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Reverse water gas shift (RWGS) reaction is a crucial process in CO2 utilization. Herein, Ni- and NiCe-containing hexagonal mesoporous silica (Ni-HMS and NiCe-HMS) catalysts were synthesized using an in-situ one-pot method and applied for RWGS reaction. At certain reaction temperatures 500-750 °C, Ni-HMS samples displayed a higher selectivity to the preferable CO than that of conventionally impregnated Ni/HMS catalyst. This could be originated from the smaller NiO nanoparticles over Ni-HMS catalyst. NiCe-HMS exhibited higher activity compared to Ni-HMS. The catalysts were characterized by means of TEM, XPS, XRD, H2-TPR, CO2-TPD, EPR and N2 adsorption-desortion technology. It was found that introduction of Ce created high concentration of oxygen vacancies, served as the active site for activating CO2. Also, this work analyzed the effect of the H2/CO2 molar ratio on the best NiCe-HMS. When reaction gas H2/CO2 molar ratio was 4 significantly decreased the selectivity to CO at low temperature, but triggered a higher CO2 conversion which is close to the equilibrium.

Purpose: There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor. Experimental Design: We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype. Results: Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the “granulocytic–myeloid-derived suppressor cell (G-MDSC) dominant” cluster, with high number of HLA-DR− CD14− myeloid cells; subtype II, the “immune exhausted” cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the “immune desert” cluster, with few immune cells. Immune cell–rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors. Conclusions: This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the “immune exhausted” subtype of patients with CHS.

Shunosaurus is a small eusauropod from China. It is characterised by solid cervical and dorsal vertebral centra without complicated pneumatic structures, platycoelous or amphicoelous middle and pos...

Bufadienolides are the main active ingredients of Venenum Bufonis, which is a widely used traditional Chinese medicine secreted from parotoid gland and skin glands of Bufo bufo gargarizans. According to the transcriptome analysis, “cholesterol-bile acid-bufadienolidies pathway” was proposed as animal-derived bufadienolides biosynthesis pathway by us previously. In this pathway 3β-hydroxysteroid dehydrogenase (3βHSD) and steroid 5β-reductase (SRD5β) might be the key enzymes to convert the A/B ring to cis-configuration. Therefore, as the second report of our group, here we report the cloning of the full length of SRD5β cDNA of B. bufo gargarizans (Bbg-SRD5β) from the parotoid gland of B. bufo gargarizans for the first time, and site-directed mutagenesis was used to explored the character of Bbg-SRD5β. Bbg-SRD5β had an open reading frame of 981 bp and encoded 326 amino acids residues. The expression conditions of the recombinant Bbg-SRD5β in E. coli BL21 (DE3) harbored with pCold-Bbg-SRD5β was optimized as induction for 10 h at 15 °C with 0.1 mM IPTG. With NADPH as a cofactor, Bbg-SRD5β can reduce the Δ4,5 double bonds of progesterone to generate dihydroprogesterone owithout substrate inhibition effect. The catalytic rate of mutant type Bbg-SRD5β-Y132G was 1.8 times higher than that of wild type Bbg-SRD5β. Although Bbg-SRD5β was almost unable to reduce the progesterone to dihydroprogesterone after mutation of V309, the affinity of enzyme with NADPH changed significantly. Bbg-SRD5β is the key enzymes to convert the A/B ring of steroid to cis-configuration, and V309 is a key site affecting the binding affinity of enzyme with NADPH, and the mutation of Y132 can adjust the catalytic rate of Bbg-SRD5β.

Influenza A virus (IAV) utilizes cap-snatching to obtain host capped small RNAs for priming viral mRNA synthesis, generating capped hybrid mRNAs for translation. Previous studies have been focusing on canonical cap-snatching, which occurs at the very 5′ end of viral mRNAs. Here we discovered noncanonical cap-snatching, which generates capped hybrid mRNAs/noncoding RNAs mapped to the region ∼300 nucleotides (nt) upstream of each mRNA 3′ end, and to the 5′ region, primarily starting at the second nt, of each virion RNAs (vRNA). Like canonical cap-snatching, noncanonical cap-snatching utilizes a base-pairing between the last nt G of host capped RNAs and a nt C of template RNAs to prime RNA synthesis. However, the nt upstream of this template C is usually A/U rather than just U; prime-realignment occurs less frequently. We also demonstrate that IAV can snatch capped IAV RNAs in addition to host RNAs. Noncanonical cap-snatching likely generates novel mRNAs with start AUG encoded in viral or host RNAs. These findings expand our understanding of cap-snatching mechanisms and suggest that IAV may utilize noncanonical cap-snatching to diversify its mRNAs/ncRNAs.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans. Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

Background and purpose In non-small-cell lung carcinoma (NSCLC) patients, the L858R/T790M mutation of the epithelial growth factor receptor (EGFR) is a major cause of acquired resistance to EGFR-TKIs treatment that limits their therapeutic efficacy. Identification of drugs that can preferentially kill the NSCLC harbouring L858R/T790M mutation is therefore critical. Here, we have evaluated the effects of ursolic acid, an active component isolated from herbal sources, on erlotinib-resistant H1975 cells that harbour the L858R/T790M mutation. Experimental approach Gene expression omnibus (GEO) profiles analyses was applied to detect differentially expressed genes in NSCLC cells harbouring EGFR mutation. AnnexinV-FITC/PI, TUNEL staining, MTT, wound healing, RT-PCR, qRT-PCR, western blots, immunostaining, dual-luciferase reporters and ChIP-PCR were utilized to investigate the effects of ursolic acid in vitro and in vivo. Key results The cancer/testis antigen family 45 member A2 (CT45A2) was highly expressed in H1975 cells. Ectopic expression of CT45A2 in H1975 cells increased cell proliferation and motility in vitro. Silencing the CT45A2 expression strongly attenuated H1975 cells motility and growth. The anti-cancer effect of ursolic acid was critically dependent on CT45A2 expression in H1975 cells. Ursolic acid suppressed CT45A2 gene transcription mediated by transcriptional factor TCF4 and β-catenin signalling. Conclusions and implications CT45A2 is a novel oncogene for NSCLC with an EGFR T790 mutation. Ursolic acid induced apoptosis and inhibited proliferation of H1975 cells by negatively regulating the β-catenin/TCF4/CT45A2 signalling pathway. Therefore, ursolic acid may be a potential candidate treatment for NSCLC harbouring the EGFR-L858R/T790M mutation.

Antibodies have a common structure consisting of two identical heavy (H) and two identical light (L) chains. It is widely accepted that a single mature B cell produces a single antibody through restricted synthesis of only one VHDJH (encoding the H-chain variable region) and one VLJL (encoding the L-chain variable region) via recombination. Naive B cells undergo class-switch recombination (CSR) from initially producing membrane-bound IgM and IgD to expressing more effective membrane-bound IgG, IgA, or IgE when encountering antigens. To ensure the “one cell — one antibody” paradigm, only the constant region of the H chain is replaced during CSR, while the rearranged VHDJH pattern and the L chain are kept unchanged. To define those long-standing classical concepts at the single-cell transcriptome level, we applied the Chromium Single-Cell Immune Profiling Solution and Sanger sequencing to evaluate the Ig transcriptome repertoires of single B cells. Consistent with the “one cell — one antibody” rule, most of the B cells showed one V(D)J recombination pattern. Intriguingly, however, two or more VHDJH or VLJL recombination patterns of IgH chain or IgL chain were also observed in hundreds to thousands of single B cells. Moreover, each Ig class showed unique VHDJH recombination pattern in a single B-cell expressing multiple Ig classes. Together, our findings reveal an unprecedented presence of multi-Ig specificity in some single B cells, implying regulation of Ig gene rearrangement and class switching that differs from the classical mechanisms of both the “one cell — one antibody” rule and CSR.

Rhein is an active component from Chinese herbal medicine. It can cause diarrhea by inhibiting Na+ , K+ -ATPase activity on intestinal epithelial cells, thus decreasing the re-absorption of Na+ from intestinal tract to blood. However, when this Na+ , K+ -ATPase inhibition was quantitated by colorimetric method that measures ATPase-catalyzed release of inorganic phosphorus, the data obtained are inconsistent and with great variation. To improve it, we developed a novel method by using inductively coupled plasma mass spectrometry (ICP-MS) to quantitate the amount of intracellular Rb+ . This method largely mimics the 86 RbCl tracer flux assay, but it uses non-radioactive RbCl as flux substrate. The results demonstrated that this method has better precision and accuracy than that of the conventional colorimetric method. More importantly, this method is free of radioactive substance, which is expected to be safer and more convenient than radioactive 86 RbCl tracer flux method. In conclusion, the ICP-MS method for Na+ , K+ -ATPase activity determination is novel and accurate. It can also provide a reference for studying the transport of other metal ions across membrane under biological conditions.

Background: Pigmented villonodular synovitis (PVNS) is a rare condition that involves benign proliferation of the synovial tissue and is characterized by severe joint destruction and high recurrence even after surgical resection. However, poor understanding of the pathogenesis limits its effective therapy.Method: In this study, gene expression profiles of six patients with PVNS and six patients with osteoarthritis (OA) were analyzed using integrating RNA sequencing (RNA-seq) and microarray to investigate the PVNS transcriptome. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, string, and cytoscape were used to determine the gene functional enrichment. Cell surface functional molecules were detected using flow cytometry to identify the cell subset. CD14 positive cells were isolated and induced to differentiate into osteoclast to evaluate the monocyte/macrophage function.Results: RNA-seq and microarray data revealed 195 common differentially expressed genes; expression change trends were consistent in both the methods. The most obvious local manifestations of PVNS were inflammation and tumor phenotypes. Infiltration of a large number of immune cells and increased cytokine secretion induced inflammation. High proportion of CD45+ inflammatory cells, including T cells (CD3+), natural killer cells (CD3-CD56+), NKT cells (CD3+CD56+), and B cells (CD19+), were recruited from the blood. Cell proliferation and migration resulted in manifestation of the tumor phenotype. Tumor checkpoint molecules, such as programmed cell death protein 1, T cell immunoglobulin and mucin domain 3, lymphocyte-activation gene 3, cytotoxic T lymphocyte-associated protein 4, and sialic-acid-binding immunoglobulin-like lectin, were expressed on the surface of CD4+ and CD8+ T cells. In addition, an obvious increase in osteoclastogenesis and macrophage activation were observed locally. Tartrate-resistant acid phosphatase-positive mature osteoclasts that differentiated from CD14+ monocytes were significantly higher in the PVNS synovium than that in OA. Conclusion: The transcriptional expression characteristics of PVNS resulted in increased immune response and cytokine expression, high cell proliferation and migration, and increased osteoclastogenesis and bone injury.

High-throughput sequencing has become a standard tool for analyzing RNA and DNA. This method usually needs a cDNA/DNA library ligated with specific 5′ and 3′ linkers. Unlike mRNA, small RNA often contains modifications including 5′ cap or triphosphate and 2′-O-methyl, requiring additional processing steps before linker additions during cloning processes; due to low expression levels, it is difficult to clone small RNA with a small amount of total RNA. Here we present a new strategy to clone 5′ modified or unmodified small RNA in an all-liquid-based reaction carried out in a single PCR tube with as little as 20 ng total RNA. The 7-h cloning process only needs ∼1 h of labor. Moreover, this method can also clone mRNA, simplifying the need to prepare two cloning systems for small RNA and mRNA; the barcoded PCR primers are also compatible with non-cDNA cloning applications, including the preparation of genomic libraries. Not only is our method more convenient for cloning modified RNA than available methods, but it is also more sensitive, versatile, and cost-effective. Moreover, the all-liquid-based reaction can be performed in an automated manner.

Six plant crude extracts were chosen to evaluate their acaricidal activity against Tetranychus cinnabarinus adults. The crude extract from the stems and leaves of Arachis hypogaea L. presented the highest activity in leaf‐dip bioassays, with an LC₅₀ value of 3,545.98 mg/L. Further extraction using four different solvents (petroleum ether, ethyl acetate, n‐butyl alcohol and distilled water) demonstrated that the active components mainly existed in the petroleum ether phase. Then, the active compound, palmitic acid, was isolated from the petroleum ether phase via two‐step column chromatography using columns filled with silica gel and C‐18 and identified via mass spectrometry and nuclear magnetic resonance analyses. The LC₅₀ value of active palmitic acid against T. cinnabarinus was 534.58 mg/L. The present study demonstrated that the active compound extracted from A. hypogaea is a potential novel botanical acaricide for controlling T. cinnabarinus.

The assembly of the root-associated microbiome provides mutual benefits for the host plant and bacteria in soils. It is interesting how invasive plants interact with the local soil microbial community and establish the soil bacterial community in the endosphere of these plants in the short term. In this study, we compared the bacterial community in the rhizosphere with that in the root endosphere of an invasive plant, Ageratina adenophora, using high-throughput sequencing. The results showed that the roots of A. adenophora selectively accumulated the genera Clostridium and Enterobacter, which are rarely distributed in the rhizosphere. This selective accumulation caused a switch in the bacterial composition at the phylum level from Bacteroidetes predominant in the rhizosphere to Proteobacteria dominant in the root endosphere of A. adenophora. Our data indicated the potential existence of a highly conserved signal recognition in which hosts, either invasive or native, enrich the endosphere bacteria, such as Clostridium, Enterobacter, etc., from the rhizosphere. Moreover, the accumulated bacteria were physiologically and genetically different at the strain level and displayed distinct roles in growth between invasive and native plants. The assembly of the bacterial community in the roots may be an advantageous strategy for A. adenophora in competition with native plants.

Heat shock protein 75 (HSP75, also known as TRAP1) as a member of the Hsp90 molecular chaperone family, has been implicated in the progression of renal fibrosis. Apoptosis of renal tubular cells is known to be the critical mechanisms of the progression of renal fibrosis, and mitochondrial dysfunction participates in this process. In this study, we investigated the effects of HSP75 on mitochondrial dysfunction and its relevance to apoptosis in human renal proximal tubular cells (HK2). HSP75 was up- and down-regulated in HK2 cells treated with TGF-β1 using letiviral vectors. HSP75 improved mitochondrial morphological injury and stabilized mitochondrial functions in HK2 cells stimulated by TGF-β1. Overexpression of HSP75 inhibited cell apoptosis, and it was reversed by using HSP75 shRNAs. HSP75 may be important for maintenance of mitochondrial function in HK2 cells under pathological conditions. Activation of HSP75 may be therapeutically useful in renal fibrosis to promote and maintain normal mitochondrial functions.

With the development of RNA-seq technology, tens of thousands of circular RNAs (circRNAs), a novel class of RNAs, have been identified. However, little is known about circRNA formation and biogenesis in hepatocellular carcinoma (HCC). We performed ribosomal-depleted RNA-seq profiling of HCC and para-carcinoma tissues and analyzed the expression of a hotspot circRNA derived from the 3'UTR of the stearoyl-CoA desaturase (SCD) gene, termed SCD-circRNA 2. It was significantly upregulated in HCC and correlated with poor patient prognosis. Moreover, we observed that the production of SCD-circRNA 2 was dynamically regulated by RNA-binding protein 3 (RBM3). RBM3 overexpression was indicative of a short recurrence-free survival and poor overall survival for HCC patients. Furthermore, by modulating the RBM3 or SCD-circRNA 2 levels, we found that RBM3 promoted the HCC cell proliferation in a SCD-circRNA 2 dependent manner. Herein, we report that RBM3 is crucial for the SCD-circRNA 2 formation in HCC cells, which not only provides mechanistic insights into cancer-related circRNA dysregulation but also establishes RBM3 as an oncogene with both therapeutic potential and prognostic value. Funding Statement: This work was supported by the National Key Research and Development Program of China (2016YFC1302303), the National Natural Science Foundation of China (Grant No. 81672345 and 81402269). Declaration of Interests: There is no conflict of interest, financial or otherwise, related to the submitted work. Ethics Approval Statement: This research study was approved by the ethics committee of the Second Military Medical University, and all patients signed the informed consent provided by the committee. Patients whose consents were unavailable were excluded from this study.

Breast cancer is a highly heterogeneous disease and numerous secreted factors may differentially contribute to a macrophage phenotype whose extensive infiltration is generally regarded as indicative of an unfavorable outcome. How different breast tumor cells and macrophage cells interplay or influence each other on the alternative splicing (AS) level have not been characterized. Here, we exploited one previous study, which investigated the interplay between macrophages and estrogen receptor‑positive (ER+) breast cancer and triple‑negative breast cancer (TNBC) at the transcriptional level, to investigate the tumor‑macrophage crosstalk at the AS level. In the present study, it was demonstrated that biological processes such as DNA damage and DNA repair were significantly affected both in ER+ breast cancer and TNBC by co‑culturing with macrophages, whereas biological pathways altered in macrophages co‑cultured with tumor cells depended on the breast cancer type. Specifically, biological processes altered in macrophages co‑cultured with ER+ breast cancer were enriched in RNA processing and translation‑related pathways whereas biological processes altered in macrophages co‑cultured with TNBC were mainly enriched in protein transport pathways. We also analyzed the sequence features of skip exons among different conditions. In addition, putative splicing factors which were responsible for the altered AS profile in each condition were identified. The findings of the present study revealed significant tumor‑macrophage crosstalk at the AS level which may facilitate the development of new therapeutic strategies for cancer.

An improved, reliable and comprehensive method for assessing the quality of the ethyl acetate extract from persimmon leaves (EAPL) and its commercial preparation, Naoxinqing (Brain and Heart Clear capsules), has been developed and validated. Based on HPLC-DAD-ESI-Q-TOF-MS analysis, myricetin-3-O-β-D-galactoside (1), myricetin-3-O-glucoside (2), quercetin-3-O-β-D-galactoside (3), quercetin-3-O-β-D-glucoside (4), quercetin-3-O-(2″-O-galloyl-β-D-galactoside) (5), quercetin-3-O-(2″-O-galloyl-β-D-glucoside) (6), kaempferol-3-O-β-D-galactoside (7), kaempferol-3-O-β-D-glucoside (8), kaempferol-3-O-(2″-O-galloyl-β-D-galactoside) (9), kaempferol-3-O-(2″-O-galloyl-β-D-glucoside) (10), quercetin (11) and kaempferol (12) were identified from 15 batch samples. A HPLC fingerprint analytical method was established. All compounds, with the exception of compound 2, were simultaneously quantified by the single standard to determine multi-components (SSDMC) method, using kaempferol-3-O-β-D-glucoside as the internal standard. The rate of analysis was found to be faster with the SSDMC method than with current acid hydrolysis method (Pharmacopoeia of the People's Republic of China 2015 edition) and the results were more intuitive and reliable. Three-dimensional principal component analysis revealed that there were similar characteristics in persimmon leaf from same district. Analysis of the myocardial cell protection activity of 11 monomeric compounds showed that compounds 12, 11 and 10 were the main active ingredients that produce pharmacologic functions in EAPL. Among these compounds, the bioactive constituent of myricetin-3-O-β-D-galactoside was determined for the first time in Diospyros khaki. Thus, we have established an effective assessment method that can be applied to the comprehensive quality evaluation of EAPL extract and Naoxinqing capsule.

Titanium dioxide nanoparticles (TiO2 NPs) can modify the behavior and bioavailability of heavy metals in aquatic environments. However, the influence of TiO2 NPs on the multigenerational impairments caused by heavy metals is largely unknown. This study revealed that parental exposure to TiO2 NPs at a non-toxic concentration could increase the reproductive toxicity of Cd in both the Caenorhabditis elegans (C. elegans) parental generation and subsequent generations (F1, F2) cultured under pollutant-free conditions. TiO2 NPs promoted the ingestion of Cd, and the lower pH environment in the gut accelerated the desorption of Cd from TiO2 NPs, leading to enhanced Cd bioaccumulation, which was confirmed by the expression of metal responsive genes mtl-2, encoding metallothionein. Using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), an in situ imaging technology, we further found that Cd burden in the gonads and embryos was increased by concurrent exposure to TiO2 NPs, indicating the potential transfer of Cd to the next generation through the germline. Our data provided new evidence that maternal exposure to TiO2 NPs amplifies the multigenerational reproductive toxicity of Cd in C. elegans by promoting the accumulation of Cd in germ cells.

Nucleotide excision repair (NER) resolves DNA adducts, such as those caused by ultraviolet light. Deficient NER (dNER) results in a higher mutation rate that can predispose to cancer development and premature ageing phenotypes. Here, we used isogenic dNER model cell lines to establish a gene expression signature that can accurately predict functional NER capacity in both cell lines and patient samples. Critically, none of the identified NER deficient cell lines harbored mutations in any NER genes, suggesting that the prevalence of NER defects may currently be underestimated. Identification of compounds that induce the dNER gene expression signature led to the discovery that NER can be functionally impaired by GSK3 inhibition, leading to synergy when combined with cisplatin treatment. Furthermore, we predicted and validated multiple novel drugs that are synthetically lethal with NER defects using the dNER gene signature as a drug discovery platform. Taken together, our work provides a dynamic predictor of NER function that may be applied for therapeutic stratification as well as development of novel biological insights in human tumors.

Nelumbo nucifera Gaertn. (lotus) roots were collected from contaminated sediments which were artificially adding different concentrations of chiral polychlorinated biphenyls (PCBs) to investigate the effect of concentration on the accumulation characteristics and chiral signatures of PCBs in lotus root during its growth period of 150 days. Under high PCB exposure concentration, the biota-sediment accumulation factors (BSAFs) of PCBs 91, 95, and 136 in the lotus root were up to 0.25-0.46 and 8.10-10.5 times higher than those under low-exposure concentration (0.024-0.052). The BSAFs of PCBs 149, 176, and 183 under high-exposure concentration were up to 0.24-0.44, while they were undetected at low concentration. The significant difference observed in the BSAFs based on different concentrations indicates that the lotus root accumulation efficiency toward chiral PCBs increases with the contaminate concentration. Although the (-)-enantiomers of PCBs 91, 95, and 136 were all preferentially accumulated in lotus root under two exposure concentrations, the extent of the preferential accumulation of (-)-PCB 95 decreased with increasing exposure concentration throughout the whole growth period (30-150 days). In addition, the (-)-enantiomers of PCBs 91 and 136 also showed the same tendency during most of the growth period. Conclusively, the exposure concentrations are an important influence factor on the enantioselective accumulation of chiral PCBs in lotus root.

PTEN/AKT signaling plays pivotal role in myocardial ischemia reperfusion injury (MIRI), and miRNAs are involved in the regulation of AKT signaling. This study was designed to investigate the interaction between miR-129 and PTEN in MIRI. A MIRI rat model and a hypoxia reoxygenation (H/R) H9C2 cell model were constructed to simulate myocardial infarction clinically. TTC staining, creatine kinase (CK) activity, TUNEL/Hoechst double staining, Hoechst staining and flow cytometer were used for evaluating myocardial infarction or cell apoptosis. miR-129 mimic transfection experiment and luciferase reporter gene assay were conducted for investigating the function of miR-129 and the interaction between miR-129 and PTEN, respectively. Real-time PCR and western blotting were performed to analyze the gene expression. Compared to the control, MIRI rats presented obvious myocardial infarction, higher CK activity, increased expression of caspase-3 and PTEN, decreased expression of miR-129, and insufficient AKT phosphorylation. Consistently, H/R significantly increased the apoptosis of H9C2 cells, concomitant with the downregulation of miR-129, upregulation of PTEN and caspase-3, and insufficient phosphorylation of AKT, while miR-129 mimic obviously inhibited the expression of PTEN and caspase-3, increased the AKT phosphorylation, and decreased the cell apoptosis. Additionally, miR-129 mimic obviously decreased the relative luciferase activity in H9C2 cells. To our best knowledge, this study firstly found that the low expression of miR-129 accelerates the myocardial cell apoptosis by directly targeting 3 ′ UTR of PTEN. miR-129 is an important biomarker for MIRI, as well as a potential therapy target.

COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.

Background: The epidemiological and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) have been reported. However, the prevalence of retesting positive by RT-PCR for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the associated patient characteristics, remain unclear. Methods: We included 90 confirmed cases of COVID-19 treated in the Nanjing Public Health Center from January 20, 2020 to February 16, 2020 in this retrospective study. All patients completed treatment for COVID-19 and were retested by RT-PCR for SARS-CoV-2 4-20 days after completion of therapy. The clinical characteristics between patients with who retested positive versus negative by RT-PCR were compared, and the factors predictive of positive retesting were analyzed. Positive retesting was modeled with the area under the receiver operating characteristic curve (AUC). Results: The age range of the study population was 0.8-97 years, and all patients were cured or showed improvement. A total of 10 (11%) patients retested positive by RT-PCR 4-20 days after completion of therapy. As compared with patients who retested negative, those who retested positive had a lower percentage of pre-admission fever, a higher percentage of post-admission fever, a lower percentage of bilateral lung infection, higher white blood cell (WBC) count and creatine phosphokinase, and lower hypersensitive c-reactive protein (hs-CRP), interleukin-6 and erythrocyte sedimentation rates (all P

Our previous article demonstrated that ar-turmerone ((6S)-2-methyl-6-(4-methylphenyl)-2-hepten-4-one) extracted from Curcuma longa L. has a significant larvicidal activity against the fourth instar larvae of Culex pipiens pallens. To reveal the effects of ar-turmerone on C. pipiens pallens larvae, light microscopy and transmission electron microscopy were used to observe the histological and ultrastructure changes in muscle and digestive tissues of fourth instar larvae. It was also revealed by detecting the activity of the acetylcholinesterase (AChE) enzyme and three detoxifying enzymes, including carboxylesterase (CarE), glutathione-S-transferase (GST) and Cytochrome P450 monooxidases (P450). The observation under the light microscope showed that the larvae displayed a disruption of myofibril in ventral muscle cells, the disappearance of nucleolus in the malpighian tubule cells, and the exfoliation of the brush border in midgut epithelial cells, 24 h after treatment. The observation under the transmission electron microscope displayed disorganized Z-lines in the ventral muscle cells, and dissolved membrane of mitochondria, nuclear and endoplasmic reticulum in abdominal cells. The enzymatic activity results showed that ar-turmerone significantly increased the level of detoxifying enzymes, while the activity of AChE was not obviously affected. All the results suggest that the larvicidal mechanism of ar-turmerone is estimated to be stomach poison and the active sites might be the muscle and digestive tissues, and the mode of action of ar-turmerone may be unrelated to AChE.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1–3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans., Phylogenetic and metagenomic analyses of the complete viral genome of a new coronavirus from the family Coronaviridae reveal that the virus is closely related to a group of SARS-like coronaviruses found in bats in China.

Summary The role of amyloplasts in the interactions between hydrotropism and gravitropism has been previously described. However, the effect of light-dark on the interactions between the two tropisms remains unclear. Here, by developing a method that makes it possible to mimic natural conditions more closely than the conventional lab conditions, we show that hydrotropism is higher in wild-type Arabidopsis seedlings whose shoots are illuminated but whose roots are grown in the dark compared with seedlings that are fully exposed to light. Root gravitropism is substantially decreased because of the reduction of amyloplast content in the root tip with decreased gene expression in PGM1 (a key starch biosynthesis gene), which may contribute to enhanced root hydrotropism under darkness. Furthermore, the starch-deficient mutant pgm1-1 exhibits greater hydrotropism compared with wild-type. Our results suggest that amyloplast response and starch reduction occur under light-dark modulation, followed by decreased gravitropism and enhanced hydrotropism in Arabidopsis root.

Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1–3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV).Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.

Tetanurae is a special group of theropod dinosaurs that originated by the late Early Jurassic. It includes several early-diverging groups of generally large-bodied predators (megalosauroids, allosauroids, tyrannosauroid coelurosaurs) as well as morphologically disparate small-bodied coelurosaurs, including birds. Aspects of the evolutionary history of tetanurans remain contested, including the topology of their deep phylogenetic divergences (among Megalosauroidea, Allosauroidea and Coelurosauria). We report a new theropod, Yunyangosaurus puanensis gen. et sp. nov., based on a fragmentary specimen recovered from the Middle Jurassic Xintiangou Formation of Chongqing, southwestern China. It shares several features uniquely with some megalosauroids (the clade of megalosaurids + spinosaurids + piatnitzkysaurids), such as prominent rims around the anterior articular surfaces of cervical centra and bifurcated anterior dorsal neural spines (present in piatnitzkysaurids). Nevertheless, it also shows several features that are rare or absent among megalosauroids and more crownward tetanurans, including prominent spinopostyzgopophyseal laminae (also present in non-tetanurans and metriacanthosaurid allosauroids), flat anterior articular surfaces of the cervical centra (also present in piatnitzkysaurids and some earlier-diverging tetanurans), and the presence of a posterior pneumatic foramen or fossa (absent in most tetanurans, but sporadically present in some cervical vertebrae of piatnitzkysaurids). Yunyangosaurus therefore presents a combination of derived and apparently primitive character states that are not seen in other theropods. This suggests that patterns of morphological evolution associated with deep tetanuran divergences were more complex than currently recognized, with implications for understanding the character evolution in theropods.

Introduction: More than 1200 different types of microbes were found in the human mouth, only some of these microorganisms were associated with intracranial bacterial infection. However, there are limited data available about the Pseudoramibacter alactolyticus (P alactolyticus) or Mycobacterium tuberculosis (MTB) intracranial infections oral origin. Patient concerns: Here, we reported a rarely case with P alactolyticus and MTB coinfection in central nervous after dental extraction. The 44-year-old man presented with progressive headache over the last 2 weeks and a sustained fever >39°C, with a dental extraction performed 2 days before the onset of headache. Diagnosis: P alactolyticus and MTB were confirmed by real-time polymerase chain reaction targeting the16S ribosomal RNA gene. The presence of MTB was also demonstrated by positive acid-fast staining of the purulent discharge. Interventions: The patient was treated by metronidazole and anti-TB treatment Outcomes: The patient fully recovered without sequela. Conclusion: In conclusion there should be awareness of the possibility of P alactolyticus or MTB intracranial infections following tooth extraction.

Background Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. Methods An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. Results This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium

Glomerular filtration rate (GFR) estimation equations using creatinine and Cystatin-C appear to be superior to those based on creatinine or Cystatin-C in older adults. We sought to compare the performances of those based on creatinine and Cystatin-C in Chinese older adults with chronic kidney disease (CKD). A total of 368 Chinese elderly with CKD underwent the dynamic imaging with technetium-99m diethylene-triamine-pentaacetic acid (99mTc-DTPA), and serum creatinine and Cystatin-C were measured on the same day. The comparison of GFR equations which were creatinine and Cystatin-C-based including chronic kidney disease epidemiology collaboration (CKD-EPI) equation (CKD-EPI-Cr-Cys), Berlin Initiative Study (BIS) equation (BIS-Cr-Cys, also known as BIS-2), MA equation (MA-Cr-Cys), and FENG equation (FENG-Cr-Cys) was conducted. Four equations overestimated GFR except for BIS-2 equation in mGFR ≥ 60 ml/min/1.73 m2 (bias: − 1.40, p = 0.7) and CKD-EPI-Cr-Cys equation in mGFR

Summary Extensive spontaneous DNA damage from oncogene-induced replication stress is ubiquitous in precancerous lesions. While this damage induces differentiation, senescence, or apoptosis in normal cells, defects in DNA replication stress response (RSR) allow cells to continue proliferating, ultimately leading to early tumorigenesis. Using systems-level approaches, we developed a replication stress response defect gene signature that predicted risk of cancer development from hyperplastic lesions. Intriguingly, we found that replication stress response defects rewire non-malignant cells into a cancer stem cell (CSC)-like state, and analysis of CSCs indicated that they inherently harbor replication stress response defects. High-throughput drug screening to elucidate molecules required for survival of replication stress response defective cells identified a dependence on MEK/ERK signaling. Inhibition of this signaling cascade restored oncogene-induced senescence through a p53-independent MDM2/p21 axis. Moreover, MEK/ERK inhibition also depleted CSC populations. Together, these findings provide insights into the role of replication stress response defects in CSCs and an actionable pathway for therapeutic targeting.

A single chain Fv fragment (scFv) is a fusion of the variable regions of heavy (VH ) and light (VL ) chains of immunoglobulins. They are important elements of chimeric antigen receptors for cancer therapy. We sought to produce a panel of 16 extracellular protein domains of tumor markers for use in scFv yeast library screenings. A series of vectors comprising various combinations of expression elements was made, but expression was unpredictable and more than half of the protein domains could not be produced using any of the constructs. Here we describe a novel fusion expression system based on mouse TEM7 (tumor endothelial marker 7), which could facilitate protein expression. With this approach we could produce all but one of the tumor marker domains that could not otherwise be expressed. In addition, we demonstrated that the tumor associated antigen hFZD10 produced as a fusion protein with mTEM7 could be used to enrich scFv antibodies from a yeast display library. Collectively our study demonstrates the potential of specific fusion proteins based on mTEM7 in enabling mammalian cell production of tumor targeting protein domains for therapeutic development.

To realize the full potential of immunotherapy, it is critical to understand the drivers of tumor infiltration by immune cells. Previous studies have linked immune infiltration with tumor neoantigen levels, but the broad applicability of this concept remains unknown. Here, we find that while this observation is true across cancers characterized by recurrent mutations, it does not hold for cancers driven by recurrent copy number alterations, such as breast and pancreatic tumors. To understand immune invasion in these cancers, we developed an integrative multi-omics framework, identifying the DNA damage response protein ATM as a driver of cytokine production leading to increased immune infiltration. This prediction was validated in numerous orthogonal datasets, as well as experimentally in vitro and in vivo by cytokine release and immune cell migration. These findings demonstrate diverse drivers of immune cell infiltration across cancer lineages and may facilitate the clinical adaption of immunotherapies across diverse malignancies., Neoantigen load has been associated with tumour immune infiltration. Here, the authors show that while this is true for tumours with recurrent mutations, cancers with recurrent CNAs show neoantigen-independent infiltration driven by cytokine production downstream of the DNA damage sensor ATM.

Arsenic (As) pollution is a serious global problem and various technologies have been developed for As detoxification. Graphene oxide (GO) with its extraordinary structure and physicochemical properties has an excellent capability for the removal of As from contaminated water; however, the influence of GO on the toxic response to As(III), a well-established human carcinogen, is largely unknown. In the present study, Caenorhabditis elegans (C. elegans) was used as an in vivo model to clarify the role of GO at a non-toxic concentration in the toxic response to As(III) and its underlying molecular mechanisms. Our data showed that GO, irrespective of pretreatment or concurrent treatment with As(III), significantly blocked the toxic response to As(III). GO not only absorbed As(III), but also triggered protective autophagy, leading to efficient inhibition of oxidative stress, a major contributing factor in As(III) toxicity. Using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) and loss-of-function mutants, our data further showed that GO accelerated the excretion of As(III) from nematodes by suppressing the expression of As(III)-binding proteins LEC-1. Our data provided clear evidence that along with adsorption, the beneficial effects of GO in reducing As(III)-induced toxicity in vivo were mainly through protective autophagy coupled with downregulation of arsenic target protein expression, which might reveal new insights into the potential application of GO in water treatment and ecological risk assessment.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia, which is characterized by the deposition of dense plaques of amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau. The two main types of AD can be classified as early-onset AD (EOAD, onset < 65 years) and late-onset AD (LOAD, onset ≥ 65 years). Evidence from family and twin studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The first milestone with linkage analysis revealed the mutations in APP, PSEN1, and PSEN2 genes that cause EOAD. But pathogenic mutations in these three genes can only explain a small fraction of EOAD families. The additional disease-causing genes have not yet been identified. This review provides an overview of the genetic basis of EOAD and the relationship between the functions of these risk genes and the neuropathologic features of AD. A better understanding of genetic mechanisms underlying EOAD pathogenesis and the potentially molecular mechanisms of neurodegeneration will lead to the development of effective diagnosis and treatment strategies for this devastating disease.

Two new dinosaur tracksites are reported from the Lower Cretaceous Jiaguan Formation in the Sichuan Basin, Qijiang District of Chongqing. These are the Gaoqing-Yongsheng and the Huibu tracksites, which represent the 13th and 14th reports from this formation. The Gaoqing-Yongsheng tracksite reveals the trackway of a large biped (ornithopod) in association with isolated sauropod tracks and large indeterminate undertracks with radial cracks. These features are preserved as natural casts with pebble infillings in a coarse, cross bedded and very thick bedded sandstone sequence. The Huibu tracksite reveals isolated theropod tracks and ornithopod tracks, the latter having a quadripartite, Caririchnium-like morphology, preserved in a thin bedded sandstone sequence with intercalated mudstone.

Endosulfan as a new member of persistent organic pollutants has been shown to induce apoptosis in various animal models. However, the mechanism underlying endosulfan-induced apoptosis has not been well elucidated thus far. Caenorhabditis elegans N2 wild type and mutant strains were used in the present study to clarify the roles of the mitochondria, the insulin/insulin-like growth factor-1 (IGF-1) signaling pathway, and mitogen-activated protein kinase (MAPK) cascades in α-endosulfan-induced apoptosis. Our results demonstrated a dose- and time-dependent increase of apoptosis in the meiotic zone of the gonad of C. elegans exposed to graded concentrations of endosulfan. The expression levels of sod-3, localized in the mitochondrial matrix, increased greatly after endosulfan exposure. A significant increase in germ cell apoptosis was observed in abnormal methyl viologen sensitivity-1 (mev-1(kn-1)) mutants (with abnormal mitochondrial respiratory chain complex II and higher ROS levels) compared to that in N2 at equal endosulfan concentrations. We found that the insulin/IGF-1 signaling pathway and its downstream Ras/ERK/MAPK did not participate in the endosulfan-induced apoptosis. However, the apoptosis in the loss-of-function strains of JNK and p38 MAPK signaling pathways was completely or mildly suppressed under endosulfan stress. The apoptotic effects of endosulfan were blocked in the mutants of jnk-1/JNK-MAPK, sek-1/MAP2K, and pmk-1/p38-MAPK, suggesting that these downstream genes play an essential role in endosulfan-induced germ cell apoptosis. In contrast, the mkk-4/MAP2K and nsy-1/MAP3K were only partially involved in the apoptosis induction. Our data provide evidence that endosulfan increases germ cell apoptosis, which is regulated by mitochondrial function, JNK and p38 MAPK cascades. These findings contribute to the understanding of the signal transduction pathways involved in endosulfan-induced apoptosis.

In natural environments, shoot was exposed to sunlight but roots are not directly exposed to light, being buried deep down in the soil and grow in darkness without sucrose addition. However, most current research in root biology has been carried out by growing the Arabidopsis root system in the presence of light and sucrose-added medium since root development is typically studied in traditional agar-plate culture system (TPG, traditional plant-growing). Here, we present a protocol for improved agar-plate culture system (IPG, improved plant-growing), allows the in vitro cultivation of Arabidopsis with the aerial part growing in normal light/dark photoperiod while roots grow in darkness without sucrose addition. IPG provides an efficient system for cultivating a large number of seedlings and easily characterizing root architecture in the dark. We also provide methods for key steps all the way through to seedlings growth.We found that the primary root lengths in TPG were significantly longer than that in IPG, and the root elongation growth is dependent on auxin-triggered acidification of the root apoplast of Arabidopsis . With this protocol, a better understanding of the mechanisms involved in root growth and responses of plants can be easily characterized.

Deficient DNA mismatch repair (dMMR) induces a hypermutator phenotype that can lead to tumorigenesis; however, the functional impact of the high mutation burden resulting from this phenotype remains poorly explored. Here, we demonstrate that dMMR-induced destabilizing mutations lead to proteome instability in dMMR tumors, resulting in an abundance of misfolded protein aggregates. To compensate, dMMR cells utilize a Nedd8-mediated degradation pathway to facilitate clearance of misfolded proteins. Blockade of this Nedd8 clearance pathway with MLN4924 causes accumulation of misfolded protein aggregates, ultimately inducing immunogenic cell death in dMMR cancer cells. To leverage this immunogenic cell death, we combined MLN4924 treatment with PD1 inhibition and found the combination was synergistic, significantly improving efficacy over either treatment alone.

The present study was designed to further explore the role and the underlying molecular mechanism of phosphocreatine (PCr) for cardiac fibrosis in vivo. Isoproterenol (ISO) was used to induce cardiac fibrosis in rats. PCr administration ameliorated fibrosis by reducing collagen accumulation and fibrosis-related signals, including transforming growth factor beta 1 (TGF-β1), alpha smooth muscle actin (α-SMA), collagen type I, and collagen type III. Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways, including p38, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p65, were highly activated by ISO and blocked by PCr. Moreover, PCr decreased ISO-induced matrix metalloproteinase-9 (MMP-9) and increased the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. Furthermore, PCr suppressed cardiomyocyte apoptosis induced by ISO, as shown by downregulated expression of the proapoptotic caspase-3, Bax, and upregulated expression of the antiapoptotic Bcl-2. Taken together, PCr can be an effective agent for preventing cardiac fibrosis and cardiomyocyte apoptosis.

Copyright © 2021 Elsevier Inc., Eukaryotic cells regulate 50-triphosphorylated RNAs (ppp-RNAs) to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the g phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR-1 (phosphatase that interacts with RNA and ribonucleoprotein particle 1) family of RNA polyphosphatases remove both the b and g phosphates from ppp-RNAs. Here, we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RNA-dependent RNA polymerases (RdRPs) and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in both somatic and germline development. Our findings suggest that PIR-1 modulates both Dicer-dependent and Dicer-independent Argonaute pathways and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species.

Cucumber powdery mildew (PM) is a destructive fungal disease which has a substantial impact on cucumber yield and quality. Our previous work has demonstrated that (+)-(S)-ar-turmerone (ATM) is an effective compound for controlling PM infected by Podosphaera xanthii in cucumber. In this study, the effect of ATM on cucumber PM was histologically investigated by observations on the morphology of the pathogenic fungus at different time points after inoculation. It was found that the ATM caused the collapse of the pathogen's conidia and mycelia structure, the cytoplasm coagulation, the reduction of the conidia germination rate, and the inhibition of the conidiophore growth, therefore, prevented the re-infection of the P. xanthii. Evaluation of the content of total phenols and flavonoids in cucumber ATM-treated leaves showed that the ATM-treatment could increase the content of total phenols and flavonoids in cucumber leaves significantly in comparison to the control. A further analysis of the contents of the compounds showed that ATM-treatment could increase the content of rutin, quercetin, hesperetin, and gallic acid, syringic acid, vanillic acid and salicylic acid. Meanwhile, the activity of phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) in cucumber leaves were increased slightly, but the activity of peroxidase (POD) and superoxide dismutase (SOD) were significantly increased through ATM treatment. It should be estimated from this study that the ATM not only directly affected the growth of P. xanthii but also enhanced the cucumber plant resistance to the disease.

The carmine spider mite Tetranychus cinnabarinus (Boisduval) is a serious pest affecting various glasshouse vegetables, fruits and crops and causes significant damage to crop yields and quality by piercing and sucking foliar tissues. The control of this mite primarily involves the application of synthetic chemical pesticides. In this study, a Solanum nigrum L. extract was evaluated for its potential acaricidal activity against adult female T. cinnabarinus in laboratory conditions, and the S. nigrum extract showed marked efficacy in controlling the carmine spider mite both in vitro and in potted seedlings. Furthermore, the active compound, a phytostanol ester (β-sitosterol-3-O-heptadeca-8Z, 11Z-dienoate), was isolated from the petroleum ether-soluble fraction of S. nigrum extract via repeated column chromatography and identified based on its physiochemical properties and spectral data. At 7 days after treatment in a potted seedling experiment, the LC50 values of the S. nigrum extract and active compound were found to be 4.70 and 1.85 g/l, respectively. All of these results demonstrated that the S. nigrum extract and its active component exhibit the potential for use as new natural acaricides for controlling carmine spider mites.

Reelin is an extracellular matrix (ECM) protein that is essential for neuron migration and positioning. The expression of reelin in multiple myeloma (MM) cells and its association with cell adhesion and survival were investigated. Overexpression, siRNA knockdown, and the addition of recombinant protein of reelin were used to examine the function of reelin in MM cells. Clinically, high expression of reelin was negatively associated with progression-free survival and overall survival. Functionally, reelin promoted the adhesion of MM cells to fibronectin via activation of α5β1 integrin. The resulting phosphorylation of Focal Adhesion Kinase (FAK) led to the activation of Src/Syk/STAT3 and Akt, crucial signaling molecules involved in enhancing cell adhesion and protecting cells from drug-induced cell apoptosis. These findings indicate reelin's important role in the activation of integrin-β1 and STAT3/Akt pathways in multiple myeloma and highlight the therapeutic potential of targeting reelin/integrin/FAK axis.

The Bajiu tracksite exposed on a fine sandstone surface at the top of the Feitianshan Formation, close the contact with the overlying Xiaoba Formation, reveals a saurischian dominated ichnofauna consisting of four sauropod and at least eight theropod trackways. The sauropod trackways display a medium-wide gauge pattern characteristic of titanosauriforms, while the theropod trackways can be subdivided into two distinct morphotypes. One is similar to the ichnogenera Eubrontes and Megalosauripus, the other (cf. Dromaeopodus) appears to represent a functionally didactyl dromaeosaur where pedal digit II is represented only by an oval basal pad. A single swim track is possibly attributable to a turtle or crocodylian. Such sauropod-theropod dominated ichnofaunas are consistently typical of the red-bed tracksites in the region and useful for characterizing a fauna that is otherwise poorly known from body fossils. The stratigraphic position and late occurrence of the (typical Jurassic) Eubrontes-Megalosauripus morphotype is well known from other Cretaceous localities in China and seems to reflect a peculiarity in the theropod faunas of East Asia.

Non-coding small RNAs play important roles in virus–host interactions. For hosts, small RNAs can serve as sensors in antiviral pathways including RNAi and CRISPR; for viruses, small RNAs can be involved in viral transcription and replication. This paper covers several recent discoveries on small RNA mediated virus–host interactions, and focuses on influenza virus cap-snatching and a few important virus sensors including PIR-1, RIG-I like protein DRH-1 and piRNAs. The paper also discusses recent advances in mammalian antiviral RNAi.

Introduction Sepsis is a potentially life-threatening complication after infection and the second-leading cause of death in non-coronary intensive care plural - units. The aim of this trial was to evaluate the efficacy and safety of Shufeng Jiedu Capsules (SFJDC) as a complementary medicine in the treatment of sepsis. Methods Hospital inpatients diagnosed with sepsis and who met the trial inclusion/exclusion criteria were randomly allocated into one of two groups; a combination group (antibiotics and SFJDC) and a routine care group (antibiotics and placebo group). The primary outcome was severity assessed by the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Secondary outcomes included the SOFA score, the traditional Chinese medicine (TCM) symptom score, and 28-day mortality. Additional outcomes included indices of infection (such as the level of procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count). Results Of 150 patients admitted between July 2016–2017, 129 patients meeting the inclusion criteria were randomly assigned to either the combination group (n = 66) or a single antibiotics group (n = 63). The APACHE II score, the TCM symptom score, the level of CRP, the neutrophil-lymphocyte ratio (NLR) and the healing rate differed significantly between the two groups on the 7th day of hospitalization(p = 0.046, p = 0.020, p = 0.009, p = 0.001, and p Conclusion A combination of antibiotics and SFJDC in the treatment of sepsis was superior to routine antibiotic treatment since combination therapy reduces the inflammatory response and improves prognosis for septic patients.

Autoimmune epilepsy (AE) refers to epilepsy mediated by autoantibodies or immune cells, and a large proportion of drug-resistant epilepsy cases are classified as AE. AE lacks standardized management guidelines. At present, little research has been conducted on the effectiveness of surgical treatment of AE. This paper reports a patient whose surgical treatment was ineffective before AE was diagnosed and who improved after immunotherapy. A literature review was conducted to examine the progress of surgical treatment of epilepsy, the relationship of temporal lobe epilepsy to neuronal antibodies, surgical and prognostic factors, research progress on the anti-Hu antibody, and treatment of autoimmune encephalitis to provide a clinical reference.

Summary: Acute cardiac hypoxia produces life-threatening elevations in late sodium current (ILATE) in the human heart. Here, we show the underlying mechanism: hypoxia induces rapid SUMOylation of NaV1.5 channels so they reopen when normally inactive, late in the action potential. NaV1.5 is SUMOylated only on lysine 442, and the mutation of that residue, or application of a deSUMOylating enzyme, prevents hypoxic reopenings. The time course of SUMOylation of single channels in response to hypoxia coincides with the increase in ILATE, a reaction that is complete in under 100 s. In human cardiac myocytes derived from pluripotent stem cells, hypoxia-induced ILATE is confirmed to be SUMO-dependent and to produce action potential prolongation, the pro-arrhythmic change observed in patients. : The cardiac channel NaV1.5 passes pro-arrhythmic late sodium currents in response to hypoxia. Plant et al. demonstrate the pathophysiological mechanism to be rapid, hypoxia-induced monoSUMOylation of NaV1.5 channels. Blocking SUMOylation of lysine442 prevents hypoxia-induced late currents and attendant prolongation of the action potential in human cardiomyocytes derived from pluripotent stem cells. Keywords: SUMO, SCN5A, late current, sudden death, ILATE, hypoxia, NaV1.5, SENP, cardiomyocyte, arrythmia