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Gliomas represent the most common and lethal category of primary brain tumors. Bisphenol A (BPA), a widely recognized endocrine disruptor, has been implicated in the progression of cancer. Despite its established links to various cancers, the association between BPA and glioma progression remains to be clearly defined. This study aimed to shed light on the impact of BPA on glioma cell proliferation and overall tumor progression. Our results demonstrate that BPA significantly accelerates glioma cell proliferation in a time- and dose-dependent manner. Furthermore, BPA has been found to enhance the invasive and migratory capabilities of glioma cells, potentially promoting epithelial–mesenchymal transition (EMT) characteristics within these tumors. Employing bioinformatics approaches, we devised a risk assessment model to gauge the potential glioma hazards associated with BPA exposure. Our comprehensive analysis revealed that BPA not only facilitates glioma invasion and migration but also inhibits apoptotic processes. In summary, our study offers valuable insights into the mechanisms by which BPA may promote tumorigenesis in gliomas, contributing to the understanding of its broader implications in oncology. [ABSTRACT FROM AUTHOR]

Climate projection requires an accurate understanding for soil organic carbon (SOC) decomposition and its response to warming. An emergent view considers that environmental constraints rather than chemical structure alone control SOC turnover and its temperature sensitivity (i.e., Q10), but direct long‐term evidence is lacking. Here, using compound‐specific radiocarbon analysis of soil profiles along a 3300‐km grassland transect, we provide direct evidence for the rapid turnover of lignin‐derived phenols compared with slower‐cycling molecular components of SOC (i.e., long‐chain lipids and black carbon). Furthermore, in contrast to the slow‐cycling components whose turnover is strongly modulated by mineral association and exhibits low Q10, lignin turnover is mainly regulated by temperature and has a high Q10. Such contrasts resemble those between fast‐cycling (i.e., light) and mineral‐associated slow‐cycling fractions from globally distributed soils. Collectively, our results suggest that warming may greatly accelerate the decomposition of lignin, especially in soils with relatively weak mineral associations. [ABSTRACT FROM AUTHOR]

Motivation: Spatially resolved gene expression profiles are the key to exploring the cell type spatial distributions and understanding the architecture of tissues. Many spatially resolved transcriptomics (SRT) techniques do not provide single-cell resolutions, but they measure gene expression profiles on captured locations (spots) instead, which are mixtures of potentially heterogeneous cell types. Currently, several cell-type deconvolution methods have been proposed to deconvolute SRT data. Due to the different model strategies of these methods, their deconvolution results also vary. Results: Leveraging the strengths of multiple deconvolution methods, we introduce a new weighted ensemble learning deconvolution method, EnDecon, to predict cell-type compositions on SRT data in this work. EnDecon integrates multiple base deconvolution results using a weighted optimization model to generate a more accurate result. Simulation studies demonstrate that EnDecon outperforms the competing methods and the learned weights assigned to base deconvolution methods have high positive correlations with the performances of these base methods. Applied to real datasets from different spatial techniques, EnDecon identifies multiple cell types on spots, localizes these cell types to specific spatial regions and distinguishes distinct spatial colocalization and enrichment patterns, providing valuable insights into spatial heterogeneity and regionalization of tissues. [ABSTRACT FROM AUTHOR]

Heparanase is elevated in various pathological conditions, primarily cancer and inflammation. To investigate the significance and involvement of heparanase in liver fibrosis, we compared the susceptibility of wild-type (WT) and heparanase-overexpressing transgenic (Hpa-tg) mice to carbon tetrachloride (CCL4)-induced fibrosis. In comparison with WT mice, Hpa-tg mice displayed a severe degree of tissue damage and fibrosis, including higher necrotic tendency and intensified expression of smooth muscle actin. While damage to the WT liver started to recover after the acute phase, damage to the Hpa-tg liver was persistent. Recovery was attributed, in part, to heparanase-stimulated autophagic activity in response to CCL4, leading to increased apoptosis and necrosis. The total number of stellate cells was significantly higher in the Hpa-tg than the WT liver, likely contributing to the increased amounts of lipid droplets and smooth muscle actin. Our results support the notion that heparanase enhances inflammatory responses, and hence may serve as a target for the treatment of liver damage and fibrosis. [ABSTRACT FROM AUTHOR]

Heparin is a polysaccharide expressed in animal connective tissue-type mast cells. Owing to the special pentasaccharide sequence, heparin specifically binds to antithrombin (AT) and increases the inhibitory activity of AT towards coagulation enzymes. Heparin isolated from porcine intestinal mucosa has an average molecular weight of 15 kDa, while heparins recovered from rat skin and the peritoneal cavity were 60–100 kDa and can be fragmented by the endo-glucuronidase heparanase in vitro. In this study, we have examined heparin isolated from in vitro matured fetal skin mast cells (FSMC) and peritoneal cavity mast cells (PCMC) collected from wildtype (WT), heparanase knockout (Hpa-KO), and heparanase overexpressing (Hpa-tg) mice. The metabolically 35S-labeled heparin products from the mast cells of WT, Hpa-KO, and Hpa-tg mice were compared and analyzed for molecular size and AT-binding activity. The results show that PCMC produced heparins with a size similar to heparin from porcine intestinal mast cells, whilst FSMC produced much longer chains. As expected, heparanase overexpression resulted in the generation of smaller fragments in both cell types, while heparins recovered from heparanase knockout cells were slightly longer than heparin from WT cells. Unexpectedly, we found that heparanase expression affected the production of total glycosaminoglycans (GAGs) and the proportion between heparin and other GAGs but essentially had no effect on heparin catabolism. [ABSTRACT FROM AUTHOR]

Motivation Differential network analysis is an important tool to investigate the rewiring of gene interactions under different conditions. Several computational methods have been developed to estimate differential networks from gene expression data, but most of them do not consider that gene network rewiring may be driven by the differential expression of individual genes. New differential network analysis methods that simultaneously take account of the changes in gene interactions and changes in expression levels are needed. Results : In this article, we propose a differential network analysis method that considers the differential expression of individual genes when identifying differential edges. First, two hypothesis test statistics are used to quantify changes in partial correlations between gene pairs and changes in expression levels for individual genes. Then, an optimization framework is proposed to combine the two test statistics so that the resulting differential network has a hierarchical property, where a differential edge can be considered only if at least one of the two involved genes is differentially expressed. Simulation results indicate that our method outperforms current state-of-the-art methods. We apply our method to identify the differential networks between the luminal A and basal-like subtypes of breast cancer and those between acute myeloid leukemia and normal samples. Hub nodes in the differential networks estimated by our method, including both differentially and nondifferentially expressed genes, have important biological functions. Availability and implementation All the datasets underlying this article are publicly available. Processed data and source code can be accessed through the Github repository at https://github.com/Zhangxf-ccnu/chNet. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Microbial carbon use efficiency (CUE), a key parameter to characterize microbial carbon conversion efficiency, is assumed to be similar in soil models for different soil functional pools with varied organic matter composition and nutrient availability, that is, particulate organic matter (POM) and mineral‐associated organic matter (MAOM). However, empirical studies comparing microbial CUE in POM versus MAOM are largely lacking. It is not known whether microbial CUE variance may underpin the variant behaviour (i.e. turnover and composition) of different soil functional pools.Here we collected surface soils from 25 natural forests and grasslands with divergent edaphic properties, and compared microbial CUE in their POM versus MAOM using soil fractionation in combination with incubation using 18O‐labelled water. We also quantified edaphic properties, organic matter composition, microbial community structures and the stoichiometric imbalance of nitrogen (N) and phosphorus (P) relative to carbon based on the dissolved pool relative to microbial biomass (ImN and ImP) to investigate variables regulating microbial CUE and its variation in POM relative to MAOM (CUEPOM/CUEMAOM).In contrast to our expectation, microbial CUE did not consistently differ between POM and MAOM across sites, albeit with large inter‐sample variations in CUEPOM/CUEMAOM (from 0.3 to 4.4). Although MAOM had higher substrate quality, indicated by lower ratios of soil organic carbon to total nitrogen (C/NOM) and higher N‐compounds/aromatic ratios, and higher proportions of r‐strategists and fast‐growing bacteria in the microbial community than POM, POM and MAOM had similar degrees of N limitation (i.e. ImN), which was the best predictor of microbial CUE across all samples. Therefore, although MAOM harboured more N‐containing compounds than POM, N limitation was not necessarily lower, leading to an overall similar microbial CUE in POM and MAOM. Nevertheless, CUEPOM/CUEMAOM decreased with increasing P limitation in POM relative to MAOM.Overall, our paper presents a comprehensive, empirical study comparing microbial CUE in POM and MAOM of diverse soils, and our results support the use of similar microbial CUE for POM and MAOM in soil models, but also highlight potential contrasts in microbial CUE between soil pools under strong P limitation. Such inferences deserve attention under potentially increasing P limitation induced by N deposition. This study advances our mechanistic understanding of ecological patterns and processes from the organismic to the ecosystem scale based on soil microbial physiology and different soil functional pools. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

X-chromosome short tandem repeat (X-STR) markers are a powerful complementary system used for paternity and forensic casework. This study presents the development and validation of a new highly efficient multiplex-fluorescent-labeled 19 X-STR typing system, including DXS10079, DXS101, DXS10135, DXS10162, DXS6795, DXS6800, DXS6803, DXS6807, DXS6809, DXS6810, DXS7133, DXS7423, DXS981, DXS9902, DXS9907, GATA165B12, GATA172D05, GATA31E08 and HPRTB along with sex-typing locus, amelogenin. The system was validated according to guidelines issued by the Scientific Working Group on DNA Analysis Methods. Allele frequency and forensic parameters were investigated from 1085 (494 males and 591 females) unrelated Beijing Han individuals, the combined power of discrimination by the 19 X-STR loci in females and males, as well as the combined mean exclusion chance in trios and duos, were 0.999999999999999995, 0.99999999995, 0.9999999995, and 0.9999996, respectively. The results demonstrate that this multiplex system is robust and reliable, and considered to be a powerful tool for forensic application. [ABSTRACT FROM AUTHOR]

Motivation Reconstruction of cancer gene networks from gene expression data is important for understanding the mechanisms underlying human cancer. Due to heterogeneity, the tumor tissue samples for a single cancer type can be divided into multiple distinct subtypes (inter-tumor heterogeneity) and are composed of non-cancerous and cancerous cells (intra-tumor heterogeneity). If tumor heterogeneity is ignored when inferring gene networks, the edges specific to individual cancer subtypes and cell types cannot be characterized. However, most existing network reconstruction methods do not simultaneously take inter-tumor and intra-tumor heterogeneity into account. Results In this article, we propose a new Gaussian graphical model-based method for jointly estimating multiple cancer gene networks by simultaneously capturing inter-tumor and intra-tumor heterogeneity. Given gene expression data of heterogeneous samples for different cancer subtypes, a non-cancerous network shared across different cancer subtypes and multiple subtype-specific cancerous networks are estimated jointly. Tumor heterogeneity can be revealed by the difference in the estimated networks. The performance of our method is first evaluated using simulated data, and the results indicate that our method outperforms other state-of-the-art methods. We also apply our method to The Cancer Genome Atlas breast cancer data to reconstruct non-cancerous and subtype-specific cancerous gene networks. Hub nodes in the networks estimated by our method perform important biological functions associated with breast cancer development and subtype classification. Availability and implementation The source code is available at https://github.com/Zhangxf-ccnu/NETI2. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Ras-related protein Rab-38 (RAB38) is a member of the Ras small G protein family that regulates intracellular vesicular trafficking. Although the expression of RAB38 is reportedly deregulated in several types of cancer, its role in tumor biology remains to be elucidated. In the present study, the expression of RAB38 was analyzed in tumor specimens from patients with non-small cell lung cancer (NSCLC) with tumor recurrence within 4 years (Group R), and those remaining disease-free following initial surgery (Group NR), by reverse transcription-semi-quantitative PCR and subsequent semi-quantification using ImageJ v4.0 software. The results revealed that the expression of RAB38 in Group R and NR specimens was positively associated with tumor recurrence; a high expression level was also associated with poor survival rate in these patients. Using NSCLC cell lines, it was demonstrated that tumor cells with mutations in the active epidermal growth factor receptor (EGFR) gene expressed higher levels of RAB38 compared with those with the wild-type gene by reverse transcription-PCR and western blot analysis. Furthermore, following specific RAB38 gene knockdown by short hairpin RNA transfection, EGFR mutants exhibited markedly reduced invasiveness when compared with cells transfected with empty vector controls by Matrigel Transwell assays. These results suggest that RAB38 is an important prognostic factor in NSCLC, and may serve a critical role in NSCLC-associated tumor metastasis. [ABSTRACT FROM AUTHOR]

As climate conditions deteriorate, human health faces a broader range of threats. This study aimed to determine the risk of death from metabolic syndrome (MetS) due to meteorological factors. We collected daily data from 2014 to 2020 in Wuhu City, including meteorological factors, environmental pollutants and death data of common MetS (hypertension, hyperlipidemia and diabetes), as well as a total number of 15,272 MetS deaths. To examine the relationship between meteorological factors, air pollutants, and MetS mortality, we used a generalized additive model (GAM) combined with a distributed delay nonlinear model (DLNM) for time series analysis. The relationship between the above factors and death outcomes was preliminarily evaluated using Spearman analysis and structural equation modeling (SEM). As per out discovery, diurnal temperature range (DTR) and daily mean temperature (T mean) increased the MetS mortality risk notably. The ultra low DTR raised the MetS mortality risk upon the general people, with the highest RR value of 1.033 (95% CI: 1.002, 1.065) at lag day 14. In addition, T mean was also significantly associated with MetS death. The highest risk of ultra low and ultra high T mean occured on the same day (lag 14), RR values were 1.043 (95% CI: 1.010, 1.077) and 1.032 (95% CI: 1.003, 1.061) respectively. Stratified analysis's result showed lower DTR had a more pronounced effect on women and the elderly, and ultra low and high T mean was a risk factor for MetS mortality in women and men. The elderly need to take extra note of temperature changes, and different levels of T mean will increase the risk of death. In warm seasons, ultra high RH and T mean can increase the mortality rate of MetS patients. [ABSTRACT FROM AUTHOR]

Highlights • The ATP/polymers composites were first prepared for solar steam generation. • It possesses a high evaporation efficiency of 85% under 1 sun irradiation. • It has advantages of cost-efficient, simple and scalable manufacture process. Abstract Solar steam generation has been attracting wide attention for boosting the evolution of solar-energy-harvesting technology. Here, we demonstrate the fabrication of a novel bilayer photothermal material based on attapulgite/poly acrylamide composite (APAC), which was prepared by the solution polymerization of acrylamide (AM) in the presence of attapulgite using N, N′-Methylene bisacrylamide (MBA) as a crosslinker, for efficient solar steam generation. The APAC shows better thermal stability with a decomposition temperature of 250 °C, good mechanical property with a compress strength of up to 125 KPa at 75% strain and a low apparent density (0.0191 g·cm−3) with abundant porosity accompanying with a low thermal conductivity (0.07 W m−1 K−1). To enhance the light absorption of APAC, a thin carbon layer was created on the surface of APAC via a facile flame treatment. Under our conditions, the bilayered APAC shows a high vapor rate of 1.2 kg m−2 h−1 under 1 sun illumination, equal to 85% solar-to-vapor efficiency. With the merits of cost-efficient, scalable manufacture, high solar energy conversion efficiency, the APAC may hold the great potential as high-performance photothermal materials for solar energy generation. [ABSTRACT FROM AUTHOR]

Lactobacillus gasseri is a kind of facultative anaerobic lactic acid bacterium, and has been defined as GRAS microorganism by the US Food and Drug Administration. We reported the whole genome sequence of L. gasseri LGZ1029. The complete genome of L. gasseri LGZ1029 was 2,027,325 bp encoding 2005 genes with an average G + C content of 35.06%. Based on the analysis of genes involved in antibiotic resistance, virulence factor, and production of harmful metabolites, we have speculated that L. gasseri LGZ1029 is safe. By genome mining tool, a complete plnABCD operon was present in the genome of L. gasseri LGZ1029, indicating that it has the potential to generate antimicrobial bacteriocin. Stress-related genes speculated that L. gasseri LGZ1029 had good gastrointestinal tolerance, bacteriostatic ability, and antioxidant activity with excellent probiotic characteristics, indicating that it can be a probiotic candidate with great potential. • Complete genome of L. gasseri LGZ1029 was firstly sequenced. • The safety and probiotic properties of L. gasseri LGZ1029 were evaluated by genome analysis. • A complete plnABCD operon was found in the genome of L. gasseri LGZ1029. • Stress response genes were identified in the genome of L. gasseri LGZ1029. [ABSTRACT FROM AUTHOR]

Novel oral therapeutic agents based on inhibition or binding activity without adverse events in CKD patients are urgently needed. Here, 5/6 nephrectomy (NX) rats were used to construct a CKD model. Aminated cellulose (AC711), which is metal-free, non-absorbable, and low-volume expansive, was used as a novel oral therapeutic agent for hyperphosphataemia treatment in rats. The efficacy of AC711 on serum and urinary phosphate levels, the expression of type II sodium-dependent phosphate cotransporter (NPT2b), and type III Na-dependent phosphate cotransporter (PiT-1/2) was examined. Serum fibroblast growth factor-23 (FGF-23) levels, parathyroid hormone (PTH) levels, and the phenotypic transformation of vascular smooth muscle cell markers (smooth muscle 22 (SM22) and Runx2) are considered an adaptive response to elevated serum phosphate levels. A similar efficacy of AC711 was observed on serum and urinary phosphate levels when the same dose of AC711 and sevelamer was administered to 5/6 NX rats. The decreasing expression of NPT2b, PiT-1, and PiT-2 was examined in the AC711 groups in a dose-dependent manner. The sevelamer and AC711-MD groups for FGF-23 and PTH indicated no significant difference. The down-regulation of Runx2 expression and up-regulation of SM22 expression were seen in the AC711 groups in a dose-dependent manner. Two suppression mechanisms (binding and inhibiting activities) were observed in the gastrointestinal (GI) tract in the AC711 groups. A novel oral phosphate binder, AC711, showed both binding and inhibition characteristics. The low-volume expansion of AC711 following exposure to simulated intestinal fluid provides the potential therapeutic benefits with the advantage of moderate GI side effects. [Display omitted] • A novel oral therapeutic agent AC711 is developed for treatment of hyperphosphataemia. • AC711 characters binding and inhibition activities. • AC711 is mental-free, non-absorbable, and low volume expansive. • AC711 has been demonstrated to exhibit good drug safety. [ABSTRACT FROM AUTHOR]

Mineral preservation and microbial residue production are vital for the accumulation of mineral‐associated organic carbon (MAOC) in soils. However, their relative importance and interactive effects remain unclear. Here MAOC content and composition are analyzed in tandem with soil mineral and microbial attributes along a weathering gradient on a volcanic soil sequence. We find that MAOC content increases with increasing mineral weathering states, accompanied by increasing microbial contribution to MAOC. Mineral attributes rather than microbial physiological traits are strongly related to MAOC contents, suggesting that weathering‐enhanced mineral preservation capacity overrides microbial residue production in governing MAOC accumulation by increasing reactive minerals. Furthermore, mineral attributes have a strong interactive effect with microbial traits on MAOC accumulation and composition, likely related to increasing fungal abundance in the microbial community with increasing weathering. These findings highlight that mineral weathering may effectively boost persistent SOC in synergy with microbial conversion in the long term. Plain Language Summary: The accrual of mineral‐associated organic carbon (MAOC) is one of the key mechanisms promoting the long‐term sequestration of atmospheric CO2 into soil organic carbon (SOC). Both microbial residue production and mineral preservation are vital for MAOC accumulation. However, their relative importance and interactive effects remain unclear, hampering our ability to understand how to effectively increase this important pool of persistent SOC. Here by analyzing MAOC content and composition in tandem with soil mineral and microbial attributes along a weathering gradient on a volcanic soil sequence (290 years–2.1 million years ago), we find that MAOC content increases with increasing weathering states, accompanied by increasing microbial contribution to MAOC. In contrast to short‐term studies where microbial residue production predominantly influences MAOC accumulation, weathering‐enhanced mineral preservation capacity overrides microbial residue production in governing MAOC accumulation in the long term by increasing reactive minerals. Furthermore, mineral attributes have a strong interactive effect with microbial traits on MAOC accumulation and composition, likely by enhancing the accumulation efficiency of microbial residues via affecting the microbial community composition. Our findings highlight mineral weathering may effectively boost persistent SOC pools in synergy with microbial conversion. Key Points: The relative importance of mineral versus microbial attributes and their interactive effects in MAOC accumulation was comparedWeathering‐enhanced mineral preservation overrode microbial residue production in governing MAOC accumulation over the weathering gradientMineral weathering strengthened microbial contribution to MAOC via affecting microbial community composition [ABSTRACT FROM AUTHOR]

Oxidative stress and apoptosis serve an important role in the development of pressure overload-induced cardiac remodelling. Carnosic acid (CA) has been found to exert antioxidant and anti-apoptotic effects. The present study investigated the underlying mechanism of CA protection and whether this effect was exerted against pressure overload-induced cardiac remodelling. Aortic banding (AB) surgery was performed to induce cardiac remodelling. Mice were randomly divided into four groups (n=15/group): i) Sham + vehicle; ii) sham + CA; iii) AB + vehicle; and iv) AB + CA. After 2 days of AB, 50 mg kg CA was administered orally for 12 days. Echocardiography, histological analysis and molecular biochemistry techniques were performed to evaluate the roles of CA. CA treatment decreased cardiac hypertrophy, fibrosis, oxidative stress and apoptosis in mice challenged with pressure overload. CA also decreased the cross-sectional area of cardiomyocytes and the mRNA and protein expression levels of hypertrophic markers. Furthermore, CA treatment decreased collagen deposition, α-smooth muscle actin expression and the mRNA and protein expression of various fibrotic markers. Additionally, CA reversed the AB-mediated increase in NAPDH oxidase (NOX) 2, NOX4 and 4-hydroxynonenal levels. The number of apoptotic cells was decreased following CA treatment following under conditions of pressure overload. CA also suppressed the activation of AKT and glycogen synthase kinase 3 β (GSK3β) in mice challenged with AB. The present results suggested that CA could inhibit pressure overload-induced cardiac hypertrophy and fibrosis by suppressing the AKT/GSK3β/NOX4 signalling pathway. Therefore, CA may be a promising therapy for cardiac remodelling. [ABSTRACT FROM AUTHOR]

Objective: Genomic biomarkers predicting immune checkpoint inhibitor (ICI) treatment outcomes for Asian metastatic melanoma have been rarely reported. This study presents data on next‐generation sequencing (NGS) and tumour microenvironment biomarkers in 33 cases. Methods: Thirty‐three patients with advanced melanoma, who underwent ICI treatment at the Chang Gung Memorial Hospital in Taiwan, were recruited. The study evaluated clinical outcomes, including response rate, disease control rate, progression‐free survival (PFS) rate and overall survival (OS) rate. Archived tissue samples from 33 cases were subjected to NGS by ACTOnco, and ACTTME was employed in 25 cases. Results: The most prevalent driver mutations were BRAF mutations (24.2%), followed by NRAS (15.2%), KIT (12.1%), KRAS (9.1%) and NF1 (9.1%) mutations. Acral/mucosal melanomas exhibited distinct mutation patterns compared to non‐acral melanomas. Tumour mutational burden estimated using ACTOnco was not associated with ICI efficacy. Notably, genetic alterations in the p53 pathway (CDKNA2 loss, MDM2 gain/amplification and TP53 mutation) accounted for 36.4% and were significantly associated with unfavourable PFS (median PFS 2.7 months vs. 3.9 months, P = 0.0394). Moreover, 26 genes were identified as differentially expressed genes that were upregulated in patients with clinical benefits compared to those without benefits. Four genes, GZMH, GZMK, AIM2 and CTLA4, were found to be associated with both PFS and OS. Conclusion: Genetic alterations in the p53 pathway may be critical in Asian patients with melanoma undergoing ICI treatment. Further investigation is required to explore this mechanism and validate these findings. [ABSTRACT FROM AUTHOR]

A gas chromatography-mass spectrometry (GC–MS) method for the determination of difenidol hydrochloride in biological specimens has been developed. The method exhibited excellent recovery (> 90%) and precision (RSD < 10%), and the LOD was 0.05 μg/mL or μg/g, which met the requirements of bioanalytical method. Through the animal model of the forensic toxicokinetics, the dynamic distribution, postmortem redistribution (PMR) and stability in specimen preservation process of difenidol in animals were studied. The experimental results showed that after intragastric administration, the difenidol's concentrations in the heart-blood and various organs increased over time except stomach, and then decreased gradually after reaching the peaks of concentration. The toxicological kinetics equation and toxicokinetic parameters were established by processing the data of the mean drug concentration of difenidol changing with time. In PMR experiment, the concentrations of difenidol in some organs closer to the gastrointestinal tract (heart-blood, heart, liver, lung, kidney, and spleen) changed significantly at different time points. But the concentration of difenidol in brain tissues which were far away from the gastrointestinal tract and muscles with larger overall mass was relatively stable. PMR of difenidol was therefore confirmed. Thus, the effect of PMR on the concentration of difenidol in the specimens should be considered in cases involving difenidol poisoning or death. Furthermore, the stability of difenidol in heart-blood samples from poisoned rats was investigated at various time points and under different preservation conditions (20 °C, 4 °C, − 20 °C and 20 °C (1% NaF)) for a period of two months. Difenidol was stable and did not decompose in the preserved blood. Therefore, this study provided the experimental basis for the forensic identification of the cases of difenidol hydrochloride poisoning (death). PMR has been verified by practical lethal cases. [ABSTRACT FROM AUTHOR]

The Fe/X (X = C, Si, Ge) films were deposited on glass substrates by magnetron sputtering, and then they were annealed in vacuum. Their magnetic and transport properties are compared. For Fe/C films, the annealing process gives rise to the enhancement of saturation magnetization, the increase of the Fe particle size, and the reduction of the magnetoresistance (MR). For Fe/Si films, the annealing process causes the appearance of the Fe particles and the enhancement of MR. For Fe/Ge films, no Fe particles can be formed in the films. The unsaturated MR was observed in the as-deposited Fe/Ge film. Thus, the microstructures, magnetism, and transport properties can be tuned by the group-IV elements and the postannealing process. This paper may be beneficial to the group-IV-based spintronics. [ABSTRACT FROM AUTHOR]

Background: Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites in urine. Objective: This study aimed to investigate the pharmacokinetics of diazepam and its metabolites, including glucuronide compounds, in the urine of Chinese participants. Methods: A total of 28 volunteers were recruited and each participant ingested 5 mg of diazepam orally. Ten milliliters of urine were collected from each participant at post-consumption timepoints of prior (zero), 1, 2, 4, 8, 12, and 24 h and 2, 3, 6, 12, and 15 days. All samples were extracted by solid-phase extraction and analyzed using high-performance liquid chromatography–tandem mass spectrometry. Diazepam and its main metabolites, except for temazepam, were detected in the urine of volunteers. Pharmacokinetic parameters were analyzed using the pharmacokinetic software DAS according to the non-compartment model. Results: Urinary diazepam peaked at 2.38 ng/mL (Cmax) and 1.93 h (Tmax). The urinary metabolite nordiazepam peaked at 1.17 ng/mL and 100.21 h; temazepam glucuronide (TG) peaked at 145.61 ng/mL and 41.14 h; and oxazepam glucuronide (OG) peaked at 101.57 ng/mL and 165.86 h. The elimination half-life (t½z) and clearance (CLz/F) for diazepam were 119.58 h and 65.77 L/h, respectively. The t½z of the metabolites nordiazepam, TG, and OG was 310.58 h, 200.17 h, and 536.44 h, respectively. Finally, this study found that both diazepam and its main metabolites in urine were detectable for at least 15 days, although there were individual differences. Conclusion: The results regarding diazepam pharmacokinetics in urine would be of great help in forensic science and drug screening. [ABSTRACT FROM AUTHOR]

In the past dozen years, the cases of tramadol intoxication have become frequent in many countries. Most previous studies focused on tramadol's pharmacology, such as pharmacokinetics, pharmacodynamics and pharmacogenetics. However, the dynamic distribution and postmortem redistribution (PMR) of tramadol remain unclear. Our study aimed to investigate these two issues systematically in various specimens of 216 poisoned male rats. A validated gas chromatography–mass spectrometry method was used in this study to measure the concentrations of tramadol. In the first part, 66 tramadol poisoned rats were sacrificed at 11 different time points and their organs were collected separately for the study of tramadol's dynamic distribution, which made it feasible to investigate its PMR later on. The results of this part showed that tramadol's concentrations varied according to the organ and time, and peaked 2 h after intragastric administration in the specimens of liver, kidney, spleen, lung, brain and heart-blood (except stomach and heart). Based on the results of the first part, the concentration of tramadol peaked 2 h in most tissues. Therefore, this time point was used for the study of tramadol's PMR. In the second part, the remaining 150 rats were sacrificed 2 h after intragastric administration of tramadol, and the carcasses were stored under three different conditions (−20, 4 and 20°C). The autopsy was carried out at eight different time points and their organs were collected separately. The results of this part showed that under storage temperatures of −20 and 4°C, the concentrations of tramadol in individual organs showed no significant changes at different time points whereas under a storage temperature of 20°C, the concentrations in certain organs (liver, kidney, spleen, lung, brain and heart-blood) increased significantly at the last few time points. PMR of tramadol was therefore confirmed. The process of PMR of tramadol could be slowed or stopped at lower storage temperatures (−20 or 4°C), which is significant in cases of suspected tramadol poisoning. [ABSTRACT FROM AUTHOR]

The pro-tumoral effects of CCL5 have been identified in numerous cancer types. We successfully cultivated 4 esophageal squamous cell carcinoma (ESCC) cell lines, including TWES-1, TWES-3 and a pair of cell lines derived from primary lesion (TWES-4PT) and metastatic lymph node (TWES-4LN) of the same patient. Whole genome screening showed that TWES-4LN expressed higher levels of CCL5 compared to that of TWES-4PT; quantification of protein secretion displayed comparable results, suggesting that CCL5 could be associated with lymph node metastasis in ESCC. CCL5 knockdown by siRNA significantly reduced basal growth rate, tumor migration and invasiveness in the paired cell lines; whereas this treatment induced cell apoptosis in TWES-1 and TWES-3. CCR5 antagonist maraviroc significantly inhibited tumor migration and invasion in the paired cell lines without affecting tumor growth. Collectively, these results suggest that CCL5 autocrine loop may promote ESCC progression; targeting the CCL5/CCR5 axis could be a potential therapeutic strategy for this deadly disease. [ABSTRACT FROM AUTHOR]

The inhibitory effect of resveratrol on the growth of gastric cancer cells through downregulation of the Wnt/β-catenin signaling pathway were studied. First we determined the effective concentration of resveratrol on the growth and proliferation of MGC-803 gastric cancer cells. Methylthiazolyl tetrazolium assay showed that resveratrol significantly inhibited the proliferation of MGC-803 cells in a dose-dependent manner. Resveratrol induced apoptotic morphological changes in MGC-803 cells. Reverse transcription-polymerase chain reaction and western blot analysis showed that resveratrol downregulated the expression of three important components of the Wnt signaling pathway, β-catenin, c-myc, and cyclin D1, at the mRNA and protein levels. Overall, resveratrol inhibits the growth of MGC-803 cells by inhibiting the Wnt signaling pathway. This study provides a new idea and direction for the antitumor mechanism of resveratrol. [ABSTRACT FROM AUTHOR]

Lactobacillus delbrueckii is widely used in the fermentation industry. Previously, we identified Lactobacillus delbrueckii DMLD-H1, a strain of Lactobacillus delbrueckii subsp. bulgaricus , from traditional Chinese fermented milk. In this research, we sequenced the complete genome of DMLD-H1, which contains 1,836,627 bp in length with a total of 1947 genes and an average G + C content of 49.86%. In total, 103 carbohydrate metabolism genes are annotated in the KEGG database, and it is showed that DMLD-H1 has the ability to transport lactose, glucose, fructose, and mannose. Antibiotic resistance genes, genes encoding toxins and virulence factor genes are absent in risk-associated sequences of DMLD-H1. We also confirm its safety by indole assay, nitroreductase assay, and antibiotic resistance tests. A wide range of stress-related proteins may contribute to the survival of DMLD-H1 in the gastrointestinal environment, including oxidative stress, pH, bile salts, and temperature stress. The large number of adhesion proteins and stress response genes identified in DMLD-H1 in the genome-wide analysis, as well as phenotypic experiments including resistance to bile salts and acid, antioxidant, antimicrobial and self-cohesion activity, exhibited its excellent probiotic properties. This study demonstrates that DMLD-H1 can be a candidate fermentative agent in fermented dairy products. [Display omitted] • The entire genome of Lactobacillus delbrueckii DMLD-H1 was firstly sequenced. • The carbohydrate metabolic pathway is revealed in DMLD-H1. • The safety and probiotic properties of DMLD-H1 are described by genome analysis. • DMLD-H1 has a gene cluster for the generation of enterolysin A. [ABSTRACT FROM AUTHOR]

A genome-based systematic analysis combined with phenotypic experiments was conducted to evaluate the safety properties and metabolic characteristics of Streptococcus thermophilus DMST-H2, isolated from Chinese traditional homemade yogurt in Inner Mongolia. Comparative genomic analysis showed that DMST-H2 had a closer genetic relationship with S. thermophilus KLDS.3.1003 based on the sequence similarities of the 1193 core-genes. No genes related to antibiotic resistance and virulence factor as well as no complete biogenic amine biosynthesis gene clusters were identified in DMST-H2 genome. DMST-H2 was sensitive to various antibiotics and had no hemolytic activity and no biogenic amine production capacity, confirming that DMST-H2 is safe and non-toxic. In addition, multiple genes for carbohydrate metabolism were predicted, including various carbohydrate-active enzymes and sugar transporters that could be involved in the transport of multiple carbon sources. Two exopolysaccharide (EPS) gene clusters (eps-1 and rgp-2) were also detected, indicating that DMST-H2 has the potential to synthesize heteropolysaccharides. Gene functional features revealed a cyclic antimicrobial peptide related gene cluster in DMST-H2, which displayed high identities with the streptide biosynthesis gene cluster as previously reported. Our comprehensive analysis of the whole genome and corresponding phenotypes of S. thermophilus DMST-H2 provides important theoretical basis for its application in food products. • Comparative genomic analysis of S. thermophilus DMST-H2 was displayed. • Systematic analysis of its safety and metabolism characteristics based on phenotype and genotype. • Two exopolysaccharide (EPS) gene clusters were found in the genome of S. thermophilus DMST-H2. • Carbohydrate metabolism pathways were predicted in the genome of S. thermophilus DMST-H2. [ABSTRACT FROM AUTHOR]

[Display omitted] • SOM diversity had varied responses to drainage in three wetlands. • SOM molecular diversity increased with SOC in a low-SOC fen after drainage. • SOM diversity did not alter after drainage in high-SOC wetlands, despite SOC increase. • Microbial inputs and processing dominated increases in wetland SOM diversity. The molecular diversity of soil organic matter (SOM) is considered to be a critical factor influencing soil organic carbon (SOC) persistence, and is found to show a positive relationship with SOC in many upland soils with relatively low SOC concentrations. However, the SOM diversity-SOC relationship remains under-investigated in high-SOC soils such as wetlands, which exhibit divergent SOC accumulation mechanisms compared to upland soils and may induce contrasting shifts in SOM composition during drainage-induced SOC changes. Here we utilized three contrasting wetlands (i.e., two fens and a bog) that encompassed a wide SOC range and experienced decades of artificial drainage to investigate shifts in SOM diversity after drainage. The molecular diversity of SOM was assessed based on SOM pyrolysis products using pyrolysis–gas chromatography-mass spectrometry, and its influencing factors (including plant inputs, soil minerals, and extracellular enzyme activity, etc.) were evaluated. We observed divergent responses of SOM diversity to long-term drainage in the investigated wetlands. While SOM diversity increased with SOC concentration in the low-SOC (i.e., ≤ 60 mg g−1 soil) fen after drainage, it did not change in high-SOC (i.e., > 60 mg g−1 soil) wetlands after drainage regardless of SOC variations. While plant inputs (e.g., root mass) drove SOC accumulation in these wetlands, microbial processing rather than plant inputs dominated increases in SOM diversity, thereby resulting in the decoupling of SOC concentration and SOM diversity in high-SOC soils. These findings suggest that SOC and SOM diversity had a non-linear relationship in divergent soils. In organic-rich soils such as peatlands, SOM diversity did not increase with SOC accumulation after drainage, in contrast to low-SOC soils. Our study provides a novel, molecular diversity-based perspective on understanding wetland SOC stability in the context of drainage caused by increasing human activity and/or climate changes. [ABSTRACT FROM AUTHOR]

HPLC-MS/MS analysis and postmortem distribution or postmortem redistribution of paraquat and its two metabolites in poisoning death cases were reported. Paraquat, monoquat, and paraquat monopyridone were extracted from the sample with acetonitrile or methanol, respectively, detected by ZORBAX HILIC Plus (4.6 × 100 mm, 3.5 μm) chromatographic column, with 0.1 % formic acid aqueous solution - 0.1 % formic acid acetonitrile solution (v/v) as mobile phase. Paraquat, monoquat, and paraquat monopyridone had a good linear relationship within the range of 10–1000, 1–400, and 1–1000 ng/mL (or g), the correlation coefficient (r) were all ≥ 0.9996. Their detection limits were lower than 1 ng/mL (or g). The detection accuracy was 91.25∼113.44 %. The intra-day and inter-day precision were 1.51–3.99 % and 1.92–4.93 %, respectively. This method was used to detect and analyze four rare paraquat poisoning cases. The distribution of paraquat, monoquat, and paraquat monopyridone is uneven, which is relatively high in the heart, blood, lung, and kidney. Heart blood/Peripheral blood ratio of paraquat, monoquat, paraquat monopyridone concentration in two poisoned cases were 1.4, 2.0, 1.5 and 1.9, 1.3, 1.2, which showed a location dependent postmortem redistribution. This is the first time that HPLC-MS/MS and the postmortem distribution or postmortem redistribution of paraquat metabolites in poisoned death cases have been reported. This research provides scientific basis for forensic identification of paraquat poisoning cases and extraction of biological specimen. • HPLC-MS/MS and PMR of PQ's metabolites in poisoned death cases were firstly reported. [ABSTRACT FROM AUTHOR]

In order to study the abnormal disturbance of the space ionosphere caused by strong earthquakes, the methods of SGF + WTA and EMD + ER are proposed and compared. The methods are applied to the 7.7 magnitude earthquake that occurred on the southern coast of Cuba on 29 January 2020 based on the electric field ultra-low frequency waveform data recorded by the ZH-1 electromagnetic satellite. Analyzing the electric field waveform data of the six orbits in and around the epicenter within five days before the earthquake and revisiting the orbit within two months, the significant information about the changes in the ionospheric electric field before the earthquake is obtained. The results demonstrate that: (1) in terms of time, large anomalies appeared before the earthquake on 16 January, and some orbital perturbations lasted until 2 February; (2) in terms of location, the disturbance changes are mainly concentrated over the central earthquake zone, and there are few conjugate zones; (3) in terms of amplitude, during the five days before the impending earthquake, most of the orbital disturbances exceeded the threshold of the background value while some of the orbital disturbances were less than the threshold; (4) in terms of morphology, the fluctuation that did not exceed the threshold appeared in the south of the earthquake area while a few appeared in the north. At the same time, the analysis method proposed in this paper is able to effectively extract the characteristics of electric field signal, clearly describe the abnormal signal change information before the earthquake, and provide a new method reference for the study of spatial electric field waveform data. [ABSTRACT FROM AUTHOR]

Four versions of tricistronic vectors expressing IgG1 light chain (LC), IgG1 heavy chain (HC), and dihydrofolate reductase (DHFR) in one transcript were designed to compare internal ribosome entry site (IRES) and furin-2A (F2A) for their influence on monoclonal antibody (mAb) expression level and quality in CHO DG44 cells. LC and HC genes are arranged as either the first or the second cistron. When using mAb quantification methods based on the detection antibodies against HC Fc region, F2A-mediated tricistronic vectors appeared to express mAb at higher levels than the IRES-mediated tricistronic vectors in both transient and stable transfections. Further analysis revealed that more than 40% of products detected in stably transfected pools generated using the two F2A-mediated tricistronic vectors were aggregates. LC and HC from the F2A stably transfected pools were not properly processed, giving rise to LC+F2A+HC or HC+F2A+LC fusion proteins, LC and HC polypeptides with F2A remnants, and incorrectly cleaved signal peptides. Both IRES-mediated tricistronic vectors express mAb with correct sizes and signal peptide cleavage. Arrangement of LC as the first cistron in the IRES-mediated tricistronic vectors exhibits increased mAb expression level, better growth, and minimized product aggregation, while arrangement of HC as first cistron results in low expression, slower growth, and high aggregation. The results obtained will be beneficial for designing vectors that enhance mAb expression level and quality in mammalian cells. [ABSTRACT FROM AUTHOR]