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Background Acute myeloid leukemia (AML) is a myeloid neoplasm accounts for 7.6% of hematopoietic malignancies. AML is a complex disease, and understanding its pathophysiology is contributing to the improvement in the treatment and prognosis of AML. In this study, we assessed the expression profile and molecular functions of CCAAT enhancer binding protein gamma (CEBPG), a gene implicated in myeloid differentiation and AML progression. Methods shRNA mediated gene interference was used to down-regulate the expression of CEBPG in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells. Genes and pathways affected by knockdown of CEBPG were identified by gene expression analysis using RNA-seq. One of the genes affected by knockdown of CEBPG was Eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1), a known repressor of translation. Knockdown of EIF4EBP1 was used to assess its potential role in AML progression downstream of CEBPG. Results We explored the ChIP-Seq data of AML cell lines and non-AML hematopoietic cells, and found CEBPG was activated through its distal enhancer in AML cell lines. Using the public transcriptomic dataset, the Cancer Cell Line Encyclopedia (CCLE) and western blotting, we also found CEBPG was overexpressed in AML. Moreover, we observed that CEBPG promotes AML cell proliferation by activating EIF4EBP1, thus contributing to the progression of AML. These findings indicate that CEBPG could act as a potential therapeutic target for AML patients. Conclusion In summary, we systematically explored the molecular characteristics of CEBPG in AML and identified CEBPG as a potential therapeutic target for AML patients. Our findings provide novel insights into the pathophysiology of AML and indicate a key role for CEBPG in promoting AML progression.

Background Wenzhou virus (WENV), a newly discovered mammarenavirus in rodents, is associated with fever and respiratory symptoms in humans. This study was aimed to detect and characterize the emerging virus in rodents in Guangzhou, China. Results A total of 100 small mammals, including 70 Rattus norvegicus, 22 Suncus murinus, 4 Bandicota indica, 3 Rattus flavipectus, and 1 Rattus losea, were captured in Guangzhou, and their brain tissues were collected and pooled for metagenomic analysis, which generated several contigs targeting the genome of WENV. Two R. norvegicus (2.9%) were further confirmed to be infected with WENV by RT-PCR. The complete genome (RnGZ37-2018 and RnGZ40-2018) shared 85.1–88.9% nt and 83.2–96.3% aa sequence identities to the Cambodian strains that have been shown to be associated with human disease. Phylogenetic analysis showed that all identified WENV could be grouped into four different lineages, and the two Guangzhou strains formed an independent clade. We also analyzed the potential recombinant events occurring in WENV strains. Conclusions Our study showed a high genetic diversity of WENV strains in China, emphasizing the relevance of surveillance of this emerging mammarenavirus in both natural reservoirs and humans.

Nonalcoholic fatty liver disease (NAFLD) is a chronic disease caused by excessive fat accumulation in the liver in addition to alcohol consumption and other pathological factors. The incidence of NAFLD is rapidly growing, currently affecting 25% of the world population. Exosomes are extracellular vesicles containing a variety of biological molecules, including microRNAs (miRNAs). To monitor the expression of exosomal microRNAs in the NAFLD. In this study, five nonalcoholic fatty liver patients were included in the disease group, and five simple obesity patients were included in the control group. Exosomes from NAFLD patient serum were collected, and exosomal miRNAs were extracted. Exosomes were isolated and then confirmed by electron microscopy, nanoparticle tracking analysis (NTA) and western blotting. High-throughput sequencing methods were used to determine the expression profile of exosome-derived miRNAs. The sequencing results revealed that a total of 2588 miRNAs were identified. The expression of 80 miRNAs significantly differed between the NAFLD and control groups, including 30 upregulated and 50 downregulated miRNAs. miR-122-5p, miR‐27a, and miR‐335-5p may play an important role in NAFLD. Finally, GO and KEGG analyses were applied to explore the function of miRNA targets. Collectively, this study identified some key exosomal miRNAs and pathways in NAFLD that might be used as molecular targets or diagnostic biomarkers for NAFLD.

Infigratinib (INF) is a promising selective inhibitor of fibroblast growth factor receptors 1-3 that has recently been accorded both orphan drug designation and priority review status by the U.S Food and Drug Administration for the treatment of advanced cholangiocarcinoma. Its propensity to undergo bioactivation to electrophilic species was recently expounded upon. However, other than causing aberrant idiosyncratic toxicities, these reactive intermediates may elicit mechanism-based inactivation (MBI) of cytochrome P450 enzymes (CYP450). In this study, we investigated the interactions between INF and the most abundant hepatic cytochrome P450 3A4 (CYP3A4). Our findings revealed that apart from being a potent noncompetitive reversible inhibitor of CYP3A4, INF inactivated CYP3A4 in a time-, concentration- and NADPH-dependent manner with KI, kinact and partition ratio of 2.45 µM, 0.053 min-1 and 41 respectively when rivaroxaban was employed as the probe substrate. Co-incubation with testosterone (alternative CYP3A substrate) or ketoconazole (direct CYP3A inhibitor) attenuated the rate of inactivation whereas the inclusion of glutathione and catalase did not confer such protection. The lack of enzyme activity recovery following dialysis for 4 hours and oxidation with potassium ferricyanide, coupled with the absence of the characteristic Soret peak signature collectively substantiated that inactivation of CYP3A4 by INF was not mediated by the formation of quasi-irreversible metabolite-intermediate complexes but rather through irreversible covalent adduction to the prosthetic heme and/or apoprotein. Finally, glutathione trapping and high-resolution mass spectrometry experimental results unravelled two plausible bioactivation mechanisms of INF arising from the generation of a p-benzoquinone diimine and epoxide reactive intermediate. Significance Statement The potential of infigratinib (INF) to cause mechanism-based inactivation (MBI) of CYP3A4 was unknown. We report the reversible noncompetitive inhibition and irreversible covalent MBI of CYP3A4 by INF and proposed two potential bioactivation pathways implicating p-benzoquinone diimine and epoxide reactive intermediates. Findings from this study lay the groundwork for future investigation of clinically-relevant drug-drug interactions between INF and concomitant substrates of CYP3A4.

A detailed knowledge on the spatial distribution of pests is crucial for predicting population outbreaks or developing control strategies and sustainable management plans. The diamondback moth, Plutella xylostella, is one of the most destructive pests of cruciferous crops worldwide. Despite the abundant research on the species’s ecology, little is known about the spatio-temporal pattern of P. xylostella in an agricultural landscape. Therefore, in this study, the spatial distribution of P. xylostella was characterized to assess the effect of landscape elements in a fine-scale agricultural landscape by geostatistical analysis. The P. xylostella adults captured by pheromone-baited traps showed a seasonal pattern of population fluctuation from October 2015 to September 2017, with a marked peak in spring, suggesting that mild temperatures, 15–25 °C, are favorable for P. xylostella. Geostatistics (GS) correlograms fitted with spherical and Gaussian models showed an aggregated distribution in 21 of the 47 cases interpolation contour maps. This result highlighted that spatial distribution of P. xylostella was not limited to the Brassica vegetable field, but presence was the highest there. Nevertheless, population aggregations also showed a seasonal variation associated with the growing stage of host plants. GS model analysis showed higher abundances in cruciferous fields than in any other patches of the landscape, indicating a strong host plant dependency. We demonstrate that Brassica vegetables distribution and growth stage, have dominant impacts on the spatial distribution of P. xylostella in a fine-scale landscape. This work clarified the spatio-temporal dynamic and distribution patterns of P. xylostella in an agricultural landscape, and the distribution model developed by geostatistical analysis can provide a scientific basis for precise targeting and localized control of P. xylostella.

Several nairo-like viruses have been discovered in ticks in recent years, but their relevance to public health remains unknown. Here, we found a patient who had a history of tick bite and suffered from a febrile illness was infected with a previously discovered RNA virus, Beiji nairovirus (BJNV), in the nairo-like virus group of the order Bunyavirales. We isolated the virus by cell culture assay. BJNV could induce cytopathic effects in the baby hamster kidney and human hepatocellular carcinoma cells. Negative-stain electron microscopy revealed enveloped and spherical viral particles, morphologically similar to those of nairoviruses. We identified 67 patients as BJNV infection in 2017–2018. The median age of patients was 48 years (interquartile range 41–53 years); the median incubation period was 7 days (interquartile range 3–12 days). Most patients were men (70%), and a few (10%) had underlying diseases. Common symptoms of infected patients included fever (100%), headache (99%), depression (63%), coma (63%), and fatigue (54%), myalgia or arthralgia (45%); two (3%) patients became critically ill and one died. BJNV could cause growth retardation, viremia and histopathological changes in infected suckling mice. BJNV was also detected in sheep, cattle, and multiple tick species. These findings demonstrated that the newly discovered nairo-like virus may be associated with a febrile illness, with the potential vectors of ticks and reservoirs of sheep and cattle, highlighting its public health significance and necessity of further investigation in the tick-endemic areas worldwide.

Premise of research. The geographic origin of Pinus krempfii Lecomte, an unusual pine endemic to Vietnam, is unknown, as are the fossil relatives of this species. Its affinity and classification ar...

During investigation of pathogenic Alternaria in China, nine Alternaria isolates were obtained from two Caryophyllaceae plants. Based on morphological and multilocus phylogenetic approaches and pathogenicity tests, three pathogenic species of Alternaria including two new species and a new record in China were identified. Phylogenetically, the present species were confirmed and grouped within two clades out of three in section Gypsophilae: clade I (Alternaria hispanica sp. nov. and A. vaccariae) and clade II (Alternaria barbata sp. nov.). Morphological comparison was conducted between the two new species and their closely related ones which verified the phylogenetic results. The two novel species were described and illustrated here.

Background Pet dogs are important companion animals that share the environment within households, and play an important role in local community life. In addition, pet dogs also are reservoirs of zoonotic agents, including Rickettsia spp., thus increasing the risk of rickettsial infections in humans. It’s meaningful to investigate the epidemiology of rickettsial agents in pet dogs, and make contribute to the surveillance of rickettsioses in human in China. Results In this study, a total of 496 pet dogs’ blood samples and 343 ticks infested in pet dogs were collected, and the presence and prevalence of Rickettsia were determined by amplifying the partial gltA and 17-kDa genes, with an overall positive rate of 8.1 % in blood samples and 14.0 % in tick samples. In addition, the rrs, gltA, groEL, and ompA genes of rickettsial were also recovered to determine the species of Rickettsia detected furtherly. Sequencing blast and phylogenetic analyses revealed the presence of three human pathogenic Rickettsia species (Rickettsia raoultii, Candidatus Rickettsia tarasevichiae and Rickettsia felis) in samples associated with pet dogs. Moreover, all the sequences of Rickettsia that we obtained presented close relationship with others available in GenBank, and Rickettsia raoultii was the most predominant Rickettsia species infected in pet dogs’ blood samples or in tick samples. Conclusions This study provides the molecular epidemiology data about the Rickettsia spp. infection associated with pet dogs in urban areas of Harbin city. Three rickettisae species pathogenic to humans were identified from pet dogs’ blood and the infested ticks in urban areas of Harbin city. Considering the intimate relationship between human and pets, these results indicate the potential transmission risk of human rickettisal infections from pet dogs through ectoparasites, and also highlighting that more attention should be paid to rickettsial infection in pet dogs and the infested ticks from the “One health” perspective.

The plastid genome of the deep-shade plant Selaginella erythropus, which has highly unusual chloroplasts, was characterized using Illumina pair-end sequencing. This plastome is 140,151 bp in length...

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2 (ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-CoV-2. We analyzed clinical data, genetic data, and receptor binding capability. Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal renin-angiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19 progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations (V354F and V470A) by receptor-ligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354F and V470A mutants has increased with the development of the SARS-CoV-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.新型冠状病毒肺炎(COVID-19)是由严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2)引起的一种大流行疾病，目前正在全球范围内迅速蔓延，其传播速度快，死亡人数高。迄今为止，尚无针对COVID-19的有效治疗或疫苗。血管紧张素转化酶2 (ACE2)和刺突蛋白（spike）在COVID-19治疗中的作用是当前的研究重点。在本研究中，我们探索了ACE2和spike作为靶点开发抗SARS-CoV-2病毒药物的潜力。我们分析了临床数据、测序数据和受体结合能力。其中，临床资料显示，COVID-19合并肾素-血管紧张素系统异常的患者早期症状多，预后差。然而，ACE2表达水平与COVID-19进展之间的关系尚不清楚。因此，ACE2可能不是一个很好的靶标适用于治疗不同人群的COVID-19。根据序列分析，与ACE2相互作用的spike-S1受体结合区域有许多氨基酸突变。通过受体-配体对接和ELISA试验，我们鉴定了两个spike-S1点突变体(V354F和V470A)。这些变异增强了spike蛋白与ACE2受体的结合，可能与突变体传染性增加有关。更重要的是，随着SARS-CoV-2的流行，感染V354F或V470A突变体的患者数量正在增加。这些结果表明，ACE2和spike-S1可能不适用设计广泛用于治疗不同人群COVID-19的药物理想靶点。.

Background: We sought to investigate whether the expression of the gene EIF2S2 is related to 18F-FDG PET/CT metabolic parameters in patients with colorectal cancer (CRC). Materials and methods: The expression of EIF2S2 in CRC and its relationship with clinicopathological features were obtained through the ONCOMINE, UALCAN and GEPIA databases. EIF2S2 and GLUT1 expression were examined by immunohistochemistry in 42 CRC patients undergoing preoperative PET-CT examination. Spearman correlation analysis was used to assess the relationship between EIF2S2 and GLUT1 levels and clinical parameters. Correlation analysis between EIF2S2 and Reactome-Glycolysis signatures was performed using GEPIA2. We describe the effect of EIF2S2 knockdown on lactate production and the mRNA levels of glycolysis-related genes in human colon cancer SW480 cells. Results: Immunohistochemistry revealed an upregulation of EIF2S2 protein expression in tumor tissues of colorectal cancer patients, which is consistent with the significant upregulation of EIF2S2 transcript levels in the database. These colorectal cancer patients included 24 cases of colon cancer and 18 cases of rectal cancer, ranging in age from 31 to 78 years. The transcription was significantly related to histological subtypes and TP53 mutations (P

Background: Carcinoembryonic antigen (CEA) is one of the important indexes for the diagnosis and prognosis of gastrointestinal cancer. Systemic inflammatory response (SIR) is closely related to the occurrence and development of gastrointestinal cancer. Methods: A total of 803 patients who underwent radical gastrectomy in Qinghai University Affiliated Hospital from January 2012 to December 2016 were included as training set. Multivariable Cox proportional hazard regression was used to identify associations with outcome of gastric cancer (GC). CNLR was established by combining CEA and the neutrophils to lymphocytes ratio (NLR, a typical parameter in SIR) to generate a novel prognostic score system and its prognostic value was externally validated. Results: Multivariate analysis showed that CEA and NLR were independent prognostic factors for GC patients (both p < 0.05). A higher CNLR was significantly associated with older age, male sex, larger tumor size, vascular invasion and advanced stages (all p < 0.05). Patients with higher CNLR had poor prognosis than those with lower CNLR (p < 0.05). Multivariate analysis showed that CNLR was an independent prognostic factor (p < 0.05). Incorporation of the CNLR into a prognostic model including age and TNM stage generated a nomogram, which predicted accurately 3- and 5-year survival for GC patients. And similar results were obtained in the external validation set. Conclusions: The CNLR prognostic scoring system established by combining CEA and NLR is an independent prognostic factor for GC, which can be incorporated into the traditional TNM staging to improve the prediction of long-term survival outcomes.

Cytochrome P450 genes are involved in the catalysis of various reactions, including growth, development and secondary metabolite biosynthetic pathways. However, little is known about the characteristics and functions of the P450 gene family in Chinese cabbage (Brassica rapa L. ssp. pekinensis). In this study, we identified 258 non-redundant members of the cytochrome P450 gene superfamily in Brassica. rapa from Brassica database (http://www.brassicadb.cn). We also did transcriptomic data mining derived from abiotic/biotic stresses and developmental related RNA-seq in Chinese cabbage. These differentially expressed genes (DEGs) were involved in cadmium (Cd) detoxification, salinity tolerance, calcium signaling transduction and homeostasis, pathogen triggered immunity and leafy head formation in Chinese cabbage. These P450 genes are essential candidates for a better understanding of the mechanism of P450 genes, which help Chinese cabbage adapt to environmental changes.

Sympathetic stimulated-cardiac fibrosis imposes great significance on both disease progression and survival in the pathogenesis of many cardiovascular diseases. However, there are few effective therapies targeting it clinically. The cardioprotective effect of aldehyde dehydrogenase 2 (ALDH2) has been explored in many pathological conditions, whether it can exert benefit effects on chronic sympathetic stimulus-induced cardiac fibrosis remains unclear. In this study, we determined to explore the role of ALDH2 on isoproterenol (ISO)-induced cardiac fibroblasts (CF) proliferation and cardiac fibrosis. It was found that ALDH2 enzymatic activity was impaired in ISO-induced HCF proliferation and Aldh2 deficiency promoted mouse CF proliferation. Alda-1, an ALDH2 activator, exerted obvious suppressive effect on ISO-induced HCF proliferation, together with the induction of cell cycle arrest at G0/G1 phase and decreased expression of cyclin E1 and cyclin-dependent kinase 2 (CDK2). Mechanistically, the inhibitory role of Alda-1 on HCF proliferation was achieved by decreasing mitochondrial reactive oxygen species (ROS) production, which was partially reversed by rotenone, an inducer of ROS. In addition, wild-type mice treated with Alda-1 manifested with reduced fibrosis and better cardiac function after ISO pump. In summary, Alda-1 alleviates sympathetic excitation-induced cardiac fibrosis via decreasing mitochondrial ROS accumulation, highlighting ALDH2 activity as a promising drug target of cardiac fibrosis.

BACKGROUND Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease (AD) patients. Exogenous neural stem cells (NSCs) improve the damaged nerve function. The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment. AIM To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment. METHODS NSCs were isolated from pregnant senescence-accelerated mouse resistant 1 (SAMR1) mice, labeled with BrdU, and injected into the hippocampus of senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old senescence-accelerated mice (SAM) were randomly divided into six groups: SAMR1 (RC), SAMP8 (PC), sham transplantation (PS), NSC transplantation (PT), NSC transplantation with acupuncture (PTA), and NSC transplantation with non-acupoint acupuncture (PTN). Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation. Hematoxylin-eosin staining and immunofluorescence were used to observe the his-topathological changes and NSC proliferation in mice. A co-culture model of hippocampal slices and NSCs was established in vitro, and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment. RESULTS Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8, which improved in all the NSC transplantation groups. The behavioral change in the PTA group was stronger than those in the other two groups (P < 0.05). Histopathologically, the hippocampal structure was clear, the cell arrangement was dense and orderly, and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group. The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups, and the number increased significantly in the PTA group than in the PT and PTN groups (P < 0.05). Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro, the synaptophysin expression in the PC group decreased in comparison to the RC group, that in PT, PTA, and PTN groups increased as compared to the PC group, and that in the PTA group increased significantly as compared to the PTN group with acupoint-related specificity (P < 0.05). CONCLUSION Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.

Leaf spot of soapberry, Sapindus mukorossi is a disease new to China. The disease significantly reduces not only the plant’s ornamental value but also its medicinal properties. Identification of pathogens timely assists preventing and controlling this disease. In July 2019, foliage of soapberry on the campus of Nanjing Forestry University, China, was infected by the disease, and the disease incidence was 96%. Symptomatic leaves were collected from three infected trees. After isolating the fungus, its pathogenicity was tested to satisfy Koch’s postulates, and the culture was identified based on its morphological features and multi-gene phylogenetic analyses. Isolates WHZ3 and YB1 from the diseased leaves were identified as Diaporthe biconispora, and the identification was confirmed using morphological features and multi-gene phylogenetic analyses derived from an internal transcribed spacer (ITS), elongation factor 1-alpha (EF1-α), beta-tubulin (β-tub), histone H3 (HIS), and calmodulin (CAL). Koch’s postulates proved the fungus to be a pathogen on soapberry. Diaporthe biconispora was previously reported as an endophyte in plants of the Citrus group, but was shown to be pathogenic to soapberry causing leaf spots.

The effect of POC1 centriolar protein A (POC1A) on gastric cancer (GC) has not been clearly defined. In this study, POC1A expression and clinical information in patients with GC were analyzed. Multiple databases were used to investigate the genes that were co-expressed with POC1A and genes whose changes co-occurred with genetic alternations of POC1A. Moreover, the TISIDB and TIMER databases were used to analyze immune infiltration. The GSE54129 GC dataset and LASSO regression model (tumor vs. normal) were employed, and 6 significant differentially expressed genes (LAMP5, CEBPB, ARMC9, PAOX, VMP1, POC1A) were identified. POC1A was selected for its high expression in adjacent tissues, which was confirmed with IHC. High POC1A expression was related to better overall and recurrence-free survival. GO and KEGG analyses demonstrated that POC1A may regulate the cell cycle, DNA replication and cell growth. Furthermore, POC1A was found to be correlated with immune infiltration levels in GC according to the TISIDB and TIMER databases. These findings indicate that POC1A acts as a tumor suppressor in GC by regulating the cell cycle and cell growth. In addition, POC1A preferentially regulates the immune infiltration of GC via several immune genes. However, the specific mechanism requires further study.

Pachyphlodes atropurpurea and P. excavata are described as new species of truffles based on both phylogenetic and morphological analyses. Phylogenetically these two species are clearly distinct from described species of Pachyphlodes. Morphologically, P. atropurpurea is characterized by subglobose, purple black ascomata, and ascospores with acute-tipped spines. P. excavata is characterized by its ascomata with an obvious basal and internal cavity and slender fusiform asci (150–180 × 30–40 μm).

We found that a rice NADPH oxidase gene OsRbohB contributes drought tolerance and its functions are involved in the interaction of the OsRbohB-mediated ROS production and ABA signaling. The plasma membrane NADPH oxidases, also known as respiratory burst oxidase homologs, are the key producers of ROS under both normal and stress conditions in plants. However, their functions in rice development and stress tolerance are still under investigation. Here, we found that a rice NADPH oxidase gene OsRbohB, also named OsNOX1, is expressed in all tissues examined throughout the development stages with higher transcripts in leaves. The transcriptional expression of OsRbohB is also strongly stimulated by dehydration, salt and several phytohormonal treatments. Compared with wide-type and the OsRbohB-overexpressing transgenic plants, osrbohB, a Tos17 insertion knockout mutant of OsRbohB, shows lower ROS production, abscisic acid (ABA) content and transcripts of a series of stress-related genes. The osrbohB mutant also exhibits lower seed germination rate, organ size and thousand seed weight, but higher stomatal aperture and sensitivity to drought. Moreover, a number of genes involved in plant development, stress response, transcriptional regulation, and particularly ABA signaling are differentially expressed in osrbohB plants under both normal growth and drought conditions. All these results suggest the roles of OsRbohB in drought tolerance of rice, which probably performed through the interaction of the OsRbohB-mediated ROS production and ABA signaling.

CD8 T‐cells are an essential component of the adaptive immune response accountable for the clearance of virus‐infected cells via cytotoxic effector functions. Maintaining a specific metabolic profile is necessary for these T‐cells to sustain their effector functions and clear pathogens. When CD8 T‐cells are activated via T‐cell receptor recognition of viral antigen, they transition from a naïve to an effector state and eventually to a memory phenotype, and their metabolic profiles shift as the cells differentiate to accomidate different metabolic demands. However, in the context of particular chronic viral infections (CVIs), CD8 T‐cells can become metabolically dysfunctional in a state known as T‐cell exhaustion. In this state, CD8 T‐cells exhibit reduced effector functions and are unable to properly control pathogens. Clearing these chronic infections becomes progressively difficult as increasing numbers of the effector T‐cells become exhausted. Hence, reversal of this dysfunctional metabolic phenotype is vital when considering potential treatments of these infections and offers the opportunity for novel strategies for the development of therapies against CVIs. In this review we explore research implicating alteration of the metabolic state as a means to reverse CD8 T‐cell exhaustion in CVIs. These findings indicate that strategies targeting dysfunctional CD8 T‐cell metabolism could prove to be a promising option for successfully treating CVIs.

Coxiella burnetii is the causative agent of query fever (Q fever), and distributes broadly in environment. Livestock are identified as main reservoirs, which may infect people through their contaminative urine, feces, milk, and birth products. Wild animals can also be the potential carriers and transmitters of C. burnetii. To understand the geographic distribution and host species of C. burnetii in China, we investigated the prevalence of C. burnetii in hedgehogs (Erinaceus amurensis) in Hubei Province. Hedgehogs were tested for C. burnetii with PCR targeting three genes (com1, rrs, and icd) followed by multispacer sequence typing (MST). We found that 12.2% (5/41) hedgehogs were PCR positive for C. burnetii. MST revealed presence of two novel genotypes and phylogenetic analysis revealed that the strains were similar to a group of isolates from chronic Q fever patients and mammals. This study showed that C. burnetii are highly prevalent in hedgehogs in Hubei Province in central China, suggesting that hedgehogs may play an important role in the ecology and transmission of C. burnetii to humans because it is captured and used as traditional medicine in China.

Background Toward identifying new strategies to target gastric cancer stem-like cells (CSCs), we evaluated the function of the tumour suppressor CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) in gastric CSC maintenance. Methods We examined the expression of CDK5RAP3 and CD44 in gastric cancer patients. The function and mechanisms of CDK5RAP3 were checked in human and mouse gastric cancer cell lines and in mouse xenograft. Results We show that CDK5RAP3 is weakly expressed in gastric CSCs and is negatively correlated with the gastric CSC marker CD44. CDK5RAP3 overexpression decreased expression of CSC markers, spheroid formation, invasion and migration, and reversed chemoresistance in gastric CSCs in vitro and vivo. CDK5RAP3 expression was found to be regulated by extracellular-related kinase (ERK) signalling. ERK inhibitors decreased spheroid formation, migration and invasion, and the expression of epithelial-to-mesenchymal transition (EMT)-related proteins in both GA cells and organoids derived from a genetically engineered mouse model of GA. Finally, CDK5RAP3 expression was associated with reduced lymph-node metastasis and better prognosis, even in the presence of high expression of the EMT transcription factor Snail, among patients with CD44-positive GA. Conclusions Our results demonstrate that CDK5RAP3 is suppressed by ERK signalling and negatively regulates the self-renewal and EMT of gastric CSCs.

Background BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. Methods We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. Results BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. Conclusions Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment.

Significance Burkholderia pseudomallei is a bacterial pathogen that causes melioidosis, an infectious disease in the tropics with high morbidity and mortality. It has a unique property among bacteria: to fuse infected host cells. We found that our immune system detects bacterial- or chemical-induced host cell fusion as a danger signal. Abnormal cell fusion leads to genomic instability and formation of micronuclei. This triggers the host to activate a signaling pathway leading to a form of cell death known as autophagic death, which likely serves to limit abnormal cellular transformation., Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease in the tropics and subtropics with high morbidity and mortality. The facultative intracellular bacterium induces host cell fusion through its type VI secretion system 5 (T6SS5) as an important part of its pathogenesis in mammalian hosts. This allows it to spread intercellularly without encountering extracellular host defenses. We report that bacterial T6SS5-dependent cell fusion triggers type I IFN gene expression in the host and leads to activation of the cGAMP synthase–stimulator of IFN genes (cGAS–STING) pathway, independent of bacterial ligands. Aberrant and abortive mitotic events result in the formation of micronuclei colocalizing with cGAS, which is activated by double-stranded DNA. Surprisingly, cGAS–STING activation leads to type I IFN transcription but not its production. Instead, the activation of cGAS and STING results in autophagic cell death. We also observed type I IFN gene expression, micronuclei formation, and death of chemically induced cell fusions. Therefore, we propose that the cGAS–STING pathway senses unnatural cell fusion through micronuclei formation as a danger signal, and consequently limits aberrant cell division and potential cellular transformation through autophagic death induction.

Objective The immune inflammation-based score is recognized as a prognostic marker for cancer. However, the most accurate prognostic marker for patients with gastric cancer remains undetermined. We aimed to evaluate the predictive value of the lymphocyte-to-C-reactive protein ratio for outcomes in gastric cancer patients after radical gastrectomy. Methods A total of 607 gastric cancer patients treated at three Chinese institutions were included. Receiver operating characteristic curves were generated, and the areas under the curve were calculated to compare the predictive value among the inflammation-based score, lymphocyte-to-C-reactive protein ratio, C-reactive protein/albumin and neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios. Cox regression was performed to determine the prognostic factors for overall survival. Results The median follow-up time was 63 months (range: 1–84 months). The optimal cut-off value for lymphocyte-to-C-reactive protein ratio was 0.63. The patients were divided into the LCR Conclusions Preoperative lymphocyte-to-C-reactive protein ratio levels can effectively predict the short-term and oncological efficacy of gastric cancer patients after radical gastrectomy with a predictive value significantly better than other inflammation-based score.

Chemical investigation into the stems of the medicinal plant Schisandra sphaerandra led to the isolation and identification of a new dibenzocyclooctadiene lignan sphaerandrin A (1) and 11 known ones gomisin B (2), schirubrisin B (3), kadsuphilin B (4), schizandrin (5), benzoylgomisin Q (6), angeloylgomisin Q (7), gomisin G (8), schisanwilsonin O (9), isogomisin O (10), schisantherin D (11), and wuweizisu C (12). The structure of the new compound was elucidated by comprehensive spectroscopic methods including 1 D/2D NMR, HRESIMS, and CD spectrometry. To the best of our knowledge, compounds 2 – 11 were obtained from this species for the first time. All the compounds were evaluated for the cytotoxic activity against the triple-negative breast cancer cell lines MDA-MB-231 and HCC-1937.

Background: To investigate the expression of methyltransferase 3 (METTL3) and its relationship with 18F-FDG uptake in patients with esophageal carcinoma (ESCA). Materials and methods: This study analyzed the expression of METTL3 in ESCA and its relationship with clinicopathological features by The Cancer Genome Atlas (TCGA) database. Immunohistochemical staining was performed on 57 tumor tissues of ESCA patients who underwent PET/CT scan before surgery to evaluate the expression of METTL3, glucose transporter 1 (GLUT1), and hexokinase 2 (HK2) in tumor tissues and peritumoral tissues. Analyze the relationship between SUVmax with METTL3, HK2, and GLUT1 expression. Results: The expression of METTL3, GLUT1, and HK2 was significantly increased in ESCA tissues compared with normal tissues (p < 0.001). The expression of METTL3 was correlated with tumor size and histological differentiation (p < 0.05), and there was no significant difference between age, sex, pathological types, tumor staging, or lymph node metastasis (p > 0.05). The SUVmax was significantly higher in tumors with high METTL3 expression (17.822±6.249) compared to low METTL3 expression (9.573±5.082) (p < 0.001). There was a positive correlation between the SUVmax and METTL3 expression in ESCA (r2 = 0.647, p < 0.001). Multivariate analysis confirmed the association between SUVmax and METTL3 expression (p < 0.05). GLUT1 and HK2 expression in ESCA was positively correlated with 18F-FDG uptake and METTL3 status (p < 0.001). Conclusions: The high expression of METTL3 is related to the high SUVmax in ESCA, and METTL3 may increase 18F-FDG uptake by regulating GLUT1 and HK2.

Background: Leptospira is the causative agent of leptospirosis, a zoonotic disease of global importance. To have a better understanding on the host species of Leptospira, we investigated the preval...

Hygrophorus subsect. Hygrophorus has been relatively well-studied in Europe and North America, but studies on the taxa in Asia, particularly in China, are still limited. In this study, phylogenetic overviews of genus Hygrophorus, based on the nuclear large subunit (LSU) ribosomal RNA gene and of subsect. Hygrophorus, based on the nuclear ribosomal internal transcribed spacer (ITS) regions were generated. Four new species, i.e. H. brunneodiscus, H. fuscopapillatus, H. glutiniceps and H. griseodiscus are described from southern China; and a rarely reported edible species H. hedrychii is described in detail, based upon the materials from north-eastern China. The main characteristics of the species under subsect. Hygrophorus worldwide are summarised in a table.

The life table is a type of research tool that is frequently used in many studies involving population and community ecology. They are the basis for many comprehensive studies in pest management, pesticide resistance, predator-prey relationships, biological control, mass-rearing and harvesting of insects, plant resistance, etc. Because the morphology, physiology, survival, fecundity, and predation/consumption rate of most arthropods will vary significantly depending on their developmental stage and sex, precise description of stage differentiation and inclusion of both sexes are critical for attaining realistic and accurate life table analyses and correctly evaluating the overall fitness of populations. Since traditional female age-specific life tables ignore the male individuals in a population and are incapable of describing the unique and important feature of stage differentiation (i.e., metamorphosis) that is a defining characteristic of insects and mites, their application to data analysis involving these groups will inevitably result in miscalculations and limit the practical application of these life tables. On the other hand, the age-stage, two-sex life table (hereafter referred to as the two-sex life table whenever appropriate), can precisely delineate stage differentiation and includes both sexes in data analysis, description, and interpretation, and in practical applications. In this review, the problems of female age-specific life tables are examined, followed by a discussion of the advantages of using the two-sex life table. Finally, applications of the two-sex life table in various types of entomological research are discussed and accompanied by examples.

Background In clinical practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most common markers measured before and after surgery for gastric cancer (GC). However, which pre- or post-operative combined tumour markers (CEA and CA19-9) have more prognostic value remains unclear. Methods Consecutive patients undergoing a resection for GC at the Fujian Medical University Union Hospital were included as a discovery database between January 2011 and December 2014. The prognostic impact of pre- and post-operative tumour markers was evaluated using Kaplan–Meier log-rank survival analysis and multivariable Cox regression analysis. The results were then externally validated. Results A total of 735 and 400 patients were identified in the discovery cohort and in the validation cohort, respectively. Overall survival rates decreased in a stepwise manner in association with the number of pre- and post-operative positive tumour markers (both P P Conclusion Pre-operative tumour markers have a better discriminatory ability for post-operative survival in GC patients than post-operative tumour markers, and the normalisation of tumour markers after surgery was associated with better survival.

PREMISE Unique among vascular plants, some species of Selaginella have single giant chloroplasts in their epidermal or upper mesophyll cells (monoplastidy, M), varying in structure between species. Structural variants include several forms of bizonoplast with unique dimorphic ultrastructure. Better understanding of these structural variants, their prevalence, environmental correlates and phylogenetic association, has the potential to shed new light on chloroplast biology unavailable from any other plant group. METHODS The chloroplast ultrastructure of 76 Selaginella species was studied with various microscopic techniques. Environmental data for selected species and subgeneric relationships were compared against chloroplast traits. RESULTS We delineated five chloroplast categories: ME (monoplastidy in a dorsal epidermal cell), MM (monoplastidy in a mesophyll cell), OL (oligoplastidy), Mu (multiplastidy, present in the most basal species), and RC (reduced or vestigial chloroplasts). Of 44 ME species, 11 have bizonoplasts, cup-shaped (concave upper zone) or bilobed (basal hinge, a new discovery), with upper zones of parallel thylakoid membranes varying subtly between species. Monoplastidy, found in 49 species, is strongly shade associated. Bizonoplasts are only known in deep-shade species (

Photosynthetic organisms regulate their responses to many diverse stimuli in an effort to balance light harvesting with utilizable light energy for carbon fixation and growth (source-sink regulation). This balance is critical to prevent the formation of reactive oxygen species that can lead to cell death. However, investigating the molecular mechanisms that underlie the regulation of photosynthesis in cyanobacteria using ensemble-based measurements remains a challenge due to population heterogeneity. Here, to address this problem, we used long-term quantitative time-lapse fluorescence microscopy, transmission electron microscopy, mathematical modelling and genetic manipulation to visualize and analyse the growth and subcellular dynamics of individual wild-type and mutant cyanobacterial cells over multiple generations. We reveal that mechanical confinement of actively growing Synechococcus sp. PCC 7002 cells leads to the physical disassociation of phycobilisomes and energetic decoupling from the photosynthetic reaction centres. We suggest that the mechanical regulation of photosynthesis is a critical failsafe that prevents cell expansion when light and nutrients are plentiful, but when space is limiting. These results imply that cyanobacteria must convert a fraction of the available light energy into mechanical energy to overcome frictional forces in the environment, providing insight into the regulation of photosynthesis and how microorganisms navigate their physical environment.

The increasing incidence of hepatocellular carcinoma (HCC) is a major challenge worldwide. In the past few years, an increasing number of studies have suggested that circular RNAs (circRNAs) play an important role in the development of human tumors, including HCC, but our understanding of their function is still limited. In this study, we investigated differences in the expression of circRNA MAN2B2 (circMAN2B2) in hepatocellular tissues and paired normal tissues. We found that knockdown of circMAN2B2 expression in the HCC cell lines Hep-G2 and Huh-7 significantly inhibited cell proliferation by sponging (miRNA) miR-217 and inhibiting its function. Through a series of experiments, we also demonstrated that miR-217 functioned as a tumor suppressor molecule in HCC cells and regulated the expression of mitogen-activated protein kinase 1 (MAPK1). Restoration of MAPK1 rescued repression of cell proliferation induced by circMAN2B2 knockdown. In summary, our study indicated that circMAN2B2 acted as an onco-miRNA in HCC by sponging miRNA-217 to promote MAPK1 expression.

Sphingosine kinase 1 (SphK1) is a potential therapeutic target for human osteosarcoma (OS). SphK1-targeting microRNAs (miRNAs) could have important therapeutic value for OS. We discovered that micorRNA-3677 (miR-3677) is a SphK1-targeting miRNA, inhibiting OS cell progression. The results of RNA-Pull down assay confirmed direct binding between biotinylated-miR-3677 and SphK1 mRNA in primary human OS cells. In established and primary human OS cells forced overexpression of miR-3677, by a lentiviral construct, decreased SphK1 3'-UTR (untranslated region) activity and downregulated SphK1 expression. Both were however enhanced with miR-3677 inhibition in OS cells. Function studies demonstrated that OS cell growth, proliferation and migration were inhibited with miR-3677 overexpression, but augmented with miR-3677 inhibition. MiR-3677 overexpression-induced anti-OS cell activity was reversed with re-expression of the 3'-UTR-depleted SphK1. Additionally, in SphK1 knockout OS cells (by CRISPR/Cas9 strategy), altering miR-3677 expression failed to further alter cell functions. Finally, we show that miR-3677 expression was significantly downregulated in primary human OS tissues, correlating with SphK1 mRNA upregulation. We conclude that targeting SphK1 by miR-3677 inhibits human OS cell progression.

Clostridium botulinum is an important pathogen that causes botulism in humans and animals worldwide. C. botulinum group III strains, which produce a single toxin of type C or D or a chimeric toxin of type C/D or D/C, are responsible for botulism in a wide range of animal species including cattle and birds. We used unbiased high-throughput RNA sequencing (i.e., metatranscriptomics) to identify a strain of group III C. botulinum from a deceased Mongolian wild ass ( Equus hemionus). The strain was closely related to some European strains. Genetic analysis of the recovered bacterial sequences showed that the C. botulinum strain identified might represent a type C/D strain of group III. Infection by C. botulinum producing the mosaic toxin of type C/D is the most likely cause of the death of the wild ass.

Sulfamethazine (SMZ) is an important sulfonamide antibiotic. Although the concentration in the environment is small, it is harmful. The drug residues can be transferred, transformed or accumulated, affecting the growth of animals and plants. In this study, the integrated fixed-film activated sludge membrane bioreactor (IFAS-MBR) were constructed to investigate the performance and degradation mechanism of SMZ. The addition of SMZ had a significant impact on the removal of the chemical oxygen demand (COD) and ammonia nitrogen (NH4+-N). The optimal operating conditions were hydraulic retention time (HRT) at 10 h and solid retention time (SRT) at 80 d, respectively. On this basis, the effects of different SMZ concentrations on nutrient removal, degradation, and sludge characteristics were compared. The removal efficiency of SMZ increased with the increase of SMZ concentration. The maximum removal rate was as high as 87%. The SMZ dosage also had an obvious effect on sludge characteristics. As the SMZ concentration increased, the extracellular polymer substances (EPS) concentration and the membrane resistance both decreased, which were beneficial for the reduction of membrane fouling. Finally, seven kinds of SMZ biodegradation intermediates were identified, and the possible degradation pathways were speculated. The microbial community results showed that the microbial diversity and richness in the reactor decreased after adding SMZ to the influent. The relative abundance of Bacteroidetes, Actinobacteria, Saccharibacteria and Nitrospirae increased at the phylum level. Sphingobacteria and Betaproteobacteria became dominant species at the class level. The relative abundance of norank-p-Saccharibacteria and Nitrospirae increased significantly, and norank-p-Saccharibacteria may be the dominant bacteria for SMZ degradation.

Glioblastoma (GBM) continues to show a poor prognosis despite advances in diagnostic and therapeutic approaches. The discovery of reliable prognostic indicators may significantly improve treatment outcome of GBM. In this study, we aimed to explore the function of verbascoside (VB) in GBM and its effects on GBM cell biological processes via let‐7g‐5p and HMGA2. Differentially expressed GBM‐related microRNAs (miRNAs) were initially screened. Different concentrations of VB were applied to U87 and U251 GBM cells, and 50 µmol/L of VB was selected for subsequent experiments. Cells were transfected with let‐7g‐5p inhibitor or mimic, and overexpression of HMGA2 or siRNA against HMGA2 was induced, followed by treatment with VB. The regulatory relationships between VB, let‐7g‐5p, HMGA2 and Wnt/β‐catenin signalling pathway were determined. The results showed that HMGA2 was a direct target gene of let‐7g‐5p. VB treatment or let‐7g‐5p overexpression inhibited HMGA2 expression and the activation of Wnt/β‐catenin signalling pathway, which further inhibited cell viability, invasion, migration, tumour growth and promoted GBM cell apoptosis and autophagy. On the contrary, HMGA2 overexpression promoted cell viability, invasion, migration, tumour growth while inhibiting GBM cell apoptosis and autophagy. We demonstrated that VB inhibits cell viability and promotes cell autophagy in GBM cells by up‐regulating let‐7g‐5p and down‐regulating HMGA2 via Wnt/β‐catenin signalling blockade.

Background: The diagnosis of contrast-induced nephropathy (CIN) is usually based on changes in serum creatinine (sCr). However, sCr has poor sensitivity as a biomarker of kidney injury. The aim of this study was to investigate the usefulness of serum cystatin C (sCysC) to predict CIN after intra-arterial interventions. Methods: A total of 360 consecutive patients underwent intra-arterial procedures using digital subtraction angiography. SCr, sCysC, and estimated glomerular filtration rate were measured at 1 to 2 days before and at 48, 72 h, and 7 days after the procedure. Results: Thirty-one patients (8.61%) developed CIN. Receiver operating characteristic (ROC) curve analysis showed that preoperative sCysC levels had good discriminatory power (area under the curve [AUC] = 0.634; 95% confidence interval [CI] = 0.526-0.743) for evaluating the risk of CIN after an endovascular procedure, with a sensitivity of 53.33% and specificity of 73.70%. ROC analysis showed that sCysC at 48 h after contrast medium administration was predictive of CIN after an endovascular procedure (AUC = 0.735; 95% CI = 0.647-0.822) with satisfactory sensitivity of 74.20% and specificity of 63.90%. Diabetes mellitus was an independent risk factor for CIN (odds ratio = 2.778; 95% CI = 1.045-7.382; P = 0.040). Conclusions: SCysC is an appropriate biomarker to predict the occurrence of CIN. Baseline sCysC before an intervention is useful to obtain a preliminary estimate of the risk of CIN. A 48-h cut-off value of sCysC of 0.99 mg/L after an endovascular procedure may help to rule out patients at lower risk of CIN. Key words: Contrast-induced nephropathy; Intra-arterial intervention; Serum cystatin C; Serum creatinine

The genus Psiloboletinus was proposed by Rolf Singer in 1945 based on Phylloporus lariceti, a species that associates with Larix in the Altai Mountains of central and eastern Asia. However, this cl...

Graphical abstract, Gastric neuroendocrine carcinoma (GNEC) is rare cancer detected in the stomach. Previously, we demonstrated that the poorer prognosis of GNEC patients compared with gastric adenocarcinoma (GAC) patients was probably due to the lack of response to chemotherapy. Thus, it is crucial to study the specific GNEC gene expression pattern and investigate chemoresistance mechanism of GNEC. The transcriptome of GNEC patients was compared with that of GAC patients using RNA-seq. The KEGG analysis was employed to explore the specific differential expression gene function enrichment pattern. In addition, the transcriptomes of two GNEC cell lines, ECC10 and ECC12, were also compared with those of two GAC cell lines, MGC-803 and AGS, using RNA-seq. Comparing patient samples and cell lines transcriptome data, we try to uncover the potential targets and pathways which may affect the chemoresistance of GNEC. By combing all transcriptome data, we identified 22 key genes that were specifically up-regulated in GNEC. This panel of genes probably involves in the chemoresistance of GNEC. From our current experimental data, NeuroD1, one of the 22 genes, is associated with the prognosis of GNEC patients. Knockdown of NeuroD1 enhanced the sensitivity to irinotecan of GNEC cell lines. Our research sheds light in identifying a panel of novel therapeutic target specifically for GNEC clinical treatment which has not been reported before.

Network analysis has contributed to studies of the interactions of microorganisms and the identification of key populations. However, such analysis has rarely been conducted in the study of reservoir bacterioplankton communities. This study investigated the bacterioplankton community composition in the surface water of the Danjiangkou Reservoir using the Illumina MiSeq sequencing platform. We observed that the bacterioplankton community primarily consisted of 27 phyla and 336 genera, including Actinobacteria, Proteobacteria, and Bacteroidetes, demonstrating the richness of the community composition. Redundancy analysis of the bacterioplankton communities and environmental variables showed that the total nitrogen (TN), pH, chemical oxygen demand (COD), and permanganate index (CODMn) were important factors affecting the bacterioplankton distribution. Network analysis was performed using the relative abundances of bacterioplankton based on the phylogenetic molecular ecological network (pMEN) method. The connectivity of node i within modules (Zi), the connectivity of node i among modules (Pi), and the number of key bacteria were high at the Taizishan and Heijizui sites, which were associated with higher TN contents than at the other sites. Among the physicochemical properties of water, TN, ammonia nitrogen (NH4-N), pH, COD, and dissolved oxygen (DO) might have great influences on the functional units of the bacterial communities in bacterioplankton molecular networks. This study improves the understanding of the structure and function of bacterioplankton communities in the Danjiangkou Reservoir.

Objective: A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride. Conclusions: Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.

Snakes are popular as food and traditional medicine in China. However, information about parasitic and bacterial infections in snakes from China is scarce. We investigated the prevalence of selected zoonotic agents including Cryptosporidium, Hepatozoon and Spirometra, in snakes in central China from June to October in 2018 by PCR amplification using parasite-specific primers. PCR amplification and DNA sequencing showed that 10.1% (15/149) of snakes were positive for Cryptosporidium spp., while 2.7% (4/149) were positive for Hepatozoon. Additionally, we found 36.9% (55/149) of snakes were infected with Spirometra erinaceieuropaei. The spargana burden per infected snake ranged from 1 to 26. BLAST and phylogenetic analysis of small subunit ribosomal RNA (SSU rRNA) gene and 60-kDa glycoprotein (gp60) gene showed that the parasites belonged to Cryptosporidium parvum genotype IIdA15G1, C. baileyi, C. serpentis and a Hepatozoon species. We conclude that intensively farmed snakes excrete C. parvum and C. baileyi oocysts due to ingestion of infected feeder animals, and that wild snakes in central China were commonly infected with S. erinaceieuropaei, suggesting that eating improperly cooked snakes could be risky to human health., Graphical abstract Image 1, Highlights • Cryptosporidium parvum and C. baileyi were reported in farmed snakes in China for the first time. • C. serpentis was detected for the first time in Ptyas dhumnades and Gloydius brevicaudus. • A tentative new Hapatozoon species was first time recorded in wild Lycodon rufozonatus and G. brevicaudus. • Spirometra erinaceieuropaei infection was found common in wild snakes from central China.

Hepaciviruses represent a group of viruses that pose a significant threat to the health of humans and animals. New members of the genus Hepacivirus in the family Flaviviridae have recently been identified in a wide variety of host species worldwide. Similar to the Hepatitis C virus (HCV), bovine hepacivirus (BovHepV) is hepatotropic and causes acute or persistent infections in cattle. BovHepVs are distributed worldwide and classified into two genotypes with seven subtypes in genotype 1. In this study, three BovHepV strains were identified in the samples of ticks sucking blood on cattle in the Guangdong province of China, through unbiased high-throughput sequencing. Genetic analysis revealed the polyprotein-coding gene of these viral sequences herein shared 67.7–84.8% nt identity and 76.1–95.6% aa identity with other BovHepVs identified worldwide. As per the demarcation criteria adopted for the genotyping and subtyping of HCV, these three BovHepV strains belonged to a novel subtype within the genotype 1. Additionally, purifying selection was the dominant evolutionary pressure acting on the genomes of BovHepV, and genetic recombination was not common among BovHepVs. These results expand the knowledge about the genetic diversity and evolution of BovHepV distributed globally, and also indicate genetically divergent BovHepV strains were co-circulating in cattle populations in China.

The Paleoproterozoic (1.7 Ga [billion years ago]) metasedimentary rocks of the Mount Barren Group in southwestern Australia contain burrows indistinguishable from ichnogenera Thalassinoides, Ophiomorpha, Teichichnus, and Taenidium, known from firmgrounds and softgrounds. The metamorphic fabric in the host rock is largely retained, and because the most resilient rocks in the sequence, the metaquartzites, are too hard for animal burrowing, the trace fossils have been interpreted as predating the last metamorphic event in the region. Since this event is dated at 1.2 Ga, this would bestow advanced animals an anomalously early age. We have studied the field relationships, petrographic fabric, and geochronology of the rocks and demonstrate that the burrowing took place during an Eocene transgression over a weathered regolith. At this time, the metaquartzites of the inundated surface had been weathered to friable sandstones or loose sands (arenized), allowing for animal burrowing. Subsequent to this event, there was a resilicification of the quartzites, filling the pore space with syntaxial quartz cement forming silcretes. Where the sand grains had not been dislocated during weathering, the metamorphic fabric was seemingly restored, and the rocks again assumed the appearance of hard metaquartzites impenetrable to animal burrowing.

T cells play an important role in antitumor immunity. Numbers and function of T cells are controlled by regulating the uptake and utilization of nutrients, and their antitumor activity can be promoted by targeting metabolic pathways. In this review, we highlight the relationship between metabolism and cellular function of T cells. Specifically, we emphasize the metabolic state of tumor-infiltrating T cells and review key pathways that affect the antitumor function of T cells. In the field of tumor immunotherapy, targeting T cell metabolism to enhance the immune response is a new therapeutic strategy for enhancing immunotherapy combined with traditional treatments.