Genetic association of lipids and lipid-lowering drugs with sepsis: a Mendelian randomization and mediation analysis.

Background: The impact of lipid-lowering medications on sepsis is still not well defined. A Mendelian randomization (MR) study was carried out to probe the causal connections between genetically determined lipids, lipid-reducing drugs, and the risk of sepsis. Materials and methods: Data on total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and triglycerides (TG) were retrieved from the MR-Base platform and the Global Lipids Genetics Consortium in 2021 (GLGC2021). Our study categorized sepsis into two groups: total sepsis and 28-day mortality of sepsis patients (sepsis28). The inverse-variance weighted (IVW) method was the primary method used in MR analysis. Cochran's Q test and the MR-Egger intercept method were used to assess the heterogeneity and pleiotropy. Results: In the MR analysis, we found that ApoA-I played a suggestively positive role in protecting against both total sepsis (OR, 0.863 per SD increase in ApoA-I; 95% CI, 0.780-0.955; P = 0.004) and sepsis28 (OR, 0.759; 95% CI, 0.598-0.963; P = 0.023). HDL-C levels were also found to suggestively reduce the incidence of total sepsis (OR, 0.891 per SD increase in HDL-C; 95% CI, 0.802-0.990; P = 0.031). Reverse-MR showed that sepsis28 led to a decrease in HDL-C level and an increase in TG level. In drug-target MR, we found that HMGCR inhibitors positively protected against total sepsis (1OR, 0.719 per SD reduction in LDL-C; 95% CI, 0.540-0.958; P = 0.024). LDL-C and HDL-C proxied CETP inhibitors were found to have a protective effect on total sepsis, with only LDL-C proxied CETP inhibitors showing a suggestively protective effect on sepsis28. In Mediated-MR, BMI exhibited a negative indirect effect in HMGCR inhibitors curing sepsis. The indirect impact of ApoA-I explained over 50% of the curative effects of CETP inhibitors in sepsis. Conclusions: Our MR study suggested that ApoA-I and HDL-C protected against sepsis, while HMGCR and CETP inhibitors showed therapeutic potential beyond lipid-lowering effects. ApoA-I explained the effects of CETP inhibitors. Our study illuminates how lipids affect sepsis patients and the effectiveness of new drugs, opening new avenues for sepsis treatment.

DECREASE IN THE PLATELET-TO-LYMPHOCYTE RATIO IN DAYS AFTER ADMISSION FOR SEPSIS CORRELATES WITH IN-HOSPITAL MORTALITY.

ABSTRACT: Background: A previous study has linked an increase in platelet-to-lymphocyte ratio (PLR) to a poor prognosis; however, the relationship between early change in PLR and outcomes in sepsis patients is unclear. Methods : The Medical Information Mart for Intensive Care IV database was for this retrospective cohort analysis on patients meeting the Sepsis-3 criteria. All the patients meet the Sepsis-3 criteria. The platelet-to-lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count. We collected all PLR measurements that were available within 3 days of admission for analysis of longitudinal changes over time. Multivariable logistic regression analysis was used to determine the relationship between the baseline PLR and in-hospital mortality. After correcting for possible confounders, the generalized additive mixed model was used to examine the trends in PLR over time among survivors and nonsurvivors. Results: Finally, 3,303 patients were enrolled, and both low and high PLR levels were significantly associated with higher in-hospital mortality in the multiple logistic regression analysis (tertile 1: odds ratio, 1.240; 95% confidence interval, 0.981-1.568 and tertile 3: odds ratio, 1.410; 95% confidence interval, 1.120-1.776, respectively). The generalized additive mixed model results revealed that the PLR of the nonsurvival group declined faster than that of the survival group within 3 days after intensive care unit admission. After controlling for confounders, the difference between the two groups steadily decreased and increased by an average of 37.38 daily. Conclusions : There was a U-shaped relationship between the baseline PLR and in-hospital mortality of sepsis patients, and there was a significant difference between the nonsurvival and survival groups in the change in PLR over time. The early decrease in PLR was related to an increase in in-hospital mortality.

Ferroptosis contributes to nickel-induced developmental neurotoxicity in zebrafish.

Nickel (Ni) is a widely utilized heavy metal that can cause environmental pollution and health hazards. Its safety has attracted the attention of both the environmental ecology and public health fields. While the central nervous system (CNS) is one of the main targets of Ni, its neurotoxicity and the underlying mechanisms remain unclear. Here, by taking advantage of the zebrafish model for live imaging, genetic analysis and neurobehavioral studies, we reveal that the neurotoxic effects induced by exposure to environmentally relevant levels of Ni are closely related to ferroptosis, a newly-described form of iron-mediated cell death. In vivo two-photon imaging, neurobehavioral analysis and transcriptome sequencing consistently demonstrate that early neurodevelopment, neuroimmune function and vasculogenesis in zebrafish larvae are significantly affected by environmental Ni exposure. Importantly, exposure to various concentrations of Ni activates the ferroptosis pathway, as demonstrated by physiological/biochemical tests, as well as the expression of ferroptosis markers. Furthermore, pharmacological intervention of ferroptosis via deferoxamine (DFO), a classical iron chelating agent, strongly implicates iron dyshomeostasis and ferroptosis in these Ni-induced neurotoxic effects. Thus, this study elucidates the cellular and molecular mechanisms underlying Ni neurotoxicity, with implications for our understanding of the physiologically damaging effects of other environmental heavy metal pollutants.

Caffeine-Induced Sleep Restriction Alters the Gut Microbiome and Fecal Metabolic Profiles in Mice.

Insufficient sleep is becoming increasingly common and contributes to many health issues. To combat sleepiness, caffeine is consumed daily worldwide. Thus, caffeine consumption and sleep restriction often occur in succession. The gut microbiome can be rapidly affected by either one's sleep status or caffeine intake, whereas the synergistic effects of a persistent caffeine-induced sleep restriction remain unclear. In this study, we investigated the impact of a chronic caffeine-induced sleep restriction on the gut microbiome and its metabolic profiles in mice. Our results revealed that the proportion of Firmicutes and Bacteroidetes was not altered, while the abundance of Proteobacteria and Actinobacteria was significantly decreased. In addition, the content of the lipids was abundant and significantly increased. A pathway analysis of the differential metabolites suggested that numerous metabolic pathways were affected, and the glycerophospholipid metabolism was most significantly altered. Combined analysis revealed that the metabolism was significantly affected by variations in the abundance and function of the intestinal microorganisms and was closely relevant to Proteobacteria and Actinobacteria. In conclusion, a long-term caffeine-induced sleep restriction affected the diversity and composition of the intestinal microbiota in mice, and substantially altered the metabolic profiles of the gut microbiome. This may represent a novel mechanism by which an unhealthy lifestyle such as mistimed coffee breaks lead to or exacerbates disease.

Wnt/ß-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging.

Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/ß-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/ß-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/ß-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of ß-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/ß-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.

Colostomy Delays Cell Loss in the Brain and Improves Juvenile Survival in a Neonatal Rat Model of Hirschsprung's Disease.

Hirschsprung's disease is a congenital malformation characterized by the absence of enteric ganglia in the distal intestine and gut obstruction. Our previous study indicates the brain pathology during the disease progression. A subpopulation of Hirschsprung's disease patients is also associated with anomalies of the central nervous system. In the investigation, we studied a rat model of Hirschsprung's disease, known as spotting lethal (sl/sl) ETB-/- rats, which carries a spontaneous deletion in endothelin receptor B (human gene name: EDNRB) and manifests a similar phenotype as humans with Hirschsprung's disease. Homozygous mutant sl/sl rats were successfully rescued from premature death by performing colostomy and dramatically survived to their juvenile age. By the body weight measured, their body growth was not revealed to be significantly different between ETB-/- and wildtype ETB+/+ or heterozygous (+/sl) ETB+/- groups while all underwent the same colostomy. Cell loss was investigated in several brain regions by using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay (TUNEL) in ETB+/+, ETB-/-, and ETB+/- rats. Number of TUNEL-positive cells in the cerebellum and the hippocampus of ETB-/- rats was significantly increased compared with that of the ETB+/+ and ETB+/- rats. TUNEL-positive cells were observed in the molecular layer and granular cell layers of the cerebellum. In contrast, no significant difference in the density of TUNEL-positive cells was revealed in the cerebral cortex. These results suggest that either endothelin receptor B sl mutation or colostomy has predominant lasting effects on the cell survival/loss in the cerebellum and hippocampus of adult ETB-/- rats. Our findings provide the information on cellular changes in the brains of patients with Hirschsprung's disease due to congenital EDNRB mutation as well as clinically relevant interventions.

Early-life lead exposure induces long-term toxicity in the central nervous system: From zebrafish larvae to juveniles and adults.

Lead induced neurotoxicity has been extensively investigated. However, the potential connections between early-life lead exposure and the frequently observed aberrant neurobehavior in juveniles and adults remain unclear. In this study, zebrafish model was used to explore the immediate and long-term effects of early-life exposure to environmental levels of lead on the central nervous system, and the cellular and molecular mechanisms underlying the consequent abnormal neurobehavior. Lead exposed zebrafish larvae exhibited neurologic damage and defective neurobehavior. Consistent with clinical studies, despite being raised in lead-free conditions, the juvenile and adult fish experienced lead exposure earlier, presented ADHD-like symptoms, and the adult fish exhibited remarkably affected vitality and shoaling behavior. Their anxiety levels were elevated, whereas their social interaction, as well as learning and memory were strongly depressed. The expression profiles of key genes involved in neurodevelopment and neurotransmitter systems were significantly modulated, in similar patterns as in the larval stage. Notably, the density of neurons was decreased and varicosities in neuronal axons were frequently observed in the lead-exposed groups. It's tempting to speculate that the disruption of early neurodevelopment as well as the prolonged modulation of neuromorphic and neurotransmitter systems contribute to the lead-induced neurobehavioral disorders observed in juveniles and adulthood.

Developmental exposure to environmental levels of cadmium induces neurotoxicity and activates microglia in zebrafish larvae: From the perspectives of neurobehavior and neuroimaging.

Cadmium (Cd) is a worldwide environmental pollutant that postures serious threats to humans and ecosystems. Over the years, its adverse effects on the central nervous system (CNS) have been concerned, whereas the underlying cellular/molecular mechanisms remain unclear. In this study, taking advantages of zebrafish model in high-throughput imaging and behavioral tests, we have explored the potential developmental neurotoxicity of Cd at environmentally relevant levels, from the perspectives of neurobehavior and neuroimaging. Briefly, Cd2+ exposure resulted in a general impairment of zebrafish early development. Zebrafish neurobehavioral patterns including locomotion and reactivity to environmental signals were significantly perturbed upon Cd2+ exposure. Importantly, a combination of in vivo two-photon neuroimaging, flow cytometry and gene expression analyses revealed notable neurodevelopmental disorders as well as neuroimmune responses induced by Cd2+ exposure. Both cell-cycle arrest and apoptosis contributed jointly to a significant decrease of neuronal density in zebrafish larvae exposed to Cd2+. The dramatic morphological alterations of microglia from multi-branched to amoeboid, the microgliosis, as well as the modulation of gene expression profiles demonstrated a strong activation of microglia and neuroinflammation triggered by environmental levels of Cd2+. Together, our study points to the developmental toxicity of Cd in inducing CNS impairment and neuroinflammation thereby providing visualized etiological evidence of this heavy metal induced neurodevelopmental disorders. It's tempting to speculate that this research model might represent a promising tool not only for understanding the molecular mechanisms of Cd-induced neurotoxicity, but also for developing pharmacotherapies to mitigate the neurological damage resulting from exposure to Cd, and other neurotoxicants.

Discovery of the antitumor activities of a potent DCN1 inhibitor compound 383 targeting LSD1 in gastric cancer.

Dual target compounds have become a hot spot in the treatment of cancer in recent years. Histone lysine specific demethylase 1 (LSD1) is identified as histone demethylase and acts as a key regulator involved in many other cellular activities through its demethylation function. We have reported a triazolo [1,5-α] pyrimidine-based DCN1(defective in cullin neddylation protein 1) inhibitor compound 383 (IC50 = 11 nM) which could selectively inhibit Cullin 3/1 neddylation in MGC-803 cells. In this research, we investigated that compound 383 could target LSD1 and inhibit the biological function of LSD1 in MGC-803 cells (IC50 = 0.53 µM). We found that compound 383 could induce the degradation of LSD1 and inhibit MGC-803 cell proliferation, migration and invasion in a dose-dependent manner. Compound 383 could cause cell cycle arrest at G2/M phase by down-regulating the expression of LSD1. In addition, compound 383 could significantly reverse epithelial-mesenchymal transition (EMT) through increase H3K4me methylation at E-cadherin promotor. Furthermore, the in vivo inhibitory effect of compound 383 without obvious toxicity was confirmed in nude mouse transplanted MGC-803 tumor cells model. Collectively, these results suggest that the DCN1 inhibitor compound 383 exhibits antiproliferative activity in gastric cancer cells by targeting LSD1 which promotes compound 383 as a good starting point for the development of dual-target therapeutics for gastric cancer.

Association of FIB-4 index and clinical outcomes in critically ill patients with acute kidney injury: a cohort study.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and clinical outcomes in patients with acute kidney injury (AKI) is unclear. We aimed to investigate the association between FIB-4 index and all-cause mortality in critically ill patients with AKI. METHODS: We used data from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) database (v1.4). The FIB-4 score was calculated using the existing formulas. logistic regression model, and Cox proportional hazards model were used to assessed the relationship between the FIB-4 index and in-hospital,28-day and 90-day mortality, respectively. RESULTS: A total of 3592 patients with AKI included in the data analysis. 395 (10.99%) patients died during hospitalization and 458 (12.74%) patients died in 28-day. During the 90-day follow-up, 893 (22.54%) patients were dead. An elevated FIB-4 value was significantly associated with increased in-hospital mortality when used as a continuous variable (odds ratio [OR] 1.183, 95% confidence interval [CI] 1.072-1.305, P = 0.002) and as a quartile variable (OR of Q2 to Q4 1.216-1.744, with Q1 as reference). FIB-4 was positively associated with 28-day mortality of AKI patients with hazard ratio (HR) of 1.097 (95% CI 1.008, 1.194) and 1.098 (95% 1.032, 1.167) for 90-day mortality, respectively. CONCLUSION: This study demonstrated the FIB-4 index is associated with clinical outcomes in critically ill patients with acute kidney injury.

Structural heart defects associated with ETB mutation, a cause of Hirschsprung disease.

BACKGROUND: HSCR, a colonic neurocristopathy affecting 1/5000 births, is suggested to associate with cardiac septal defects and conotruncal malformations. However, we question subtle cardiac changes maybe more commonly present due to multi-regulations by HSCR candidate genes, in this instance, ETB. To investigate, we compared the cardiac morphology and quantitative measurements of sl/sl rat to those of the control group. METHODS: Eleven neonatal rats were generated from heterozygote (ETB+/-) crossbreeding. Age and bodyweight were recorded at time of sacrifice. Diffusion-staining protocols with 1.5% iodine solution was completed prior to micro-CT scanning. All rats were scanned using an in vivo micro-CT scanner, Caliper Quantum FX, followed by two quality-control scans using a custom-built ex vivo micro-CT system. All scans were reviewed for gross cardiac dysmorphology. Micro-CT data were segmented semi-automatically post-NLM filtering for: whole-heart, LV, RV, LA, RA, and aortic arch. Measurements were taken with Drishti. Following image analysis, PCR genotyping of rats was performed: five sl/sl rats, three wildtype, and three heterozygotes. Statistical comparisons on organ volume, growth rate, and organ volume/bodyweight ratios were made between sl/sl and the control group. RESULTS: Cardiac morphology and constituents were preserved. However, significant volumetric reductions were recorded in sl/sl rats with respect to the control: whole heart (38.70%, p value = 0.02); LV (41.22%, p value = 0.01), RV (46.15%, p value = 0.02), LA (44.93%, p value = 0.06), and RA (39.49%, p value = 0.02). Consistent trend was observed in growth rate (~ 20%) and organ-volume/bodyweight ratios (~ 25%). On the contrary, measurements on aortic arch demonstrated no significant difference among the two groups. CONCLUSION: Despite the presence of normal morphology, significant cardiac growth retardation was detected in sl/sl rat, supporting the likely association of cardiac anomalies with HSCR, at least in ETB-/- subtype. Structural reduction was likely due to a combination of failure to thrive from enteric dysfunction, alterations to CaNCC colonization, and importantly coronary hypoperfusion from elevated ET-1/ETA-mediated hypervasoconstriction. Little correlation was detected between aortic arch development and sl/sl rat, supporting minor ETB role in large vessels. Although further clinical study is warranted, HSCR patients may likely require cardiac assessment in view of potential congenital cardiac defects.

Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer.

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan Rabdosia rubescens with anti-tumor activity, unclear anti-tumor mechanisms and limited water solubility hamper its clinical application. Here, we showed a2, a new JDA derivative, inhibited the growth of gastric cancer cells. Subsequently, we discovered for the first time that a2 induced ferroptosis. Importantly, compound a2 decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity of a2. Furthermore, we demonstrated that a2 caused ferrous iron accumulation through the autophagy pathway, prevention of which rescued a2 induced ferrous iron elevation and cell growth inhibition. Moreover, a2 exhibited more potent anti-cancer activity than 5-fluorouracil in gastric cancer cell line-derived xenograft mice models. Patient-derived tumor xenograft models from different patients displayed varied sensitivity to a2, and GPX4 downregulation indicated the sensitivity of tumors to a2. Finally, a2 exhibited well pharmacokinetic characteristics. Overall, our data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2, and a2 will hopefully serve as a promising compound for gastric cancer treatment.

Brain size reductions associated with endothelin B receptor mutation, a cause of Hirschsprung's disease.

BACKGROUND: ETB has been reported to regulate neurogenesis and vasoregulation in foetal development. Its dysfunction was known to cause HSCR, an aganglionic colonic disorder with syndromic forms reported to associate with both small heads and developmental delay. We therefore asked, "is CNS maldevelopment a more general feature of ETB mutation?" To investigate, we reviewed the micro-CT scans of an ETB-/- model animal, sl/sl rat, and quantitatively evaluated the structural changes of its brain constituents. METHODS: Eleven neonatal rats generated from ETB+/- cross breeding were sacrificed. Micro-CT scans were completed following 1.5% iodine-staining protocols. All scans were reviewed for morphological changes. Selected organs were segmented semi-automatically post-NLM filtering: TBr, T-CC, T-CP, OB, Med, Cer, Pit, and S&I Col. Volumetric measurements were made using Drishti rendering software. Rat genotyping was completed following analysis. Statistical comparisons on organ volume, organ growth rate, and organ volume/bodyweight ratios were made between sl/sl and the control groups based on autosomal recessive inheritance. One-way ANOVA was also performed to evaluate potential dose-dependent effect. RESULTS: sl/sl rat has 16.32% lower body weight with 3.53% lower growth rate than the control group. Gross intracranial morphology was preserved in sl/sl rats. However, significant volumetric reduction of 20.33% was detected in TBr; similar reductions were extended to the measurements of T-CC, T-CP, OB, Med, and Pit. Consistently, lower brain and selected constituent growth rates were detected in sl/sl rat, ranging from 6.21% to 11.51% reduction. Lower organ volume/bodyweight ratio was detected in sl/sl rats, reflecting disproportional neural changes with respect to body size. No consistent linear relationships exist between ETB copies and intracranial organ size or growth rates. CONCLUSION: Although ETB-/- mutant has a normal CNS morphology, significant size reductions in brain and constituents were detected. These structural changes likely arise from a combination of factors secondary to dysfunctional ET-1/ET-3/ETB signalling, including global growth impairment from HSCR-induced malnutrition and dysregulations in the neurogenesis, angiogenesis, and cerebral vascular control. These changes have important clinical implications, such as autonomic dysfunction or intellectual delay. Although further human study is warranted, our study suggested comprehensive managements are required for HSCR patients, at least in ETB-/- subtype.

The association between triglyceride glucose index and depression: data from NHANES 2005-2018.

BACKGROUND: The association between triglyceride glucose (TyG) index and depression is unclear. We conducted this analysis to explore whether higher TyG index is associated with a higher odd of depression. METHODS: This was an observational study using data from the National Health and Nutrition Examination Survey (2005-2018), a cross-sectional and nationally representative database. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). TyG index was calculated based on the equation as follows: ln [triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2], and participants were divided into quartiles based on TyG index. Weighted multivariable logistic regression models were used to explore the relationship between the TyG index and depression. RESULTS: A total of 13,350 patients were included, involving 1001 (7.50%) individuals with depression. Higher TyG index is significantly associated with elevated depressive symptoms in U.S. adults. Multivariate-adjusted HRs for patients in the TyG index 4th quartile were higher for depression (OR = 1.46; 95% confidence interval (CI) 1.30, 1.64) compared with the 1st quartile of TyG index. Similar results were seen in men and women, across age groups, and baseline comorbidities. CONCLUSION: In this large cross-sectional study, our result suggests that population with higher TyG index are significantly more likely to have depressive symptoms in U.S. adults.

Nitrogen removal from domestic wastewater using core-shell anthracite/Mg-layered double hydroxides (LDHs) in constructed wetlands.

To investigate the mechanism of nitrogen removal by anthracites and enhance the nitrogen removal efficiency in constructed wetland, three kinds of layered double hydroxides (MgFe-LDHs, MgCo-LDHs, MgAl-LDHs) were prepared by co-precipitation under alkaline conditions and coated in situ on the surface of anthracites to synthesize core-shell anthracites/Mg-LDHs composites. Experiments with different treatments (columns loaded with original anthracites and anthracite/Mg-LDH composites) were conducted to study the nitrogen removal efficiency of domestic wastewater in constructed wetlands. The results of nitrogen removal experiments showed that the anthracite/MgAl-LDH composite had the best performance with average removal rates of 53.69%, 72.91%, and 47.43% for TN, NH4+-N, and organic nitrogen, respectively. Modification changed the denitrification mode of the anthracites. The data of adsorption isothermal experiments were fitted better with the Freundlich model. The amount of ammonifier, nitrosobacteria, nitrobacter, and denitrifier on the surface of the Mg-LDH-modified anthracite was higher than that of the original anthracite. The performance of the anthracite in removing nitrogen was attributed to physical interception, chemical adsorption, and biological degradation. Moreover, the modified anthracites were superior to the original anthracite in the chemical adsorption and biodegradation, which indicated that coating the Mg-LDHs on the surface of common anthracite was a potential method to improve the nitrogen removal efficiency of domestic wastewater and to restore the eutrophic water body.

Clinical Characteristics and Outcomes of Severe and Critical Patients With 2019 Novel Coronavirus Disease (COVID-19) in Wenzhou: A Retrospective Study.

Information about severe cases of 2019 novel coronavirus disease (COVID-19) infection is scarce. The aim of this study was to report the clinical characteristics and outcomes of severe and critical patients with confirmed COVID-19 infection in Wenzhou city. In this single-centered, retrospective cohort study, we consecutively enrolled 37 RT-PCR confirmed positive severe or critical patients from January 28 to February 16, 2020 in a tertiary hospital. Outcomes were followed up until 28-day mortality. Fifteen severe and 22 critical adult patients with the COVID-19 infection were included. Twenty-six (68.4%) were men. Echocardiography data results suggest that normal or increased cardiac output and diastolic dysfunction are the most common manifestations. Compared with severe patients, critical patients were older, more likely to exhibit low platelet counts and high blood urea nitrogen, and were in hospital for longer. Most patients had organ dysfunction during hospitalization, including 11 (29.7%) with ARDS, 8 (21.6%) with acute kidney injury, 17 (45.9%) with acute cardiac injury, and 33 (89.2%) with acute liver dysfunction. Eighteen (48.6%) patients were treated with high-flow ventilation, 9 (13.8%) with non-invasive ventilation, 10 (15.4%) with invasive mechanical ventilation, 7 (18.9%) with prone position ventilation, 6 (16.2%) with extracorporeal membrane oxygenation (ECMO), and 3 (8.1%) with renal replacement therapy. Only 1 (2.7%) patient had died in the 28-day follow up in our study. All patients had bilateral infiltrates on their chest CT scan. Twenty-one (32.3%) patients presented ground glass opacity (GGO) with critical patients more localized in the periphery and the center. The mortality of critical patients with the COVID-19 infection is low in our study. Cardiac function was enhanced in the early stage and less likely to develop into acute cardiac injury, but most patients suffered with acute liver injury. The CT imaging presentations of COVID-19 in critical patients were more likely with consolidation and bilateral lung involvement.

Comparison of transesophageal echocardiography findings after different anticoagulation strategies in patients with atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: High risk of embolic events exists in both patients with chronic atrial fibrillation (AF) and patients in the perioperative period of ablation (effective treatment for AF). Therefore, anticoagulant therapy is important. Oral anticoagulants can be divided into two major categories: vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs). VKAs, represented by warfarin, have been widely used as traditional anticoagulants, whereas NOACs have been used in clinical practice, but their anticoagulant effects and side effects are still the focus of research. We used a meta-analysis to compare the incidence of left atrial thrombi (LAT) between different anticoagulants. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases for observational studies that compared the transesophageal echocardiography (TEE) findings for patients treated with NOACs and VKAs. The incidence of LAT and dense spontaneous echocardiographic contrast (dense SEC) were extracted as the basis of the meta-analysis. RESULTS: Fifteen studies were included in the meta-analysis. We found that patients anticoagulated with NOACs and VKAs had similar incidence of LAT (OR = 0.74, 95%CI: 0.55-1.00). After excluding the heterogeneous article by sensitivity analysis, we found the incidence of LAT in patients anticoagulated with NOACs is lower than VKAs (OR = 0.59, 95%CI: 0.42-0.84). The results of subgroup analysis showed that the incidence of LAT among three types of NOACs have no significant difference (dabigatran vs. rivaroxaban, OR = 1.16 [0.75, 1.81]; rivaroxaban vs. apixaban, OR = 0.97 [0.54, 1.74]; dabigatran vs. apixaban, OR = 1.09 [0.55, 2.16]). CONCLUSION: Patients anticoagulated with NOACs may have lower incidence of LAT than VKAs. The incidence of LAT among different type of NOACs are similar.

High-definition neural visualization of rodent brain using micro-CT scanning and non-local-means processing.

BACKGROUND: Micro-CT holds promising potential for phenotyping and histological purposes. However, few have clarified the difference in the neuroimaging quality between ex vivo and in vivo micro-CT scanners. In addition, no direct comparison has been made between micro-CT scans and standard microscopy. Furthermore, while the efficacy of various stains for yielding soft-tissue contrast in CT scans have been compared in other studies for embryos, staining protocols for larger samples have yet to be clarified. Lastly, post-acquisition processing for image enhancements have not been addressed. METHODS: Comparisons of postnatal rat brain micro-CT scans obtained through custom-built ex vivo and commercially available in vivo micro-CT scanners were made. Subsequently, the scanned rat brains were then H&E stained for microscopy. Neuroanatomy on micro-CT scanning and 4× microscopy of rat brain were compared. Diffusion and perfusion staining using iodine or PTA were trialled on adult and neonatal encapsulated rat brains. Different combinations of stain concentration and staining time were trialled. Post-acquisition denoising with NLM filter was completed using a modern General-Purpose Graphic Processing Unit (GPGPU) and custom code for prompt processing. RESULTS: Ex vivo micro-CT scans of iodine-stained postnatal rat brains yields 3D images with details comparable to 4× H&E light micrographs. Neural features shown on ex vivo micro-CT scans were significantly more distinctive than those on in vivo micro-CT scans. Both ex vivo and in vivo micro-CT scans required diffusion staining through small craniotomy. Perfusion staining is ineffective. Iodine staining was more efficient than PTA in terms of time. Consistently, enhancement made by NLM denoising on in vivo micro-CT images were more pronounced than that on ex vivo micro-CT scans due to their difference in image signal-to-noise indexes. CONCLUSIONS: Micro-CT scanning is a powerful and versatile visualization tool available for qualitative and potential quantitative anatomical analysis. Simple diffusion staining via craniotomy with 1.5% iodine is an effective and minimal structural-invasive method for both in vivo and ex vivo micro-CT scanning for studying the microscopic morphology of neonatal and adult rat brains. Post-acquisition NLM filtering is an effective enhancement technique for in vivo micro-CT brain scans.