Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

[Effects of Combined Stress of High Density Polyethylene Microplastics and Chlorimuron-ethyl on Soybean Growth and Rhizosphere Bacterial Community].

With the vigorous development of agriculture in China， plastic mulch film and pesticides are widely used in agricultural production. However， the accumulation of microplastics （formed by the degradation of plastic mulch film） and pesticides in soil has also caused many environmental problems. At present， the environmental biological effects of microplastics or pesticides have been reported， but there are few studies on the combined effects on crop growth and the rhizosphere soil bacterial community. Therefore， in this study， the high density polyethylene microplastics （HDPE， 500 mesh） were designed to be co-treated with sulfonylurea herbicide chlorimuron-ethyl to study their effects on soybean growth. In addition， the effects of the combined stress of HDPE and chlorimuron-ethyl on soybean rhizosphere soil bacterial community diversity， structure composition， microbial community network， and soil function were investigated using high-throughput sequencing technology， interaction network， and PICRUSt2 function analysis to clarify the combined toxicity of HDPE and chlorimuron-ethyl to soybean. The results showed that the half-life of chlorimuron-ethyl in soil was prolonged by the 1% HDPE treatment （from 11.5 d to 14.3 d）， and the combined stress of HDPE and chlorimuron-ethyl had more obvious inhibition effects on soybean growth than that of the single pollutant or control. The HiSeq 2 500 sequencing showed that the rhizosphere bacterial community of soybean was composed of 20 phyla and 312 genera under combined stress， the number of phyla and genera was significantly less than that of the control and single pollutant treatment， and the relative abundances of bacteria with potential biological control and plant growth-promoting characteristics （such as Nocardioides and Sphingomonas） were reduced. Alpha diversity analysis showed that the combined stress significantly reduced the richness and diversity of the soybean rhizosphere bacterial community， and Beta diversity analysis showed that the combined stress significantly changed the structure of the bacterial community. The dominant flora of the rhizosphere bacterial community were regulated， and the abundances of secondary functional layers such as amino acid metabolism， energy metabolism， and lipid metabolism were reduced under combined stress by the analysis of LEfSe and PICRUSt2. It was inferred from the network analysis that the combined stress of HDPE and chlorimuron-ethyl reduced the total number of connections and network density of soil bacteria， simplified the network structure， and changed the important flora species to maintain the stability of the network. The results above indicated that the combined stress of HDPE and chlorimuron-ethyl significantly affected the growth of soybean and changed the rhizosphere bacterial community structure， soil function， and network structure. Compared with that of the single pollutant treatment， the potential risk of combined stress was greater. The results of this study can provide guidance for evaluating the ecological risks of polyethylene microplastics and chlorimuron-ethyl and for the remediation of contaminated soil.

Plant growth-promoting bacteria improve the Cd phytoremediation efficiency of soils contaminated with PE-Cd complex pollution by influencing the rhizosphere microbiome of sorghum.

Composite pollution by microplastics and heavy metals poses a potential threat to the soilplant system and has received increasing attention. Plant growth-promoting bacteria (PGPB) have good application potential for the remediation of combined microplastic and heavy metal pollution, but few related studies exist. The present study employed a pot experiment to investigate the effects of inoculation with the PGPB Bacillus sp. SL-413 and Enterobacter sp. VY-1 on sorghum growth and Cd accumulation under conditions of combined cadmium (Cd) and polyethylene (PE) pollution. Cd+PE composite contamination led to a significant reduction in sorghum length and biomass due to increased toxicity. Inoculation with Bacillus sp. SL-413 and Enterobacter sp. VY-1 alleviated the stress caused by Cd+PE complex pollution, and the dry weight of sorghum increased by 25.7% to 46.1% aboveground and by 12.3% to 45.3% belowground. Bacillus sp. SL-413 and Enterobacter sp. VY-1 inoculation increased the Cd content and accumulation in sorghum and improved the phytoremediation efficiency of Cd. The inoculation treatment effectively alleviated the nutrient stress caused by the reduction in soil mineral nutrients due to Cd+PE composite pollution. The composition of the soil bacterial communities was also affected by the Cd, Cd+PE and bacterial inoculation treatments, which affected the diversity of the soil bacterial communities. Network analyses indicated that bacterial inoculation regulated the interaction of rhizospheric microorganisms and increased the stability of soil bacterial communities. The Mantel test showed that the changes in the soil bacterial community and function due to inoculation with Bacillus sp. SL-413 and Enterobacter sp. VY-1 were important factors influencing sorghum growth and Cd remediation efficiency. The results of this study will provide new evidence for the research on joint plantmicrobe remediation of heavy metal and microplastic composite pollution.

[Transcriptome Analysis of Plant Growth-promoting Bacteria Alleviating Microplastic and Heavy Metal Combined Pollution Stress in Sorghum].

Microplastics can become potential transport carriers of other environmental pollutants (such as heavy metals), so the combined pollution of microplastics and heavy metals has attracted increasing attention from researchers. To explore the mechanism of plant growth-promoting bacteria VY-1 alleviating the combined pollution stress of heavy metals and microplastics in sorghum, the effects of inoculation on biomass and accumulation of heavy metals in sorghum were analyzed using a hydroponics experiment, and the effects of inoculation on gene expression in sorghum were analyzed via transcriptomics. The results showed that the combined pollution of polyethylene (PE) and cadmium (Cd) decreased the dry weight of above-ground and underground parts by 17.04% and 10.36%, respectively, compared with that under the single Cd pollution, which showed that the combined toxicity effect of the combined pollution on plant growth was enhanced. The inoculation of plant growth-promoting bacteria VY-1 could alleviate the toxicity of Cd-PE combined pollution and increase the length of aboveground and underground parts by 33.83% and 73.21% and the dry weight by 56.64% and 33.44%, respectively. Transcriptome sequencing showed that 904 genes were up-regulated after inoculation with VY-1. Inoculation with growth-promoting bacteria VY-1 could up-regulate the expression of several genes in the auxin, abscisic acid, flavonoid synthesis, and lignin biosynthesis pathways, which promoted the response ability of sorghum under Cd-PE combined pollution stress and improved its resistance. The above results indicated that plant growth-promoting bacteria could alleviate the stress of heavy metal and microplastic combined pollution by regulating plant gene expression, which provided a reference for plant-microbial joint remediation of heavy metal and microplastic combined pollution.

[Effects of Combined Pollution of Microplastics and Cadmium on Microbial Community Structure and Function of Pennisetum hydridum Rhizosphere Soil].

The combined pollution of microplastics and heavy metals can potentially interact. This may have an important impact on the growth and development of plants and the rhizosphere microbial community and function. In this study, the effects of heavy metal cadmium combined with different types of microplastics(PE and PS), different particle sizes(13 µm and 550 µm), and different concentrations(0.1% and 1%) on Pennisetum hydridum growth were studied under pot conditions. The results showed that the effects of the combined pollution of MPs and Cd on plant dry weight and Cd accumulation varied with different types, concentrations, and particle sizes of MPs, and the combined pollution stress increased, whereas the Cd content and Cd accumulation decreased. Metagenomic analysis showed that the combined contamination of MPs and Cd could change the composition of the bacterial community and reduce bacterial diversity, among which the ACE index and Chao1 index in the 550 µm 0.1% PE+Cd treatment group were the most significant. Metagenomic analysis of microbial species function showed that the main functional groups were metabolism, amino acid transport and metabolism, energy generation and conversion, and signal transduction mechanisms. Compared with that under single Cd pollution, the addition of MPs could change the gene abundance of functional groups such as metabolism, amino acid transport and metabolism, and energy generation and conversion, and the effects of different MPs types, concentrations, and particle sizes varied. In this study, metagenomics and amplification sequencing were used to analyze the effects of the combined pollution of MPs and Cd on the bacterial community and function in P. hydridum in order to provide basic data and scientific basis for the ecotoxicological effects of the combined heavy metal pollution of MPs and its biological remediation.

Associations between Phthalate Metabolite Concentrations in Follicular Fluid and Reproductive Outcomes among Women Undergoing in Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

BACKGROUND: Phthalates have been reported to impair fertility in various studies. However, evidence exploring the associations between phthalate metabolites in follicular fluid (FF) and reproductive outcomes is lacking. OBJECTIVES: To investigate the associations between phthalate metabolite concentrations in FF and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes among women recruited from a fertility clinic. METHODS: We included 641 women undergoing IVF/ICSI treatment from December 2018 to January 2020. The levels of eight phthalate metabolites, including monoethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), were quantified in FF collected on the oocyte retrieval day. Associations between quartiles of individual phthalate metabolite concentrations and nine IVF/ICSI outcomes, including oocyte yield, mature oocyte number, two distinct pronuclei (2PN) zygote number, fertilization rate, blastocyst formation rate, implantation, clinical pregnancy, miscarriage, and live birth, were estimated with generalized linear models. The effects of phthalate mixtures on IVF/ICSI outcomes were assessed using Bayesian kernel machine regression (BKMR) models. RESULTS: After adjusting for relevant confounders, elevated quartiles of MBzP, MEHHP, and MEHP in FF were inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes (all p for trends <0.10). In comparison with the lowest quartile, the highest quartile of molar sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) was associated with a reduction of 9.1% [95% confidence interval (CI): -17.1%, -0.37%] and 10.3% (95% CI: -18.8%, -0.94%) in yielded oocyte and mature oocyte numbers, respectively. Furthermore, the BKMR models revealed inverse associations between phthalate mixtures and the numbers of retrieved oocytes and mature oocytes. We generally found null results for implantation, clinical pregnancy, miscarriage, and live birth. DISCUSSION: Certain phthalate metabolites in FF are inversely associated with the numbers of retrieved oocytes, mature oocytes, and 2PN zygotes among women undergoing IVF/ICSI treatment. https://doi.org/10.1289/EHP11998.

Seneca Valley virus 3Cpro antagonizes host innate immune responses and programmed cell death.

Seneca Valley virus (SVV), a member of the Picornaviridae family, may cause serious water blister diseases in pregnant sows and acute death in newborn piglets, which have resulted in economic losses in pig production. The 3C protease is a vital enzyme for SVV maturation and is capable of regulating protein cleavage and RNA replication of the virus. Additionally, this protease can impede the host's innate immune response by targeting the interferon pathway's principal factor and enhance virus replication by modulating the host's RNA metabolism while simultaneously triggering programmed cell death. This article reviews recent studies on SVV 3C functions, which include viral replication promotion, cell apoptosis modulation and host immune response evasion, and provides a theoretical basis for research on preventing and controlling SVV infection.

Plant growth-promoting bacteria modulate gene expression and induce antioxidant tolerance to alleviate synergistic toxicity from combined microplastic and Cd pollution in sorghum.

Microplastics (MPs) can act as carriers for environmental pollutants; therefore, MPs combined with heavy metal pollution are attracting increasing attention from researchers. In this study, the potential of the plant growth-promoting bacterium Bacillus sp. SL-413 to mitigate the stress caused by exposure to both MPs and cadmium (Cd) in sorghum plants was investigated. The effects of inoculation on sorghum biomass were investigated using hydroponic experiments, and evaluation of Cd accumulation and enzyme activity changes and transcriptomics approaches were used to analyze its effect on sorghum gene expression. The results showed that combined polyethylene (PE) and Cd pollution reduced the length and the fresh and dry weights of sorghum plants and thus exerted a synergistic toxic effect. However, inoculation with the strains alleviated the stress caused by the combined pollution and significantly increased the biomass. Inoculation increased the dry weights of the aboveground and belowground parts by 11.5-44.6% and 14.9-38.4%, respectively. Plant physiological measurements indicated that inoculation reduced the reactive oxygen species (ROS) content of sorghum by 10.5-27.2% and thereby alleviated oxidative stress. Transcriptome sequencing showed that exposure to combined Cd+MP contamination induced downregulation of gene expression, particularly that of genes related to amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, and plant hormone signal transduction, in sorghum. However, inoculation with Bacillus sp. SL-413 resulted in an increase in the proportion of upregulated genes involved in signal transduction, antioxidant defense, cell wall biology, and other metabolic pathways, which included the phenylpropanoid biosynthesis, photosynthesis, flavonoid biosynthesis, and MAPK signaling pathways. The upregulation of these genes promoted the tolerance of sorghum under combined Cd+MP pollution stress and alleviated the stress induced by these conditions. This study provides the first demonstration that plant growth-promoting bacteria can alleviate the stress caused by combined pollution with MPs and Cd by regulating plant gene expression. These findings provide a reference for the combined plant-microbial remediation of MPs and Cd.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) Nsp5 antagonizes type I interferon signaling by cleaving DCP1A.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which is a recently discovered enteric coronavirus, is the major aetiological agent that causes severe clinical diarrhoea and intestinal pathological damage in pigs, and it has caused significant economic losses to the swine industry. Nonstructural protein 5, also called 3C-like protease, cleaves viral polypeptides and host immune-related molecules to facilitate viral replication and immune evasion. Here, we demonstrated that SADS-CoV nsp5 significantly inhibits the Sendai virus (SEV)-induced production of IFN-ß and inflammatory cytokines. SADS-CoV nsp5 targets and cleaves mRNA-decapping enzyme 1a (DCP1A) via its protease activity to inhibit the IRF3 and NF-κB signaling pathways in order to decrease IFN-ß and inflammatory cytokine production. We found that the histidine 41 and cystine 144 residues of SADS-CoV nsp5 are critical for its cleavage activity. Additionally, a form of DCP1A with a mutation in the glutamine 343 residue is resistant to nsp5-mediated cleavage and has a stronger ability to inhibit SADS-CoV infection than wild-type DCP1A. In conclusion, our findings reveal that SADS-CoV nsp5 is an important interferon antagonist and enhance the understanding of immune evasion by alpha coronaviruses.

Efficient detection of metronidazole by a glassy carbon electrode modified with a composite of a cyclotriveratrylene-based metal-organic framework and multi-walled carbon nanotubes.

Constructing a sensitive and efficient sensor for determination of metronidazole (MNZ) is crucial in food field. Herein, a new cyclotriveratrylene-based metal-organic framework (MOF), namely, [Cd6L2(cyclen)2(H2O)2] (1), was constructed by self-assembly of functionalized 5,6,12,13,19,20-hexacarboxy-propoxy-cyclotriveratrylene (H6L), 1,4,7,10-tetraazacyclododecane (cyclen) and Cd(II) cation under solvothermal condition. In 1, adjacent Cd(II) cations are linked by L6- to produce a 2D polymeric structure with carboxylate and phenolic oxygen atoms. To enhance conductivity of 1, it was combined with conducting carbon materials, including mesoporous carbon (MC), reduced graphene oxide (RGO) and multi-walled carbon nanotubes (MWCNT), respectively, producing a series of composite materials. Remarkably, electrochemical tests showed that 1@MWCNT(1:1) featured a much better electrochemical detection performance for metronidazole (MNZ) than 1@MC and 1@RGO. The linear range for the detection of MNZ is up to 0.4-500 µM and the limit of detection (LOD) for MNZ reached 0.25 µM. Importantly, the fabricated sensor 1@MWCNT(1:1) was employed for the detection of MNZ in honey and egg with satisfactory result. High-performance liquid chromatography (HPLC) validated the high accuracy of the electrochemical method for the determination of honey and egg.

[Solid-solution Partitioning Coefficients and Environmental Risk of Cd and Pb in Soil in Chang-Zhu-Tan Area].

The leaching risk of heavy metals in soil has a large spatial variability on a regional scale. Taking the Chang-Zhu-Tan area as the research object, this work studied the distribution and influencing factors of available contents and solid-solution partition coefficient (Kd) of Cd and Pb in soil with land uses and clarified the environmental risk of heavy metals in soil based on Kd values measured by CaCl2 (soil-to-water ratio, 1:0.5). The results showed that the contents of available Cd and Pb in soil followed the order of forest land>suburban farmland>urban green space>industrial green space. The average Kd of Cd in soil was 449.79 L·kg-1, and that of Pb was 27604.07 L·kg-1, indicating that the mobility of Cd in the soil was significantly higher than that of Pb. The Kd values of forest soil were significantly lower than that in the other land uses. The Kd values were mainly affected by soil pH and the total content of heavy metals in soil. Adopting the available content of heavy metals measured by CaCl2 (soil-to-water ratio, 1:10) as a dependent variable, the multiple regressions effectively predicted the Kd values of Cd and Pb in soil, with R2 values of 84.2% and 67.6%, respectively. The environmental risk assessment indicated that the leaching risk in 93.8%-96.1% of the sampling sites could be ignored, whereas a few sampling sites near factories with low pH may pose a risk to the groundwater environment. The mobility of heavy metals in soil and the distribution of pollution sources determined the leaching risk of heavy metals. The results provide a method and theoretical support for preventing the environmental risk of heavy metals in soil on a regional scale.

LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma.

Human microproteins encoded by long non-coding RNAs (lncRNA) have been increasingly discovered, however, complete functional characterization of these emerging proteins is scattered. Here, we show that LINC00493-encoded SMIM26, an understudied microprotein localized in mitochondria, is tendentiously downregulated in clear cell renal cell carcinoma (ccRCC) and correlated with poor overall survival. LINC00493 is recognized by RNA-binding protein PABPC4 and transferred to ribosomes for translation of a 95-amino-acid protein SMIM26. SMIM26, but not LINC00493, suppresses ccRCC growth and metastatic lung colonization by interacting with acylglycerol kinase (AGK) and glutathione transport regulator SLC25A11 via its N-terminus. This interaction increases the mitochondrial localization of AGK and subsequently inhibits AGK-mediated AKT phosphorylation. Moreover, the formation of the SMIM26-AGK-SCL25A11 complex maintains mitochondrial glutathione import and respiratory efficiency, which is abrogated by AGK overexpression or SLC25A11 knockdown. This study functionally characterizes the LINC00493-encoded microprotein SMIM26 and establishes its anti-metastatic role in ccRCC, and therefore illuminates the importance of hidden proteins in human cancers.

Glucose Biosensor Based on Glucose Oxidase Immobilized on BSA Cross-Linked Nanocomposite Modified Glassy Carbon Electrode.

Glucose sensors based blood glucose detection are of great significance for the diagnosis and treatment of diabetes because diabetes has aroused wide concern in the world. In this study, bovine serum albumin (BSA) was used to cross-link glucose oxidase (GOD) on a glassy carbon electrode (GCE) modified by a composite of hydroxy fullerene (HFs) and multi-walled carbon nanotubes (MWCNTs) and protected with a glutaraldehyde (GLA)/Nafion (NF) composite membrane to prepare a novel glucose biosensor. The modified materials were analyzed by UV-visible spectroscopy (UV-vis), transmission electron microscopy (TEM), and cyclic voltammetry (CV). The prepared MWCNTs-HFs composite has excellent conductivity, the addition of BSA regulates MWCNTs-HFs hydrophobicity and biocompatibility, and better immobilizes GOD on MWCNTs-HFs. MWCNTs-BSA-HFs plays a synergistic role in the electrochemical response to glucose. The biosensor shows high sensitivity (167 µA·mM-1·cm-2), wide calibration range (0.01-3.5 mM), and low detection limit (17 µM). The apparent Michaelis-Menten constant Kmapp is 119 µM. Additionally, the proposed biosensor has good selectivity and excellent storage stability (120 days). The practicability of the biosensor was evaluated in real plasma samples, and the recovery rate was satisfactory.

Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance.

INTRODUCTION: Acquired resistance to BRAF inhibitor vemurafenib is frequently observed in metastatic colorectal cancer (CRC), and it is a thorny issue that results in treatment failure. As adaptive responses for vemurafenib treatment, a series of cellular bypasses are response for the adaptive feedback reactivation of ERK signaling, which warrant further investigation. OBJECTIVES: We identified ARF1 (ADP-ribosylation factor 1) as a novel regulator of both vemurafenib resistance and cancer metastasis, its molecular mechanism and potential inhibitor were investigated in this study. METHODS: DIA-based quantitative proteomics and RNA-seq were performed to systematic analyze the profiling of vemurafenib-resistant RKO cells (RKO-VR) and highly invasive RKO cells (RKO-I8), respectively. Co­immunoprecipitation assay was performed to detect the interaction of ARF1 and IQGAP1 (IQ-domain GTPase activating protein 1). An ELISA-based drug screen system on FDA-approved drug library was established to screen the compounds against the interaction of ARF1-IQGAP1.The biological functions of ARF1 and LY2835219 were determined by transwell, western blotting, Annexin V-FITC/PI staining and in vivo experimental metastasis assays. RESULTS: We found that ARF1 strongly interacted with IQGAP1 to activate ERK signaling in VR and I8 CRC cells. Deletion of IQGAP1 or inactivation of ARF1 (ARF-T48S) restored the invasive ability induced by ARF1. As ARF1-IQGAP1 interaction is essential for ERK activation, we screened LY2835219 as novel inhibitor of ARF1-IQGAP1 interaction, which inactivated ERK signaling and suppressed CRC metastasis and vemurafenib-resistance in vitro and in vivo with no observed side effect. Furthermore, LY2835219 in combined treatment with vemurafenib exerted significantly inhibitory effect on ARF1-mediated cancer metastasis than used independently. CONCLUSION: This study uncovers that ARF1-IQGAP1 interaction-mediated ERK signaling reactivation is critical for vemurafenib resistance and cancer metastasis, and that LY2835219 is a promising therapeutic agent for CRC both as a single agent and in combination with vemurafenib.

A five-protein prognostic signature with GBP2 functioning in immune cell infiltration of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is of poor clinical outcomes, and currently lacks reliable prognostic biomarkers. By analyzing the datasets of the Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), we established a five-protein prognostic signature containing GBP2, HLA-DRA, ISG15, ISG20 and ITGAX. Our data indicate that this signature was closely correlated with advanced stage, higher pathological grade, and unfavorable survivals in patients with ccRCC. We further functionally characterized GBP2. Overexpression of GBP2 enhanced the phosphorylation of STAT2 and STAT3 to trigger JAK-STAT signaling and promote cell migration and invasion in ccRCC. Treatment of Ruxolitinib, a specific inhibitor of JAK/STAT, attenuated the GBP2-mediated phenotypes. Patients with high GBP2 expression were accompanied with more infiltration of immune cells positively stained with CD3, CD8, CD68, and immune checkpoint markers PD-1 and CTLA4, which was validated by Opal multiplex immunohistochemistry in ccRCC tissues. More CD8 + T cells and CD68 + macrophages were observed in patients expressing high GBP2. Taken together, a five-protein prognostic signature was constructed in our study. GBP2 has an oncogenic role via modulating JAK-STAT signaling and tumor immune infiltration, and thus may serve as a potential therapeutic target in ccRCC.

Medium chain triglycerides improve the growth performance, immune and antioxidant functions, and intestinal health of weaned rabbits.

The purpose is to study the effects of different doses of medium chain triglyceride (MCT) on growth performance, immune and oxidative functions, and intestinal health of weaned rabbits. A total of 600 weaned rabbits weighing about 993.26 g and at 35 d of age were randomly divided into five groups. The control group was fed a basal diet containing 2400 mg/kg soybean oil, and the experimental group was substituted with 600, 1200, 1800, and 2400 mg/kg MCT. The whole trial period lasted for 48 d. The results showed that treatment with 2400 mg/kg MCT significantly increased the weaning survival rate and crude fat digestibility (p < 0.05) and dramatically raised the levels of serum immunoglobulin (Ig)A, IgG, IgM, catalase, superoxide dismutase, and total antioxidant capability (p < 0.05). The villus height and crypt depth in 1800 mg/kg MCT group were observably enhanced (p < 0.05). The abundance of Bacteroidetes was significantly increased in 1800 and 2400 mg/kg MCT groups (p < 0.05). In conclusion, 1800 and 2400 mg/kg MCT substituting soybean oil in the diet of weaned rabbits can improve the growth performance and intestinal barrier function of weaned rabbits.

[Effect of Butyl Xanthate on Pb2+ and Cd2+ Adsorption by Soil Around a Dressing Plant].

Flotation agents can enter the soil and water environment around mining areas through beneficiation wastewater discharge and overflow from tailings ponds. The adsorption of Pb2+ and Cd2+ on soil around a lead-zinc dressing plant was investigated in the presence of potassium butyl xanthate (PBX). Batch experiments were conducted with different initial pH, PBX, Pb2+, and Cd2+solution concentrations. The fractions of lead and cadmium were altered after treatment with different concentrations of PBX. The results showed that adsorption of Pb2+and Cd2+ on soil was seriously inhibited by PBX. When PBX concentration was 40 mg·L-1, the adsorption capacity of Pb2+ and Cd2+ decreased from 3540 mg·kg-1 and 387 mg·kg-1 to 3085 mg·kg-1 and 100 mg·kg-1, respectively. The Pb2+ and Cd2+ adsorption kinetic process was best fitted by the quasi-second-order kinetic model, which indicated that the adsorption process of Pb2+ and Cd2+ on soil was mainly chemical adsorption. The formation of a hydrophobic and insoluble complex and competitive adsorption between PBX, Pb2+, and Cd2+ on the soil surface was the main reason for reducing the adsorption capacity. The results showed that PBX could increase the mobility of Pb2+ and Cd2+ on soil. The degree of impact improved with increasing initial concentration of PBX and pH but decreased with increasing initial concentration of Pb2+ and Cd2+, and the adsorption isotherms conformed to the Freundlich isotherm. Under low PBX content (100 mg·kg-1), exchangeable and reducible cadmium contents in the soil increased, which could lead to the activation of cadmium in soil. However, the addition of PBX to the treated soil could reduce the content of exchangeable and reducible lead. As the concentration of PBX increased, the reduction effect also increased, which was related to the stronger complex stability of Pb(C4H9OCS2)2 than that of Cd(C4H9OCS2)2. The results showed that residual flotation reagents in beneficiation wastewater may increase the potential ecological risk of heavy metals such as Pb and Cd in soil, and the prevention and control of the potential ecological risk should be strengthened.

Inhibition of GSDMD Activates Poly(ADP-ribosyl)ation and Promotes Myocardial Ischemia-Reperfusion Injury.

The precise control of cardiomyocyte viability is imperative to combat myocardial ischemia-reperfusion injury (I/R), in which apoptosis and pyroptosis putatively contribute to the process. Recent researches indicated that GSDMD is involved in I/R as an executive protein of pyroptosis. However, its effect on other forms of cell death is unclear. We identified that GSDMD and GSDMD-N levels were significantly upregulated in the I/R myocardium of mice. Knockout of GSDMD conferred the resistance of the hearts to reperfusion injury in the acute phase of I/R but aggravated reperfusion injury in the chronic phase of I/R. Mechanistically, GSDMD deficiency induced the activation of PARylation and the consumption of NAD+ and ATP, leading to cardiomyocyte apoptosis. Moreover, PJ34, a putative PARP-1 inhibitor, reduced the myocardial injury caused by GSDMD deficiency. Our results reveal a novel action modality of GSDMD in the regulation of cardiomyocyte death; inhibition of GSDMD activates PARylation, suggesting the multidirectional role of GSDMD in I/R and providing a new theory for clinical treatment.

The Seasonal Patterns, Ecological Function and Assembly Processes of Bacterioplankton Communities in the Danjiangkou Reservoir, China.

As the water source for the Middle Route Project of the South-to-North Water Diversion Project (MR-SNWD) of China, the Danjiangkou Reservoir (DJR) is in the process of ecosystem reassembly, but the composition, function, and assembly mechanisms of bacterioplankton communities are not yet clear. In this study, the composition, distribution characteristics and influencing factors of bacterioplankton communities were analyzed by high-throughput sequencing (HTS); PICRUSt2 was used to predict community function; a molecular ecological network was used to analyze bacterioplankton interactions; and the assembly process of bacterioplankton communities was estimated with a neutral model. The results indicated that the communities, function and interaction of bacterioplankton in the DJR had significant annual and seasonal variations and that the seasonal differences were greater than that the annual differences. Excessive nitrogen (N) and phosphorus (P) nutrients in the DJR are the most important factors affecting water quality in the reservoir, N and P nutrients are the main factors affecting bacterial communities. Season is the most important factor affecting bacterioplankton N and P cycle functions. Ecological network analysis indicated that the average clustering coefficient and average connectivity of the spring samples were lower than those of the autumn samples, while the number of modules for the spring samples was higher than that for the autumn samples. The neutral model explained 66.3%, 63.0%, 63.0%, and 70.9% of the bacterioplankton community variations in samples in the spring of 2018, the autumn of 2018, the spring of 2019, and the autumn of 2019, respectively. Stochastic processes dominate bacterioplankton community assembly in the DJR. This study revealed the composition, function, interaction, and assembly of bacterioplankton communities in the DJR, providing a reference for the protection of water quality and the ecological functions of DJR bacterioplankton.

The complete chloroplast genome of Bothriochloa ischaemum.

Bothriochloa ischaemum (Linn.) 1936 is a high-quality perennial forage in Loess Plateau of China. In this study, we sequenced and characterized the complete chloroplast genome of B. ischaemum, which was a circular DNA of 138,316 bp in length, including a large single copy (LSC) region of 80,226 bp, a small single copy (SSC) region of 12,526 bp, and the circular DNA was separated by a pair of identical inverted repeat regions (IRs) of 22,782 bp each. A total of 134 genes were identified, including 87 protein-coding genes, 39 tRNA genes, and eight rRNA genes. Phylogenetic tree showed that B. ischaemum was closer to B. decipiens and B. alta, genus Bothriochloa was closely related to genus Pseudanthistiria. Our findings will be helpful for better understanding of genetic diversity of Bothriochloa plants.