highlights the potential clinical utility of DWI in guiding treatment decisions for this population.

Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.

INTRODUCTION: The heritability of Alzheimer's disease (AD) is estimated to be 58%-79%. However, known genes can only partially explain the heritability. METHODS: Here, we conducted gene-based exome-wide association study (ExWAS) of rare variants and single-variant ExWAS of common variants, utilizing data of 54,569 clinically diagnosed/proxy AD and related dementia (ADRD) and 295,421 controls from the UK Biobank. RESULTS: Gene-based ExWAS identified 11 genes predicting a higher ADRD risk, including five novel ones, namely FRMD8, DDX1, DNMT3L, MORC1, and TGM2, along with six previously reported ones, SORL1, GRN, PSEN1, ABCA7, GBA, and ADAM10. Single-variant ExWAS identified two ADRD-associated novel genes, SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. The druggability evidence suggests that DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets. DISCUSSION: Our study contributes to the current body of evidence on the genetic etiology of ADRD. HIGHLIGHTS: Gene-based analyses of rare variants identified five novel genes for Alzheimer's disease and related dementia (ADRD), including FRMD8, DDX1, DNMT3L, MORC1, and TGM2. Single-variant analyses of common variants identified two novel genes for ADRD, including SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets.

The modified Surgical Apgar Score predictive value for postoperative complications after robotic surgery for rectal cancer.

OBJECTIVE: The Surgical Apgar Score quantifies three intraoperative parameters: lowest heart rate, lowest mean arterial pressure, and estimated blood loss (EBL). This scoring system predicts postoperative complications based on these measured factors. The aim of this study was to investigate the value of modified Surgical Apgar Score (mSAS) in predicting postoperative complications in patients with rectal cancer treated with robotic surgery in order to improve the survival and quality of life of rectal cancer patients. METHODS: The study included patients with rectal cancer who underwent robotic surgery in the Department of Gastrointestinal Surgery at the First Affiliated Hospital of Nanchang University from January 2015 to December 2023. In minimally invasive surgery, we developed a modified Surgical Apgar Score (mSAS) tailored for robotic rectal cancer surgery, incorporating an adjusted threshold for EBL. This threshold was derived from quartile analysis of a cohort of 524 patients, with a median EBL of 100 mL (IQR 80-130 mL). We analyzed the association of postoperative complications with low mSAS. RESULTS: This study included 524 patients, of which 91 (17.4%) experienced complications and 22 (4.2%) suffered severe complications. mSAS of 6 provided maximal Youden index and were determined as the cut-off values. The area under the ROC curve for predicting complications using the mSAS was 0.740. Univariate and multivariate analyses indicated that an older age, lower tumor localization, longer operation time, radiotherapy alone, combined chemoradiotherapy, and lower mSAS as independent risk factors for complications. The AUC of the prediction nomogram was 0.834 (95% CI 0.774-0.867). The calibration curve demonstrated excellent concordance with the nomogram, indicating the prediction curve ft the diagonal well. CONCLUSION: This study suggests that mSAS might be a valuable predictive indicator for postoperative complications following robotic rectal cancer surgery, with potentially higher clinical utility.

Individual and combined effects of famine exposure and obesity parameters on type 2 diabetes in middle-aged and older adults: A population-based cross-sectional study.

Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (P < .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China.

Targeted Reprogramming of Pathogenic Fibroblast Genes at the 3'-Untranslated Regions by DNA Nanorobots for Periodontitis.

Periodontitis, with its persistent nature, causes significant distress for most sufferers. Current treatments, such as mechanical cleaning and surgery, often fail to fully address the underlying overactivation of fibroblasts that drives this degradation. Targeting the post-transcriptional regulation of fibroblasts, particularly at the 3'-untranslated regions (3'UTR) of pathogenic genes, offers a therapeutic strategy for periodontitis. Herein, we developed a DNA nanorobot for this purpose. This system uses a dynamic DNA nanoframework to incorporate therapeutic microRNAs through molecular recognition and covalent bonds, facilitated by DNA monomers modified with disulfide bonds. The assembled-DNA nanoframework is encapsulated in a cell membrane embedded with a fibroblast-targeting peptide. By analyzing the 3'UTR regions of pathogenic fibroblast genes FOSB and JUND, we identified the therapeutic microRNA as miR-1-3p and integrated it into this system. As expected, the DNA nanorobot delivered the internal components to fibroblasts by the targeting peptide and outer membrane that responsively releases miR-1-3p under intracellular glutathione. It resulted in a precise reduction of mRNA and suppression of protein function in pathogenic genes, effectively reprogramming fibroblast behavior. Our results confirm that this approach not only mitigates the inflammation but also promotes tissue regeneration in periodontal models, offering a promising therapeutic avenue for periodontitis.

Bidirectional Mendelian randomization to explore the causal relationships between the gut microbiota and male reproductive diseases.

Gut bacteria might play an important role in male reproductive disorders, such as male infertility and sperm abnormalities; however, their causal role is unclear. Herein, Mendelian randomization (MR)-Egger, weighted median, inverse variance weighting, Simple mode, and Weighted mode were used to test the causal relationship between gut microbes and male reproductive diseases. The MR results were validated using various metrics. The MR results were also consolidated using reverse causality speculation, conducted using two-way MR analysis and Steiger filtering. Biological function was analysed using enrichment analyses. The results suggested that eight intestinal microflorae were causally associated with male infertility. The Eubacterium oxidoreducens group was associated with an increased risk of male infertility, while the family Bacteroidaceae was negatively associated with male reproductive diseases. Eight intestinal microflorae were causally associated with abnormal spermatozoa. The family Streptococcaceae was associated with a high risk of abnormal spermatozoa, whereas the family Porphyromonadaceae was associated with a low risk of abnormal spermatozoa. No pleiotropy was observed, this study identified a high correlation between the gut flora and the likelihood of male reproductive diseases. Future research will attempt to advance microbial-focused treatments for such diseases.

In situ polymerization of 1,3-dioxolane and formation of fluorine/boron-rich interfaces enabled by film-forming additives for long-life lithium metal batteries.

In situ polymerized 1,3-dioxolane (PDOL) is widely utilized to construct solid polymer electrolytes because of its high room-temperature ionic conductivity and good compatibility with lithium metal. However, the current polymerization additives used in PDOL do not effectively contribute to the formation of a robust solid electrolyte interphase (SEI), leading to decreased cycle life. Herein, a film-forming Lewis acid, tris(hexafluoroisopropyl) borate (THB), is demonstrated not only to be a catalyst for the ring-opening polymerization of DOL, but also an additive for the formation of a stable fluorine- and boron-rich SEI to improve the interfacial stability and suppress the Li dendrite growth. Moreover, molecular dynamics simulations and experimental results demonstrate that the introduction of THB can promote the dissociation of lithium salt and release more Li+ while the boron site can effectively restrict the free movement of TFSI- anion, thus increasing Li+ transference numbers (0.76) and ensuring the long-term cycling stability of cells. By using THB-PDOL, a stable cycling of Li‖Li symmetric cell for 600 h at a capacity of 0.5 mA h cm-2 can be achieved. Furthermore, employing THB-PDOL in Li‖LiFePO4 full cell enables a capacity retention of 98.64% after 300 cycles at 1C and a capacity retention of 95.39% after 200 cycles at a high temperature (60 °C). At the same time, this electrolyte is also suitable for the Li‖NCM523 full cell, which also achieves excellent stability of more than 180 cycles. This film-forming Lewis acid additive provides ideas for designing low-cost, high-performance PDOL-based lithium metal batteries.

Bacteria-Derived Cellulose Membranes Modified with Graphene Oxide-Silver Nanoparticles for Accelerating Wound Healing.

This study reports on the modification of bacterial cellulose (BC) membranes produced by static fermentation of Komagataeibacter xylinus bacterial strains with graphene oxide-silver nanoparticles (GO-Ag) to yield skin wound dressings with improved antibacterial properties. The GO-Ag sheets were synthesized through chemical reduction with sodium citrate and were utilized to functionalize the BC membranes (BC/GO-Ag). The BC/GO-Ag composites were characterized to determine their surface charge, morphology, exudate absorption, antimicrobial activity, and cytotoxicity by using fibroblast cells. The antimicrobial activity of the wound dressings was assessed against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The results indicate that the BC/GO-Ag dressings can inhibit ∼70% of E. coli cells. Our findings also revealed that the porous BC/GO-Ag antimicrobial dressings can efficiently retain 94% of exudate absorption after exposure to simulated body fluid (SBF) for 24 h. These results suggest that the dressings could absorb excess exudate from the wound during clinical application, maintaining adequate moisture, and promoting the proliferation of epithelial cells. The BC/GO-Ag hybrid materials exhibited excellent mechanical flexibility and low cytotoxicity to fibroblast cells, making excellent wound dressings able to control bacterial infectious processes and promote the fast healing of dermal lesions.

Discovery of mmu-lncRNA129814/hsa-lncRNA582795 as a Potential Biomarker and Intervention Target for Ischemia Reperfusion Injury-Induced AKI.

Background: Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity, as well as increased medical expenses. The molecular mechanisms underlying ischemia-reperfusion (I/R)-induced AKI remain unclear. Methods and Results: We applied an RT-qPCR assay to measure the expression of mmu-lncRNA129814, hsa-lncRNA582795, and miRNA-494-5p, immunoblotting to detect IL-1α and cleaved caspase-3 expression, and TUNEL staining and flow cytometry (FCM) to evaluate apoptosis. The experiments were conducted using BUMPT and HK-2 cells, as well as C57BL/6J mice. Mechanistically, mmu-lncRNA129814 could sponge miRNA-494-5p and upregulate IL-1α expression to promote cell apoptosis. Furthermore, knockdown of mmu-lncRNA129814 ameliorated I/R-induced progression of AKI by targeting the miRNA-494-5p/IL-1α pathways. Interestingly, hsa-lncRNA582795, a homolog of mmu-lncRNA129814, also promoted I/R-stimulated HK-2 cell apoptosis and AKI progression by regulating the miRNA-494-5p/IL-1α axis. Finally, we found that patients with I/R-induced AKI exhibited significantly elevated plasma and urinary levels of hsa-lncRNA582795 compared to those who underwent ischemia-reperfusion without developing AKI. Spearman's test demonstrated a significant correlation between serum creatinine and plasma hsa-lncRNA582795 in I/R patients. Plasma hsa-lncRNA582795 showed high sensitivity but low specificity (86.7%) compared to urinary hsa-lncRNA582795. Conclusion: The mmu-lncRNA129814/hsa-lncRNA582795/miRNA-494-5p/IL-1α axis was found to modulate the progression of ischemic AKI, and hsa-lncRNA582795 could act as a diagnosis biomarker and potential therapy target of I/R-induced AKI.

Selective recognition and enrichment of C70 over C60 using an anthracene-based nanotube.

Selective recognition and enrichment of fullerenes (e.g., C60 and C70) remains challenging due to the same diameter and geometrical similarity. Herein, we report a hexagonal anthracene-based nanotube (1) through a one-pot Suzuki-Miyaura cross-coupling reaction. With anthracene-based side walls and pyridine linkers, 1 features a nano-scale tubular cavity measuring 1.2 nm in diameter and 0.9 nm in depth, along with pH-responsive properties. Interestingly, the electron-rich 1 shows high binding affinity (K a ≈ 106 M-1) and selectivity (K s ≈ 140) to C70 over C60 in toluene, resulting from their different contribution of π-π interactions with the host. The protonation of 1 simultaneously alters the electronic properties within the nanotube, resulting in the release of the fullerene guests. Lastly, the selective recognition and pH stimuli-responsive properties of the nanotube have been utilized to enrich C70 from its low-content mixtures of fullerenes in chloroform.

Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

New advances in drug development for metabolic dysfunction-associated diseases and alcohol-associated liver disease.

Metabolic disorders are currently threatening public health worldwide. Discovering new targets and developing promising drugs will reduce the global metabolic-related disease burden. Metabolic disorders primarily consist of lipid and glucose metabolic disorders. Specifically, metabolic dysfunction-associated steatosis liver disease (MASLD) and alcohol-associated liver disease (ALD) are two representative lipid metabolism disorders, while diabetes mellitus is a typical glucose metabolism disorder. In this review, we aimed to summarize the new drug candidates with promising efficacy identified in clinical trials for these diseases. These drug candidates may provide alternatives for patients with metabolic disorders and advance the progress of drug discovery for the large disease burden.

Repellency, toxicity, and physiological actions of low molecular weight basic amines in mosquitoes.

BACKGROUND: This study investigated the behavioral responses and toxicity of three basic amines: 1-methylpiperazine, 1-methylpyrrolidine, and triethylamine (TEA), compounds suggested previously to be anosmic in vapor exposures to caged mosquitoes. RESULTS: These compounds showed repellency of Aedes aegypti mosquitoes, followed by flightlessness, knockdown, and paralysis, all increasing with exposure time and dosage. Electrophysiological experiments showed a blocking effect on nerve discharge of the Drosophila melanogaster larval central nervous system (CNS) with little evidence of hyperexcitation. Blockage of voltage-gated (Kv2) potassium channel currents under patch clamp occurred at similar concentrations. Involvement of K+ channels in the action of basic amines was supported by behavior and CNS recordings of a Shaker Kv1 mutant exposed to TEA, where instead of blockage, a hyperexcitation of nerve firing was observed. Experiments on cockroach leg mechanoreceptors demonstrated neuronal excitation and on mosquito antennae strong electroantennogram (EAG) signals with an augmentation of blank air responses after a single puff of basic amine. CONCLUSIONS: The neurophysiological effects of basic amines are consistent with K+ channel block, whereas the antennal EAG response was not obviously associated with anosmia. The low-dose effects of basic amines appear to be repellency and bradykinesia. Overall, the findings provide key insights into the mechanisms underlying the biological activity of basic amines. © 2024 Society of Chemical Industry.

Epidemiological characteristics of first-time SARS-CoV-2 Omicron infection among hospital staff in Chengdu, China.

BACKGROUND: After China ended its 'dynamic zero-COVID policy' on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected. METHODS: All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection. RESULTS: A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females [adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07-1.88] and clinical practitioners (aOR: 10.32, 95% CI: 6.57-16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age ≥ 60 years (aOR: 0.30, 95% CI: 0.19-0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23-0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22-0.97 for within 1-3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms. CONCLUSION: Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China's deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak.

Exome sequencing identifies novel genetic variants associated with varicose veins.

BACKGROUND: Varicose veins (VV) are one of the common human diseases, but the role of genetics in its development is not fully understood. METHODS: We conducted an exome-wide association study of VV using whole-exome sequencing data from the UK Biobank, and focused on common and rare variants using single-variant association analysis and gene-level collapsing analysis. FINDINGS: A total of 13,823,269 autosomal genetic variants were obtained after quality control. We identified 36 VV-related independent common variants mapping to 34 genes by single-variant analysis and three rare variant genes (PIEZO1, ECE1, FBLN7) by collapsing analysis, and most associations between genes and VV were replicated in FinnGen. PIEZO1 was the closest gene associated with VV (P = 5.05 × 10-31), and it was found to reach exome-wide significance in both single-variant and collapsing analyses. Two novel rare variant genes (ECE1 and METTL21A) associated with VV were identified, of which METTL21A was associated only with females. The pleiotropic effects of VV-related genes suggested that body size, inflammation, and pulmonary function are strongly associated with the development of VV. CONCLUSIONS: Our findings highlight the importance of causal genes for VV and provide new directions for treatment.

Comprehensive evaluation of urban river ecological bank protection based on AHP-TOPSIS method.

An ecological revetment is a new type that combines natural vegetation with civil engineering technology to establish functions, such as flood control, drainage, ecology, and landscape. Various types of ecological and other bank protection lead to different bank protection effects. Urban river ecological bank protection can effectively prevent bank collapse and promote mutual infiltration between river water and soil and is important for maintaining the balance of the river ecosystem and enhancing the ecological service function of river bank protection. To scientifically and accurately evaluate the ecological protection of riverbanks, this study screened 16 evaluation indicators based on four aspects: structural stability, ecological functionality, landscape suitability, and socio-economic status. A comprehensive evaluation index system for urban river ecological protection was constructed and an urban river ecological protection evaluation model based on the AHP - TOPSIS method was established. The model was used to evaluate the ecological protection of the rivers in the study area. The results revealed that the evaluation value, 0.830, of the self-embedded retaining wall exhibited the best performance among the current slope protection types. In addition, structural stability is a crucial factor in river ecological revetments, and the evaluation results were consistent with the revetment type selected in actual engineering. Therefore, the evaluation system constructed in this study is reasonable and reliable and has strong generalizability. This study provides theoretical guidance for selecting ecological protection banks for future river management projects and has specific references important for academic research and the development of environmental protection banks.