Search

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]

Negative temperature coefficient (NTC) thermistors are expected to be developed at cryogenic temperature sensing. In this paper, a kind of cryogenic thermistor was developed based on NTC response of single crystal ZnO microwires (MWs). The current–voltage (I–V) characterization demonstrated a NTC response, which was temperature dependence of resistance that decreased with increasing temperature. A sensitive NTC response, especially at the cryogenic temperature range, was observed. The defects in ZnO MWs play an important role in NTC response; therefore, we studied the origin of NTC effect associated with defects to improve the recognition of relationship between defects and the NTC effect and further optimize the temperature sensor design for high performance. Annealing at 800 °C in air was undertaken to make a significant influence on the concentration of defects in as-grown sample, and a series of temperature-dependent features were investigated by photoluminescence, Raman, XPS, and EPR measurements. The results indicated the zinc interstitials to be effective donors for sensitive NTC effect at the cryogenic region. This study provides insight into the ZnO NTC effect and sensitive cryogenic sensing technology. [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]

The efficient and green removal technology of refractory organics such as atrazine in water has been an important topic of research in water treatment. A novel membrane composite biocatalyst Lac-HBT-Pd/BC as prepared for the first time by co-immobilizing laccase, mediator 1-hydroxybenzotriazole (HBT) and metal Pd on functionalized bacterial cellulose (BC) to investigate the removal of atrazine and degradation of its intermediates under mild ambient conditions. It was found that atrazine could be completely degraded in 5 h by the catalysis of Lac-HBT-Pd/BC, and the removal rate of degradation intermediates from atrazine was about 85% after continuous catalysis, which achieved deep degradation of atrazine. The effect of electrochemical activity and radical stability of the membrane composite biocatalysts loaded with Pd was investigated. The possible degradation pathways were proposed by identifying and analyzing the deep degradation products of atrazine. The Lac-HBT-Pd/BC demonstrated deep degradation of atrazine and favorable reusability as well as considerable adaptability to various water qualities. This work provides an important reference for preparing new kinds of biocatalysts to degrade refractory organic pollutants in water. [Display omitted] • The co-immobilized laccase-1-HBT-Pd membrane biocatalyst was prepared. • The membrane biocatalyst can degrade effectively and deeply atrazine in water. • Atrazine could be completely degraded in 5 h by the membrane biocatalyst. • The removal rate of degradation intermediates from atrazine was up to 85%. [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]

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]

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]

Subsoil contains more than half of soil organic carbon (SOC) globally and is conventionally assumed to be relatively unresponsive to warming compared to the topsoil. Here, we show substantial changes in carbon allocation and dynamics of the subsoil but not topsoil in the Qinghai‐Tibetan alpine grasslands over 5 years of warming. Specifically, warming enhanced the accumulation of newly synthesized (14C‐enriched) carbon in the subsoil slow‐cycling pool (silt‐clay fraction) but promoted the decomposition of plant‐derived lignin in the fast‐cycling pool (macroaggregates). These changes mirrored an accumulation of lipids and sugars at the expense of lignin in the warmed bulk subsoil, likely associated with shortened soil freezing period and a deepening root system. As warming is accompanied by deepening roots in a wide range of ecosystems, root‐driven accrual of slow‐cycling pool may represent an important and overlooked mechanism for a potential long‐term carbon sink at depth. Moreover, given the contrasting sensitivity of SOC dynamics at varied depths, warming studies focusing only on surface soils may vastly misrepresent shifts in ecosystem carbon storage under climate change. [ABSTRACT FROM AUTHOR]

The lysosome is known to be an acidic organelle that is ubiquitous in cells. Acidic pH is a characteristic feature of lysosomes, and aberrant lysosomal pH values have been manifested to be associated with diverse diseases. In order to monitor the lysosomal pH changes, we developed a ratiometric emission NIR-fluorescent probe (CzQl) for the quantitative analysis of the lysosomal pH in living cells and in vivo. CzQl was constructed via the ethylene bridging of carbazole derivatives and quinoline. The protonation of the probe resulted in a marked green-to-red emission color change. The probe exhibited an ideal pKa value of 4.60 with a linear relationship in the pH range of 3.9–5.3, which covered most of the pH ranges of lysosomes, and was useful for the quantitative detection and imaging of lysosomal pH changes. Moreover, CzQl exhibited easy loading capability, high selectivity, a large Stokes shift, specific lysosome-targeting ability and low cytotoxicity; thereby, it was successfully used for monitoring the lysosomal pH changes at a cellular level as well as the LPS-mediated inflammation in vivo. [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]

Lignin is a key component of soil dissolved organic carbon (DOC) and is recently suggested to track 14C-young DOC components. However, direct evidence is still lacking to prove this hypothesis in the soil. Here, utilizing molecular radiocarbon dating, we present the first 14C dataset on dissolved lignin through a Podzol soil profile. Dissolved lignin and hydroxy phenols had similar 14C content as soil organic carbon (SOC) and DOC in the surface organic layer. However, in contrast to SOC, both DOC and dissolved lignin phenols exhibited consistent and higher Δ14C values in the mineral soils. Coupled with lignin phenol concentration data, our results suggest that dissolved lignin comprises a key DOC component throughout this Podzol profile and is mainly supplied by surface leachates with young 14C ages. Image 1 • We present the first 14C dataset on dissolved lignin along a Podzol profile. • Dissolved phenols exhibited similar Δ14C values to SOC and DOC in surface organic layer. • Unlike SOC, DOC and dissolved lignin were enriched in 14C in mineral soils. • Surface leachate was the main source of DOC components in this Podzol profile. • Dissolved lignin may exhibit larger 14C variability in other (non-Podzol) profiles. [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]

Abstract In this work, a rapid and sensitive paper-based analytical device (PAD) method was developed for screening detection of total tetracyclines (TCs) in environment water. TCs form firstly a narrow stacking band on a paper channel by field amplification stacking, and then the band was visualized by fluorescent imaging which was induced by an ultraviolet light-emitting diode (UV LED). The image was acquired by a smartphone camera for quantitative analysis. Under optimal conditions, the sensitivity of this portable PAD system was 250 times enhanced within 2 min by online electrokinetic stacking and linear response was demonstrated in the range of 5–80 ng mL−1(R2 = 0.997) with detection limit of 4.5 ng mL−1. The applicability was demonstrated by detection of total TCs in environmental water with recovery ranging from 87 to 112% (RSD = 4.1–16.3%). Graphical abstract Unlabelled Image Highlights • Fluorescent colorimetric detection of total tetracyclines was implemented simply with UV LED and smartphone camera on a portable PAD system. • The sensitivity for tetracyclines was 250 times enhanced by field amplification sample stacking. • Fast instrument-free tetracyclines detection was achieved within 5 min in range of 5–80 ng mL−1 (R2 = 0.997) with detection limit of 4.5 ng mL−1. [ABSTRACT FROM AUTHOR]

A sensitive detection method combined with an effective on-line concentration may improve the analytical performance of a paper-based analytical device (PAD), and its merits of low cost and portability in POCT are fully demonstrated. Here, a sensitive PAD system with chemiluminescence (CL) detection and electrokinetic preconcentration was introduced, and the performance was demonstrated by the detection of hemin. A commercially available low cost and miniaturized optical detection module was used for the CL detection. Firstly, hemin was stacked on a simple paper fluidic channel based on field amplified stacking (FAS), and then a CL reagent (luminol–H2O2) was loaded on the stacked band to initiate the CL reaction. The photons were directly detected using the detection module. With optimization of the background electrolyte (BGE), voltage and CL reagent, a limit of detection (LOD) of 0.58 nM for hemin was obtained with a linear range of 1–1000 nM (R2 = 0.995). With FAS, the signal intensity was about 13-fold enhanced. This PAD also exhibited satisfactory selectivity over possible interfering components at a 104 times higher concentration. The applicability of the PAD was demonstrated by the detection of hemin from iron supplements and human serum samples. With total manual operation, recovery rates of 84.8–115.6% were obtained with an RSD of less than 14.3%. With the introduction of the optical detection model, and together with FAS, both the LOD and dynamic range of this PAD were effectively improved. [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]

• Cryoablation synergized with PD-1 blockade can elicit a robust antitumor immune response. • Anti-PD-L1/cryoablation therapy selectively derived the improvement of depolarized mitochondria in PD-1+CD8+T cells. • Mitochondrial dynamics in CD8+TILs were involved in modulating the local immune response. Immune checkpoint blockade (ICB) has shown improvement in overall survival for lung cancer in clinical trials. However, monotherapies have limited efficacy in improving outcomes and benefit only a subset of patients. Combination therapies targeting multiple pathways can augment an immune response to improve survival further. Here, we demonstrate that combinatorial anti-PD-L1/cryoablation therapy generated a synergistic antitumor activity in the established lung cancer model. Importantly, it was observed that this favorable antitumor immune response comes predominantly from the PD-1+CD8+ T cells generated after the combination therapy, referred as improvement of IFN-γ production and mitochondrial metabolism, which resembled highly functional effectors CD8+ T cells. Notably, the cellular levels of mitochondrial reactive oxygen and mitochondria mass excessively coincided with alteration of IFN-γ secretion in PD-1+CD8+T cell subset. So far, anti-PD-L1/cryoablation therapy selectively derived the improvement of depolarized mitochondria in PD-1+CD8+T cell subset, subsequently rebuild the anti-tumor function of the exhausted CD8+ T cells. Collectively, there is considerable interest in anti-PD-L1 plus cryoablation combination therapy for patients with lung cancer, and defining the underlying mechanisms of the observed synergy. [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]

Subsoils of alpine grasslands on the Qinghai-Tibetan Plateau represent a tremendous yet poorly investigated reservoir of soil organic carbon (SOC) on a global “hotspot” of warming. Compared with the temperature sensitivity of SOC decomposition, microbial anabolism of new carbon and priming of native SOC remain poorly constrained under warming-enhanced labile carbon input in these subsoils. Here we employed an innovative approach to investigate the sequestration of freshly added carbon in microbial necromass versus SOC priming in the top- (0–10 cm) and subsoils (30–40 cm) from a field experiment that simulated varied warming scenarios in an alpine grassland on the Qinghai-Tibetan Plateau. The 13 C composition of microbial necromass-derived amino sugars was analyzed in tandem with respired CO 2 and dissolved SOC components (including dissolved lignin) in an 86-day laboratory incubation with 13 C-labeled glucose. A higher fraction of freshly added carbon was respired while a smaller proportion was stabilized as amino sugars in the subsoil relative to the topsoil, leading to a much lower microbial carbon accumulation efficiency at depth. Meanwhile, a higher relative priming effect was observed in the subsoil (47± 14%) compared to the topsoil (14± 4%), suggesting a higher vulnerability to substrate-induced SOC loss at depth, although such changes may be associated with higher glucose addition rate (relative to SOC) in the subsoil. Furthermore, enhanced winter warming significantly reduced degradable SOC (assessed by SOC mineralization and dissolved lignin content) in the subsoil and potentially intensified nitrogen limitation under labile carbon additions, which further decreased microbial carbon accumulation (in the form of amino sugars) in the subsoil without affecting the topsoil. These results collectively indicate a limited microbial carbon sequestration potential and a higher vulnerability to warming-induced substrate changes in the subsoil of this alpine grassland, which warrants better understanding to predict soil carbon responses to climate warming on the Qinghai-Tibetan Plateau. [ABSTRACT FROM AUTHOR]

In this work, the industrial bacterial cellulose was functionalized by grafting glycidyl methacrylate and dopamine after regeneration with mixed ionic liquids of [AMIM]Cl and [Emim][OAc] and used as support for co-immobilizing laccase and acetosyringone molecule to achieve the recyclable solid spherical biocatalyst. It was found that the pesticide intermediate 2,4,5-trichlorophenol of 20 mg/L could be degraded effectively in water using the biocatalyst microspheres with the degradation efficiency of 98.3% at 30 ℃, which was much higher than that of the microspheres containing laccase without acetosyringone. The seed germination results showed that compared with untreated 2,4,5-trichlorophenol solution, the phytotoxicity of 2,4,5-trichlorophenol solution treated by the biocatalyst microspheres was significantly reduced, leading to the significantly higher seed germination rate. The solid biocatalyst maintained the high catalytic degradation activity for 2,4,5-trichlorophenol in the actual industrial water conditions of lake water, coal washing water, as well as coking wastewater. This study provided a green, safe and efficient approach to removing harmful 2,4,5-trichlorophenol from water. [Display omitted] • The solid biocatalyst was achieved by co-immobilizing laccase and acetosyringone. • The degradation efficiency of 98.3% for 2,4,5-trichlorophenol was obtained. • The immobilized acetosyringone has a synergistic catalytic function. • The biocatalyst exhibited high catalytic activity in the industrial water environment. [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]

Wide angle X-ray diffraction is used to measure the texture evolution of isotactic polypropylene (iPP) during rolling. Pole figures, orientation distribution functions and crystallinities of the rolled iPP are obtained and calculated. The texture evolution is also simulated by the modeling. It can be drawn that the main deformation mechanisms occurred at low strain is the coarse slips on few planes and the amorphization because of the special mother and daughter lamellae of the material, which leads to the crystallinity decreases greatly. As the true strain increases, mother and daughter lamellae are broken, then, the following deformation does not be controlled by the special structure of α-iPP. The basic deformation mechanisms in the rolled iPP is the crystallographic slips, and the main slip systems are (010)[001] and (100)[001] chain slips and (010)[100] transverse slip and so on. Amorphization is also a deformation mechanism which may take place as an alternative to crystallographic slip depending on the crystallographic orientation of a lamella. The [001]|RD fiber texture, which includes several (hk0)[001] texture components is the main texture component in the rolled iPP. [ABSTRACT FROM AUTHOR]

This case report describes a rare and interesting case of a patient with multiple myeloma complicated with light chain (LC) cast nephropathy and focal amyloidosis. The patient presented with acute kidney injury, anaemia and bone lesions. The diagnosis was confirmed by bone marrow biopsy, serum and urine electrophoresis and kidney biopsy. The patient was treated with isazomil, pomalidomide and dexamethasone combination chemotherapy, followed by autologous stem cell transplantation. The patient achieved clinical remission, stable renal function and improved serum lambda free LC levels. This case highlights the challenges and advances in the diagnosis and treatment of this condition. [ABSTRACT FROM AUTHOR]

Sorafenib, a multikinase inhibitor of tumour-cell proliferation and angiogenesis, has been shown to have a role in the treatment of metastatic renal cell carcinoma (RCC). Xpl 1 translocation carcinoma is a rare subtype of RCC. We report an 18-year-old male patient with metastatic Xpll trans- location RCC who was responsive to sorafenib treatment. Six weeks after commencement of treatment with sorafenib, a CT scan of the patient showed increased central necrosis of the kidney mass and para-aortic lymph nodes as well as regression of the lung and pleural masses. The patient had a progression-free survival of 12 months, and overall survival of 15 months. The most severe adverse effects were gradc 3 dermatitis and grade 3 anaemia. This case has demonstrated for the first time that sorafenib is active against Xpl 1 translocation RCC. [ABSTRACT FROM AUTHOR]

Abstract: Heparanase is a heparan sulfate (HS) degrading endoglucuronidase that has been implicated in cell migration and inflammatory conditions. Here we used mice deficient of heparanase (Hpse −/−) to study the impact of heparanase on airway leukocytes. Normal numbers of macrophages and lymphocytes were present in bronchoalveolar lavage fluid of Hpse −/− mice, indicating that heparanase is not essential for proper homing of leukocytes to airways. While lymphocytes from Hpse −/− mice displayed normal morphology, Hpse −/− alveolar macrophages showed a striking, age-dependent appearance of granule-like structures in the cytoplasm. Transmission electron microscopy revealed that these structures corresponded to membrane-enclosed crystalline bodies that closely resembled the intracellular crystals known to be formed by the HS-binding protein Ym1, suggesting that heparanase deficiency is associated with intracellular Ym1 deposition. Indeed, applying immunocytochemistry, we found markedly higher levels of intracellular Ym1 protein in Hpse −/− versus WT alveolar macrophages, and there was a significant correlation between levels of Ym1 protein detected by immunoblotting and amounts of crystalline material in BAL cells. Biosynthetic radio-labeling of the macrophages revealed accumulation of non-degraded HS chains in Hpse −/− macrophages. Together, these findings implicate heparanase in normal processing of HS in macrophages, and indicate that heparanase regulates intracellular Ym1 accumulation and crystal formation in airways. [Copyright &y& Elsevier]

Multivariate outcomes measured longitudinally over time are common in medicine, public health, psychology and sociology. The typical (saturated) longitudinal multivariate regression model has a separate set of regression coefficients for each outcome. However, multivariate outcomes are often quite similar and many outcomes can be expected to respond similarly to changes in covariate values. Given a set of outcomes likely to share common covariate effects, we propose the clustered outcome common predictor effect model and offer a two step iterative algorithm to fit the model using available software for univariate longitudinal data. Outcomes that share predictor effects need not be chosen a priori; we propose model selection tools to let the data select outcome clusters. We apply the proposed methods to psychometric data from adolescent children of HIV+ parents. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Patients with non-small cell lung carcinoma (NSCLC) bearing epidermal growth factor receptor (EGFR) gene mutations are good responders to gefitinib (Iressa), an EGFR tyrosine kinase inhibitor (EGFR-TKI), yet these patients may eventually develop acquired resistance to all available EGFR-TKIs. Nitrogen-containing bisphosphonates (N-BPs) are inhibitors of farnesyl diphosphate (FPP) synthase as well as chelators of divalent cations. This study was undertaken to examine if the N-BP zoledronic acid (zoledronate) possessing antitumor activity could enhance the antitumor effect of gefitinib on the HCC827 NSCLC cell line expressing mutated EGFR. Both gefitinib and zoledronate were cytotoxic to HCC827 cells when treated alone. Combined treatment with gefitinib (0.025μM) that induced G 0/G 1 arrest and zoledronate (50μM) that caused S/G 2/M accumulation generated an additive induction in cell cytotoxicity, sub-G 1 cell population, and apoptosis. Gefitinib suppressed EGF-activated phosphorylation of ERK1/2 and Akt, while zoledronate seemed to impose its pharmacological effect independent of ERK1/2 and Akt phosphorylation. The volumes of xenografted tumors in nude mice co-administered with gefitinib (1mg/kg/day, five days a week, p.o.) and zoledronate (10μg/kg, twice weekly, i.p.) were significantly smaller than those of tumors in mice treated with gefitinib alone at the last stage of a 6-week in vivo study. Severe peri-tumoral fat loss frequently observed in gefitinib-treated mice disappeared in mice receiving the combined treatment. Hence, combined treatment of gefitinib with zoledronate may form a basis to develop a more effective and less toxic therapy for NSCLC with EGFR gene mutations. [Copyright &y& Elsevier]

The lipase (LA) and peroxidase (POD) activities, as well as morphological structure, physicochemical and digestion properties of sand rice flour (SRF) treated with superheated steam (SS), were investigated. SS treatment at 165 °C completely deactivated LA and resulted in a 98% deactivation of POD activities in SRF. This treatment also intensified gelatinization, induced noticeable color alterations, and decreased pasting viscosities. Furthermore, there was a moderate reduction in crystal structure, lamellar structure, and short-range ordered structure, with a pronounced reduction at temperatures exceeding 170 °C. These alterations significantly impacted SRF digestibility, leading to increased levels of rapidly digestible starch (RDS) and resistant starch (RS), with the highest RS content achieved at 165 °C. The effectiveness of SS treatment depends on temperature, with 165 °C being able to stabilize SRF with moderate changes in color and structure. These findings will provide a scientific foundation for SS applicated in SRF stabilization and modification. [Display omitted] • Superheated steam (SS) treatment deactivates lipase and peroxidase. • SS treatment efficiency depends on the temperature input. • SS treatment is potential for sand rice flour stabilization. [ABSTRACT FROM AUTHOR]

The orientation and crystallinity evolution of isotactic polypropylene (iPP) induced by rolling were studied using wide angle X-ray scattering with an area detector. The tensile mechanical properties of rolled isotactic polypropylene sheets were also measured in this work. The texture component method was used to analyze the rolling texture. The rolling texture consists mainly of (010)[001], (130)[001] and [001]//RD fiber components in the sample with a rolling true strain of 1.5. The results reveal that crystallinity drastically decreases during rolling. It is suggested that amorphization is a deformation mechanism which takes place as an alternative to crystallographic intralamellar slip depending on the orientation of the lamellae. Both the orientation and crystallinity affect the tensile mechanical properties of rolled polypropylene. Crystallinity influences the elastic modulus on both directions and yield strength on transverse direction at the first stage of deformation. Orientation is the main reason for the changes of mechanical properties, especially at the latter part of deformation. The changes of both tensile strength and elongation percentage on rolling direction are larger than those on transverse direction, which results from the orientation. At last, the anisotropic mechanical properties occur on the rolling and transverse direction: high tensile strength with low elongation percentage on rolling direction and low tensile strength with high elongation percentage on transverse direction. [ABSTRACT FROM AUTHOR]

Microbial necromass carbon (MNC) is key to soil organic carbon (SOC) storage. However, mechanisms regulating MNC accumulation on large scales are poorly understood. Here we provide the first batch of regional-scale MNC data based on amino sugars for the Qinghai-Tibet Plateau alpine grasslands. We show that Qinghai-Tibet grasslands have similar microbial biomass carbon (MBC) but lower MNC concentrations in SOC than Mongolian and other grasslands. The low contribution of MNC to SOC is mainly attributed to high aridity and low net primary productivity of the Qinghai-Tibet grasslands. Our findings highlight climatic and plant influences on MNC accumulation at regional scales. • Qinghai-Tibet grasslands have lower microbial necromass carbon (MNC) in SOC. • The MNC content of grasslands is regulated by aridity at global scale. • Low MNC in Qinghai-Tibet grasslands is attributed to the low NPP and high aridity. [ABSTRACT FROM AUTHOR]

Achieving efficient artificial nitrogen fixation similar to nitrogenase under mild conditions has always been a goal pursued by human beings, but it remains a huge challenge. Herein, a novel photothermal catalyst UiO-66(Zr-Fe)/Fe-dispersed MXene having nitrogenase-mimicking electron transfer structure and electron donation mechanism is fabricated and applied in a designed gas-vapor-solid bi-phase system for efficient N 2 -to-NH 3 conversion. The complementary role playing of UiO-66(Zr-Fe), Ti 3 C 2 MXene and well-dispersed Fe sites are capable of simulating nitrogenase triple tandem system that in charge of electron generation, electron transfer and N 2 fixation, respectively. In this well-designed catalyst, a remarkably high NH 3 formation rate of 133.2 μmol g−1 h−1 under solar level illumination is recorded. This superior performance of the biomimetic structure is related to the enhanced light-to-matter interaction for effective multi-electron extraction and promoted photothermal response for accelerating surface reaction dynamics. [Display omitted] • Nitrogenase-mimicking photothermal catalyst U6(Zr-Fe)/Fe-MXene is designed. • Gas-Vapor-Solid reaction system is created for photocatalytic nitrogen reduction. • High NH 3 production rate is recorded under solar level intensity. [ABSTRACT FROM AUTHOR]

The study investigated the effect of removing protein and/or lipid on the physicochemical characteristics and digestibility of sand rice flour (SRF). Morphological images showed that protein removal had a greater impact on exposing starch granules, while lipids acted as an adhesive. The treatment altered starch content in SRF samples, leading to increased starch crystallinity, denser semi-crystalline region, lower onset gelatinization temperature (T o), higher peak viscosity and gelatinization enthalpy (ΔH), where Protein removal showed a more pronounced effect on altering physicochemical properties compared to lipid removal. The research revealed a positive correlation between rapidly digestible starch (RDS), maximum degree of starch hydrolysis (C ∞), digestion rate constant (k) values and 1047/1022 cm−1 ratio, showing a strong connection between short-range structure and starch digestibility. The presence of endogenous proteins and lipids in SRF hinder digestion by restricting starch swelling and gelatinization, and physically obstructing enzyme-starch interaction. Lipids had a greater impact on starch digestibility than proteins, possibly due to their higher efficacy in reducing digestibility, higher lipid content with greater potential to form starch-lipid complexes. This study provides valuable insights into the interaction between starch and proteins/lipids in the sand rice seed matrix, enhancing its applicability in functional and nutritional food products. [ABSTRACT FROM AUTHOR]

Pentosan polysulfate sodium (PPS; Elmiron) is a FDA-approved heparanase inhibitor for the treatment of bladder pain and interstitial cystitis. The chronic use of PPS has been associated with a novel pigmentary maculopathy, associated with discrete vitelliform deposits that exhibit hyperfluorescence, macular hyper-pigmentary spots, and foci of nodular RPE enlargement. Therefore, this study aimed to investigate the retinal morphology of heparanase knockout mice. The retinal morphology of heparanase knock-out and age-matched control wild type mice of 3-, 9- and 15-weeks old was characterized by means of histological evaluation. Immuno-histological stains for RPE65, F4/80 and Ki67 were performed for investigating the RPE, inflammatory and proliferating cells, respectively. Histological analysis showed no changes in age-matched wild-type controls, whereas the eyes of heparanase null mice were characterized by alterations in RPE and neural retina, as manifest by RPE folds and choroidal thickening, detached RPE cells, thickening of the photoreceptor layer and retinal disorganization. The presence of discrete hyperfluorescent foci, however, was absent. The prevalence of the RPE/choroidal changes or protrusions seemed to progress over time and were correlated with more RPE65 signal rather than influx of F4/80- or Ki67-positive cells. These results indicate that the subretinal alterations were mostly RPE driven, without influx of inflammatory or proliferating cells. Our results indicate that heparanase deficiency in the mice leads to RPE folds, choroidal thickening, and retinal disorganization. The presence of discrete hyperfluorescent foci, a key characteristic of the human disease, was not observed. However, it can be concluded that some of the observations in mice are similar to those seen after chronic use of PPS in humans. These findings indicate that the toxicity observed in the presence of heparanase inhibitors is target-related and will preclude the clinical use of heparanase inhibition as a therapeutic intervention. [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]

Organophosphorus pesticides (OPS) are widely used in the world, and many poisoning cases were caused by them. Phorate intoxication is especially common in China. However, there are currently few methods for discriminating phorate poisoning death from phorate exposure after death and interpretation of false-positive results due to the lack of effective biomarkers. In this study, we investigated the metabonomics of rat plasma at different dose levels of acute phorate intoxication using ultra-performance liquid chromatography quadrupole-time of flight mass spectrometry (UPLC-Q-TOF–MS) analysis. A total of 11 endogenous metabolites were significantly changed in the groups exposed to phorate at LD50 level and three times of LD50 (3LD50) level compared with the control group, which could be potential biomarkers of acute phorate intoxication. Plasma metabonomics analysis showed that diethylthiophosphate (DETP) could be a useful biomarker of acute phorate intoxication. The levels of uric acid, acylcarnitine, succinate, gluconic acid, and phosphatidylcholine (PC) (36:2) were increased, while pyruvate level was decreased in all groups exposed to phorate. The levels of ceramides (Cer) (d 18:0/16:0), palmitic acid, and lysophosphatidylcholine (lysoPC) (18:1) were only changed after 3LD50 dosage. The results of this study indicate that the dose-dependent relationship exists between metabolomic profile change and toxicities associated with apoptosis, fatty acid metabolism disorder, energy metabolism disorder especially tricarboxylic acid (TCA) cycle, as well as liver, kidney, and nervous system functions after acute exposure of phorate. This study shows that metabonomics is a useful tool in identifying biomarkers for the forensic toxicology study of phorate poisoning. [ABSTRACT FROM AUTHOR]

Subsoils contain >50% of soil organic carbon (SOC) globally yet remain under‐investigated in terms of their response to climate changes. Recent evidence suggests that warmer, drier conditions in alpine grasslands induce divergent responses in SOC decomposition and carbon accrual in top‐ versus subsoils. However, longer term effects on microbial activity (i.e., catabolic respiration vs. anabolic growth) and belowground carbon cycling are not well understood. Here we utilized a field manipulation experiment on the Qinghai‐Tibetan Plateau and conducted a 110‐day soil incubation with and without 13C‐labeled grass litter to assess microbes' role as both SOC "decomposers" and "contributors" in the top‐ (0–10 cm) versus subsoils (30−40 cm) after 5 years of warming and drought treatments. Microbial mineralization of both SOC and added litter was examined in tandem with potential extracellular enzyme activities, while microbial biomass synthesis and necromass accumulation were analyzed using phospholipid fatty acids and amino sugars coupled with 13C analysis, respectively. We found that warming and, to a lesser extent, drought decreased the ratio of inorganic nitrogen (N) to water‐extractable organic carbon in the subsoil, intensifying N limitation at depth. Both SOC and litter mineralization were reduced in the subsoil, which may also be related to N limitation, as evidenced by lower hydrolase activity (especially leucine aminopeptidase) and reduced microbial efficiency (lower biomass synthesis and necromass accumulation relative to respiration). However, none of these effects were observed in the topsoil, suggesting that soil microbes became inactive and inefficient in subsoil but not topsoil environments. Given increasing belowground productivity in this alpine grassland under warming, both elevated root deposits and diminished microbial activity may contribute to new carbon accrual in the subsoil. However, the sustainability of plant growth and persistence of subsoil SOC pools deserve further investigation in the long term, given the aggravated N limitation at depth. [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]

Electrokinetic stacking (ES) is effective for improving sensitivity of paper-based analytical device (PAD) for charged analytes. In this paper, we successfully demonstrated ES of electrically neutral analytes on PAD, and the performance was characterized by smartphone-based colorimetry and fluorescence. Firstly, SDS from cathode reservoir stacked as a micelle band on an open paper fluidic channel by ES, and the target analyte was swept by the micelle. Meanwhile, the probes at the other side were carried by electroosmotic flow (EOF). Eventually, neutral components preloaded on the channel were concentrated as the narrow stacking band. Taking the rhodamine B as a probe, the effects of EOF, background electrolyte concentration and anionic surfactant concentration were investigated. Fluorescence detection of rhodamine B and colorimetric analysis of Sudan III demonstrated the sensitivity enhanced and its potential for the semi-quantitative test. Under the optimized conditions, fluorescence detection limit of 50 nM of rhodamine B was achieved with a linear range of 1.0–10 μM (R 2 = 0.99). The colorimetric detection limit for Sudan III was 5.2 μM and the linear range was 5–40 μM (R 2 = 0.99). Compared with direct analysis without stacking, the signal levels of rhodamine B and Sudan III were increased by 30-fold and 6-fold, respectively. This study showed that with ES, sensitive and rapid PAD detection of electrically neutral analytes could be achieved. [ABSTRACT FROM AUTHOR]

A novel ratiometric emission NIR-fluorescence probe N , N -dimethyl-4-((1E, 3E)-4-(3,3-dimethyl-3H-indol-2-yl)buta-1,3-dienyl)benzenamine, namely, DIDBA, is facilely synthesized on the basis of ethylene bridging of indole derivatives and 4-(dimethylamino) cinnamaldehyde. The probe exhibits a remarkable NIR ratiometric fluorescence emission ( F 618nm / F 697nm ) characteristic with p K a 4.5, and the linear response over the pH range of 3.5–5.2. DIDBA also displays favorable features include large Stokes shift of 200 nm under acidic conditions, high sensitivity, good selectivity, fine photostability and reversibility. The probe has low cytotoxicity and excellent cell membrane permeability, and is applied successfully to visualize intracellular pH fluctuations in live cells without influence of autofluorescence and native cellular species in biological systems. [ABSTRACT FROM AUTHOR]

We have synthesized graphene frameworks (GFs) with different SSA and pore structure by regulating the ratio of glucose and Na 2 CO 3 through one-step fast pyrolysis process. The tailored GFs has been used as electrode materials for constructing non-enzymic electrochemical sensor with catechol (CC) used as model analyte, and the result indicates GFs abundant hierarchical pore structure and relatively large SSA can achieve the best electrochemical sensing behaviour. [Display omitted] • GFs with different SSA and pore size can be successfully synthesized via one-step fast pyrolysis process. • Both the SSA and pore size impact the electrochemical sensing performance of catechol. • The optimized GFs as electrode materials for electrochemical detection of catechol could achieve a low detection limit of 0.19 μM. Rational design porous nanomaterials with high specific surface area (SSA) have become an effective approach to improve their electrocatalytic activity, and thus enhancing the electrochemical sensing performance. However, increasing of SSA generally accompanied by magnifying the background current signal, which results in the electrochemical sensors may not achieve the optimal sensing performance. For porous nanomaterials, not only the appropriate SSA but also the pore size probably impacts the electrochemical sensing performance, while this aspect has seldomly studied in electrochemical sensor. Herein, the different SSA and pore size of graphene frameworks (GFs) are successfully synthesized by adjusting the ratio of the mixture of glucose and Na 2 CO 3 via one-step fast pyrolysis process. The tailored GFs has been used as electrode material for constructing non-enzymic electrochemical sensor with catechol (CC) used as model analyte. Electrochemical analysis result suggests that GFs with the highest SSA do not obtain the best behavior, while GFs with abundant hierarchical pore structure and relatively large SSA can achieve the best performance. The optimized GFs as electrode materials for electrochemical detection of CC exhibit a low detection limit of 0.19 μM, and a relatively wide linear range between 1 and 201 μM. This work provides a guide for developing new porous carbon materials for electrochemical sensor with better performance. [ABSTRACT FROM AUTHOR]

Forest ecosystems are important global soil carbon (C) reservoirs, but their capacity to sequester C is susceptible to climate change factors that alter the quantity and quality of C inputs. To better understand forest soil C responses to altered C inputs, we integrated three molecular composition published data sets of soil organic matter (SOM) and soil microbial communities for mineral soils after 20 years of detrital input and removal treatments in two deciduous forests: Bousson Forest (BF), Harvard Forest (HF), and a coniferous forest: H.J. Andrews Forest (HJA). Soil C turnover times were estimated from radiocarbon measurements and compared with the molecular‐level data (based on nuclear magnetic resonance and specific analysis of plant‐ and microbial‐derived compounds) to better understand how ecosystem properties control soil C biogeochemistry and dynamics. Doubled aboveground litter additions did not increase soil C for any of the forests studied likely due to long‐term soil priming. The degree of SOM decomposition was higher for bacteria‐dominated sites with higher nitrogen (N) availability while lower for the N‐poor coniferous forest. Litter exclusions significantly decreased soil C, increased SOM decomposition state, and led to the adaptation of the microbial communities to changes in available substrates. Finally, although aboveground litter determined soil C dynamics and its molecular composition in the coniferous forest (HJA), belowground litter appeared to be more influential in broadleaf deciduous forests (BH and HF). This synthesis demonstrates that inherent ecosystem properties regulate how soil C dynamics change with litter manipulations at the molecular‐level. Across the forests studied, 20 years of litter additions did not enhance soil C content, whereas litter reductions negatively impacted soil C concentrations. These results indicate that soil C biogeochemistry at these temperate forests is highly sensitive to changes in litter deposition, which are a product of environmental change drivers. [ABSTRACT FROM AUTHOR]

Soil carbon sequestration is listed by the United Nations Framework Convention on Climate Change as one of the key ways to achieve long-term “carbon neutrality” in the context of global warming. Soil carbon sequestration is a complex biogeochemical process that involves plants, microbes, and rock minerals at its core. Yet, its regulation mechanisms and promotion pathways remain unclear. This paper reviews recent progress in the related domestic and international research and provides an overview of the key processes and mechanisms of soil carbon sequestration. The main pathways for enhancing soil carbon sequestration (including plant inputs, mineral protection, microbial transformation, and rock weathering) are summarized. The paper also discusses and synthesizes how advanced biogeochemical methods and technologies may be employed to explore soil carbon sequestration mechanisms and potentials. The overall aim of this review is to improve our understanding of soil carbon sequestration as a nature-based solution to combatting climate change from the biogeochemistry perspective, and to highlight the role of fundamental research in Earth Sciences in helping to achieve China’s carbon neutrality goals. [ABSTRACT FROM AUTHOR]