[Association of metal/metalloids exposure with abnormal liver function among occupational population in a mining area of Hunan Province:a prospective study].

OBJECTIVE: To investigate the association of metals/metalloids exposure with risk of liver disfunction among occupational population in Hunan Province, and to explore the potential dose-response relationship. METHODS: In 2017, a mining area in Hunan Province was chosen as the research site, and eligible workers were recruited as study subjects. General demographic characteristics, levels of 23 metals/metalloids in plasma and urine, and liver function index(total bilirubin(TBIL), alanine amino transferase(ALT), globulin(GLB) and γ-glutamyl transferase(GGT)) were obtained by questionnaire, physical examination and laboratory tests. Participants were followed up in 2018, 2019 and 2020 respectively. Cox proportional risk model was used to evaluate the relationship between metal/metalloids exposure and risk of liver disfunction, and dose-response relationship curves were plotted by using the restricted cubic spline function. RESULTS: A total of 891 employees were recruited in the study, 576(65.0%)were aged ≤45 years, 832(93.4%) were male and 530(59.5%) worked as smelters. After adjusting various factors such as age, gender, BMI, type of work, education, smoking, alcohol consumption, diet, stress, medical history, exercise and tea consumption, positive correlations were found between plasma tungsten(HR=4.90, 95%CI 1.17-20.48) and urinary barium(HR=1.07, 95%CI 1.02-1.12) levels with abnormally elevated TBIL levels. Additionally, a significant association was observed between plasma thallium and the risk of elevated ALT levels(HR=11.15, 95%CI 1.97-63.29). CONCLUSION: Plasma tungsten and thallium, along with barium found in urine, are risk factors for the development of abnormally elevated liver function indices in occupational groups.

Exposure to ambient air pollutants is associated with an increased incidence of hyperuricemia: A longitudinal cohort study among Chinese government employees.

BACKGROUND: It is widely recognized that ambient air pollution can induce various detrimental health outcomes. However, evidence linking ambient air pollutants and hyperuricemia incidence is scarce. OBJECTIVES: To assess the association between long-term air pollution exposure and the risk of hyperuricemia. METHODS: In this study, a total of 5854 government employees without hyperuricemia were recruited and followed up from January 2018 to June 2021 in Hunan Province, China. Hyperuricemia was defined as serum uric acid (SUA) level of >420 µmol/L for men and >360 µmol/L for women or use of SUA-lowering medication or diagnosed as hyperuricemia during follow-up. Data from local air quality monitoring stations were used to calculate individual exposure levels of PM10, PM2.5, SO2 and NO2 by inverse distance weightingn (IDW) method. Cox proportional hazard model was applied to evaluate the causal relationships between air pollutant exposures and the risk of hyperuricemia occurrence after adjustment for potential confounders and meanwhile, restricted cubic spline was used to explore the dose-response relationships. RESULTS: The results indicated that exposures to PM10 (hazard ratio, HR = 1.042, 95% conficence interal, 95% CI: 1.028, 1.057), PM2.5 (HR = 1.204, 95% CI: 1.141, 1.271) and NO2 (HR = 1.178, 95% CI: 1.125,1.233) were associated with an increased HR of hyperuricemia. In addition, a nonlinear dose-response relationship was found between PM10 exposure level and the HR of hyperuricemia (p for nonlinearity = 0.158) with a potential threshold of 50.11 µg/m3. Subgroup analysis demonstrated that participants usually waking up at night and using natural ventilation were more vulnerable to the exposures of PM10, PM2.5, NO2, and SO2. CONCLUSION: Long-term exposures to ambient PM10, PM2.5 and NO2 are associated with an increased incidence of hyperuricemia among Chinese government employees.

Emerging Signaling Regulation of Sinoatrial Node Dysfunction.

PURPOSE OF REVIEW: The sinoatrial node (SAN), the natural pacemaker of the heart, is responsible for generating electrical impulses and initiating each heartbeat. Sinoatrial node dysfunction (SND) causes various arrhythmias such as sinus arrest, SAN block, and tachycardia/bradycardia syndrome. Unraveling the underlying mechanisms of SND is of paramount importance in the pursuit of developing effective therapeutic strategies for patients with SND. This review provides a concise summary of the most recent progress in the signaling regulation of SND. RECENT FINDINGS: Recent studies indicate that SND can be caused by abnormal intercellular and intracellular signaling, various forms of heart failure (HF), and diabetes. These discoveries provide novel insights into the underlying mechanisms SND, advancing our understanding of its pathogenesis. SND can cause severe cardiac arrhythmias associated with syncope and an increased risk of sudden death. In addition to ion channels, the SAN is susceptible to the influence of various signalings including Hippo, AMP-activated protein kinase (AMPK), mechanical force, and natriuretic peptide receptors. New cellular and molecular mechanisms related to SND are also deciphered in systemic diseases such as HF and diabetes. Progress in these studies contributes to the development of potential therapeutics for SND.

[Associations of plasma metals/metalloids with arrhythmia among occupational population: a prospective study].

OBJECTIVE: To investigate the association between levels of twenty-three plasma metals/metalloids and the risk of arrhythmia among occupational population. METHODS: In 2017, a total of 765 workers aged 18 and above were recruited from a non-ferrous metal factory. The general demographic characteristics were obtained by using questionnaire. Plasma metal/metalloid levels were determined by inductively coupled plasma mass spectrometry(ICP-MS). Participants were followed up in 2018, 2019 and 2020 respectively. After the elements that may affect the incidence of arrhythmia were screened out by least absolute shrinkage and selection operator(LASSO) regression, Cox regression model was used to analyze the relationship between levels of selected elements and risk of arrhythmia occurrence, Quantile g-computation model was used to analyze the effect of element mixture exposure on arrhythmia, and the dose-response curve was estimated by using restricted cubic spline(RCS) function. RESULTS: Of all the research subjects, 386(50.5%) were ≤45 years old; 401(52.4%) had 20 years or more of work experience; 712(93.1%) subjects were male workers. The incidence of arrhythmia was 17.6%. After adjusting for age, seniority, gender, body mass index(BMI), marital status, education level, smoking, drinking, drinking tea, regular exercise, chronic diseases(hypertension, hyperlipidemia), sleep quality and psychological stress, chromium, molybdenum and antimony increased the risk of arrhythmia with HR(95%CI) values of 1.22(1.11-1.34), 1.51(1.20-1.90) and 2.38(1.03-5.49), respectively, while barium reduced the risk of arrhythmia with HR(95%CI) value of 0.98(0.95-1.00). CONCLUSION: Chromium, molybdenum and antimony are the risk factors while barium is the protective factor for arrhythmia.

Malus asiatica as a natural host of apple scar skin viroid in China.

Malus asiatica (Rosaceae, Malus) is a small deciduous tree, which has been cultivated in China more than 450 years (Jin, 2019). M. asiatica is deeply favored by consumers because of its sweet taste and high nutritional attributes, rich in vitamins, minerals and dietary fiber (Xue et al, 2013). Although the M. asiatica annual output is nearly 30 000 kg, it still cannot meet the market demand in China (Jin, 2019). In August 2021, the virus-like symptom such as colored spots on fruit epidermis of M. asiatica were observed in an orchard of Langfang (38°42'16.88″N, 116°39'15.23″E) of Hebei province, China. To investigate whether this symptom is related to virus infection, the symptomatic sample was subjected to small RNA sequencing. Total RNA was extracted from branch bark of a symptomatic tree using an RNAprep Pure Plant Kit (TianGen, China), The extracted RNA was used to construct a small RNA library using NEBNext® Multiplex Small RNA Library Prep Set for Illumina® (Set 1), (NEB, USA), then the resulting library was sequenced using Illumina novoseq 6000 (Illumina, USA) at Tianjin Novogene company (China). A total of 14,685,616 sequence reads were obtained. After filtering the low-quality reads, polyA, adaptor contaminants, fragments < 18 nt and > 26 nt, and reads matching apple genome, the number of reads reduced to 392,883. Finally, assembly of these clean reads generated 225 non-redundant contigs with Velvet software and 55 assembled contigs were aligned to Refseq viral database of NCBI by Bowtie software. One viral contig with length of 329 nt showed 98.48% significant similarity to genome sequences of Hohhot isolate of ASSVd (ASSVd-Hohhot) (GenBank Accession No. MZ476527.1) (Yuan et al, 2022). We then used a specific primer pair (ASSVd-F: 5'-G G T A A A C A C C G T G C G G T T C C-3'; ASSVd-R: 5'-G G G A A A C A C C A A T T G T G T T T T A-3') for reverse transcription (RT)-PCR to amplify the genome sequence of ASSVd. A 330 bp amplified product was cloned into the pGEM-T easy vector (Promega, USA), then sequenced by Sanger sequencing using T7 primer by Sangon Biotech (Shanghai) Co., Ltd. in China. The sequence of ASSVd has been deposited in the GenBank datebase (GenBank Accession No. ON093255). Blast analysis showed that the sequence had highest identity (326/330, 98.79%) with ASSVd-Hohhot (GenBank Accession No. MZ476527.1) (Yuan et al, 2022). To confirm the pathogenicity of ASSVd, fifteen healthy cucumber seedlings were inoculated mechanically with the extracts of ASSVd-infected branch bark of M. asiatica. There were no obvious symptoms were observed at 14 days post inoculation (dpi), however, the result of RT-PCR and Sanger sequencing showed four cucumber samples were positive for ASSVd. In addition, another 19 randomly collected M. asiatica samples with or without clear symptoms from Langfang were detected by RT-PCR, and ten (52.6%) of them were confirmed the presence of ASSVd. And all ten positive samples were symptomatic, while nine nonsymptomatic M. asiatica samples tested negative. The positive amplicons were cloned into the pGEM-T easy vector and sequenced using T7 primer by Sanger sequencing. All of the sequences were essentially identical to one another (GenBank Accession No. ON093255), which indicates that the positive samples are indeed ASSVd infected. To the best of our knowledge, this is the first report of ASSVd infection in M. asiatica, which expands our understanding of the host range of ASSVd.

Ticagrelor alleviates sepsis-induced myocardial injury via an adenosine-dependent pathway in a mouse sepsis model.

PURPOSE: The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury. METHODS: The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue. RESULTS: The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR. CONCLUSION: The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.

Role of spleen-derived CD11b+Gr-1+ cells in sepsis-induced acute kidney injury.

PURPOSE: CD11b+Gr-1+ cells play a key role in inflammation and the purpose of this study was to determine whether splenic CD11b+Gr-1+ cells are mobilized to the kidney and lead to acute kidney injury during sepsis. METHODS: The sepsis model was generated via cecum ligation and puncture (CLP). The mice were randomly distributed into control, sham operated, CLP and CLP+splenectomy (CLPS) groups (n=5-10/group). The percentage of CD11b+Gr-1+ cells in circulating, bone marrow and spleen were determined. Plasma concentrations of interleukin-6, interleukin-1ß, creatinine (Cr) and neutrophil gelatinase-associated lipocalin were measured. CD11b+Gr-1+ cells were detected by immunofluorescence and qRT-PCR. Hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) were performed. Expression of mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1α (HIF-1α) and cleaved caspase-3 was measured. RESULTS: The percentage of CD11b+Gr-1+ cells in blood was significantly higher in the CLP group and lower in CLPS group. CD11b+Gr-1+ cells in the spleen were significantly lower in the CLP group. In the CLP group, the plasma concentrations of interleukin-6, interleukin-1ß, Cr and neutrophil gelatinaseassociated lipocalin were higher. The expression of Gr-1 and CD11b were higher in CLP. The CD11b+Gr-1+ cells were detected in the kidneys of the CLP group. HE, PAS and TUNEL showed inflammatory cell infiltration and cell apoptosis in CLP. Western blot indicated dephosphorylation of mTOR, down-expression of HIF-1α and increased expression of cleaved caspase-3 in sepsis kidney. CONCLUSION: Splenic CD11b+Gr-1+ cells migrated to the kidney in sepsis, which led to acute kidney injury via the inhibition of mTOR/HIF-1α.

Bradykinin protects cardiac c-kit positive cells from high-glucose-induced senescence through B2 receptor signaling pathway.

Cardiac c-kit positive cells are cardiac-derived cells that exist within the heart and have a great many protective effects. The senescence of cardiac c-kit positive cells probably leads to cell dysfunction. Bradykinin plays a key role in cell protection. However, whether bradykinin prevents cardiac c-kit positive cells from high-glucose-induced senescence is unknown. Here, we found that glucose treatment causes the premature senescence of cardiac c-kit positive cells. Bradykinin B2 receptor (B2R) expression was declined by glucose-induced senescence. Bradykinin treatment inhibited senescence and reduced intracellular oxygen radicals according to senescence-associated ß-galactosidase staining and 2',7'-dichlorodihydrofluorescein diacetate staining. Moreover, the mitochondrial membrane potential was damaged, as measured by JC-1 staining. The mitochondrial membrane potential was preserved under bradykinin treatment. The concentration of superoxide was decreased, and the concentration of intracellular adenosine triphosphate was increased after bradykinin treatment. Western blot showed that bradykinin leads to AKT and mammalian target of rapamycin (mTOR) phosphorylation and decreased levels of P53 and P16 when compared with glucose treatment alone. Antagonists of B2R, phosphoinositide 3-kinase (PI3K), mTOR, and B2R small interfering RNA prevented the protective effect of bradykinin. P53 antagonist also inhibited the glucose-induced senescence of cardiac c-kit positive cells. In conclusion, bradykinin prevents the glucose-induced premature senescence of cardiac c-kit positive cells through the B2R/PI3K/AKT/mTOR/P53 signal pathways.

Urinary vimentin mRNA as a potential novel biomarker of renal fibrosis.

Renal fibrosis is a histological outcome of chronic kidney disease (CKD) progression. However, the noninvasive detection of renal fibrosis remains a challenge. Here we constructed a renal fibrosis target mRNA array and used it to detect urinary mRNAs of CKD patients for investigating potential noninvasive biomarkers of renal fibrosis. We collected urine samples from 39 biopsy-proven CKD patients and 11 healthy controls in the training set. Urinary mRNA profiles of 86 genes showed a total of 21 mRNAs that were differentially expressed between CKD patients and controls (P < 0.05), and vimentin (VIM) mRNA demonstrated the highest change fold of 9.99 in CKD vs. controls with robust correlations with decline of renal function and severity of tubulointerstitial fibrosis. Additionally, VIM mRNA further differentiated patients with moderate-to-severe fibrosis from none-to-mild fibrosis group with an area of the curve of 0.796 (P = 0.008). A verification of VIM mRNA in the urine of an additional 96 patients and 20 controls showed that VIM is not only well correlated with renal function parameters but also correlated with proteinuria and renal fibrosis scores. Multiple logistic regression and receiver-operating characteristics analysis further showed that urine VIM mRNA is the best predictive parameter of renal fibrosis compared with estimated glomerular filtration rate, serum creatinine, and blood urea nitrogen. In addition, there is no improved predictive performance for the composite biomarkers to predict renal fibrosis severity compared with a single gene of VIM. Overall, urinary VIM mRNA might serve as a novel independent noninvasive biomarker to monitor the progression of kidney fibrosis.

The miR-17-92 cluster in cardiac health and disease.

MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post-transcriptional regulation. The miR-17-92 cluster includes six individual members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. The miR-17-92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR-17-92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR-17-92 during cardiac development, regeneration, and aging. Additionally, we highlight the indispensable roles of the miR-17-92 cluster in pathogenesis and therapeutic potential in cardiac birth defects and adult cardiac diseases.

Ticagrelor regulates the differentiation of MDSCs after acute myocardial infarction to reduce cardiac injury.

Myeloid-derived suppressor cells (MDSCs) are important participants after acute myocardial infarction (AMI), but the role of their different subtypes in AMI remains controversial. The anti-inflammatory effect of ticagrelor in AMI has been discovered. However, the detailed anti-inflammatory mechanism has not been fully demonstrated. In this study, we aimed to determine whether ticagrelor can regulate the differentiation of MDSCs into anti-inflammatory subgroups to exert anti-inflammatory effects after AMI. In vitro experiments revealed no difference in the mRNA and protein expression of P2Y12 receptors on MDSCs and macrophages. Ticagrelor promotes the differentiation of in vitro cultured MDSCs to monocytic-MDSCs (M-MDSCs). A mouse AMI model was established to investigate the anti-inflammatory effects of ticagrelor in vivo after AMI by interfering with the differentiation of MDSCs. On the first day after AMI, spleen-derived polymorphonuclear-MDSCs (PMN-MDSCs) were predominant in the circulation and infarcted heart. Ticagrelor increased the percentage of M-MDSCs in the circulation and infarcted heart of AMI mice in a dose-dependent manner, attenuated cardiac inflammation and increased cardiac contractile function. M-MDSC injection significantly decreased cardiac inflammation levels and improved cardiac function in splenectomized AMI mice compared with PMN-MDSC injection. These data point to a novel anti-inflammatory role for ticagrelor after AMI by interfering with the differentiation of MDSCs.

Molecular-level insights into the temperature-dependent formation dynamics and mechanism of water-soluble dissolved organic carbon derived from biomass pyrolysis smoke.

Water soluble organic carbon (WSOC) derived from biomass pyrolytic smoke is deposited through atmospheric aerosols, negatively affecting aquatic ecological quality and safety. However, the temperature-dependent molecular diversity and dynamic formation of smoke-derived WSOC remain poorly understood in water. Herein, we explored the molecular-level formation mechanism of pyrolytic smoke-derived WSOC in water to explain the evolution, heterogeneous correlations, and sequential responses of molecules and functional groups to increasing pyrolysis temperature. Two-dimensional correlation spectroscopy was used to innovatively establish the characteristic correlations between spectroscopy and Fourier transform-ion cyclotron resonance mass spectrometry. Temperature-dependent formation of WSOC exhibited diversity in absorbance/fluorescent components, unique/common molecules, and their chemical parameters, showing the simultaneous formation and degradation reactions. The common WSOC molecules with lower and higher degrees of oxidation showed significant positive and negative correlations with the fluorescent components, respectively. The primary sequential response of WSOC molecules to increasing pyrolysis temperature (lignin-like molecules â†’ unsaturated hydrocarbons, condensed aromatic molecules â†’ lipid-like/aliphatic-/peptide-like molecules) corresponded to the temperature response of functional groups (carboxylic/alcoholic â†’ polysaccharides â†’ aromatics/amides/phenolic/aliphatic groups), demonstrating well synergistic relationships between them. These novel findings will contribute to the comprehensive understanding and assessments of potential environmental behavior or risks of WSOC in aquatic ecosystems.

Tropical cyclone FANTALA's three turnbacks in the northeast of Madagascar Island.

The unique Tropical cyclone (TC) Fantala appeared in the central Indian Ocean (12.4°S, 73.5°E) at 00Z on April 11 in 2016 and moved northwestward along the northeast of Madagascar at 18 Z on April 15. Then, two incomprehensible turnbacks formed a unique TC track. The dynamic mechanisms of the three turnbacks were first studied based on remote sensing and multisource reanalysis data. The results reveal that the wind field with upper divergence and lower convergence promotes the development of Fantala. The anticyclone high pressure on the middle level atmosphere is an important factor for TC turnbacks. On 15 April, the TC made the first turnback to turn northwest due to the southward anticyclone weakened to moving northwest. On 18 April, the TC made the second turnback along the anticyclone edge due to the northern high-pressure and southern low-pressure trough. On 22 April, the TC made the third turnback because the anticyclonic high press center broke into two small independent anticyclonic centers in the southwest and northeast, which created a barrier band and pushed the northern TC to move to the northwest. Meanwhile, the vertical wind shear (VWS) also provides favorable conditions for TC turnbacks. On April 18, the middle atmosphere of the TC was affected by strong easterly shear and weak southerly shear, and the second turnback was completed. On April 22, the middle level environment was affected by strong westerly shear and weak north shear, and the third turnback was completed. Additionally, heat transport from the ocean to the atmosphere provides favorable conditions for TC development. On April 18, The maximum mean latent heat flux over northeastern Madagascar was 112.94 W/m2, Tropical Cyclone Heat Potential was 39.05 kJ/cm2, and the maximum wind speed at the center of the TC was 155 kts. On April 22, The heat transfer from the equator increased by 18.08 W/m2 compared with the latent heat on 21 April, the Tropical Cyclone Heat Potential was 33.30 kJ/cm2, the maximum wind speed in the TC center was 90 kts, the high PV centerspread down from 850 mb to 900 mb. This study deepens the understanding of track forecasting during the development of a TC.

Construction and analysis of protein-protein interaction network for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract. Clinical findings reveal that the five-year survival rate for mid-to late-stage ESCC patients is merely around 20 %, whereas those diagnosed at an early stage can achieve up to a 95 % survival rate. Consequently, early detection is paramount to improving ESCC patient survival. Protein markers are essential for diagnosing diseases, and the identification of new candidate proteins associated with ESCC through the protein-protein interaction (PPI) network is aimed for in this paper. The PPI network related to ESCC was constructed using protein data, comprising 2094 nodes and 19,660 edges. To assess the nodes' importance in the network, three metrics-degree centrality, betweenness centrality, and closeness centrality-were employed, leading to the identification of 81 key proteins. Subsequently, the biological significance of these proteins in the network was explored, combining biomedical knowledge from three perspectives: network, node, and cluster. The results demonstrated that 52 out of 81 key proteins were confirmed to be linked to ESCC. Among the remaining 29 unreported proteins, 18 displayed significant biological significance, indicating their potential as protein markers related to ESCC.

Based on Cardiopulmonary Exercise Testing to Construct and Validate Nomogram of Long-Term Prognosis Within 12 Months for NSCLC.

OBJECTIVE: Construction nomogram was to effectively predict long-term prognosis in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The nomogram is developed by a retrospective study of 347 patients with NSCLC who underwent cardiopulmonary exercise testing (CPET) before surgery from May 2019 to February 2022. Cross-validation divided the data into a training cohort and validation cohort. The discrimination and accuracy ability of the nomogram were proofed by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, the area under the curve (AUC), and time-dependent ROC in validation cohort. RESULTS: Age, intraoperative blood loss, VO2 peak, and VE/VCO2 slope were included in the model of nomogram. The model demonstrated good discrimination and accuracy with C-index of 0.770 (95% CI: 0.712-0.822). AUC of 6 (AUC: 0.789, 95% CI: 0.726-0.851) and 12 months (AUC: 0.787, 95% CI: 0.724-0.850) were shown in ROC. Time-independent ROC maintains a good effect within 12 months. CONCLUSION: We developed a nomogram based on CPET. This model has a good ability of discrimination and accuracy. It could help clinicians to make treatment decision in clinical decision.

Exposure risks of lead and other metals to humans: A consideration of specific size fraction and methodology.

Particle size is a critical influencing factor in assessing human exposure risk as fine particles are generally more hazardous than larger coarse particles. However, how particle composition influences human health risk is only poorly understood as different studies have different utilised different definitions and as a consequence there is no consensus. Here, with a new methodology taking insights of each size fraction load (%GSFload), metal bioaccessibility, we classify which specific particle size can reliably estimate the human exposure risk of lead and other metals. We then validate these by correlating the metals in each size fraction with those in human blood, hair, crop grain and different anthropogenic sources. Although increasing health risks are linked to metal concentration these increase as particle size decrease, the adjusted-risk for each size fraction differs when %GSFload is introduced to the risk assessment program. When using a single size fraction (250-50 µm, 50-5 µm, 5-1 µm, and < 1 µm) for comparison, the risk may be either over- or under-estimated. However, by considering bulk and adjusting the risk, it would be possible to obtain results that are closer to the real scenarios, which have been validated through human responses and evidence from crops. Fine particle size fractions (< 5 µm) bearing the mineral crystalline or aggregates (CaCO3, Fe3O4, Fe2O3, CaHPO4, Pb5(PO4)3Cl) alter the accumulation, chemical speciation, and fate of metals in soil/dust/sediment from the different sources. Loaded lead in the size fraction of < 50 µm has a significantly higher positive association with the risk-receptor biomarkers (BLLs, Hair Pb, Corn Pb, and Crop Pb) than other size fractions (bulk and 50-250 µm). Thus, we conclude that the < 50 µm fraction would be likely to be recommended as a reliable fraction to include in a risk assessment program. This methodology acts as a valuable instrument for future research undertakings, highlighting the importance of choosing suitable size fractions and attaining improved accuracy in risk assessment results that can be effectively compared.

Molecular-level insights into the brewing-dependent chemical diversity, properties, and formation mechanism of Moutai Base baijiu using Fourier transform ion cyclotron resonance mass spectrometry.

The brewing-dependent molecular diversity, properties, and formation mechanism of Moutai (a typical sauce-flavor Baijiu) base Baijiu, were explored using FT-ICR MS combined with various visualization methods. Seven-round Moutai base Baijiu exhibited significant diversity and heterogeneity, containing more unsaturated/saturated reduced molecules. The increased brewing round increased the molecular unsaturation/aromaticity and enhanced the transformation between saturated/oxidized and unsaturated/reduced molecules. Moreover, lignin-/aliphatic-/peptide-/lipid-like molecules dominated the molecular characteristics of Moutai base Baijiu. The basic and acidic components contained more reduced carbohydrate-/lipid-like molecules and oxidized tannin-like/condensed aromatic molecules, respectively, contributing to the molecular stability and diversity, respectively. More unique lipid-like and lignin-like molecules newly formed in the early and late brewing rounds, respectively, and the increased brewing shifted the chemical reaction from a single dominant to a multi-dimensional balance. More unique N-containing molecules (>450 Da) significantly contributed the specific brewing characteristics. These new findings help to understand the molecular-level formation mechanism of Moutai base Baijiu.

Zexie-Baizhu Decoction ameliorates non-alcoholic fatty liver disease through gut-adipose tissue crosstalk.

ETHNOPHARMACOLOGICAL RELEVANCE: Zexie-Baizhu Decoction (AA), a Chinese Classical Formula composed of Alisma orientalis (Sam.) Juzep. and Aractylodes Macrocephala Koidz in the specific ratio of 5:2, has a long history of use in treating metabolic disorders. Recent studies have demonstrated AA's ameliorative effects on non-alcoholic fatty liver disease (NAFLD); however, the mechanism underlying its action on the gut and adipose tissue, key regulators of metabolism, have not been fully explored. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which AA regulates the homeostasis of gut and adipose tissue in NAFLD. MATERIALS AND METHODS: AA (1500 mg/kg/day) or vehicle was administrated to the high-fat diet-induced and normal chow-fed mice (C57BL/6J). Plasma, the liver, gut microbiota, bile acids, and short-chain fatty acids in the gut, were systematically investigated. RNA sequencing analysis, reverse transcription quantitative real-time PCR, and Western Blotting were performed on the epididymal white adipose tissues (eWAT) to explore AA's influence on NAFLD. Lipidomics of the liver and eWAT were analyzed by liquid chromatography-mass spectrometry and desorption electrospray ionization mass spectrometry imaging. RESULTS: Our study demonstrated that AA administration effectively alleviated liver injury induced by NAFLD, as evidenced by reduced hepatic fat accumulation and inflammation. Mechanistically, AA modulated the composition of the gut microbiota, promoting the growth of beneficial bacteria such as Akkermansia muciniphila and restoring the balance between Firmicutes and Bacteroidetes. Furthermore, AA regulated the levels of bile acids and short-chain fatty acids in the intestine, plasma, and liver. Correspondingly in the eWAT, AA administration activated bile acid receptor (Gpbar1) and short-chain fatty acid receptor (Ffar2), facilitating lipid breakdown and attenuating triglyceride accumulation. Transcriptome analysis revealed that AA influenced gene expression related to fatty acid metabolism, thermogenesis, insulin resistance, AMPK signaling, and the tricarboxylic acid (TCA) cycle, thereby improving NAFLD at the transcriptional level. Additionally, AA treatment significantly altered the lipid composition in the liver, reducing levels of diacylglycerols, triacylglycerols, phosphatidylserines, and cholesterol esters, while increasing levels of phosphatidic acids, phosphatidylethanolamines, and sphingomyelins. CONCLUSION: Our study builds a connection between the gut and adipose tissue to understand the mechanism of AA on alleviating NAFLD, providing new insights into the development of targeted therapies for this condition.

MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis.

Micro (mi)RNAs are frequently dysregulated in the development of renal fibrosis. Exosomes are small membrane vesicles that could be isolated from urine secreted from all nephron segments. Here we sought to observe for the first time whether miRNA in urine exosome could serve as a potential biomarker of renal fibrosis. Urine samples were collected from 32 chronic kidney disease (CKD) patients who underwent kidney biopsy and 7 controls. Exosome was isolated and confirmed by immunogold staining of exosome marker. Members of miR-29, miR-200, and RNU6B as endogenous control were detected by RT quantitative PCR. Electronic microscopy verified a typical shape of exosome with average size of 65.1 nm and labeled it with anti-CD9 and anti-aquaporin 2 antibody. Members of miR-29 and miR-200 are readily measured with reduced levels compared with controls (P < 0.05) and can robustly distinguish CKD from controls [area under the curve (AUC) varied from 0.902 to 1 by receiver operating characteristics analysis]. miR-29c correlated with both estimated glomerular filtration rate (r = 0.362; P < 0.05) and degree of tubulointerstitial fibrosis (r = -0.359; P < 0.05) for CKD patients. Moreover, miRNA in exosome was decreased in mild fibrosis group compared with moderated to severe group. miR-29a and miR-29c could predict degree of tubulointerstitial fibrosis with AUC of 0.883 and 0.738 (P < 0.05). The sensitivity and specificity for distinguishing mild from moderate to severe fibrosis were 93.8 and 81.3% with the use of miR-29a and 68.8 and 81.3% for miR-29c. Overall, miR-29c in urinary exosome correlates with both renal function and degree of histological fibrosis, suggesting it as a novel, noninvasive marker for renal fibrosis.

Achieving carbon neutrality: the effect of China pilot Free Trade Zone policy on green technology innovation.

Evaluating the effect of China pilot Free Trade Zone (FTZ) policy on green technology innovation is important for achieving China's carbon neutrality targets. Based on the panel data of 30 provincial administrative regions in China from 2009 to 2019, this study investigates the effect of the pilot FTZ policy on green technology innovation by using the difference-in-differences method. The study's findings indicate the following: (1) The pilot FTZ policy promotes the development of green technology innovation, and there is a policy lag in a few pilot regions. (2) The mediation effect analysis shows that the pilot FTZ policy promotes the development of green technology innovation by improving the marketization process and enhancing innovative talent gathering. (3) The heterogeneity analysis shows that the pilot FTZ policy is more effective in promoting green technology innovation when implemented in regions with developed economies or higher levels of human capital. Moreover, the pilot FTZ policy mainly has a significant promoting effect on green utility model patents. Based on these results, policy recommendations are proposed to promote the development of green technology innovation and the achievement of China's carbon neutrality targets.