Deciphering the seasonal dynamics of multifaceted aerosol-ozone interplay: Implications for air quality management in Eastern China.

We employed an enhanced WRF-Chem to investigate the discrete mechanisms of aerosol-radiation-feedback (ARF), extinction-photochemistry (AEP), and heterogeneous-reactions (AHR) across different seasons in eastern China, aiming to assess the synergistic effects arising from the simultaneous operation of multiple processes on O3 and PM2.5. Our findings demonstrated that ARF fostered the accumulation of pollutants and moisture, initiating two distinct feedback mechanisms concerning O3. The elevation in the NO/NO2 ratio amplified O3 consumption. Increased near-surface moisture diminished upper-level cloud formation, thereby enhancing photolysis rates and O3 photochemical production. The pronounced impact of heightened NO/NO2 on O3 led to a decrease of 0.1-2.7 ppb. When decoupled from ARF, AEP led to a more significant reduction in photolysis rates, resulting in declines in both O3 and PM2.5, except for an anomalous increase observed in summer, with O3 increasing by 1.6 ppb and PM2.5 by 2.5 µg m-3. The heterogeneous absorption of hydroxides in spring, autumn, and winter predominantly governed the AHR-induced variation of O3, leading to a decrease in O3 by 0.7-1 ppb. Conversely, O3 variations in summer were primarily dictated by O3-sensitive chemistry, with heterogeneous absorption of NOy catalyzing a decrease of 2.4 ppb in O3. Furthermore, AHR accentuated PM2.5 by facilitating the formation of fine sulfates and ammonium while impeding nitrate formation. In summer, the collective impact of ARF, AEP, and AHR (ALL) led to a substantial reduction of 6.2 ppb in O3, alleviating the secondary oxidation of PM2.5 and leading to a decrease of 0.3 µg m-3 in PM2.5. Conversely, albeit aerosol substantially depleted O3 by 0.4-4 ppb through their interactions except for summer, aerosol feedback on PM2.5 was more pronounced, resulting in a significant increase of 1.7-6.1 µg m-3 in PM2.5. Our study underscored the seasonal disparities in the ramifications of multifaceted aerosol-ozone interplay on air quality.

Correlation between dysbiosis of vaginal microecology and endometriosis: A systematic review and meta-analysis.

BACKGROUND: Endometriosis, a complex gynecological condition, involves inflammation and immune dysregulation. The vaginal microbiota, characterized by its diversity, is an integral part of the vaginal microecology-interacting with vaginal anatomy, the endocrine system, and local mucosal immunity. Imbalances in this microecology are known to precipitate various inflammatory diseases. Despite extensive research, the connection between vaginal microbiota dysbiosis and endometriosis remains a subject of debate. Our study assesses the association between vaginal microecology dysbiosis and endometriosis. METHODS: We systematically searched major electronic databases in English, including Embase, PubMed, The Cochrane Library, MEDLINE (Ovid), BIOSIS (Ovid), China National Knowledge Infrastructure (CNKI), and Wanfang, up to August 15, 2023. Selected articles underwent screening based on predefined inclusion and exclusion criteria. Normal vaginal microecology was defined as a negative Amsel/Spiegel test or Nugent score of 0-3, or Lactobacillus predominance determined by 16S rRNA gene amplification sequencing. Deviations from this norm were classified as dysbiosis, further categorized into bacterial vaginosis (BV) and intermediate BV. Data analysis utilized Revman 5.4, with effect sizes presented as Odds Ratios (OR) and 95% Confidence Intervals (CI). RESULTS: Out of 1081 articles, eight met the inclusion criteria. Utilizing fixed-effect models due to low heterogeneity, the analysis revealed a positive association between dysbiosis and endometriosis (OR = 1.17, 95% CI 0.81-1.70; I2 = 0%), but showed a slight negative association between normal vaginal microecology with endometriosis (OR = 0.90, 95% CI 0.55-1.46; I2 = 29%). However, the association was not significant. Subgroup and sensitivity analyses corroborated the stability of these associations. CONCLUSION: A positive correlation exists between vaginal microecology dysbiosis and endometriosis, notably with intermediate BV. However, the mechanisms underpinning this relationship remain elusive, highlighting the need for further research to overcome limitations. TRIAL REGISTRATION: Registration number: CRD42023445163.

Particle-ozone complex pollution under diverse synoptic weather patterns in the Yangtze River Delta region: Synergistic relationships and the effects of meteorology and chemical compositions.

There is considerable academic interest in the particle-ozone synergistic relationship (PO) between fine particulate matter (PM2.5) and ozone (O3). Using various synoptic weather patterns (SWPs), we quantitatively assessed the variations in the PO, which is relevant to formulating policies aimed at controlling complex pollution in the air. First, based on one-year sampling data from March 2018 to February 2019, the SWPs classification of the Yangtze River Delta (YRD) was conducted using the sum-of-squares technique (SS). Five dominant SWPs can be found in the YRD region, including the Aleutian low under SWP1 (occurring 45 % of the year), a tropical cyclone under SWP2 (21 %), the tropical cyclone and western Pacific Subtropical High (WPSH) under SWP3 (15.4 %), the WPSH under SWP4 (6.9 %), and a continental high pressure under SWP5 (3.1 %). The phenomenon of a "seesaw" between PM2.5 and O3 concentrations exhibited significant spatial heterogeneity, which was influenced by meteorological mechanisms. Second, the multi-linear regression (MLR) model and the partial correlation (PCOR) analysis were employed to quantify the effects of dominant components and meteorological factors on the PO. Meteorological variables could collectively explain only 33.0 % of the PM2.5 variations, but 58.0 % for O3. O3 promoted each other with low concentrations of PM2.5 but was inhibited by high concentrations of PM2.5. High relative humidity (RH) was conducive to the generation of PM2.5 secondary components and enhanced the radiative effects of aerosols and the negative correlation of PO. In addition, attention should be paid to assessing the combined effects of precursor levels, weather, and chemical reactions on the particle-ozone complex pollution. The control of O3 pollutants should be intensified in summer, while the focus should be on reducing PM2.5 pollutants in winter. Prevention and control measures need to reflect the differences in weather conditions and pollution characteristics, with a focus on RH and secondary components of PM2.5.

Homeostatic measure of insulin resistance is associated with future asthma exacerbations: a 1-year prospective cohort study.

BACKGROUND AND AIMS: Recent evidence suggests that insulin resistance affects asthma outcomes; however, the effect of the homeostatic measure of insulin resistance (HOMA-IR) on airway inflammation and asthma exacerbations (AEs) is poorly understood. OBJECTIVES: To analyze the relationship between HOMA-IR and clinical and inflammatory characteristics in patients with asthma, and the association between HOMA-IR and asthma exacerbations (AEs) in the following year. METHODS: A prospective cohort study recruited participants with asthma, who were classified into the HOMA-IRhigh group and HOMA-IRlow group based on the cutoff value of 3.80 for HOMA-IR and were observed within 12 months. We evaluated the clinical and inflammatory features, and a 1-year follow-up was conducted to study the exacerbations. A negative binomial regression model was used to analyze the association between HOMA-IR and AEs. RESULTS: Compared with the patients in the HOMA-IRlow group (n = 564), patients in the HOMA-IRhigh group (n = 61) had higher levels of BMI, higher waist circumference and waist/hip ratio, higher triglycerides, lower cholesterol high-density lipoproteins (HDL), more neutrophils in the peripheral blood, and elevated IL-5 levels in the induced sputum. Furthermore, patients in the HOMA-IRhigh group had a significantly increased risk for moderate-to-severe AEs (adjusted incidence rate ratio (aIRR) = 2.26, 95% confidence interval (CI) = [1.38, 3.70]), severe AEs (aIRR = 2.42, 95% CI = [1.26, 4.67]), hospitalization(aIRR = 2.54, 95% CI = [1.20, 5.38]), and emergency visits (aIRR = 3.04, 95% CI = [1.80, 8.53]). CONCLUSION: HOMA-IR was associated with asthma-related clinical features, and airway inflammation, as well as being an independent risk factor for future AEs. Therefore, insulin resistance may have important implications for managing asthma as a potential treatable trait.

BMAL1 plays a crucial role in immune homeostasis during sepsis-induced acute lung injury.

Sepsis is a widespread and life-threatening disease characterised by infection-triggered immune hyperactivation and cytokine storms, culminating in tissue damage and multiple organ dysfunction syndrome. BMAL1 is a pivotal transcription factor in the circadian clock that plays a crucial role in maintaining immune homeostasis. BMAL1 dysregulation has been implicated in inflammatory diseases and immunodeficiency. However, the mechanisms underlying BMAL1 disruption in sepsis-induced acute lung injury (ALI) remain poorly understood. In vitro, we used THP1 and mouse peritoneal macrophages to elucidate the potential mechanism of BMAL1 function in sepsis. In vivo, an endotoxemia model was used to investigate the effect of BMAL1 on sepsis and the therapeutic role of targeting CXCR2. We showed that BMAL1 significantly affected the regulation of innate immunity in sepsis-induced ALI. BMAL1 deficiency in the macrophages exacerbated systemic inflammation and sepsis-induced ALI. Mechanistically, BMAL1 acted as a transcriptional suppressor and regulated the expression of CXCL2. BMAL1 deficiency in macrophages upregulated CXCL2 expression, increasing the recruitment of polymorphonuclear neutrophils and the formation of neutrophil extracellular traps (NETs) by binding to the chemokine receptor CXCR2, thereby intensifying lung injury in a sepsis model. Furthermore, a selective inhibitor of CXCR2, SB225002, exerted promising therapeutic effects by markedly reducing neutrophil infiltration and NETs formation and alleviating lung injury. Importantly, CXCR2 blockade mitigated multiple organ dysfunction. Collectively, these findings suggest that BMAL1 controls the CXCL2/CXCR2 pathway, and the therapeutic efficacy of targeting CXCR2 in sepsis has been validated, presenting BMAL1 as a potential therapeutic target for lethal infections.

Plasma IL-6 levels and their association with brain health and dementia risk: A population-based cohort study.

BACKGROUND: Recent studies have associated immune abnormalities with dementia. IL-6 is a crucial cytokine in inflammatory responses, and recent evidence has linked elevated IL-6 levels to changes in brain structure and cognitive decline. However, the connection between IL-6 levels, cognition, brain volumes, and dementia risk requires exploration in large prospective cohorts. METHODS: This study utilized a longitudinal cohort from the UK Biobank to analyze the correlation between IL-6 expression levels, cognitive performance, and cortical and subcortical brain volumes through linear regression. Additionally, we assessed the association between IL-6 levels and long-term dementia risk using Cox regression analysis. We also used one-sample Mendelian randomization to analyze the impact of genetic predisposition of dementia on elevated IL-6 levels. RESULTS: A total of 50,864 participants were included in this study, with 1,391 new cases of all-cause dementia identified. Higher plasma IL-6 levels are associated with cortical and subcortical atrophy in regions such as the fusiform, thalamus proper, hippocampus, and larger ventricle volumes. IL-6 levels are negatively associated with cognitive performance in pair matching, numeric memory, prospective memory, and reaction time tests. Furthermore, elevated IL-6 levels are linked to a 23-35 % increased risk of all-cause dementia over an average follow-up period of 13.2 years. The one-sample Mendelian randomization analysis did not show associations between the genetic predisposition of dementia and elevated IL-6 levels. CONCLUSIONS: Increased IL-6 levels are associated with worse cognition, brain atrophy, and a heightened risk of all-cause dementia. Our study highlights the need to focus on the role of peripheral IL-6 levels in managing brain health and dementia risk.

C-C Motif Chemokine Ligand 5 (CCL5) as a Predictive Marker for Non-sentinel Lymph Node Presence in Initial-Stage Breast Cancer with 1-2 Affected Sentinel Lymph Nodes.

The objective of our study was to use quantum dots for the purpose of seeing and detecting C-C motif chemokine ligand 5 (CCL5) inside the tissue of sentinel lymph nodes (SLN) and primary tumors. This endeavor aimed to enhance the accuracy of predicting the condition of non-sentinel lymph nodes and provide valuable insights for making informed treatment choices. We analyzed breast cancer patients who underwent sentinel lymph node biopsy followed by axillary lymph node removal due to one or two positive sentinel lymph nodes at the Second People's Hospital of Wuhu, China, between August 2018 and July 2022. Quantum dot technology was employed to visualize and determine CCL5 in the tissue samples from 84 patients. Out of a group diagnosed with breast cancer, 208 underwent sentinel lymph node biopsy. From this pool, 84 tested positive and subsequently underwent axillary lymph node removal. The presence of distinct orange-red fluorescence, linked to quantum dots, was evident in the cellular components of both primary tumors and positive sentinel lymph node tissues. We found a significant relationship between higher levels of SLNCCL5 and advanced tumor growth (P < 0.05). To understand the predictive value of SLN CCL5 related to non-sentinel lymph node status, we utilized the receiver operating characteristic (ROC) method. The area under the curve (AUC) calculated was 0.745 with a cutoff point of 23.285. Multivariate logistic regression was used to understand the effect of tumor dimensions and SLNCCL5 levels on non-sentinel lymph node status in specific patients. Both the size of the tumor and SLNCCL5 levels were found to have a significant impact (P < 0.05). Data suggested that the presence of positive SLNCCL5 might serve as an assessment parameter for anticipating the condition of non-SLN in cases of breast cancer involving T1 or T2 tumors with one or two positive sentinel lymph nodes.

The clinical features and prognostic factors of miliary tuberculosis in a high tuberculosis burden area.

BACKGROUND: Miliary Tuberculosis (TB) remains an important infectious disease that threatens human health. The clinical characteristics and prognostic factors of miliary TB are summarized in this study. METHODS: The clinical information of miliary TB patients between 2010 and 2022 was retrospectively analyzed. Patients with miliary TB were characterized and compared to adverse outcomes cases. Factors independently associated with adverse outcomes were determined via multivariate logistic regression analysis. RESULTS: A total of 288 patients were analyzed, including 181 with adverse outcomes. The clinical manifestations are atypical. 88.54% Of them experienced systemic symptoms, whilst 69.79% manifested respiratory symptoms. 40.97% Presented with neurologic symptoms, while 35.07% reported gastrointestinal symptoms. The major comorbidities were pharmacological immunosuppression (21.53%), pneumoconiosis (15.28%), diabetes (10.76%), and pregnancy or postpartum (7.29%). Regarding microbiology, most patients were diagnosed via sputum or Bronchoalveolar Lavage Fluid (BALF), pleural effusion, ascites, cerebrospinal fluid, urine TB-DNA, and tuberculosis culture. Meanwhile, 2.43% of patients were diagnosed via cerebrospinal fluid NGS. Independent risk factors predictive of adverse outcomes were current smoking, leukocytosis, elevated alanine aminotransferase (ALT) levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis. The accuracy of the model was validated by an area under the ROC curve of 0.753 (95% IC 0.697-0.810). CONCLUSIONS: The clinical manifestations of miliary TB are atypical, and early diagnosis is challenging. The major comorbidities in miliary TB patients were pharmacological immunosuppression, pneumoconiosis, diabetes, pregnancy, and postpartum. Regarding etiological detection, multi-site and multi-type specimens should be collected for a timely diagnosis. Cerebrospinal fluid mNGS test may be a viable choice in some cases. Finally, current smoking, leukocytosis, elevated ALT levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis were identified as independent risk factors for adverse outcomes.

The clinical manifestations of miliary TB are atypical, and early diagnosis is challenging. The major comorbidities in miliary TB patients were pharmacological immunosuppression, pneumoconiosis, diabetes, pregnancy, and postpartum. Current smoking, leukocytosis, elevated ALT levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis were identified as independent risk factors for adverse outcomes.

Microfluidic Electrochemical Integrated Sensor for Efficient and Sensitive Detection of Candida albicans.

Traditional methods for the detection of pathogenic bacteria are time-consuming, less efficient, and sensitive, which affects infection control and bungles illness. Therefore, developing a method to remedy these problems is very important in the clinic to diagnose the pathogenic diseases and guide the rational use of antibiotics. Here, microfluidic electrochemical integrated sensor (MEIS) has been investigated, functionally for rapid, efficient separation and sensitive detection of pathogenic bacteria. Three-dimensional macroporous PDMS and Au nanotube-based electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow separator" and "electrochemical detector," respectively. The 3D chaotic flow separator enhances the turbulence of the fluid, achieving an excellent bacteria capture efficiency. Meanwhile, the electrochemical detector provides a quantitative signal through enzyme-linked immunoelectrochemistry with improved sensitivity. The microfluidic electrochemical integrated sensor could successfully isolate Candida albicans (C. albicans) in the range of 30-3,000,000 CFU in the saliva matrix with over 95% capture efficiency and sensitively detect C. albicans in 1 h in oral saliva samples. The integrated device demonstrates great potential in the diagnosis of oral candidiasis and is also applicable in the detection of other pathogenic bacteria.

Proton Transfer Processes in 2-Butenenitrile Dimer Cation Studied by Mass-Selective Infrared Spectroscopy.

2-Butenenitrile (2-Bu) is a recently discovered crucial interstellar molecule. Herein, an abnormal NH band was observed in the infrared spectrum of the 2-Bu dimer cation, suggestive of a proton transfer reaction within the cluster. Through a comprehensive theoretical analysis of the IR spectrum of (2-Bu)2+, we discovered not only the formation of a new C-N bond through the attachment of one 2-Bu to another but also the occurrence of a proton transfer reaction in the cluster. This proton was identified as originating from the methyl group of the attaching 2-Bu in the cluster based on the analysis of IR spectra of (2-Bu)+ and [2-Bu-acrylonitrile (AN)]+. Furthermore, the detailed reaction process of this ion-molecule reaction is examined with theoretical calculation. This finding contributes significantly to our deeper understanding of ion-molecule reactions in the gas phase and the formation of nitrogen-containing prebiotic molecules in the interstellar medium.

Associations between specific volatile organic chemical exposures and cardiovascular disease risks: insights from NHANES.

Introduction: An increasing body of research has demonstrated a correlation between pollutants from the environment and the development of cardiovascular diseases (CVD). However, the impact of volatile organic chemicals (VOC) on CVD remains unknown and needs further investigation. Objectives: This study assessed whether exposure to VOC was associated with CVD in the general population. Methods: A cross-sectional analysis was conducted utilizing data from five survey cycles (2005-2006, 2011-2012, 2013-2014, 2015-2016, and 2017-2018) of the National Health and Nutrition Examination Survey (NHANES) program. We analyzed the association between urinary VOC metabolites (VOCs) and participants by multiple logistic regression models, further Bayesian Kernel Machine Regression (BKMR) models and Weighted Quantile Sum (WQS) regression were performed for mixture exposure analysis. Results: Total VOCs were found to be positively linked with CVD in multivariable-adjusted models (p for trend = 0.025), independent of established CVD risk variables, such as hypertension, diabetes, drinking and smoking, and total cholesterol levels. Compared with the reference quartile of total VOCs levels, the multivariable-adjusted odds ratios in increasing quartiles were 1.01 [95% confidence interval (CI): 0.78-1.31], 1.26 (95% CI: 1.05-1.21) and 1.75 (95% CI: 1.36-1.64) for total CVD. Similar positive associations were found when considering individual VOCs, including AAMA, CEMA, CYMA, 2HPMA, 3HPMA, IPM3 and MHBMA3 (acrolein, acrylamide, acrylonitrile, propylene oxide, isoprene, and 1,3-butadiene). In BKMR analysis, the overall effect of a mixture is significantly related to VOCs when all chemicals reach or exceed the 75th percentile. Moreover, in the WQS models, the most influential VOCs were found to be CEMA (40.30%), DHBMA (21.00%), and AMCC (19.70%). Conclusion: The results of our study indicated that VOC was all found to have a significant association with CVD when comparing results from different models. These findings hold significant potential for public health implications and offer valuable insights for future research directions.

Investigating Immunotoxicity in Black Carp (Mylopharyngodon piceus) Fingerlings Exposed to Niclosamide.

Niclosamide (NIC) is a potent salicylanilide molluscicide/helminthicide commonly utilized for parasite and mollusc control in aquatic environments. Due to its persistent presence in water bodies, there is growing concern regarding its impact on aquatic organisms, yet this remains inadequately elucidated. Consequently, this study aims to assess the hepatotoxic effects and detoxification capacity of black carp (Mylopharyngodon piceus) in a semi-static system, employing various parameters for analysis. NIC was applied to juvenile black carp at three different concentrations (0, 10 and 50 µg/L) for 28 days in an environmentally realistic manner. Exposure to 50 µg/L NIC resulted in an increase in hepatic lysozyme (LYZ), alkaline phosphatase (ALP), and complement 4 (C4) levels while simultaneously causing a decrease in peroxidase (POD) activity. Additionally, NIC exposure exhibited a dose-dependent effect on elevating serum levels of LYZ, ALP, complement 3 (C3), C4, and immunoglobulin T (IgT). Notably, the mRNA levels of immune-related genes tnfα, il8, and il6, as well as nramp and leap2, were upregulated in fish exposed to NIC. RNA-Seq analysis identified 219 differentially expressed genes (DEGs) in M. piceus after NIC exposure, with 94 upregulated and 125 downregulated genes. KEGG and GO analyses showed enrichment in drug metabolism pathways and activities related to oxidoreductase, lip oprotein particles, and cholesterol transport at 50 µg/L NIC. Additionally, numerous genes associated with lipid metabolism, oxidative stress, and innate immunity were upregulated in NIC-exposed M. piceus. Taken together, these findings indicate that NIC has the potential to cause hepatotoxicity and immunotoxicity in M. piceus. This research offers important insights for further understanding the impact of molluscicide/helminthicide aquatic toxicity in ecosystems.

One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

BACKGROUND: Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN. METHODS: A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays. RESULTS: OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats. CONCLUSION: OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.

The spectinamides are novel, narrow-spectrum semisynthetic analogs of spectinomycin, modified to avoid intrinsic efflux by Mycobacterium tuberculosis . Spectinamides, including lead MBX-4888A (Lee-1810), exhibit promising therapeutic profiles in mice, as single drugs and as partner agents with other anti-tuberculosis antibiotics including rifampin and/or pyrazinamide. To demonstrate that this translates to more effective cure, we first confirmed the role of rifampin, with or without pyrazinamide, as essential to achieve effective bactericidal responses and sterilizing cure in the current standard of care regimen in chronically infected C3HeB/FeJ mice compared to BALB/c mice. Thus, demonstrating added value in testing clinically relevant regimens in murine models of increasing pathologic complexity. Next we show that MBX-4888A, given by injection with the front-line standard of care regimen, is treatment shortening in multiple murine tuberculosis infection models. The positive treatment responses to MBX-4888A combination therapy in multiple mouse models including mice exhibiting advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in caseum, along with favorable effects with rifampin and pyrazinamide under conditions achieved in necrotic lesions. This study also provides an additional data point regarding the safety and tolerability of spectinamide MBX-4888A in long-term murine efficacy studies.

Niclosamide subacute exposure alters the immune response and microbiota of the gill and gut in black carp larvae, Mylopharyngodon piceus.

Niclosamide (NIC) is a commonly used insecticide and molluscicide in the prevention and treatment of parasitic diseases in fish. The utilization of NIC has the potential to disrupt the microbial community present on the mucosal tissue of fish, leading to localized inflammatory responses. The objective of this study was to evaluate the impact of NIC on the immune system and bacterial populations within the gill and gut of Mylopharyngodon piceus. Fish were subjected to varying concentrations of NIC, including a control group (0 µg/L), a low NIC group (15% 96 h LC50, LNG, 9.8 µg/L), and a high NIC group (80% 96 h LC50, HNG, 52.5 µg/L). Gill and gut samples were collected 28 days post-exposure for analysis. The findings revealed that the 96-h LC50 for NIC was determined to be 65.7 µg/L, and histopathological examination demonstrated that exposure to NIC resulted in gill filament subepithelial edema, exfoliation, degeneration, and a decrease in gill filament length. Furthermore, the gut exhibited apical enterocyte degeneration and leucocyte infiltration following NIC exposure. Additionally, NIC exposure led to a significant elevation in the levels of immunoglobulin M (IgM), complement component 3 (C3), and complement component 4 (C4) in both gill and gut tissues. Moreover, the activity of lysozyme (LYZ) was enhanced in the gill, while the activities of peroxidase (POD) and immunoglobulin T (IgT) were increased in gut tissue. The exposure to NIC resulted in enhanced mRNA expression of c3, c9, tnfα, il6, il8, and il11 in the gill tissue, while decreasing c3 and il8 expression in the gut tissue. Furthermore, the natural resistance-associated macrophage protein (nramp) mRNA increased, and liver-expressed antimicrobial peptide 2 (leap2) mRNA decreased in gill and gut tissues. And hepcidin (hepc) mRNA levels rose in gill but fell in gut tissue. NIC exposure also led to a decrease in gill bacterial richness and diversity, which significantly differed from the control group, although this separation was not significant in the gut tissue. In conclusion, the administration of NIC resulted in alterations in both the immune response and mucosal microbiota of fish. Furthermore, it was noted that gills displayed a heightened vulnerability to sublethal effects of NIC in comparison to gut tissues.

Analysis of Factors Influencing Prognosis and Assessment of 60 Cases of Decompensated Cirrhotic Patients with Portal Hypertension.

Objective: To investigate the risk factors for the development of portal hypertension in patients with decompensated cirrhosis and analyze their prognosis. Methods: Patients with decompensated cirrhosis who were admitted to our hospital and Qu fu People's Hospital from June 2022 to June 2023 were included in this study. Among them, there were 45 male and 15 female patients, with a median age of 56 (range: 35-77) years. A comparative analysis was performed between Group A (hepatic venous pressure gradient, HVPG <16 mmHg) and Group B (HVPG ≥16 mmHg) patients, along with various clinical outcomes. Multivariate analysis was conducted to explore the risk factors influencing the occurrence of portal hypertension and adverse prognosis in patients with cirrhosis. Results: In Group A patients with portal hypertension, we observed lower levels of aspartate aminotransferase, laminin, serum hyaluronic acid, type III procollagen N-terminal peptide, total bile acids, and cholylglycine acid compared to Group B. On the other hand, levels of alanine aminotransferase, white blood cells, and serum albumin were higher in Group A than in Group B. These differences between the groups were statistically significant (P < 0.05). Multivariate analysis of the aforementioned risk factors indicated that low white blood cell count, high cholylglycine acid levels, and high serum hyaluronic acid levels were identified as independent risk factors for the occurrence of difficult-to-control complications in decompensated portal hypertension among patients with liver cirrhosis (P < 0.05). Conclusion: Liver cirrhosis patients with portal hypertension and multiple risk factors like low white blood cell count and high liver transaminase levels should be cautious regarding the progression of portal hypertension when combined with splenomegaly, liver fibrosis, and bile stasis, as it often indicates a poor prognosis.

Are children with IgA nephropathy different from adult patients?

BACKGROUND: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN. METHODS: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN. RESULTS: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m2, p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids. CONCLUSIONS: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children.

Comparison of safety and effectiveness of different sheaths in ablation of focal atrial tachycardia: a retrospective study.

Background: A novel visualized steerable sheath, referred to as the Vizigo sheath, has been utilized in clinical interventions. The objective of this study was to evaluate and contrast the efficacy and safety of the Vizigo sheath with other sheaths in the catheter ablation (CA) for focal atrial tachycardia (FAT). Methods: A retrospective cohort study was conducted on consecutive patients with CA for FAT from March 2019 to February 2022. Objectives were to assess the impact of the Vizigo sheath on acute and long-term ablation success rates, procedural and fluoroscopy times, and contact force (CF). Results: A total of 164 patients, mean age 50±15 years, 97 (59.1%) women, underwent CA of FAT using the Vizigo sheath (N=42), non-visualized steerable sheath (N=36), or other conventional sheath (N=86). Age, sex, body mass index (BMI), presence of hypertension, heart failure, and diabetes mellitus were not significantly different among the three groups. The acute success rate of 94.0% was similar among the three groups. Over a follow-up of 14±2 months, the Vizigo sheath was associated with superior arrhythmia-free survival (88.1%) when compared to non-visualized steerable (69.4%; P=0.04) and other conventional (72.1%, P=0.046) sheaths. Procedural duration, number of ablation lesions, and ablation times were similar among the three groups. However, the Vizigo sheath was associated with lower fluoroscopy times (e.g., 145 vs. 250 s with Vizigo versus non-visualized steerable sheaths, P=0.03) and higher CF (e.g., average CF 12.0 versus 8.0 g with Vizigo versus non-visualized steerable sheaths, P=0.003). Conclusions: The application of Vizigo sheath can improve the long-term success rate of FAT and reduce the radiation exposure of patients and medical staff in our single-center limited sample study. More research may be needed in the future to confirm our findings.