Integrating Multiple Bacterial Phenotypes and Bayesian Network for Analyzing Health Risks of Pathogens in Plastisphere.

Plastic pollution represents a critical threat to soil ecosystems and even humans, as plastics can serve as a habitat for breeding and refuging pathogenic microorganisms against stresses. However, evaluating the health risk of plastispheres is difficult due to the lack of risk factors and quantification model. Here, DNA sequencing, single-cell Raman-D2O labeling, and transformation assay were used to quantify key risk factors of plastisphere, including pathogen abundance, phenotypic resistance to various stresses (antibiotic and pesticide), and ability to acquire antibiotic resistance genes. A Bayesian network model was newly introduced to integrate these three factors and infer their causal relationships. Using this model, the risk of pathogen in the plastisphere is found to be nearly 3 magnitudes higher than that in free-living state. Furthermore, this model exhibits robustness for risk prediction, even in the absence of one factor. Our framework offers a novel and practical approach to assessing the health risk of plastispheres, contributing to the management of plastic-related threats to human health.

Comparison and phylogenetic analysis of the mitochondrial genomes of Synodontis eupterus and Synodontis polli.

We aimed to distinguish Synodontis eupterus and Synodontis polli. We performed sequencing and bioinformatic analysis of their mitochondrial genomes and constructed a phylogenetic tree of Mochokidae fish using maximum likelihood and Bayesian methods based on protein-coding gene (PCG) sequences of 14 Mochokidae species. The total length of the S. eupterus mitochondrial genome was 16,579 bp, including 13 (PCGs), 22 tRNA genes, two rRNA genes, and one D-loop, with an AT-biased nucleotide composition (56.0%). The total length of the S. polli mitochondrial genome was 16,544 bp, including 13 PCGs, 22 tRNA genes, two rRNA genes, and one D-loop, with an AT-biased nucleotide composition (55.0%). In both species, except for COI, PCGs use ATG as the starting codon, the vast majority use TAG or TAA as the ending codon, and a few use incomplete codons (T - or TA -) as the ending codon. Phylogenetic analysis showed that S. eupterus and Synodontis clarias converged into one branch, S. polli and Synodontis petricola converged into one branch, Mochokiella paynei, Mochokus brevis, and nine species of the genus Synodontis converged into one branch, and M. paynei clustered with the genus Synodontis. This study lays a foundation for rebuilding a clearer Mochokidae fish classification system.

Double tract reconstruction improves the quality of life and better maintain the BMI of patients with proximal gastric cancer.

PURPOSE: The aim of this study is to investigate the effect of double-tract reconstruction on short-term clinical outcome, quality of life and nutritional status of patients after proximal gastrectomy by comparing with esophagogastrostomy and total gastrectomy with Roux-en-Y reconstruction. METHODS: The clinical data of patients who underwent double tract reconstruction (DTR), esophagogastrostomy (EG), total gastrectomy with Roux-en-Y reconstruction (TG-RY) were retrospectively collected from May 2020 to May 2022. The clinical characteristics, short-term surgical outcomes, postoperative quality of life and nutritional status were compared among the three groups. RESULTS: Compared with the DTR group, the operation time in the TG group was significantly shorter (200(180,240) minutes vs. 230(210,255) minutes, p < 0.01), and more lymph nodes were removed (28(22, 25) vs. 22(19.31), p < 0.01), there were no significant differences in intraoperative blood loss, first flatus time, postoperative hospital stay and postoperative complication rate among the three groups. Postoperative digestive tract angiography was completed in 36 patients in the DTR group, of which 21 (58.3%) showed double-tract type of food passing. The incidence of postoperative reflux symptoms was 9.2% in the DTR group, 43.8% in the EG group and 23.2% in the TG group, repectively (P < 0.01). EORTCQLQ-STO22 questionnaire survey showed that compared with EG group, DTR group had fewer reflux symptoms (P < 0.05), fewer anxiety symptoms (P < 0.05) and more swallowing symptoms (P < 0.05). Compared with TG group, DTR group had fewer reflux symptoms (P < 0.05). There were no other significant differences between the two groups. Compared with TG group and EG group, DTR can better maintain postoperative BMI, and there is no statistical difference between the three groups in terms of hemoglobin and albumin. CONCLUSIONS: Although partial double-tract reconstruction approach does not always ensure food to enter the distal jejunum along the two pathways as expected, it still shows satisfactory anti-reflux effect. Moreover, it might improve patients' quality of life and maintain better nutritional status comparing with gastroesophageal anastomosis and total gastrectomy with Roux-en-Y reconstruction.

[Research on mechanism of hypolipidemic effect of Massa Medicata Fermentata based on metabolomics].

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.

Mechanism of synergistic remediation of soil phenanthrene contamination in paddy fields by rice-crab coculture and bioaugmentation with Pseudomonas sp.

Polycyclic aromatic hydrocarbons (PAHs) are persistent and harmful pollutants with high priority concern in agricultural fields. This work constructed a rice-crab coculture and bioaugmentation (RCM) system to remediate phenanthrene (a model PAH) contamination in rice fields. The results showed that RCM had a higher remediation performance of phenanthrene in rice paddy compared with rice cultivation alone, microbial addition alone, and crab-rice coculture, reaching a remediation efficiency of 88.92 % in 42 d. The concentration of phenanthrene in the rice plants decreased to 6.58 mg/kg, and its bioconcentration effect was efficiently inhibited in the RCM system. In addition, some low molecular weight organic acids of rice root increased by 12.87 %∼73.87 %, and some amino acids increased by 140 %∼1150 % in RCM. Bioturbation of crabs improves soil aeration structure and microbial migration, and adding Pseudomonas promoted the proliferation of some plant growth-promoting rhizobacteria (PGPRs), which facilitated the degradation of phenanthrene. This coupling rice-crab coculture with bioaugmentation had favorable effects on soil enzyme activity, microbial community structure, and PAH degradation genes in paddy fields, enhancing the removal of and resistance to PAH contamination in paddy fields and providing new strategies for achieving a balance between production and remediation in contaminated paddy fields.

Clinicopathological characteristics and its association with digestive system tumors of 1111 patients with Schistosomiasis japonica.

Schistosomiasis japonicum can cause different degrees of organ damage and complex human immune pathological reactions, which often invade the intestine and liver. The purpose of this study was to explore the pathological types and pathological changes of Schistosomiasis and their correlation with some digestive system tumors. Hematoxylin eosin staining was performed on the diseased tissues of 1111 Schistosomiasis cases. We counted the deposition sites of Schistosoma eggs, analyzed the pathological characteristics, and compared the clinicopathological characteristics of Schistosomiasis associated digestive system tumors and non-Schistosomiasis digestive system tumors. We found that Schistosoma japonicum can cause multi organ and multi system damage, with 469 cases of inflammation, 47 cases of adenoma, and 519 cases of adenocarcinoma. Other types include cysts, stromal tumors, malignant lymphomas, and neuroendocrine tumors. Schistosomiasis associated tumors, including gastric cancer, liver cancer, colon cancer and rectal cancer, were compared with non-Schistosomiasis tumors. There were significant differences in age, gender and tumor differentiation between the two groups. Our study shows Schistosomiasis is a systemic disease, causing multiple organ and system damage in the human body. Its clinicopathological types are diverse, and there may be a pathological change process of "Inflammation-adenoma-carcinoma". Schistosomiasis associated digestive system tumors differ from non-Schistosomiasis tumors in some clinicopathological features.

Effect of humic acid-modified attapulgite on polycyclic aromatic hydrocarbon adsorption and release from paddy soil into the overlying water in a rice-crab coculture paddy ecosystem and the underlying process.

Phenanthrene (Phe), a typical polycyclic aromatic hydrocarbon (PAH) pollutant, poses an enormous safety risk to rice-crab coculture (RC) paddy ecosystems. In this study, humic acid-modified purified attapulgite (HA-ATP) with a composite structure was successfully fabricated to adsorb PAHs released from paddy soil to overlying water in RC paddy ecosystems in Northeast China. The maximum crab bioturbation intensities for dissolved Phe and particulate Phe were 64.83nullng/L·(cm2·d) and 214.29nullng/L·(cm2·d), respectively. The highest concentration of dissolved Phe released from paddy soil to overlying water due to crab bioturbation reached 80.89nullng/L, while the corresponding concentration of particulate Phe reached 267.36nullng/L. The dissolved organic carbon (DOC) and total suspended solid (TSS) concentrations in overlying water increased correspondingly and were strongly correlated with dissolved Phe and particulate Phe concentrations, respectively (P < 0.05). When 6% HA-ATP was added to the surface layer of paddy soil, the efficiency of the adsorption of Phe release was 24.00%-36.38% for particulate Phe and 89.99%-91.91% for dissolved Phe. Because HA-ATP has a large adsorption pore size (11.33 nm) and surface area (82.41nullm2/g) as well as many HA functional groups, it provided multiple hydrophobic adsorption sites for dissolved Phe, which was conducive to competitive adsorption with DOC in the overlying water. In contrast to that adsorbed by DOC, the average proportion of dissolved Phe adsorbed by HA-ATP reached 90.55%, which reduced the dissolved Phe concentration in the overlying water. Furthermore, even though the particulate Phe was resuspended by crab bioturbation, HA-ATP immobilized particulate Phe due to its capacity to inhibit desorption, which achieved the goal of reducing the Phe concentration in the overlying water. This result was confirmed by research on the adsorption-desorption characteristics of HA-ATP. This research provides an environmentally friendly in situ remediation method for reducing agricultural environmental risks and improving rice crop quality.

Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

Comprehensive Identification of Ginsenosides in the Roots and Rhizomes of Panax ginseng Based on Their Molecular Features-Oriented Precursor Ions Selection and Targeted MS/MS Analysis.

Panax ginseng is widely used in Asian countries and its active constituents-ginsenosides-need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.

Upregulation of TUBG1 expression promotes hepatocellular carcinoma development.

Tubulin γ-1 (TUBG1) is a highly conserved component of the centrosome and its deregulation is involved in the development of several types of cancer. However, the role of TUBG1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TUBG1 was upregulated in human HCC cells and tissues and that TUBG1 upregulation was associated with promoter hypomethylation in HCC tissues. TUBG1 knockdown suppressed the proliferation, invasion, and migration of HCC cells. While TUBG1 expression was positively correlated with CD4 + memory T lymphocyte infiltration, it was negatively correlated with CD4 + regulatory T-cell infiltration in human HCC tissues. Furthermore, TUBG1 expression was positively correlated with the expression of genes involved in cell division. Noticeably, high expression of TUBG1 was associated with poor prognosis in patients with HCC. Overall, our findings revealed that TUBG1 promotes hepatocarcinogenesis by increasing proliferation, invasion, and migration of HCC cells and may regulate T lymphocyte infiltration. The current findings provide important insights into TUBG1 regulation in HCC, which could provide new therapeutic targets for hepatocarcinoma which has a very high incidence and mortality rate worldwide.

Sublethal effects of an indoxacarb enantiomer insecticide on Plutella xylostella caterpillar and Chrysoperla sinica predator.

Plutella xylostella (L.) is a migratory species and an important insect pest of cruciferous crops worldwide, and Chrysoperla sinica (Tjeder) is a predaceous insect of agricultural and forest pests in the field. Indoxacarb has two enantiomers: (+)-S-indoxacarb and (-)-R-indoxacarb. This study was conducted to clarify the selective toxicity and sublethal effects of both enantiomers on P. xylostella and C. sinica. The (+)-S-indoxacarb isomer had greater acute toxicity to P. xylostella and C. sinica, while (-)-R-indoxacarb had less toxicity to P. xylostella and low toxicity to C. sinica. Lethal concentration 25 % (LC25) of (+)-S-indoxacarb had significant effects on the development, population, and fecundity of P. xylostella and C. sinica. The LC25 concentration of (-)-R-indoxacarb had a significant effect on the oviposition of P. xylostella. The field recommended concentration of (-)-R-indoxacarb significantly affected the pupal stage, adult survival rate, oviposition, and larval survival rate of C. sinica. Both enantiomers could significantly affect the search efficiency, successful attack rate, prey handling time, and maximum predation of C. sinica larvae, and the effects of (+)-S-indoxacarb alone were greater than those of (-)-R-indoxacarb. This study provided evidence of the different selective toxicity, sublethal effects of indoxacarb enantiomers on P. xylostella and C. sinica, which of the results could provide a basis for more rational use of indoxacarb in ecosystems.

Biodegradable Redox-Responsive AIEgen-Based-Covalent Organic Framework Nanocarriers for Long-Term Treatment of Myocardial Ischemia/Reperfusion Injury.

Timely restoration of blood supply after myocardial ischemia is imperative for the treatment of acute myocardial infarction but causes additional myocardial ischemia/reperfusion (MI/R) injury, which has not been hitherto effectively targeted by interventions for MI/R injury. Hence, the development of advanced nanomedicine that can reduce apoptosis of cardiomyocytes while protecting against MI/R in vivo is of utmost importance. Herein, a redox-responsive and emissive TPE-ss covalent organic framework (COF) nanocarrier by integrating aggregation-induced emission luminogens and redox-responsive disulfide motifs into the COF skeleton is developed. TPE-ss COF allows for efficient loading and delivery of matrine, a renowned anti-cryptosporidial drug, which significantly reduces MI/R-induced functional deterioration and cardiomyocyte injury when injected through the tail vein into MI/R models at 5 min after 30 min of ischemia. Moreover, TPE-ss COF@Matrine shows a drastic reduction in cardiomyocyte apoptosis and improvements in cardiac function and survival rate. The effect of the TPE-ss COF carrier is further elucidated by enhanced cardiomyocyte viability and triphenyltetrazolium chloride staining in vitro. This work demonstrates the cardioprotective effect of TPE-ss COFs for MI/R injury, which unleashes the immense potential of using COFs as smart drug carriers for the peri-reperfusion treatment of ischemic heart disease with low cost, high stability, and single postoperative intervention.

Xin-Ji-Er-Kang Alleviates Isoproterenol-Induced Myocardial Hypertrophy in Mice through the Nrf2/HO-1 Signaling Pathway.

Xin-Ji-Er-Kang (XJEK) inhibited cardiovascular remodeling in hypertensive mice in our previous studies. We hypothesized that XJEK may prevent isoproterenol (ISO)-induced myocardial hypertrophy (MH) in mice by ameliorating oxidative stress (OS) through a mechanism that may be related to the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1(HO-1) pathways. Forty SPF male Kunming mice were randomized into 5 groups (n = 8 mice per group): control group, MH group, MH + different doses of XJEK (7.5 g/kg/day and 10 g/kg/day), and MH + metoprolol (60 mg/kg/day). On the eighth day after drug treatment, electrocardiogram (ECG) and echocardiography were performed, the mice were sacrificed, and blood and heart tissues were collected for further analysis. XJEK administration markedly ameliorated cardiovascular remodeling (CR), as manifested by a decreased HW/BW ratio and CSA and less collagen deposition after MH. XJEK administration also improved MH, as evidenced by decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC) levels. XJEK also suppressed the decreased superoxide dismutase (SOD) and catalase (CAT) activities and increased malondialdehyde (MDA) levels in serum of mice with MH. XJEK-induced oxidative stress may be related to potentiating Nrf2 nuclear translocation and HO-1 expression compared with the MH groups. XJEK ameliorates MH by activating the Nrf2/HO-1 signaling pathway, suggesting that XJEK is a potential treatment for MH.

Metal-Organic Frameworks-Mediated Assembly of Gold Nanoclusters for Sensing Applications.

Gold nanoclusters (AuNCs) are an emerging type of ultrasmall nanomaterials possessing unique physicochemical characteristics. Metal-organic frameworks (MOFs), a singular kind of porous solid and crystalline material, have attracted tremendous attention in recent years. The combination of AuNCs and MOFs can integrate and improve the prominent properties of both components, such as high catalytic activities, tunable optical properties, good biocompatibility, surface functionality and stability, which make the composites of MOFs and AuNCs promising for sensing applications. This review systematically summarizes the recent progress on the sensing of various analytes via MOFs-mediated AuNCs assemblies based on strategies of luminescence sensing, colorimetric sensing, electrochemiluminescence sensing, and electrochemical and photoelectrochemical sensing. A brief outlook regarding the future development of MOFs-mediated AuNCs assemblies for sensing application is presented as well.

A risk prediction model for acute kidney injury in patients with pulmonary tuberculosis during anti-tuberculosis treatment.

BACKGROUND: Acute kidney injury (AKI) is not a rare complication during anti-tuberculosis treatment in some patients with pulmonary tuberculosis (PTB). We aimed to develop a risk prediction model for early recognition of patients with PTB at high risk for AKI during anti-TB treatment. METHODS: This retrospective cohort study assessed the clinical baseline, and laboratory test data of 315 inpatients with active PTB who were screened for predictive factors from January 2019 to June 2020. The elements were analyzed by logistic regression analysis. A nomogram was established by the results of the logistic regression analysis. The prediction model discrimination and calibration were evaluated by the concordance index (C-index), ROC curve, and Hosmer-Lemeshow analysis. RESULTS: A total of 315 patients with PTB were enrolled (67 patients with AKI and 248 patients without AKI). Seven factors, including microalbuminuria, hematuria, cystatin-C (CYS-C), albumin (ALB), creatinine-based estimated glomerular filtration rates (eGFRs), body mass index (BMI), and CA-125 were acquired to develop the predictive model. According to the logistic regression, microalbuminuria (OR = 3.038, 95%CI 1.168-7.904), hematuria (OR = 3.656, 95%CI 1.325-10.083), CYS-C (OR = 4.416, 95%CI 2.296-8.491), and CA-125 (OR = 3.93, 95%CI 1.436-10.756) were risk parameter, while ALB (OR = 0.741, 95%CI 0.650-0.844) was protective parameter. The nomogram demonstrated good prediction in estimating AKI (C-index= 0.967, AUC = 0.967, 95%CI (0.941-0.984), sensitivity = 91.04%, specificity = 93.95%, Hosmer-Lemeshow analysis SD = 0.00054, and quantile of absolute error = 0.049). CONCLUSIONS: Microalbuminuria, hematuria, ALB reduction, elevated CYS-C, and CA-125 are predictive factors for the development of AKI in patients with PTB during anti-TB treatments. The predictive nomogram based on five predictive factors is achieved good risk prediction for AKI during anti-TB treatments.

Sublethal effects of tolfenpyrad on the development, reproduction, and predatory ability of Chrysoperla sinica.

The lacewing, Chrysoperla sinica, is a predaceous insect that is important in crop pest management. Chemical pesticides have adversely impacted predaceous insect species. Here we studied the effect of tolfenpyrad on C. sinica. The acute toxicity of tolfenpyrad to the second-instar larvae was determined and indicated that tolfenpyrad is a medium-risk insecticide. Sublethal concentrations (LC10, LC20, and LC30) of tolfenpyrad had effects on the development, reproduction, and predatory ability of C. sinica. When the second-instar larvae of C. sinica were exposed to sublethal concentrations of tolfenpyrad, the activities of protective enzymes, such as superoxide dismutase, peroxidase, and catalase, and detoxification enzymes, including carboxylesterase, glutathione-S-transferase, and P450 monooxygenases, were increased with exposure time. The second-instar larvae of C. sinica exposed to sublethal concentrations of tolfenpyrad exhibited an oxidative stress response that increased the levels of malondialdehyde and reactive oxygen species (ROS). Within 48-120 h after treatment, the contents of mitochondrial respiratory chain complex I and adenosine triphosphate in the second-instar larvae were decreased. This resulted in an imbalance between the production and clearance of ROS and caused cellular damage.

Long-term exposure to copper induces mitochondria-mediated apoptosis in mouse hearts.

Copper is a trace element necessary for the normal functioning of organisms, but excessive copper contents may be toxic to the heart. The goal of this study was to investigate the role of excessive copper accumulation in mitochondrial damage and cell apoptosis inhibition. In vivo, the heart copper concentration and cardiac troponin I (c-TnI) and N-terminal forebrain natriuretic peptide (NT-pro-BNP) levels increased in the copper-laden model group compared to those of the control group. Histopathological and ultrastructural observations revealed that the myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA) and cardiomyocyte cross-sectional area (CSA) were markedly elevated in the copper-laden model group compared with the control group. Furthermore, transmission electron microscopy (TEM) showed that the mitochondrial double-layer membrane was incomplete in the copper-laden model groups. Furthermore, cytochrome C (Cyt-C) expression was downregulated in mitochondria but upregulated in the cytoplasm in response to copper accumulation. In addition, Bcl-2 expression decreased, while Bax and cleaved caspase-3 levels increased. These results indicate that copper accumulation in cardiomyocyte mitochondria induces mitochondrial injury, and Cyt-C exposure and induces apoptosis, further resulting in heart damage.

[Intervention effects of estradiol on myocardial ischemia- reperfusion injury of rat and its mechanisms].

Objective: To study the effects of estradiol (E2) on alleviating myocardial ischemia/reperfusion(I/R) injury through estrogen receptorß(ERß) mediated extracellular regulated protein kinases(ERK) pathway activation. Methods: Eighty-four adult female SD rats were ovariectomized and randomly divided into control group, NC siRNA adeno-associated virus (AAV) group received sham operation, the myocardial I/R injury model was prepared by ligation of the left anterior descending coronary artery in I/R group, E2+I/R group, NC siRNA AAV+I/R group, NC siRNA AAV+E2+I/R group and ERß-siRNA AAV+E2+I/R group. E2+I/R group, NC siRNA AAV+E2+I/R group and ERß-siRNA AAV+E2+I/R group were treated with E2 0.8 mg/kg by gavage for 60 days before modeling. NC siRNA AAV+I/R group, NC siRNA AAV+E2+I/R group, and ERß-siRNA AAV+E2+I/R group were treated with AAV by caudal vein injection 24 h before modeling. After 120 min of reperfusion, the contents of serum lactate dehydrogenase (LDH), phosphocreatine kinase (CK), phosphocreatine kinase isoenzyme (CK-MB), myocardial infarction area and the expressions of ERß, p-ERK, the contents of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1 ß), malondialdehyde (MDA) and total antioxidant capacity (T-AOC) in myocardium were measured. Results: The contents of serum LDH, CK, CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 ß, MDA in myocardium of I/R group were higher than those of the control group, the expression levels of ERß and p-ERK and the content of T-AOC were lower than those in the control group (P＜0.05). The contents of serum LDH, CK and CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 ß and MDA in myocardium of E2+I/R group were lower than those of the I/R group, the expression levels of ERß and p-ERK and the content of T-AOC were higher than those of the I/R group(P＜0.05). After knockdown ERß by caudal vein injection of ERß-siRNA AAV, the contents of serum LDH, CK and CK-MB, myocardial infarction area and the contents of TNF-α, IL-1 ß and MDA in myocardium of ERß-siRNA AAV+E2+I/R group were higher than those of NC-siRNA AAV+E2+I/R, the expression levels of ERß and p-ERK and the content of T-AOC were lower than those of NC-siRNA AAV+E2+I/R(P＜0.05). Conclusion: E2 has protective effects on myocardial I / R injury in ovariectomized rats, which are related to the promotion of ERß mediating the activation of ERK pathway, reducing inflammatory and oxidative stress responses.

Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERß and oxytocin of C57BL/6J female mice.

Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors ß immunoreactive neurons (ERß-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there's increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERß-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERß/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.

Ratiometric fluorescence detection of anthrax biomarker based on terbium (III) functionalized graphitic carbon nitride nanosheets.

Detection of anthrax biomarker dipicolinic acid (DPA) is of great importance upon the crisis of bioterrorism. Development of fluorescent materials for DPA detection, particularly one that fully depends on single luminescent response, faces the challenge of being susceptible to interferences. The accompanying accuracy problems offer great opportunities for the establishment of more reliable ratiometric analysis method. Herein, a ratiometric fluorescent probe based on terbium functionalized graphitic carbon nitride nanosheets (Tb-g-C3N4NS) is attempted for quantitative detection of DPA to address the distinct function of g-C3N4NS as both carrier and reference fluorophore, which is a so-far unexplored option in fluorescent detection approaches. We achieve the incorporation of Tb3+ into framework of g-C3N4NS by using a simple synthetic strategy comprised of thermal pyrolysis and ultrasonic exfoliation. Combining the reference signal over g-C3N4NS at 440 nm (I440) with the response signal of Tb3+ at 546 nm (I546), concentration of DPA can be easily calculated via its linear correlation with the intensity ratio (I546/I440), giving a precise measurement towards DPA with a detection limit as low as 9.9 nM. Besides enabling an excellent self-calibrating detection of DPA, this work also inspires broader use of g-C3N4NS for relevant process.