Effects of Zinc Thiazole and Oxytetracycline on the Microbial Metabolism, Antibiotic Resistance, and Virulence Factor Genes of Soil, Earthworm Gut, and Phyllosphere.

Pesticides and antibiotics are believed to increase the incidence of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs), constituting a serious threat to global health. However, the impact of this combined pollution on the microbiome and that of the related ARGs and VFGs on soil-plant-animal systems remain unknown. In this study, a 60-day microcosm experiment was conducted to reveal the effects of zinc thiazole (ZT) and oxytetracycline (OTC) on microbial communities, antibiotic resistomes, and virulence factors in soil, earthworm gut, and phyllosphere samples using metagenomics. ZT exposure perturbed microbial communities and nutrient metabolism and increased the abundance of ARGs and VFGs in the gut. Combined exposure changed the profiles of ARGs and VFGs by decreasing microbial diversity in the phyllosphere. Host-tracking analysis identified some genera, such as Citrobacter and Aeromonas, as frequent hosts of ARGs and VFGs in the gut. Notably, some co-occurrence patterns of ARGs and MGEs were observed on the metagenome-assembled contigs. More importantly, ZT markedly increased the abundance of potentially drug-resistant pathogens Acinetobacter soli and Acinetobacter junii in the phyllosphere. Overall, this study expands our current understanding of the spread of ARGs and VFGs in soil-plant-animal systems under pollutant-induced stress and the associated health risks.

[Spatial and Temporal Distribution Characteristics of Heavy Metals in Main Rivers Sediments and Ecological Risk Assessment in Kaifeng City].

Heavy metal pollution in urban river sediments is an important threat to river ecosystem health. To explore the temporal and spatial distribution characteristics of heavy metals in river sediments of Kaifeng City, the surface sediments of rivers were sampled in 2015 and 2021, respectively, and the contents of Cd, Cr, Cu, Ni, Pb, and Zn in sediments at different periods were compared. The heavy metal pollution in the two periods was evaluated using the indices of geo-accumulation, bio-toxicity risk assessment, and potential ecological risk. The results showed that the content of heavy metals in river sediments of Kaifeng City in 2021 were decreased significantly compared with that in 2015. Cd, Cr, Cu, Ni, Pb, and Zn decreased by 94.42%, 18.4%, 85.7%, 45.19%, 75.61%, and 92.28%, respectively. The heavy metal content in the Huafei River and Huiji River was higher than that in other rivers in both periods. Correlation and principal component analyses showed that the heavy metal pollution sources of river sediments in Kaifeng City were highly similar, and human activities such as industrial layout, road traffic, and land use were the main pollution sources. However, the results showed that the main pollutants were different between the two sampling times. In 2015, Cd, Cr, Pb, and Zn were the main pollutants, and in 2021, Cd, Cu, Pb, and Zn were the main pollutants. The results of the geo-accumulation, bio-toxicity risk assessment, and potential ecological risk indices showed that the temporal and spatial differences in heavy metal pollution in river sediments in Kaifeng City were large. However, the heavy metal pollution of the Huiji River and Huafei River was still serious, with contents in the medium and high pollution levels, especially to Cd. The heavy metal treatment of rivers in Kaifeng City has a long way to go, and it is particularly necessary to strengthen the engineering treatment for key river sections and effectively monitor key pollution elements.

[Distribution Characteristics and Pollution Risk of Heavy Metals in River Sediment of Suzhou Water Network Area, China].

The average contents of the heavy metals Cd, Cu, Cr, As, Ni, Pb, and Zn in the sediment of sampling points in the Suzhou water network area were 1.4, 127.4, 83.2, 18.2, 51.7, 145.1, and 350.7 mg·kg-1, respectively, which were 13.7, 5.7, 1.1, 1.7, 1.9, 5.5, and 5.6 times the background values, respectively. The proportions of points exceeding the risk screening values of the GB 15618-2018 standard were 100.0%, 97.3%, 38.4%, 83.6%, 97.3%, 90.4%, and 100.0%, respectively. The pollution degree of single heavy metal elements was evaluated using the improved ground accumulation index method. The pollution degree of the seven heavy metal elements in the sediment of the Suzhou water network area was in the order of Cd>Cu>Pb>Zn>As>Cr>Ni. Among them, Cd showed extremely strong pollution, Cu and Pb showed intense to extremely strong pollution, Zn showed strong pollution, As showed moderate to intense pollution, and Cr and Ni showed moderate pollution. Cd, Pb, Cu, and Zn in the sediment samples of the ancient city area, northwest area, southwest area, and east area were the heavy metal elements with high pollution contributions. The potential ecological risk degree of heavy metals was ranked as northwest>southwest>ancient city area>east. Correlation analysis and principal component analysis showed that Cd, Cu, Cr, As, Ni, Pb, and Zn may have come from anthropogenic factors such as tail gas emissions, the use of chemical fertilizers and pesticides, and the pollutant emissions of the electronic manufacturing industry.

Deciphering roles of microbiota in arsenic biotransformation from the earthworm gut and skin.

Biotransformation mediated by microbes can affect the biogeochemical cycle of arsenic. However, arsenic biotransformation mediated by earthworm-related microorganisms has not been well explored, especially the role played by earthworm skin microbiota. Herein, we reveal the profiles of arsenic biotransformation genes (ABGs) and elucidate the microbial communities of the earthworm gut, skin, and surrounding soil from five different soil environments in China. The relative abundance of ABGs in the earthworm skin microbiota, which were dominated by genes associated with arsenate reduction and transport, was approximately three times higher than that in the surrounding soil and earthworm gut microbiota. The composition and diversity of earthworm skin microbiota differed significantly from those of the soil and earthworm gut, comprising a core bacterial community with a relative abundance of 96% Firmicutes and a fungal community with relative abundances of 50% Ascomycota and 13% Mucoromycota. In addition, stochastic processes mainly contributed to the microbial community assembly across all samples. Moreover, fungal genera such as Vishniacozyma and Oomyces were important mediators of ABGs involved in the biogeochemical cycle of arsenic. This is the first study to investigate earthworm skin as a reservoir of microbial diversity in arsenic biotransformation. Our findings broaden the current scientific knowledge of the involvement of earthworms in the arsenic biogeochemical cycle.

Expression,purification and bioinformatics analysis of PE＿PGRS35 protein of Mycobacterium tuberculosis H37Rv strain / 中国生物制品学杂志

@#Abstract： Objective To clone PE_PGRS35 gene of Mycobacterium tuberculosis（MTB），construct recombinant vector pET28a⁃PE_PGRS35，express and purify the PE_PGRS35 protein of MTB H37Rv heterologously，and explore a new target against MTB after bioinformatics analysis. Methods The PE_PGRS35 coding gene was amplified by PCR and used to construct the expression vector pET28a⁃PE_PGRS35 by recombinant cloning technology，which was transformed to E. coli BL21（DE3）after successful sequencing and induced by using IPTG. The obtained PE_PGRS35 protein was purified by Ni column affinity chromatography and analyzed by bioinformatics. Results The pET28a⁃PE_PGRS35 prokaryotic expression vector was constructed correctly as identified by sequencing. The PE_PGRS35 protein was mainly expressed in the form of inclusion bodies，with a relative molecular mass of about 53 000 and a purity of 90%. Bioinformatics analysis showed that PE_PGRS35 protein was an acid⁃labile protein，with main secondary structure of β⁃sheet and random coil，and no transme⁃ mbrane region，which was presumed to be an extramembrane protein with 39 phosphorylation sites and two conserved domains. Total 10 proteins，including Rv1769，PPE8，PPE64，PPE54，PPE24，PPE16，PPE35，PPE6，PPE28 and PE2， interacted with PE_PGRS35 protein. Conclusion PE_PGRS35 protein with high purity was successfully obtained，which provided a reference for the further development of new targets for drugs against MTB.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

Autophagy-related long non-coding RNA prognostic model predicts prognosis and survival of melanoma patients.

BACKGROUND: Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin, mucous membrane, uvea, and pia mater. Long non-coding RNAs (lncRNAs) are key factors in the occurrence and development of many malignant tumors, and are involved in the prognosis of some patients. AIM: To identify autophagy-related lncRNAs in melanoma that are crucial for the diagnosis, treatment, and prognosis of melanoma patients. METHODS: We retrieved transcriptome expression profiles and clinical information of 470 melanoma patients from The Cancer Genome Atlas (TCGA) database. Then, we identified autophagy-related genes in the Human Autophagy Database. Using R, coexpression analysis of lncRNAs and autophagy-related genes was conducted to obtain autophagy-related lncRNAs and their expression levels. We also performed univariate and multivariate Cox proportional risk analyses on the obtained datasets, to systematically evaluate the prognostic value of autophagy-related lncRNAs in melanoma. Fifteen autophagy-related lncRNAs were identified and an autophagy-related prognostic signature for melanoma was established. The Kaplan-Meier and univariate and multivariate Cox regression analyses were used to calculate risk scores. Based on the risk scores, melanoma patients were randomly divided into high- and low-risk groups. Receiver operating characteristic curve analysis, dependent on time, was performed to assess the accuracy of the prognostic model. At the same time, we also downloaded the melanoma data sets GSE65904, GSE19234, and GSE78220 from the GENE EXPRESSION OMNIBUS database for model verification. Finally, we performed Gene Set Enrichment Analysis functional annotation, which showed that the low and the high-risk groups had different enriched pathways. RESULTS: The co-expression network for autophagy-related genes was constructed using R, and 936 lncRNAs related to autophagy were identified. Then, 52 autophagy-related lncRNAs were significantly associated with TCGA melanoma patients' survival by univariate Cox proportional risk analysis (P < 0.01). Further, the 52 autophagy-related lncRNAs mentioned above were analyzed by multivariate Cox analysis with R. Fifteen lncRNAs were selected: LINC01943, AC090948.3, USP30-AS1, AC068282.1, AC004687.1, AL133371.2, AC242842.1, PCED1B-AS1, HLA-DQB1-AS1, AC011374.2, LINC00324, AC018553.1, LINC00520, DBH-AS1, and ITGB2-AS1. The P values in all survival analyses using these 15 lncRNAs were < 0.05. These lncRNAs were used to build a risk model based on the risk score. Negative correlations were observed between risk scores and overall survival rate in melanoma patients over time. Additionally, the melanoma risk curve and scatter plot analyses showed that the death number increased along with the increase in the risk score. Overall, we identified and established a new prognostic risk model for melanoma using 15 autophagy-related lncRNAs. The risk model constructed with these lncRNAs can help and guide melanoma patient prognosis predictions and individualized treatments in the future. CONCLUSION: Overall, the risk model developed based on the 15 autophagy-related lncRNAs can have important prognostic value and may provide autophagy-related clinical targets for melanoma treatment.

Diagnostic accuracy of red blood cell distribution width for neonatal sepsis.

INTRODUCTION: Red blood cell distribution width (RDW) is a biomarker for the diagnosis and prognosis of many diseases. However, the relevance between RDW and neonatal sepsis (NS) have not reached a consensus yet; the perform of RDW in the diagnosis of neonatal sepsis is still not clear. The aim of this meta-analysis was to estimate the significance of RDW in neonatal sepsis and the perform of RDW in diagnosis of neonatal sepsis. EVIDENCE ACQUISITION: We used Pubmed, Embase, Web of science, CNKI and Google academic database to find all articles that met the inclusion criteria until July 1, 2020. EVIDENCE SYNTHESIS: Fifteen eligible studies involving 1362 newborns were included in the meta-analysis after two independent investigators read the title, abstract and full text in detail. The pooled result of this meta-analysis showed that RDW was significantly higher in the NS group than in the control group (WMD=3.224; 95%CI: 2.359-4.090, P<0.001). In addition, the overall pooled sensitivity, specificity, PLR, NLR and DOR were 0.88 (95%CI:0.66-0.96), 0.90 (95%CI:0.65-0.98), 9.2 (95%CI:2.1-40.3), 0.14(95%CI:0.04-0.43) and 66.9 (95%CI:8.73-513.26), respectively. The area under the SROC curve (AUC) was 0.95 (95%CI:0.93-0.96). CONCLUSIONS: The meta-analysis demonstrated that newborns with sepsis had an elevated RDW level than healthy controls. RDW levels have significant correlated with neonatal sepsis; and RDW can be used as a cheap and satisfactory diagnostic biomarker for neonatal sepsis with a relatively high performance.

Insights Into Ferroptosis, a Novel Target for the Therapy of Cancer.

Ferroptosis is a new form of programmed cell death (PCD) characterized by an excess iron accumulation and subsequent unbalanced redox states. Ferroptosis is different from the already reported PCD and has unique morphological features and biochemical processes. Ferroptosis was first elaborated by Brent R. Stockwell's lab in 2012, in which small molecules erastin and RSL-3 induce PCD in Ras mutant cell lines. Ferroptosis involves various physiological processes and occurrence of disease and especially shows strong potential in cancer treatment. Development of small molecule compounds based on Stockwell's research was found to kill cancer cells, and some FDA-approved drugs were discovered to result in ferroptosis of cancer cells. Radiotherapy and checkpoint therapy have been widely used as a treatment for many types of cancer. Recently, some papers have reported that chemotherapy, radiotherapy, and checkpoint therapy induce ferroptosis of cancer cells, which provides new strategies for cancer treatment. Nevertheless, the limitless proliferation of tumor cells and the lack of cell death mechanisms are important reasons for drug resistance for tumor therapy. Therefore, we reviewed the molecular mechanism of ferroptosis and sensitivity to ferroptosis of different cancer cells and tumor treatment strategy.

Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis.

Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

Responses of earthworm Metaphire vulgaris gut microbiota to arsenic and nanoplastics contamination.

The growing contamination of arsenic and plastics has severely effects on the soil fauna health, including shifts of gut microbiota community. A few studies have focused on effects of microplastics and metal(loid) in soil and fauna gut microbiome. However, the environmental effect of nanoplastics and arsenic on the earthworm gut microbiota, especially on arsenic biotransformation in the gut, remain largely unknown. Here, a microcosm study was performed to explore the effects of nanoplastics and arsenic on the microbiota characteristics in earthworm Metaphire vulgaris gut using Illumina high throughput sequencing, and to investigate changes in the gut microbiota-mediated arsenic biotransformation genes (ABGs) by using high-throughput quantitative PCR. Our results demonstrated that the concentration of arsenic in the earthworm body tissues after exposure to arsenic and nanoplastics was significantly lower from that with arsenic alone exposure. Moreover, the clearly different bacterial community was observed in the soil compared with the earthworm gut, which was dominated by Proteobacteria, Actinobacteria, and Firmicutes at phylum level. Arsenic exposure significantly disturbed bacterial community structure in the earthworm gut, but exposure to nanoplastics did not induce gut microbiota changes. More interestingly, nanoplastics can relieve adverse effect of arsenic on the gut microbiota possibly by adsorbing arsenic. In addition, a total of 16 ABGs were detected, and predominant genes involved in arsenic reduction and transport process were observed in the earthworm guts. In short, this study provides a new picture of the effects of nanoplastics and arsenic on the gut microbiota and arsenic biotransformation in soil fauna gut.

[Pollution Distribution and Ecological Risk Assessment of Heavy Metals in River Sediments from the Ancient Town of Suzhou].

The contents of heavy metals (Cd, Cu, Cr, As, Mn, Ni, Pb, and Zn) in sediments from 20 representative sections of the ancient town of Suzhou were analyzed to determine the pollution degree and potential ecological risk, and pollution sources were identified. The results showed that the average concentrations of Cd, Cu, Cr, As, Mn, Ni, Pb, and Zn in river sediments from the ancient town of Suzhou were 1.1, 142.6, 90.2, 17.2, 800.1, 63.3, 199.1, and 384.2 mg·kg-1, respectively, and the proportions of sampling points that exceeded the soil background value of Jiangsu Province were 100%, 100%, 65%, 95%, 70%, 100%, 95%, and 100%, respectively. The geo-accumulation index indicated that the pollution degree of heavy metals followed the order of Pb > Cd > Cu > Zn > Cr > Ni > As > Mn. In general, high Pb pollution, moderate Cd, Cu, Zn, and Cr pollution, slight Ni and As pollution, and no Mn pollution were observed. The potential ecological risk index for heavy metals was determined to follow the order of Cd > Pb > Cu > As > Ni > Zn > Cr > Mn. Generally, Cd, Pb, and Cu presented moderate potential ecological risk, and the others presented low potential ecological risk. The average concentration of heavy metals, geo-accumulation index, and potential ecological risk index of river sediments in the northern and southern of ancient town were all higher than that of Ganjiang River and Huancheng River, indicating that the control of heavy metals should focus on the inner part of the ancient town. According to correlation analysis and principal component analysis, Cd, Cu, Cr, As, Ni, Pb, and Zn might be derived from man-made factors such as fertilizer, road aging, tire wear, exhaust emissions and so on, which Mn was mainly derived from natural factors.

Effects of nano- or microplastic exposure combined with arsenic on soil bacterial, fungal, and protistan communities.

The soil protistan community makes important contributions to the ecological functions of soil. However, our knowledge of the effects of pollutants, especially plastic particles, on the soil protistan community is still very limited compared to our knowledge on other soil microbes, such as bacterial and fungi. In this study, we revealed the effects of combined and single pollution caused by arsenic (As) and microplastics/nanoplastics (MPs/NPs) on bacterial, fungal and protistan communities. Our results revealed that combined pollution through As and MPs/NPs distinctly affected the composition and structure of the soil protistan communities (P < 0.05), but in the case of bacteria, only some families were altered, and there was no impact on fungi. Changes of soil protistan communities might be mainly due to As pollution, and MPs/NPs exposure increased this detrimental effect. Further, As + MPs exposure greatly increased the abundance of soil protistan parasites, and As + NPs exposure caused an evident decrease in the abundance of soil protistan consumers (P < 0.05). These findings indicate that combined pollution by As and MPs/NPs can affect the ecological functions of soil by altering soil protistan communities. These results will help enhance our understanding of the impact of plastic particles on soil ecosystems.

[Prognostic Significance of CD27 and CD56 on Newly Diagnosed MM Patients Treated with Bortezomib].

OBJECTIVE: To investigate the significance of CD27 and CD56 in the prognosis of multiple myeloma (MM) patients, and to establish a simple and convenient prognostic risk score. METHODS: One hundred and eleven newly diagnosed MM patients treated by bortezomib in Shengjing hospital from January 1, 2013 to January 1, 2019 were selected, and the relationship between clinical characteristics and survival time of patients was analyzed. RESULTS: The overall survival (OS) of patients in CD27+CD56+ group was longer than that of patients in non-CD27+CD56+ group (P<0.05). ß2-microglobulin≥5.5 mmol/L, serum calcium >2.5 mmol/L and expression of non-CD27+CD56+ were the independent risk factors in patients with MM treated by bortezomib. CONCLUSION: Among patients with MM treated by bortezomib, CD27+CD56+ patients show better prognosis than non-CD27+CD56+ patients. The prognosis of patients with 3 risk factors of ß2-MG and serum calcium concentration above the critical value and non-CD27+CD56+ expression is very poor, and clinical trials or hematopoietic stem cell transplantation or other treatment measures should be given as soon as possible.

Arsenic bioaccumulation in the soil fauna alters its gut microbiome and microbial arsenic biotransformation capacity.

The biotransformation of arsenic mediated by microorganisms plays an important role in the arsenic biogeochemical cycle. However, the fate and biotransformation of arsenic in different soil fauna gut microbiota are largely unknown. Herein the effects of arsenic contamination on five types of soil fauna were compared by examining variations in arsenic bioaccumulation, gut microbiota, and arsenic biotransformation genes (ABGs). Significant difference was observed in the arsenic bioaccumulation across several fauna body tissues, and Metaphire californica had the highest arsenic bioaccumulation, with a value of 107 ± 1.41 mg kg-1. Arsenic exposure significantly altered overall patterns of ABGs; however, dominant genes involved in arsenic redox and other genes involved in arsenic methylation and demethylation were not significantly changed across animals. Except for M. californica, the abundance of ABGs in other animal guts firstly increased and then decreased with increasing arsenic concentrations. In addition, exposure of soil fauna to arsenic led to shifts in the unique gut-associated bacterial community, but the magnitude of these changes varied significantly across ecological groups of soil fauna. A good correlation between the gut bacterial communities and ABG profiles was observed, suggesting that gut microbiota plays important roles in the biotransformation of arsenic. Overall, these results provide a universal profiling of a microbial community capable of arsenic biotransformation in different fauna guts. Considering the global distribution of soil fauna in the terrestrial ecosystem, this finding broadens our understanding of the hidden role of soil fauna in the arsenic bioaccumulation and biogeochemical cycle.

Anti-arrhythmic and anti-heart failure effects of low-level electrical stimulation on aortic root ventricular ganglionated plexi.

BACKGROUND: It remains uncertain whether low-level electrical stimulation (LL-ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigated the anti-arrhythmic and anti-heart failure effects of LL-ES of the aortic root ventricular GP (ARVGP). METHODS: Thirty dogs were divided randomly into control, drug, and LL-ES groups after performing rapid right ventricular pacing to establish a heart failure (HF) model. The inducing rate of arrhythmia; levels of bioactive factors influencing HF, including angiotensin II type I receptor (AT-1R), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMP), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2); left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF)were measured after treatment with placebo, drugs, and LL-ES. RESULTS: The inducing rate of atrial arrhythmia decreased from 60% in the control group to 50% in the drug group and 10% in the LL-ES group (p = .033 vs. drug group) after 1 week of treatment. The ventricular effective refractory period was prolonged from 139 ± 8 ms in the drug group to 166 ± 13 ms in the LL-ES group (p = .001). Compared to the drug group, the expressions of AT-1R, TGF-ß, and MMP proteins were down-regulated in the LL-ES group, whereas that of p-ERK1/2 was significantly increased (all p = .001). Moreover, in the LL-ES group, LVSV increased markedly from 13.16 ± 0.22 to 16.86 ± 0.27 mL, relative to that in the drug group (p = .001), and LVEF increased significantly from 38.48% ± 0.53% to 48.94% ± 0.57% during the same time frame (p = .001). CONCLUSION: Short-term LL-ES of ARVGP had both anti-arrhythmic and anti-inflammatory effects and contributed to the treatment of tachycardia-induced HF and its associated arrhythmia.

Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

Soil pH has a stronger effect than arsenic content on shaping plastisphere bacterial communities in soil.

Microplastic (MP) pollution is widespread in various ecosystems and is colonized by microbes that form biofilms with compositions and functions. However, compared with aquatic environments, the soil environment has been poorly studied in terms of the taxonomic composition of microbial communities and the factors influencing the community structure of microbes in the plastisphere. In the present study, a microcosm experiment was conducted to investigate the plastisphere bacterial communities of MP (polyvinyl chloride, PVC) in soils with different pH (4.62, 6.5, and 7.46) and arsenic (As) contents (13 and 74 mg kg-1). Bacterial communities in the plastisphere were dominated by Proteobacteria and Firmicutes, with distinct compositions and structures compared with soil bacterial communities. Soil pH and As content significantly affected the plastisphere bacterial communities. Constrained analysis of principal coordinates and a structural equation model demonstrated that soil pH had a stronger influence on the dissimilarity and diversity of bacterial communities than did soil As content. Soil pH affected As speciation in soil and on MP. The concentration of dimethylarsinic acid (DMA) was significantly higher on MP than that in soil, indicating that As methylation occurred on MP. These results suggest that environmental fluctuations govern plastisphere bacterial communities with cascading effects on biogeochemical cycling of As in the soil ecosystems.

[Distribution Characteristics of Carbon, Nitrogen, and Phosphorus Bearing Pollutants in the Ancient Town Rivers of Suzhou].

Suzhou is a water-deficient city with water quality issues. Despite water conservation measures, emission reductions, source control, and pollution interception, water quality remains poor. To understand the total mass and distribution characteristics of carbon, nitrogen, and phosphorus bearing pollutants and inform decisions regarding river dredging, sediment and water samples were collected from 20 representative sections in the town's rivers during the spring of 2019. The depths of the sediments were measured along with the concentrations of carbon, nitrogen, and phosphorus bearing pollutants in the sediments and water, and the pollution degree was evaluated. Variations in various parameters were predicted for change water, diversion water, rainfall, and dredging. The results show that the sediment depths ranged between 22 and 1025 mm (average=266 mm), and the total mass of sediment was approximately 5.2×105 t in the ancient town rivers of Suzhou. The average proportions and concentrations of TOC, TN, NH4+-N, TP, and AP in the sediments were 3.4%, 2074 mg·kg-1, 140.2 mg·kg-1, 1765 mg·kg-1, and 57.2 mg·kg-1, respectively, indicating a moderate level of pollution. The concentration of TP in the sediments at 90% of the sampling points exceeds the national standard. Huancheng River was found to have the highest concentration of TP, suggesting that dredging shuld be targeted here first. In the water samples, the average concentrations of TOC, BOD5, COD, TN, NH4+-N, Kjeldahl nitrogen, TP, and PO43--P were 7.8, 0.6, 13.1, 2.5, 0.643, 1.3, 0.18, and 0.09 mg·L-1, respectively, indicating a severe level of pollution. Overall, water quality in these rivers falls below Class V surface water, and the concentration of TN seriously exceeds the national standard. Based on the patterns of total carbon mass and nitrogen and phosphorus bearing pollutants, the recommended order of dredging in Suzhou is the Huancheng River, the northern rivers of the ancient town, Ganjiang River, and the southern rivers of the ancient town. Under the rainfall scenario, the initial concentrations of pollutants in runoff were high, which leads to a decline in water quality. The total mass of TN in the water was reduced by 0.2 t under the change water and diversion water scenarios, and was further reduced by 4.58 t and 2.19 t, respectively, after dredging. Phosphorus bearing pollutants in the sediment were mainly imported from other sources, meaning that the total mass of TP in the water may increase following dredging activities.

Antibiotic exposure decreases soil arsenic oral bioavailability in mice by disrupting ileal microbiota and metabolic profile.

Oral bioavailability of arsenic (As) determines levels of As exposure via ingestion of As-contaminated soil, however, the role of gut microbiota in As bioavailability has not evaluated in vivo although some in vitro studies have investigated this. Here, we made a comparison in As relative bioavailability (RBA) estimates for a contaminated soil (3913 mg As kg-1) using a mouse model with and without penicillin perturbing gut microbiota and metabolites. Compared to soil exposure alone (2% w/w soil in diets), addition of penicillin (100 or 1000 mg kg-1) reduced probiotic Lactobacillus and sulfate-reducing bacteria Desulfovibrio, enriched penicillin-resistant Enterobacter and Bacteroides, and decreased amino acid concentrations in ileum. With perturbed gut microbiota and metabolic profile, penicillin and soil co-exposed mice accumulated 2.81-3.81-fold less As in kidneys, excreted 1.02-1.35-fold less As in urine, and showed lower As-RBA (25.7-29.0%) compared to mice receiving diets amended with soil alone (56 ± 9.63%). One mechanism accounted for this is the decreased concentrations of amino acids arising from the gut microbiota shift which resulted in elevated iron (Fe) and As co-precipitation, leading to reduced As solubilization in the intestine. Another mechanism was conversion of bioavailable inorganic As to less bioavailable monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by the antibiotic perturbed microflora. Based on in vivo mouse model, we demonstrated the important role of gut microbiota and gut metabolites in participating soil As solubilization and speciation transformation then affecting As oral bioavailability. Results are useful to better understand the role of gut bacteria in affecting As metabolism and the health risks of As-contaminated soils.