Dual thermal ecotypes coexist within a nearly genetically identical population of the unicellular marine cyanobacterium Synechococcus.

The extent and ecological significance of intraspecific functional diversity within marine microbial populations is still poorly understood, and it remains unclear if such strain-level microdiversity will affect fitness and persistence in a rapidly changing ocean environment. In this study, we cultured 11 sympatric strains of the ubiquitous marine picocyanobacterium Synechococcus isolated from a Narragansett Bay (RI) phytoplankton community thermal selection experiment. Thermal performance curves revealed selection at cool and warm temperatures had subdivided the initial population into thermotypes with pronounced differences in maximum growth temperatures. Curiously, the genomes of all 11 isolates were almost identical (average nucleotide identities of >99.99%, with >99% of the genome aligning) and no differences in gene content or single nucleotide variants were associated with either cool or warm temperature phenotypes. Despite a very high level of genomic similarity, sequenced epigenomes for two strains showed differences in methylation on genes associated with photosynthesis. These corresponded to measured differences in photophysiology, suggesting a potential pathway for future mechanistic research into thermal microdiversity. Our study demonstrates that present-day marine microbial populations can harbor cryptic but environmentally relevant thermotypes which may increase their resilience to future rising temperatures.

Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer.

BACKGROUND: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. METHODS: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. RESULTS: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. CONCLUSION: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.

Clinical characteristics and risk factors for late-onset pneumocystis jirovecii pneumonia in kidney transplantation recipients.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a common and troublesome complication of kidney transplantation. In the era of prophylaxis, the peak incidence of PJP after kidney transplantation and specific characteristics of late-onset PJP have always been debated. METHODS: We performed a retrospective study by analysing the data of post-transplantation pneumonia in adult kidney transplantation recipients between March 2014 and December 2021 in The Affiliated First Hospital of University of Science and Technology of China (USTC). A total of 361 patients were included and divided into early-onset PJP, late-onset PJP and non-PJP groups. The characteristics of each group and related risk factors for the late-onset patients were investigated. RESULTS: Some patients developed PJP 9 months later with a second higher occurrence between month 10 and 15 after transplantation. Compared with non-PJP, ABO-incompatible and cytomegalovirus (CMV) viremia were significantly associated with late onset of PJP in multivariate analysis. The use of tacrolimus, CMV viremia, elevated CD8(+) T cell percent and hypoalbuminemia were risk factors for late PJP. Receiver operating characteristic curve analysis demonstrated that a combination of those factors could increase the sensitivity of prediction remarkably, with an area under the curve of 0.82, a sensitivity of 80% and a specificity of 83%. CONCLUSIONS: PJP could occur months after kidney transplantation. ABO-incompatible transplant recipients are at high risk of PJP. In the later stages of transplantation, CMV viremia, T lymphocyte subsets percentage and serum albumin levels should be monitored in patients using tacrolimus.

Expression of long non-coding RNA GAS5 by first trimester screening predicts the occurrence of gestational hypertension and pre-eclampsia.

AIMS: Hypertensive disorders of pregnancy (HDP) is a unique disease during gestational period, which is detrimental to pregnancy outcome. This study examined the clinical significance of long non-coding RNA GAS5 in gestational hypertension (GH) and preeclampsia (PE), aiming to explore potential biomarkers for the disease detection. METHODS: 180 pregnant women with HPD including 90 cases with GH and 90 cases with PE, and another 100 healthy pregnant women were enrolled. Serum GAS5 levels were measured by RT-qPCR method. The diagnostic performance of GAS5 was assessed in GH and PE through plotting receiver operating characteristic (ROC) curve. Logistic regression was applied for the identification of independent factors. RESULTS: Elevated serum GAS5 was identified in GH patients, and its diagnostic performance in discriminating GH cases from healthy people was determined by ROC curve. Serum GAS5 was positively associated with SBP, DBP, LDL-C and CRP values. Cases with PE had an increased serum GAS5 level relative to those with GH. Serum GAS5 was identified to be an independent predictor for PE, and can differentiate PE cases from GH ones. with a good diagnositc performance. Cases with high levels of serum GAS5 had a high risk of poor pregnancy outcomes. CONCLUSION: Elevated serum GAS5 could serve as an effective diagnostic biomarker in discriminating GH patients from healthy people by first trimester screening. Detection of serum GAS5 level has a certain predictive value for PE.

Deep learning, geometric characterization and hydrodynamic modeling for assessing sewer defect impacts on urban flooding: A case study in Guangzhou, China.

Deep learning techniques have offered innovative and efficient tools for accurate and automated detection of sewer defects by leveraging large-scale sewer data and advanced feature learning algorithms. However, there has been a lack of thorough characterization of the geometric properties of segmented defects, let alone systematically calculate the severity level of sewer defects and quantitatively evaluate their impacts on flood conditions in hydrodynamic models. This study proposed a comprehensive framework and related metrics to accurately and automatically detect, segment, characterize, and evaluate the impacts of sewer defects on flooded nodes and volumes by integrating a DeepLabv3+-based segmentation technique, an automated geometric characterization and severity quantification module, and a GIS and SWMM-based hydrodynamic modeling. The results clearly showed in details where and how much the urban flooding was affected by the different defect types. The segmentation model achieved satisfactory detection performance, with mean pixel accuracy (MPA), mean intersection over union (MIoU), and frequency weighted intersection over union (FWIoU) of 0.99, 0.74 and 0.95, respectively. In terms of severity level quantification, there were 98%, 90%, 90% and 83% of predictions consistent with real conditions for falling off, obstacle, disjoint and leakage. It was shown that the number of surcharging manholes and total flood volume (TFV) were greatly affected by sewer defects, with over 16% increase in TFVs under all investigated rainfall events. The results addressed the impacts of sewer defects on urban flooding and demonstrated the powerful tools provided by the proposed framework for decision-making on sewer defect detection and management.

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OBJECTIVES: To investigate the risk factors for the failure of ibuprofen treatment in preterm infants with hemodynamically significant patent ductus arteriosus (hsPDA). METHODS: A retrospective collection of clinical data was conducted on preterm infants with a gestational age of <34 weeks who were diagnosed with hsPDA and treated at the Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, from January 2018 to June 2023. The subjects were divided into two groups based on the treatment approach: the ibuprofen group (95 cases) and the ibuprofen plus surgery group (44 cases). The risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA were identified by binary logistic regression analysis. RESULTS: The binary logistic regression analysis revealed that an increased diameter of the ductus arteriosus, a resistance index (RI) value of the middle cerebral artery ≥0.80, and prolonged total invasive mechanical ventilation time were risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). Receiver operating characteristic curve analysis showed that a ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days had significant predictive value for the failure of ibuprofen treatment in preterm infants with hsPDA (P<0.05). The combined predictive value of these three factors was the highest, with an area under the curve of 0.843, a sensitivity of 86.5%, and a specificity of 75.0% (P<0.05). CONCLUSIONS: A ductus arteriosus diameter >2.85 mm, a middle cerebral artery RI value ≥0.80, and a total invasive mechanical ventilation time >16 days are risk factors for the failure of ibuprofen treatment in preterm infants with hsPDA, and they are of significant predictive value for the necessity of surgical treatment following the failure of ibuprofen treatment.

Biallelic mutations in LSS in autosomal-recessive mutilating palmoplantar keratoderma.

Mutilating palmoplantar keratoderma (PPK) is a heterogeneous genetic disease that poses enormous challenges to clinical diagnosis and genetic counselling. Lanosterol synthase (LSS) gene encodes LSS involved in the biosynthesis pathway of cholesterol. Biallelic mutations in LSS were found to be related to diseases such as cataracts, hypotrichosis and palmoplantar keratoderma-congenital alopecia syndrome. The aim of this study was to investigate the contribution of the LSS mutation to mutilating PPK in a Chinese patient. The clinical and molecular characteristics of the patient were evaluated. A 38-year-old male patient with mutilating PPK was recruited in this study. We identified biallelic variants in the LSS gene (c.683C > T, p.Thr228Ile and c.779G > A, p.Arg260His). Immunoblotting revealed that the Arg260His mutant showed a significantly reduced expression level while Thr228Ile showed an expression level similar to that of the wild type. Thin layer chromatography revealed that mutant Thr228Ile retained partial enzymatic activity and mutant Arg260His did not show any catalytic activity. Our findings show the correlation between LSS mutations and mutilating PPK.

Advancing targeted protein degradation for metabolic diseases therapy.

The development and application of traditional drugs represented by small molecule chemical drugs and biological agents, especially inhibitors, have become the mainstream drug development. In recent years, targeted protein degradation (TPD) technology has become one of the most promising methods to remove specific disease-related proteins using cell self-destruction mechanisms. Many different TPD strategies are emerging based on the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), including but not limited to proteolysis-targeting chimeras (PROTAC), molecular glues (MG), lysosome targeting chimeras (LYTAC), chaperone-mediated autophagy (CMA)-targeting chimeras, autophagy-targeting chimera (AUTAC), autophagosome-tethering compound (ATTEC), and autophagy-targeting chimera (AUTOTAC). The advent of targeted degradation technology can change most protein targets in human cells from undruggable to druggable, greatly expanding the therapeutic prospect of refractory diseases such as metabolic syndrome. Here, we summarize the latest progress of major TPD technologies, especially in metabolic syndrome and look forward to providing new insights for drug discovery.

Berberine inhibits breast carcinoma proliferation and metastasis under hypoxic microenvironment involving gut microbiota and endogenous metabolites.

A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16 S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35 µM, 26.53 ± 3.12 µM and 11.62 ± 1.44 µM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.

Design and synthesis of 1H-pyrazolo[3,4-d]pyrimidine derivatives as hematopoietic progenitor kinase 1 (HPK1) inhibitors.

Despite immune checkpoint inhibitors' tremendous success in the treatment of tumors, the moderate response rate limits their widespread use. Hematopoietic progenitor kinase 1 (HPK1) is served as an essential negative regulator of T-cell receptor, which has been identified as a promising target for enhancing antitumor immunity. However, the development of a selective HPK1 inhibitor is still challenging. Herein, we reported a novel series of 1H-pyrazolo[3,4-d]pyrimidine derivatives as HPK1 inhibitors by structure-based rational design. The optimal compound 10n significantly inhibited HPK1 with an IC50 value of 29.0 nM and the phosphorylation of SLP76 at a concentration as low as 0.1 µM. Furthermore, compound 10n exhibited good selectivity over a panel of 25 kinases, including GLK from the same MAP4K family. Together, the current study provided a novel, potent, and selective HPK1 inhibitor, acting as a lead compound for the future development of cancer immunotherapy.

Host genetics and gut microbiota jointly regulate blood biochemical indicators in chickens.

Blood biochemical indicators play a crucial role in assessing an individual's overall health status and metabolic function. In this study, we measured five blood biochemical indicators, including total cholesterol (CHOL), low-density lipoprotein cholesterol (LDL-CH), triglycerides (TG), high-density lipoprotein cholesterol (HDL-CH), and blood glucose (BG), as well as 19 growth traits of 206 male chickens. By integrating host whole-genome information and 16S rRNA sequencing of the duodenum, jejunum, ileum, cecum, and feces microbiota, we assessed the contributions of host genetics and gut microbiota to blood biochemical indicators and their interrelationships. Our results demonstrated significant negative phenotypic and genetic correlations (r = - 0.20 ~ - 0.67) between CHOL and LDL-CH with growth traits such as body weight, abdominal fat content, muscle content, and shin circumference. The results of heritability and microbiability indicated that blood biochemical indicators were jointly regulated by host genetics and gut microbiota. Notably, the heritability of HDL-CH was estimated to be 0.24, while the jejunal microbiability for BG and TG reached 0.45 and 0.23. Furthermore, by conducting genome-wide association study (GWAS) with the single-nucleotide polymorphism (SNPs), insertion/deletion (indels), and structural variation (SV), we identified RAP2C, member of the RAS oncogene family (RAP2C), dedicator of cytokinesis 11 (DOCK11), neurotensin (NTS) and BOP1 ribosomal biogenesis factor (BOP1) as regulators of HDL-CH, and glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5), dihydrodiol dehydrogenase (DHDH), and potassium voltage-gated channel interacting protein 1 (KCNIP1) as candidate genes of BG. Moreover, our findings suggest that cecal RF39 and Clostridia_UCG_014 may be linked to the regulation of CHOL, and jejunal Streptococcaceae may be involved in the regulation of TG. Additionally, microbial GWAS results indicated that the presence of gut microbiota was under host genetic regulation. Our findings provide valuable insights into the complex interaction between host genetics and microbiota in shaping the blood biochemical profile of chickens. KEY POINTS: • Multiple candidate genes were identified for the regulation of CHOL, HDL-CH, and BG. • RF39, Clostridia_UCG_014, and Streptococcaceae were implicated in CHOL and TG modulation. • The composition of gut microbiota is influenced by host genetics.

Cerium Synchronous Doping in Anatase for Enhanced Photocatalytic Hydrogen Production from Ethanol-Water Mixtures.

Cerium element with a unique electric structure can be used to modify semiconductor photocatalysts to enhance their photocatalytic performances. In this work, Ce-doped TiO2 (Ce/TiO2) was successfully achieved using the sol-gel method. The structural characterization methods confirm that Ce was doped in the lattice of anatase TiO2, which led to a smaller grain size. The performance test results show that the Ce doped in anatase TiO2 significantly enhances the charge transport efficiency and broadens the light absorption range, resulting in higher photocatalytic performance. The Ce/TiO2 exhibited a photocurrent density of 10.9 µA/cm2 at 1.0 V vs. Ag/AgCl, 2.5 times higher than that of pure TiO2 (4.3 µA/cm2) under AM 1.5 G light. The hydrogen (H2) production rate of the Ce/TiO2 was approximately 0.33 µmol/h/g, which is more than twice as much as that of the pure anatase TiO2 (0.12 µmol/h/g). This work demonstrates the effect of Ce doping in the lattice of TiO2 for enhanced photocatalytic hydrogen production.

Elucidation of the melitidin biosynthesis pathway in pummelo.

Specialized plant metabolism is a rich resource of compounds for drug discovery. The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate, but its biosynthetic route in plants has not yet been fully characterized. Here, we describe the gene discovery and functional characterization of a new flavonoid gene cluster (UDP-glucuronosyltransferases (CgUGTs), 1,2 rhamnosyltransferase (Cg1,2RhaT), acyltransferases (CgATs)) that is responsible for melitidin biosynthesis in pummelo (Citrus grandis (L.) Osbeck). Population variation analysis indicated that the tailoring of acyltransferases, specific for bitter substrates, mainly determine the natural abundance of melitidin. Moreover, 3-hydroxy-3-methylglutaryl-CoA reductase enzyme inhibition assays showed that the product from this metabolic gene cluster, melitidin, may be an effective anti-cholesterol statin drug candidate. Co-expression of these clustered genes in Nicotiana benthamiana resulted in the formation of melitidin, demonstrating the potential for metabolic engineering of melitidin in a heterologous plant system. This study establishes a biosynthetic pathway for melitidin, which provides genetic resources for the breeding and genetic improvement of pummelo aimed at fortifying the content of biologically active metabolites.

Circular RNA circ-RCCD promotes cardiomyocyte differentiation in mouse embryo development via recruiting YY1 to the promoter of MyD88.

Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of live births. Genetic and environmental factors are leading factors to CHD, but the mechanism of CHD pathogenesis remains unclear. Circular RNAs (circRNAs) are kinds of endogenous non-coding RNAs (ncRNAs) involved in a variety of physiological and pathological processes, especially in heart diseases. In this study, three significant differently expressed circRNA between maternal embryonic day (E) E13 and E17 was found by microarray assay. Among them, the content of circ-RCCD increases with the development of heart and was enriched in primary cardiomyocytes of different species, which arouses our attention. Functional experiments revealed that inhibition of circ-RCCD dramatically suppressed the formation of beating cell clusters, the fluorescence intensity of cardiac differentiation marker MF20, and the expression of the myocardial-specific markers CTnT, Mef2c, and GATA4. Next, we found that circ-RCCD was involved in cardiomyocyte differentiation through negative regulation of MyD88 expression. Further experiments proved that circ-RCCD inhibited MyD88 levels by recruiting YY1 to the promoter of MyD88; circ-RCCD inhibited nuclear translocation of YY1. These results reported that circ-RCCD promoted cardiomyocyte differentiation by recruiting YY1 to the promoter of MyD88. And, this study provided a potential role and molecular mechanism of circ-RCCD as a target for the treatment of CHD.

Functional nanovesicles displaying anti-PD-L1 antibodies for programmed photoimmunotherapy.

BACKGROUND: Photoimmunotherapy is one of the most promising strategies in tumor immunotherapies, but targeted delivery of photosensitizers and adjuvants to tumors remains a major challenge. Here, as a proof of concept, we describe bone marrow mesenchymal stem cell-derived nanovesicles (NVs) displaying anti-PD-L1 antibodies (aPD-L1) that were genetically engineered for targeted drug delivery. RESULTS: The high affinity and specificity between aPD-L1 and tumor cells allow aPD-L1 NVs to selectively deliver photosensitizers to cancer tissues and exert potent directed photothermal ablation. The tumor immune microenvironment was programmed via ablation, and the model antigen ovalbumin (OVA) was designed to fuse with aPD-L1. The corresponding membrane vesicles were then extracted as an antigen-antibody integrator (AAI). AAI can work as a nanovaccine with the immune adjuvant R837 encapsulated. This in turn can directly stimulate dendritic cells (DCs) to boast the body's immune response to residual lesions. CONCLUSIONS: aPD-L1 NV-based photoimmunotherapy significantly improves the efficacy of photothermal ablation and synergistically enhances subsequent immune activation. This study describes a promising strategy for developing ligand-targeted and personalized cancer photoimmunotherapy.

Correlation between nutrition, oral health, and different sarcopenia groups among elderly outpatients of community hospitals: a cross-sectional study of 1505 participants in China.

BACKGROUND: Studies have rarely explored the association between oral health status and different sarcopenia groups (possible sarcopenia, diagnosed sarcopenia, and severe sarcopenia). Moreover, these studies have not reported any definitive conclusions of their relationship. We aimed to characterize the oral health status, prevalence of sarcopenia, and risk factors in different sarcopenia groups of elderly outpatients of community hospitals. Furthermore, we determined the correlation among nutrition, oral health, and different sarcopenia groups. METHODS: Overall, 1505 elderly participants (aged ≥ 65 years) completed the survey. The Mini Nutritional Assessment short-form (MNA-SF) was used to assess the nutrition status of the elderly. Oral health was assessed using the instrument of the oral health assessment index of the elderly (General Oral Health Assessment Index [GOHAI]), and the number of remaining natural teeth (NRT) was counted. Data on muscle mass, muscle strength, and gait speed were collected, and sarcopenia was classified into three groups (possible sarcopenia, diagnosed sarcopenia, and severe sarcopenia) according to the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression multivariate analysis was used to test their relationships. RESULTS: Eighty-eight (5.8%) participants were identified as having possible sarcopenia; 142 (9.5%), diagnosed sarcopenia; 136 (9.0%), severe sarcopenia; and 1139 (75.7%), no sarcopenia. Of the seven variables, advancing age was typically associated with an increasing prevalence of sarcopenia (odds ratio [OR] = 1.06-1.47, 95% confidence interval [CI] = 1.06-1.47). The results showed that household income (OR = 0.57, 95% CI = 0.33-0.98), education level (OR = 3.32, 95% CI = 1.09-10.07), and chronic diseases (OR = 0.34, 95% CI = 0.19-0.62) were significantly associated with the severe sarcopenia group. Physical activity scores were significantly associated with the diagnosed sarcopenia and severe sarcopenia groups. Participants with < 20 NRT were more likely to have diagnosed sarcopenia (OR = 5.55, 95% CI = 3.80-8.12) or severe sarcopenia (OR = 6.66, 95% CI = 4.13-10.76) than participants with > 20 NRT. The GOHAI score was associated with the diagnosed sarcopenia (OR = 5.55, 95% CI = 3.80-8.12) and severe sarcopenia (OR = 6.66, 95% CI = 4.13-10.78) groups. The MNA-SF score was associated with the different sarcopenia groups. CONCLUSIONS: Assessing early and improving lifestyle with respect to nutrition and oral health may be an effective way to reduce or delay the occurrence of sarcopenia.

TNF-α derived from arsenite-induced microglia activation mediated neuronal necroptosis.

Arsenic, an identified environmental toxicant, poses threats to the health of human beings through contaminated water and food. Recently, increasing reports focused on arsenic-induced nerve damage, however, the underlying mechanism remains elusive. Microglia are important immune cells in the nervous system, which produce a large number of inflammatory factors including TNF-α when activated. Recent reports indicated that TNF-α is involved in the process of necroptosis, a new type of programmed cell death discovered recently. Although there were evidences suggested that arsenic could induce both microglia activation and TNF-α production in the nervous system, the mechanism of arsenic-induced neurotoxicity due to microglia activation is rarely studied. In addition, the role of microglia-derived TNF-α in response to arsenic exposure in necroptosis has not been documented before. In this study, we found that arsenite induced microglial activation through p38 MAPK signaling pathway, leading to the production of TNF-α. Microglia-derived TNF-α further induced necroptosis in the neuronal cells. Our findings suggested that necroptosis induced by microglia-derived TNF-α upon arsenite exposure partially played a role in arsenic-induced cell death which underlie the fundamental event of arsenic-related neurotoxicity.

FASTNN: A Deep Learning Approach for Traffic Flow Prediction Considering Spatiotemporal Features.

Traffic flow forecasting is a critical input to intelligent transportation systems. Accurate traffic flow forecasting can provide an effective reference for implementing traffic management strategies, developing travel route planning, and public transportation risk assessment. Recent deep learning approaches of spatiotemporal neural networks to predict traffic flow show promise, but could be difficult to separately model the spatiotemporal aggregation in traffic data and intrinsic correlation or redundancy of spatiotemporal features extracted by the filter of the convolutional network. This can introduce biases in the predictions that interfere with subsequent planning decisions in transportation. To solve the mentioned problem, the filter attention-based spatiotemporal neural network (FASTNN) was proposed in this paper. First, the model used 3-dimensional convolutional neural networks to extract universal spatiotemporal dependencies from three types of historical traffic flow, the residual units were employed to prevent network degradation. Then, the filter spatial attention module was constructed to quantify the spatiotemporal aggregation of the features, thus enabling dynamic adjustment of the spatial weights. To model the intrinsic correlation and redundancy of features, this paper also constructed a lightweight module, named matrix factorization based resample module, which automatically learned the intrinsic correlation of the same features to enhance the concentration of the model on information-rich features, and used matrix factorization to reduce the redundant information between different features. The FASTNN has experimented on two large-scale real datasets (TaxiBJ and BikeNYC), and the experimental results show that the FASTNN has better prediction performance than various baselines and variant models.

Peptide Biomarkers Discovery for Seven Species of Deer Antler Using LC-MS/MS and Label-Free Approach.

Deer antler is a globally widely used precious natural medicine and the material of deer horn gelatin. However, identification of deer antler species based on traditional approaches are problematic because of their similarity in appearance and physical-chemical properties. In this study, we performed a comprehensive antler peptidome analysis using a label-free approach: nano LC-Orbitrap MS was applied to discover peptide biomarkers in deer adult beta-globin (HBBA), and HPLC-Triple Quadrupole MS was used to verify their specificity. Nineteen peptide biomarkers were found, on which foundation a strategy for antlers and a strategy for antler mixtures such as flakes or powder are provided to identify seven species of deer antler including Eurasian elk (Alces alces), reindeer (Rangifer tarandus), white-tailed deer (Odocoileus viginianus), white-lipped deer (Przewalskium albirostris), fallow deer (Dama dama), sika deer (Cervus nippon), and red deer (Cervus elaphus) simultaneously. It is worth noting that our search found that the HBBA gene of sika deer, red deer, and North American wapiti (Cervus canadensis) in China may have undergone severe genetic drifts.

Cerium-Doped Iron Oxide Nanorod Arrays for Photoelectrochemical Water Splitting.

In this work, a simple one-step hydrothermal method was employed to prepare the Ce-doped Fe2O3 ordered nanorod arrays (CFT). The Ce doping successfully narrowed the band gap of Fe2O3, which improved the visible light absorption performance. In addition, with the help of Ce doping, the recombination of electron/hole pairs was significantly inhibited. The external voltage will make the performance of the Ce-doped sample better. Therefore, the Ce-doped Fe2O3 has reached superior photoelectrochemical (PEC) performance with a high photocurrent density of 1.47 mA/cm2 at 1.6 V vs. RHE (Reversible Hydrogen Electrode), which is 7.3 times higher than that of pristine Fe2O3 nanorod arrays (FT). The Hydrogen (H2) production from PEC water splitting of Fe2O3 was highly improved by Ce doping to achieve an evolution rate of 21 µmol/cm2/h.