The increasing non-medical use of dextromethorphan (DM), particularly among adolescents, has raised concerns regarding its potential neurobiological consequences. However, the precise mechanisms underlying its neurotoxicity, particularly the involvement of the gut microbiota, remain unclear. A novel probiotic strain, Bacillus aerolatus CX253, has demonstrated the capacity to regulate gut microbial homeostasis and attenuate inflammatory responses, yet whether it can mitigate DM-induced neurotoxicity remains unknown. In the present study, a subchronic dose-escalation DM exposure model was established in mice. Through behavioral assessments, 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, and molecular-level investigations, we systematically evaluated the neurobehavioral effects of DM and the prophylactic efficacy of CX253. The results showed that DM exposure significantly altered gut microbial composition, characterized by increased abundance of Akkermansia and Desulfovibrionaceae and decreased abundance of Muribaculaceae. These alterations were accompanied by reduced fecal butyrate levels, impaired intestinal barrier function, and elevated circulating lipopolysaccharide (LPS) and inflammatory cytokines. At the central level, DM exposure led to upregulation of pro-inflammatory cytokines in the hippocampus, glial activation, and marked suppression of the pro-survival Apelin-PI3K/Akt/mTOR signaling pathway, ultimately manifesting as increased anxiety-like behaviors and impaired spatial memory. Prophylactic administration of CX253 preserved gut microbial diversity, enriched beneficial taxa including Bifidobacteriaceae, Bacteroides, and Lachnospiraceae_NK4A136_group, increased fecal butyrate levels, alleviated intestinal barrier dysfunction as well as peripheral and central inflammatory responses, and specifically restored the DM-suppressed Apelin-PI3K/Akt/mTOR pro-survival signaling pathway, thereby improving neurobehavioral performance. Correlation and mediation analyses further suggested that these protective effects were closely associated with elevated butyrate levels. Collectively, these findings not only expand the current understanding of the mechanisms underlying DM-induced neurotoxicity but also provide a novel mechanistic framework and a translationally promising candidate strain for microbiota-based preventive strategies targeting substance misuse-related neuropsychiatric disorders.

Tetrachlorobisphenol A (TCBPA), a widely used chemical on material modification and flame retardant synthesis, bioaccumulates through the food chain and presents significant health concerns. However, the long-term effects of TCBPA exposure on gut microbial ecosystems and their metabolic functions remain poorly characterized. The present study developed a gestational/lactational exposure model in rats to systematically evaluate the impact on maternal and offspring gut microbiomes and fecal metabolomes by TCBPA exposure. 16S rRNA sequencing analysis demonstrated that TCBPA exposure significantly reduced both α-diversity indices and the relative abundance of critical short-chain fatty acid (SCFA)-producing genera, including Lachnospiraceae, Ruminococcus, Lactobacillus, and the unclassified norank_o_Clostridia_UCG-014. These results suggested that TCBPA perturbs gut microbiota by reducing key SCFA-producing bacteria. These microbial alterations were accompanied by corresponding decreases in fecal SCFA levels, indicating impaired microbial metabolic capacity. Metabolomics analysis revealed 18 metabolic pathways significantly affected by TCBPA, with the most marked changes in the arginine and proline metabolism pathway and the primary bile acid biosynthesis pathway. A strong correlation between gut microbiota and SCFA/metabolite levels suggests that alterations in gut microbiota may influence fecal metabolite metabolism. These findings collectively demonstrate that gestational/lactational TCBPA exposure induces persistent disruptions in gut microbial communities and their metabolic functions, which may underlie observed intergenerational health effects.

Wastewater treatment plants have peculiar bioaerosol feature. However, limited research has focused on bacterial function in bioaerosols from pharmaceutical wastewater treatment plants (PWWTPs). Here, airborne bacterial communities of two PWWTPs were analyzed using culturable and 16S rRNA gene high-throughput sequencing. The results revealed the bacterial aerosols collected from the PWWTPs differed significantly owing to the treatment process. The genera Pseudocyanosarcina, Potamoosiphon and Sphingomonas were the dominant genera in the two plants. Bacillus velezensis strain PB131 (Laboratory designation) was screened based on inhibition of Klebsiella pneumoniae (Kp) in vitro and in vivo. This strain colonizes the lungs, intestines, and trachea, and its mechanism for alleviating Kp-induced inflammation was investigated through modulation of gut microbiota. Strain PB131 inhibited the maturation and release of interleukin-1β (Il-1β), interleukin-6 (Il-6), and tumor necrosis factor α (Tnf-α) in the Prevention group (1.35 ± 0.08, 1.26 ± 0.27 and 1.20 ± 0.10) compared with the Kp infection group (2.23 ± 0.21, 2.10 ± 0.18 and 1.49 ± 0.19). These change mechanisms were related to gut microbial composition and short-chain fatty acids (SCFAs) levels, such as affecting Limosilactobacillus, Duncaniella, Bifidobacterium, and butyric acid content. This study provides valuable insights from microbiome research that enable an assessment of gut colonization by probiotics. These findings could potentially lead to the use of in vitro-derived probiotics as an alternative method for preventing respiratory inflammation.

Bisphenol-A bis(diphenyl phosphate) (BDP) has been detected in biological organisms, but its toxicological effects remain unclear. In this study of 4376 participants, the characteristic BDP metabolite diphenyl phosphate was associated with gastrointestinal diseases via a nonlinear dose-response relationship, and was identified as a risk factor (OR = 1.02; 95% CI: 1.01-1.04; P = 0.013). Pregnant rats received 50 mg/kg/day BDP during gestation (GD 14-20) or gestation plus lactation (GD 14-PND 35). Both regimens triggered colonic inflammation and gut microbiome dysbiosis in offspring. The combined exposure group showed more severe effects, including persistent histopathological damage, elevated Il-1β and Il-6, and reduced microbial diversity. LC-MS/MS and 16S rRNA sequencing were used to assess BDP distribution and gut microbiome alterations. BDP crossed the placental barrier. SourceTracker analysis confirmed maternal microbiome transmission as the primary source (>70%) of offspring gut microbiome, accompanied by Streptococcus enrichment and Bifidobacterium depletion. Metabolite-inflammation network analysis showed positive correlations of butyrate and negative correlations of propionate with proinflammatory cytokines (IL-1β, IL-6, and TNF-α), which were subsequently confirmed by in vitro experiments. These findings demonstrate a transgenerational mechanism whereby prenatal BDP exposure induces offspring colonic inflammation via the gut microbiome-metabolite axis, informing maternal-infant intervention strategies.

The rapid diversification of new psychoactive substances (NPS), often fueled by AI-driven de novo drug design, renders traditional structure-based forensic identification increasingly obsolete. This shift necessitates a transition toward receptor-based functional characterization to evaluate biological impact rather than mere molecular form. This paper proposes that leveraging preclinical PET and PET/MR imaging can provide a high-sensitivity functional filter to quantify drug-target engagement and receptor occupancy in vivo. Within this framework, a contingent screening strategy would allow direct radiolabeling to be reserved for high-priority analogs with accessible structures, while prioritizing indirect functional classification via receptor displacement assays for substances with unknown or synthetically complex scaffolds. Such a mechanism-based workflow represents a strategic opportunity for forensic resources to bypass pharmacologically inert compounds and focus exclusively on bioactive threats. By integrating AI-assisted analysis with standardized pharmacological models, including binding potential (BPnd) and distribution volume (VT), this approach can ensure forensic admissibility and offer a cost-effective, proactive solution for international Early Warning Systems. These strategic advantages position molecular imaging as a potential pillar for safeguarding public health against the next generation of synthetic psychoactive threats.

In oncology clinics, anthracyclines remain a cornerstone of cancer therapy. However, their clinical benefits are accompanied by substantial toxicities. As cumulative exposure increases and patient survival improves, the incidence of treatment-related adverse effects also increases, particularly those affecting the heart and kidneys. Rather than existing in isolation, these two forms of damage often interact: impaired cardiac function can accelerate renal injury through hemodynamic changes and neuroendocrine activation, whereas renal dysfunction further exacerbates cardiac injury via toxin accumulation and inflammation. This interaction leads to the well-recognized cardiorenal vicious cycle, which substantially limits the safe use of anthracyclines in clinical practice. Although dexrazoxane is currently the only approved cardioprotective agent, its renoprotective effect remains limited. Moreover, there are no clear guidelines or standardized strategies for preventing or managing anthracycline-induced cardiorenal toxicity. Therefore, a deeper understanding of the underlying mechanisms, along with effective monitoring and intervention strategies, is crucial for optimizing anthracycline therapy and improving patient survival. This review explores the pathological basis, molecular mechanisms, risk factors, monitoring approaches, and treatment strategies related to anthracycline-induced cardiorenal toxicity. It aims to develop a comprehensive strategy to protect both cardiac and renal function and to provide a scientific foundation for the development of safer and more effective cancer treatment regimens.

Tris (n-butyl) phosphate (TnBP), a heavily utilized organophosphate ester, remains poorly characterized with respect to its long-term effects on the structure and metabolic capacity of the gut microbiota. The purpose of this study is to explore how TnBP exposure affects the intestinal microbiota of maternal Sprague-Dawley (SD) rats and their corresponding progeny, as well as the impact of its metabolite, dibutyl phosphate (DBP), in the human population. A cross-sectional analysis revealed a significant positive correlation between DBP concentrations and the C-reactive protein/albumin ratio (CAR) in the United States population. Results of 16S rRNA gene sequencing revealed that maternal TnBP exposure significantly increased gut bacterial α-diversity in both dams and their F1-generation offspring (Shannon index, P < 0.05). Principal-coordinate analysis (PCoA) based on Bray-Curtis dissimilarity showed distinct clustering of the microbial communities, and PERMANOVA confirmed significant differences between the exposed and control groupsAt the phylum level, TnBP exposure elicited a proportional expansion of Proteobacteria coupled with concomitant reductions in Bacillota and Bacteroidetes in both dams and their F1 offspring. Genus-level profiling further revealed a selective enrichment of Bifidobacterium and significant perturbations in Lactobacillus, Limosilactobacillus, Muribaculum, Turicibacter, Allobaculum, and Clostridium.Furthermore, TnBP exposure significantly elevated total short-chain fatty acid (SCFA) levels in the offspring, indicating a functional shift in microbial metabolism. Correlation analysis further revealed that under TnBP treatment the relative abundances of Allobaculum and Collinsella were positively associated with the concentrations of acetate, propionate, and butyrate (P < 0.05 for each). Quantitative PCR and histopathological examination collectively demonstrated a pronounced inflammatory signature in the colons of juvenile offspring exposed to TnBP. These observations underscore the potential for persistent adverse health outcomes following developmental exposure and warrant comprehensive mechanistic and epidemiological investigations.

Tris(2-chloroethyl) phosphate (TCEP), one of the most widely used organophosphate flame retardants, is frequently detected in environmental and biological samples. However, its toxic effects on the offspring remain unknown. To explore the health risks posed by TCEP in susceptible populations, we investigated the intergenerational transmission of TCEP, gut microbiome, and disruptive effects of intestinal metabolites in the offspring. Different doses of TCEP were administered orally to female Sprague-Dawley (SD) rats throughout pregnancy or during both pregnancy and lactation periods. Concentrations of TCEP and its metabolite, BCEP, composition of the gut microbiota, and fecal concentrations of short-chain fatty acids were measured. The concentration of TCEP in the placenta of rats in the high-dose group was significantly higher than that in the control group, and BCEP was also present. Serum and fecal samples from immature offspring contained TCEP; however, no BCEP was detected in serum. Exposure to TCEP altered the intestinal microbiota of both the maternal rats and their offspring. The relative abundance of Coelenterata was significantly increased in the immature offspring. Exposure to TCEP altered the concentration of SCFAs in the feces of the rats and their offspring. Lower concentrations of acetic, propionic, and butyric acids were observed in the feces of immature offspring. Holdemanella had a significant mediating effect between TCEP exposure and intestinal concentrations of acetic and propionic acids. Maternal exposure to TCEP affects the gut microbiota balance and metabolism of offspring, suggesting the presence of a long-term risk associated with metabolic disease.

Current research on bioaerosol diversity in pharmaceutical wastewater treatment plants (PWWTPs) remains limited, especially concerning pulmonary injury mechanisms. Bacterial diversity in two PWWTPs was investigated via high-throughput sequencing and culture-based isolation, revealing functional interactions with pathogenic Klebsiella pneumoniae (Kpn). Emissions showed bimodal size distributions: Plant A dominated by ≥ 7μm particles, Plant B by 0.65-1.1μm submicron fractions enriched with Pseudomonadota (formerly Proteobacteria). Strain S361 (Bacillus sp., Bacillota) isolated from AeT1 exhibited significant synergistic pathogenicity with Kpn. Whole-genome sequencing identified 51 antibiotic resistance genes (ARGs) across 12 resistance mechanisms and 86 virulence factors in Bacillus sp. S361. Mechanistically, Bacillus sp. S361 synergistically enhances pulmonary colonization and pathogenicity of Kpn via distinctive metabolic crosstalk. Co-exposure to S361 and Kpn disrupts gut microbiota homeostasis, inducing dysregulated short-chain fatty acid (SCFA) metabolism and intestinal barrier impairment. This gut-derived dysfunction mediates systemic inflammation through the gut-lung axis, ultimately amplifying Kpn-induced lung injury. Fecal microbiota transplantation (FMT) experiments confirmed gut microbiota's mediating role, as recipient rats developed pathological changes (alveolar septal thickening, inflammatory infiltration) mirroring co-infected groups. Notably, microbiota-depleted rats suffered more severe lung injury than protected counterparts, establishing gut dysbiosis as a critical determinant of pulmonary damage. These findings implicate PWWTP bioaerosols in driving Kpn pathogenicity via Bacillus sp. S361-mediated synergy and gut-lung dysregulation, necessitating targeted interventions for occupational risk mitigation.

Antibiotics and vaccines have long been major key interventions against Streptococcus pneumoniae (Spn) infection. However, alternative therapies are urgently needed with the original therapies becoming suboptimal efficacy. A beneficial bacterium, Microcella aerolata strain GA224, with protective potential against Spn infection was isolated in previous study. Here, this protective effect was investigated at the bacterial, cellular and animal levels, exploring the mechanisms from the perspective of the gut-lung axis. Cellular and animal models of Spn infection were established and GA224 was administered for prevention or treatment. Spn adherence, inflammatory gene expression, histopathological features, gut microbial profiles and fecal metabolomic signatures were examined. In vitro, GA224 inhibited Spn growth with a bacteriostatic diameter of 16 mm and reduced adherence by 83.4

Diethyl ethylphosphonate (DEEP) is a new type of highly effective organophosphorus flame retardant that is widely used in various industrial products, but there have been no reports on its potential health risks. In this study, we exposed pregnant rats to different DEEP doses (23.3 mg·kg-1·BW-1 and 233 mg·kg-1·BW-1) via gavage during gestation and lactation, and measured the DEEP content in the placenta of pregnant rats. We also looked into the impacts of varying DEEP doses on the growth phenotype, gut microbiota, and metabolite SCFAs of female and male offspring. According to the findings, DEEP exceeded the detection limit in the high-dose exposure group. Maternal high-dose DEEP exposure reduced body weight in both immature male and female offspring. Compared to the low-dose exposure, high-dose DEEP significantly decreased the richness and diversity of both male and female offspring gut microbiota. Low-dose exposure increased the Pseudomonadota and decreased the Bacillota. In immature female offspring, high-dose exposure increased the genus Lactobacillus and Bacteroides and reduced Clostridium, Adlercreutzia, and Segatella. The proportions of fecal acetic and butyric acid in male and female immature offspring were elevated after maternal high-dose exposure. But the fecal butyric acid in adult offspring decreased after maternal low-dose exposure during gestation. PICURSt2 analysis confirmed that changes in gut microbiota composition altered its function. In the correlation analysis, SCFAs showed significant positive or negative correlation with 11 genera. This study helped to elucidate the long-term effects of maternal DEEP exposure and provided a basis for assessing the health risk management of analogous flame retardants.

AbstractThe fine particulate matter (PM2.5) in air pollution is a critical risk factor influencing human health. Our study included 8144 participants and showed that the risk of major adverse cardiovascular events increases by 35% (HR, 1.35; 95% CI, 1.14–1.60) for participants with the highest quartile to PM2.5 exposure as compared to those with lowest quartile. Bioaerosols, as an important environmental exposure in PM2.5, can induce systemic chronic inflammation leading to vascular aging. Thus, the effects of bioaerosols are investigated from household garbage stations in PM2.5 on vascular aging, and the underlying mechanisms are explored. In vivo, chronic exposure to bioaerosols upregulated senescence marker expression levels while causing vascular dysfunction and remodeling. In vitro, bioaerosol exposure induced decreased proliferation, G0/G1 arrest, and impaired migration of human umbilical vein endothelial cells (HUVECs). Furthermore, a single bacterium (AS22a) from the bioaerosol community was isolated and demonstrated that it upregulated inflammatory factors and accelerated cell senescence and vascular aging by activating the NF‐κB/NLRP3 signaling pathway, which may serve as a primary mechanism underlying vascular aging induced by bioaerosols in PM2.5. These findings suggest that high levels of bioaerosols in household garbage stations may adversely affect cardiovascular health.

Streptococcus pneumoniae (Spn) is the predominant pathogen responsible for community-acquired pneumonia (CAP) in children under five years old, and it can induce over 17

Abstract Background Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [18F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis. Methods After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [18F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [18F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson’s trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUVmean) was calculated. Results PET signals revealed that in areas with evident lesions on CT, the SUVmean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUVmean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson’s trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [18F]F-FAPI-42 binding to activated fibroblasts. Conclusion [18F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.

Diethyl ethylphosphonate (DEEP) as a novel organophosphorus flame retardant received increasing attention and its structure was discovered. But there are currently insufficient studies on how DEEP exposure affects the gut microbiome. In this study, the effects of DEEP on the structure and function of the human gut microbiota were examined using the SHIME system. Results from high-throughput sequencing of the 16S rRNA gene show that the high dose DEEP exposure reduced the Shannon and Simpson index in the transverse and descending colon. The Bacillota had the highest proportion while the proportion of Proteobacteria gradually decreased at the phylum level. The abundance of Escherichia, Prevotella, and Bilophila at the genus level increased with increasing doses of DEEP exposure. On the contrary, the abundance of Megasphaera, Klebsiella, and Phascolarctobacterium decreased. The short-chain fatty acids had a significant shift. With increasing doses of DEEP exposure, the concentration of acetic acid and propionic acid increased, while the concentration of butyric acid reached the highest at the medium dose of exposure. In addition, Bilophila, Psychrobacter, Escherichia, and Nostoe showed strong beneficial associations with acetic and propionic acids under DEEP exposure. Phocaeicola, Agathobacter, Klebsiella, Megasphaera, Phascolarctobacterium, and Bacteroides were negatively association with acetic and propionic acids. In a word, the study verified that exposure to different doses of DEEP can cause changes in the composition of the gut microbiome and metabolite SCFAs, which provides ideas for the investigation of other potential hazards of DEEP on human beings.

With the prolonged survival of individuals with cancer, the emergence of cardiovascular diseases (CVD) induced by cancer treatment has become a significant concern, ranking as the second leading cause of death among cancer survivors. This review explores three distinct types of programmed cell death (PCD): ferroptosis, cuproptosis, and PANoptosis, focusing on their roles in chemotherapy-induced cardiotoxicity. While ferroptosis and cuproptosis are triggered by excess iron and copper (Cu), PANoptosis is an inflammatory PCD with features of pyroptosis, apoptosis, and necroptosis. Recent studies reveal intricate connections among these PCD types, emphasizing the interplay between cuproptosis and ferroptosis. Notably, the role of intracellular Cu in promoting ferroptosis through GPX4 is highlighted. Additionally, ROS-induced PANoptosis is influenced by ferroptosis and cuproptosis, suggesting a complex interrelationship. This review provides insights into the molecular mechanisms of these PCD modalities and their distinct contributions to chemotherapy-induced cardiotoxicity. Furthermore, we discuss the potential application of cardioprotective drugs in managing these PCD types. This comprehensive analysis aims to advance the understanding, diagnosis, and therapeutic strategies for cardiotoxicity associated with cancer treatment.

BackgroundThe relationship between hemorrhagic transformation (HT) and uric acid (UA) remains controversial. This study aimed to investigate the relationship between UA concentrations and the risk of HT following acute ischemic stroke (AIS).MethodsElectronic databases were searched for studies on HT and UA from inception to October 31, 2023. Two researchers independently reviewed the studies for inclusion. STATA Software 16.0 was used to compute the standardized mean difference (SMD) and 95% confidence interval (CI) for the pooled and post-outlier outcomes. Heterogeneity was evaluated using the I2 statistic and the Galbraith plot. Additionally, sensitivity analysis was performed. Lastly, Begg’s funnel plot and Egger’s test were used to assess publication bias.ResultsA total of 11 studies involving 4,608 patients were included in the meta-analysis. The pooled SMD forest plot (SMD = −0.313, 95% CI = −0.586–−0.039, p = 0.025) displayed that low UA concentrations were linked to a higher risk of HT in post-AIS patients. However, heterogeneity (I2 = 89.8%, p < 0.001) was high among the studies. Six papers fell outside the Galbraith plot regression line, and there exclusive resulted in the absence of heterogeneity (I2 = 52.1%, p = 0.080). Meanwhile, repeated SMD analysis (SMD = −0.517, 95% CI = −0.748–−0.285, p = 0.000) demonstrated that the HT group had lower UA concentrations. Finally, Begg’s funnel plot and Egger’s test indicated the absence of publication bias in our meta-analysis.ConclusionThis meta-analysis illustrated a substantial connection between UA concentrations and HT, with lower UA concentrations independently linked with a higher risk of HT post-AIS. These results lay a theoretical reference for future studies.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/CRD42023485539.

BackgroundThe therapeutic effects of vitamin D supplementation on Coronavirus disease 2019 (COVID-19) aggravation remain controversial and inconclusive. To probe into this contentious issue, we performed the present meta-analysis of randomized controlled trials (RCTs).MethodsLiterature published up to June 2023 was retrieved from Cochrane Library, PubMed, Web of Science and Embase. RCTs assessing mortality, intensive care unit (ICU) admission, mechanical ventilation (MV), length of hospitalization (LOH), and inflammatory markers containing C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), lactate dehydrogenase (LDH) were included. 19 RCTs were involved in the analysis and were conducted subgroup analyses on the baseline COVID-19 severity and vitamin D administration.ResultsIn the severity subgroup, statistically significant effects in moderate to severe group were observed in ICU admission (OR 0.43, 95% CI 0.23, 0.80; p = 0.008), MV (OR 0.44, 95% CI 0.27, 0.72; p = 0.001) and LOH (SMD –0.49, 95% CI –0.92, −0.06; p = 0.027). In the administration subgroup, effects of ICU admission (OR 0.39, 95% CI 0.16, 0.97; p = 0.044), MV (OR 0.18, 95% CI 0.07, 0.46; p = 0.000) and LOH (SMD –0.50, 95% CI –0.96, −0.04; p = 0.034) were more pronounced in patients supplied with multiple-dose vitamin D than single-dose. Although the result of mortality showed no statistically significant effect, it indicated a reduced trend (OR 0.87, 95% CI 0.63, 1.12; p > 0.05). The results of inflammatory markers reached no statistical differences.ConclusionThis meta-analysis revealed that moderate to severe COVID-19 patients supplied with multiple doses of vitamin D were less apt to need ICU admission, mechanical ventilation and have shorter hospital stays.

AIMS:Atrial fibrillation (AF) has high mortality and morbidity rates. However, the intracellular molecular complexity of the atrial tissue of patients with AF has not been adequately assessed. METHODS AND RESULTS:We investigated the cellular heterogeneity of human atrial tissue and changes in differentially expressed genes between cells using single-cell RNA sequencing, fluorescence in situ hybridization, intercellular communication, and cell trajectory analysis. Using genome-wide association studies (GWAS) and proteomics, we discovered cell types enriched for AF susceptibility genes. We discovered eight different cell types, which were further subdivided into 23 subpopulations. In AF, the communication strength between smooth muscle cells (SMCs) and fibroblast (FB) 3 cells increased and the relevant signaling pathways were quite similar. Subpopulations of endothelial cells (ECs) are mainly involved in fibrosis through TXNDC5 and POSTN. AF susceptibility genes revealed by GWAS were especially enriched in neuronal and epicardial cells, FB3, and lymphoid (Lys) cells, whereas proteomic sequencing differential proteins were concentrated in FB3 cells and SMCs. CONCLUSIONS:This study provides a cellular landscape based on the atrial tissue of patients with AF and highlights intercellular changes and differentially expressed genes that occur during the disease process. A thorough description of the cellular populations involved in AF will facilitate the identification of new cell-based interventional targets with direct functional significance for the treatment of human disease.