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Summary Faecal Microbiota Transplantation (FMT) is considered as a promising technology to fight against obesity. Wild boar has leanermuscle and less fat in comparison to the domestic pig, which were thought to be related with microbiota. To investigate the function and mechanism of the wild boar microbiota on obesity, we first analysed the wild boar microbiota composition via 16S rDNA sequencing, which showed that Firmicutes and Proteobacteria were the dominant bacteria. Then, we established a high‐fat diet (HFD)‐induced obesity model, and transfer low and high concentrations of wild boar faecal suspension in mice for 9 weeks. The results showed that FMT prevented HFD‐induced obesity and lipid metabolism disorders, and altered the jejunal microbiota composition especially increasing the abundance of the Lactobacillus and Romboutsia, which were negatively correlated with obesity‐related indicators. Moreover, we found that the anti‐obesity effect of wild boar faecal suspension was associated with jejunal N6‐methyladenosine (m6A) levels. Overall, these results suggest that FMT has a mitigating effect on HFD‐induced obesity, which may be due to the impressive effects of FMT on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m6A levels to achieve resistance to obesity., Our results suggest that the fecal bacteria of wild boar have a mitigating effect on HFD‐induced obesity, which may be due to the impressive effects of wild boar fecal microbiota transplantation on the microbial composition and structure of the jejunum. These changes further alter intestinal lipid metabolism and m6A levels to achieve resistance to obesity.

Phytochemical investigation of the fruits of Crataegus pinnatifida Bunge led to the isolation of four pairs enantiomeric benzofuran lignans (1a/1b���4a/4b) including four undescribed compounds (1a, 2b, 3b and 4b). Their structures were determined by extensive spectroscopic methods and the absolute configurations were further determined by the comparison of experimental and calculated ECD spectra. All the enantiomeric lignans were evaluated for their inhibitory activities to tyrosinase. Among them, compound 4a showed moderate inhibition activity (IC50 = 0.54 mM).

The genus Dlhawksworthia presently includes three species. All the previously described species have been isolated from plants. Besides, none of these three species have ever been recorded in China. We conducted surveys in various regions of China to isolate and identify endolichenic fungi associated with diverse lichen species. During these surveys, we isolated both previously known and undescribed fungi associated with lichens. Among these, there was an isolate of an unknown fungus. The morphological and molecular analyses indicated that this isolate represented a new species from the genus Dlhawksworthia. As a consequence, we described this fungus as Dlhawksworthia flavoparmeliae sp. nov. This is the first report of Dlhawksworthia isolated from a lichen in China and globally.

Genome-wide association studies (GWASs) have revealed substantial genetic components comprised of single nucleotide polymorphisms (SNPs) in the heritable risk of psychiatric disorders. However, genetic risk factors not covered by GWAS also play pivotal roles in these illnesses. Tandem repeats, which are likely functional but frequently overlooked by GWAS, may account for an important proportion in the "missing heritability" of psychiatric disorders. Despite difficulties in characterizing and quantifying tandem repeats in the genome, studies have been carried out in an attempt to describe impact of tandem repeats on gene regulation and human phenotypes. In this review, we have introduced recent research progress regarding the genomic distribution and regulatory mechanisms of tandem repeats. We have also summarized the current knowledge of the genetic architecture and biological underpinnings of psychiatric disorders brought by studies of tandem repeats. These findings suggest that tandem repeats, in candidate psychiatric risk genes or in different levels of linkage disequilibrium (LD) with psychiatric GWAS SNPs and haplotypes, may modulate biological phenotypes related to psychiatric disorders (e.g., cognitive function and brain physiology) through regulating alternative splicing, promoter activity, enhancer activity and so on. In addition, many tandem repeats undergo tight natural selection in the human lineage, and likely exert crucial roles in human brain evolution. Taken together, the putative roles of tandem repeats in the pathogenesis of psychiatric disorders is strongly implicated, and using examples from previous literatures, we wish to call for further attention to tandem repeats in the post-GWAS era of psychiatric disorders.

Though the genomes of many rice herbivorous pests have recently been well characterized, little is known about the genome of their natural enemies. Here, by using the Illumina and PacBio platforms, we sequenced and assembled the whole genome of the mirid species Cyrtorhinus lividipennis Reuter (Hemiptera: Miridae), which is an economically and ecologically important natural enemy in the rice ecosystem acting as a dominant predator for planthoppers and leafhoppers in the field. Through Hi-C scaffolding, 1615 scaffolds with a total size of 338.08 Mb were successfully anchored onto 13 chromosomes. The assembled genome size was 345.75 Mb with a final scaffold N50 of 27.58 Mb. Approximately 107.51 Mb of sequences accounting for 31.10% of the genome were identified as repeat elements, and 14,644 protein-coding genes were annotated. Phylogenetic analysis showed that C. lividipennis clustered with other Hemipteran species and diverged from Apolygus lucorum about 66.7 million years ago. Gene families related to detoxification, environmental adaptation and digestion were analysed comparatively with other Hemipteran species, but no significant expansion or contraction was found in C. lividipennis. We also observed male meiosis in C. lividipennis, which showed a typical post-reduction of sex chromosomes and a karyotype of 2n = 22 + XY. As the first natural-enemy genome in the rice ecosystem, the genomic resource of C. lividipennis not only expands our understanding of the multitrophic interactions (host plant-prey-predator), but also provides a genomic basis for better understanding this dominant predator and therefore promotes sustainable rice pest management and food grain production.

Genome-wide association studies (GWAS) have identified a large number of schizophrenia risk variants, and most of them are mapped to noncoding regions. By leveraging multiple joint-tissue gene expression data and GWAS data, we herein performed a transcriptome-wide association study (TWAS) and Mendelian randomization (MR) analysis and identified 144 genes whose mRNA levels were related to genetic risk of schizophrenia. Most of these genes exhibited diametrically opposite trends of expression in prenatal and postnatal brain tissues, despite that their expression levels in dorsolateral prefrontal cortex (DLPFC) tissues did not significantly differ between schizophrenics and healthy controls. We then found significant enrichment of these genes in dopamine-related pathways that were repeatedly implicated in schizophrenia pathogenesis and in the action of antipsychotic drugs. Gene expression analysis using single cell RNA-sequencing (scRNA-seq) data of mid-gestation fetal brains further revealed enrichment of these genes in glutamatergic excitatory neurons and cycling progenitors. These lines of evidence, in consistency with previous findings, confirmed the polygenic nature of schizophrenia and highlighted involvement of early neurodevelopment aberrations in this disorder. Further investigations using advanced algorithms in both bulk brain tissues and in single cells and at different developmental stages are necessary to characterize transcriptomic features of schizophrenia pathogenesis along brain development.

A limited delivery of oxygen and metabolic substrate to the heart caused by myocardial infarction (MI) impairs the cardiac function, and often results in heart failure. Here, we identified a circRNA (circ-SNRK) from SNRK (sucrose nonfermenting 1-related kinase, which can increase the cardiac mitochondrial efficiency) in cardiomyocytes (CMs). Circ-SNRK can sponge the miR-33 and in turn improved the ATP synthesis via SNRK, proving the existence of circ-SNRK - miR-33 - SNRK axis. Furthermore, we found that protein NOVA1 (NOVA alternative splicing regulator 1) could accelerate the circ-SNRK formation; a cleaved peptide (~55 kDa) from SNRK enters the nucleus and blocks the cyclization of circ-SNRK via binding to NOVA1. The aforementioned negative feedback of SNRK to circ-SNRK limited the SNRK at a proper level, and inhibited the protective role of circ-SNRK in ischemic heart. In addition, our in vivo experiment indicated that the overexpression of exogenic circ-SNRK could break this loop and improves the cardiac function post-MI in rats. Together, our results demonstrated that the negative loop of circ-SNRK with SNRK regulates the energy metabolism in CMs, thus might be a potential therapeutic target for heart failure.

Daphnenoids A-C (1-3), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D (4) were obtained from the herb of Daphne penicillata by molecular networking strategies. Daphnenoid A (1) possesses a unique caged tetracyclo [5.3.2.01,6.04,11] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C (2 and 3) were the first discovered natural sesquiterpenes with unique 5/5 spirocyclic systems in nature. Their structures were determined by NMR spectroscopic analysis, computer-assisted structure elucidation methods, quantum chemical calculations, and X-ray diffraction. A hypothetical biogenetic pathway begins with typical guaiane sesquiterpene (a), including a key intermediate (4) was proposed. Daphnenoids B and C (2 and 3) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.

The F115C mutation in the MATR3 gene has been linked to amyotrophic lateral sclerosis (ALS). To determine the pathogenicity of the F115C mutation and the mechanism by which this mutation causes ALS, we generated mice that harbor the F115C mutation in the endogenous murine Matr3 locus. Heterozygous or homozygous MATR3 F115C knock-in mice were viable and did not exhibit motor deficits up to 2 years of age. The mutant mice showed no significant differences in the number of Purkinje cells or motor neurons compared to wild-type littermates. Neuropathological examination revealed an absence of MATR3 and TDP-43 pathology in Purkinje cells and motor neurons in the mutant mice. Together, our results suggest that the F115C mutation in MATR3 may not confer pathogenicity.

Objective This study aimed to analyze the influence of SLCO1B1 and APOE gene polymorphisms on coronary heart disease in Mongolian population who living in Ordos area. Methods From January 2019 to J...

Sphingolipids (SPLs), a group of membrane and intracellular lipids, mediate numerous cellular processes. The composition and metabolism of sphingolipids varies according to species and the sphingolipid studies of insects, as compared to mammals, are not yet clear. In the current study, we subjected three auchenorrhynchous insects, including whitebacked planthopper (WBPH), Sogatella furcifera, small brown planthopper (SBPH), Laodelphax striatellus, and green rice leafhopper (GRLH), Nephotettix cincticeps, as representative rice pests for sphingolipid analysis. We performed sphingolipid species profiling using UPLC-Q-TOF-MS/MS and isolated sphingolipid metabolic genes from their transcriptomic data. C14-, C16-, C18- and C20-sphingoid base were detected in both planthoppers, but no C14- sphingoid base was found in GRLH. The planthoppers had more abundant sphingosine-1-phosphates (Sph-1-P) and ceramides than leafhopper. A total of 14, 13 and 16 sphingomyelin species were found in SBPH, WBPH and GRLH, respectively. The composition of sphingomyelin species varied in three insects. Coordinated with the abundance in sphingomyelin species, the leafhopper possessed more sphingomyelinase (SMase) gene isoforms for metabolism of different sphingomyelins than planthoppers. The phylogenetic analysis showed the three tested insects all possessed one potential neutral-SMase homologue, whereas SBPH and GRLH both had another potential acid-SMase homologue. This study is a comprehensive sphingolipidomic analysis, suggesting that sphingolipid profiles significantly differed among the three insects. By providing information of sphingolipid metabolic gene homologues of these three insects, our findings will contribute to the further sphingolipid studies of auchenorrhynchous insects and provide a research foundation for rice pest management.

Natural product–derived crude drugs are expected to yield an abundance of new drugs to treat infectious diseases. Hepatitis C virus (HCV) is an oncogenic virus that significantly impacts public health. In this study, we sought to identify anti-HCV compounds in extracts of natural products. A total of 110 natural compounds extracted from several herbal medicine plants were examined for antiviral activity against HCV. Using a Huh7-mCherry-NLS-IPS reporter system for HCV infection, we first performed a rapid screening for anti-HCV compounds extracted from crude drugs. The compounds threo-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-butoxypropan-1-ol (#106) and medioresinol (#110), which were extracted from Crataegus cuneate, exhibited anti-HCV activity and significantly inhibited HCV production in a dose-dependent manner. Analyses using HCV pseudoparticle and subgenomic replicon systems indicated that compounds #106 and #110 specifically inhibit HCV RNA replication but not viral entry or translation. Interestingly, compound #106 also inhibited the replication and production of hepatitis A virus. Our findings suggest that C. cuneate is a new source for novel anti-hepatitis virus drug development.

Spinal cord injury (SCI) is a salient traumatic disease that often leads to permanent disability, and motor and sensory impairments. Human umbilical cord mesenchymal stem cells (HucMSCs) have a wide application prospect in the treatment of SCI. This study explored the repair effect of HucMSCs-derived extracellular vesicles (HucMSCs-EVs) on SCI. HucMSCs and HucMSCs-EVs were cultured and identified. The rat model of SCI was established, and SCI rats were treated with HucMSCs-EVs. The motor function of SCI rats and morphology of spinal cord tissues were evaluated. Levels of NeuN, GFAP, and NF200 in spinal cord tissues were detected and cell apoptosis was measured. SCI rats were treated with EVs extracted from miR-29b-3p inhibitor-transfected HucMSCs. The downstream gene and pathway of miR-29b-3p were examined. HucMSCs-EVs-treated rats showed obvious motor function recovery and reduced necrosis, nuclear pyknosis, and cavity. HucMSCs-EVs alleviated spinal cord neuronal injury. miR-29b-3p was poorly expressed in SCI tissues, but highly expressed in EVs and SCI rats treated with EVs. miR-29b-3p targeted PTEN. Inhibition of miR-29b-3p or overexpression of PTEN reversed the repair effect of EVs on SCI. EVs activated the AKT/mTOR pathway via the miR-29b-3p/PTEN. In conclusion, HucMSCs-EVs reduced pathological changes, improved motor function, and promoted nerve function repair in SCI rats via the miR-29b-3p/PTEN/Akt/mTOR axis.

Zu-Qin Yang,1 Jing-Yun Mai,2 Min-Li Zhu,2 Xiu-Man Xiao,2 Xiao-Xiao He,2 Shang-Qin Chen,2 Zhen-Lang Lin,2 Xing Feng1 1Department of Neonatology, Children’s Hospital of Soochow University, Suzhou, 215025, Jiangsu, People’s Republic of China; 2Department of Neonatology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of ChinaCorrespondence: Xing FengDepartment of Neonatology, Children’s Hospital of Soochow University, No. 92 Zhongnan Street, Wuzhong District, Suzhou, 215025, Jiangsu, People’s Republic of ChinaTel +86 0512 80692700Fax +86 0512 80693599Email fengxing1938@21cn.comBackground: Neonatal ventilator-associated pneumonia (NVAP) is one of the main infections acquired in hospitals, and soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) are a TREM-1 subtype that can be released into the blood or bodily fluids during an infection.Methods: The patients included in the present study were divided into three groups: the NVAP group, the first control group, and the second control group (n = 20, each). Children requiring respiratory treatment were assigned to the NVAP group, newborns who received mechanical ventilation and had neonatal respiratory distress syndrome were assigned to the first control group, and newborns with normal X-ray and electrocardiogram results but no non-pulmonary infection was assigned to the second control group. The blood and bronchoalveolar lavage fluid (BALF) sTREM-1 levels in all newborns were analyzed.Results: The acute-phase blood and BALF sTREM-1 levels were significantly higher in the NVAP group than in the first control group, and the blood sTREM-1 expression level was lower in the second control group than in the NVAP group.Conclusion: The present results suggest that sTREM-1 might be a useful biomarker for NVAP prediction in the Department of Pediatrics.Keywords: pneumonia, neonatal ventilator-associated pneumonia, soluble TREM-1, neonate, C-reactive protein

We previously obtained and characterized a novel sulfated derivative of the exopolysaccharides from Enterobacter cloacae Z0206 (SEPS). This study aimed at investigating the effects and mechanism of SEPS against dextran sulfate sodium (DSS) induced intestinal injury. The results showed that SEPS increased the proliferation and survival of intestinal epithelial cells during DSS stimulation. Furthermore, SEPS maintained the barrier function and inflammatory response via JAK2 and MAPK signaling to protect against DSS-induced intestinal injury. Mechanistically, SEPS elevated the DNA methylation in the promoter region to negatively regulate the JAK2 and MAPKs expression. Thus, the current study shows the potential effects and mechanism of SEPS on DSS-induced intestinal epithelial cell injury.

B cells constitute a major component of tumor-infiltrating leukocytes. However, the influence of these cells on malignancy is currently under debate, reflecting the heterogeneity of B cell subsets in tumors. With recent advances, it becomes apparent that this debate includes not only the evaluation of B cells themselves, but also the underlying immune microenvironment network, which scripts the highly heterogeneous B cell populations in tumors and directs the roles of those sub-populations in disease progression and clinical treatment. In this review, we summarize recent findings on the heterogeneous subset composition of B cells in both human and mouse tumor models and their different impacts on disease progression. We further describe the multidimensional interplays between B cells and other immune cells in the tumor microenvironment, which account for the regulation of B cell differentiation and function in situ. We also assess the potential influences of distinct sub-tumor locations on B cell function in primary tumors during development and those under immunotherapy treatment. Illuminating the heterogeneous nature of B cell subset composition, generation, localization, and related immune network in tumor is of immense significance for comprehensively understanding B cell response in tumor and designing more efficacious cancer immunotherapies.

Hui Ma,1,2 Ping Kuen Lam,3 Wing Sum Siu,1,2 Cindy See Wai Tong,3 Kin Ki Yan Lo,3 Chi Man Koon,1,2 Xiao Xiao Wu,1,2 Xiang Li,1,2 Wen Cheng,1,2 Wai Ting Shum,1,2 Ping Chung Leung1,2 1Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China; 2State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China; 3Chow Tai Fook-Cheng Yu Tung Surgical Stem Cell Research Center, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of ChinaCorrespondence: Ping Chung LeungInstitute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of ChinaTel +85222528868Email pingcleung@cuhk.edu.hkIntroduction: The biological role of mesenchymal stem cells (MSCs) in wound healing has been demonstrated. However, there were limited studies on the healing effect of secretome which consists of many biological factors secreted by MSCs. In this study, we aimed to compare the therapeutic effects of secretome with MSCs on facilitating wound healing.Methods: Green fluorescent protein labelled adipose-derived MSCs (GFP-ADMSCs) or secretome was injected in the full-thickness skin excision model on SD rats. The wound healing process was evaluated by calculating the healing rate and the histological examinations on skin biopsy. The cell viability, proliferation and mobility of the rat dermal fibroblasts were compared after different treatments. The inflammatory response in macrophages was indicated by the level of nitric oxide (NO) and inflammatory cytokines through NO assay and ELISA.Results: On day 5 and day 14, both MSCs and secretome accelerated the wound healing, secretome further enhanced the process. GFP-MSCs were detected 10 days after transplantation. The level of IL-6 and TNF-α in blood was reduced after MSCs and secretome treatments. The expressions of VEGF and PCNA were increased after treatment, higher intensity of VEGF was observed in secretome-injected tissue. The concentrations of total protein and VEGF in secretome were 2.2 ± 0.5 mg/mL and 882.0 ± 72.7 pg/mL, respectively. The cell viability and proliferation of FR were promoted significantly after the treatment. The scratch test showed that secretome accelerated the wound healing speed. Secretome reduced the metabolism of macrophages remarkably, but it did not decrease the level of macrophage-secreted NO. The expression of the pro-inflammatory cytokines (IL-6, MCP-1 and TNF-α) was downregulated significantly.Conclusion: Our study indicated both MSCs and MSCs-derived secretome enhanced the wound healing process in early phase. Secretome further promoted the healing effects through promoting the fibroblast proliferation and migration and suppressing the inflammatory response.Keywords: MSCs, secretome, wound healing, local injection, skin

Objective:. Biallelic mutations in the RecQ like helicase (RECQL) 4 gene, a guardian of the genome, cause Rothmund–Thomson syndrome type II (RTS-II). Two Chinese girls with mild-phenotype RTS-II mainly restricted to their skin are herein described. Methods:. Blood specimens from two families with mild-phenotype RTS-II were collected. DNA isolation, RNA isolation and complementary DNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the underlying pathogenic variants in the causative RECQL4 gene. Results:. We analyzed two patients with mild phenotypes. One patient had an unreported paternal c.2885+1G>A alteration in intervening sequence 16 and the previously reported maternal exon 14 c.2272C>T (p.R758X), both resulting in premature termination codons. The other patient carried two novel alterations, c.2886-1G>A and c.2752G>T (p.E918X). Complementary DNA sequencing showed that different splice-site mutations within the same intron could lead to completely different splicing modes. Conclusion:. We identified three novel pathogenic RECQL4 variants in two patients with RTS, thus expanding the mutational spectrum of RTS-II. We also explored their pathogenic effect by transcripts analysis to address genotype–phenotype correlations.

Introduction A vaccine for malaria is urgently required but no vaccine has yet shown satisfactory protective efficacy especially for Plasmodium falciparum. P. falciparum infection can progress to cerebral malaria (CM), a neurological syndrome with exceedingly high mortality. Designing effective P. falciparum vaccines require more understanding of the protective immune response while the host immune response to CM and the mechanisms are still elusive. Here, we aim to identify host gene responses to CM and host gene networks associated with CM pathogenesis. Methods An innovative genomic analysis strategy, the weighted gene coexpression network analysis (WGCNA) combined with differential gene expression analysis, was used in this study. Data for analysis contain 93 whole blood samples, derived from two previous public transcriptome datasets. Results This approach led to the identification of numerous differentially expressed human transcripts and dozens of coexpression gene modules. We further identified nine key genes, including MBP, SAMSN1, PSMF1, SLC39A8, EIF3B, SMPDL3A, FABP5, SPSB3, and SHARPIN, of which the last four genes were first identified to be related to CM in the present study. Conclusion The results provided a comprehensive characterization of host gene expression profiles in CM and offered some new insight into malaria vaccine design. These identified key genes could be potential targets or immune modulators for novel therapeutic interventions of CM., Graphical abstract The present study used an innovative genomic analysis strategy to explored gene coexpression networks associated with cerebral malaria (CM) pathogenesis and identified several key host genes. The findings will be of interest to host–parasite interaction study and would be of assistance to further investigate CM pathology.

Autism spectrum disorders (ASDs) are highly associated with oxidative stress. We have recently shown that Disconnected-interacting protein homolog 2 A (DIP2A) functions in ASD pathophysiology by regulating cortactin acetylation for spine development and synaptic transmission. However, its role is not fully understood in the context of its abundant expression in mitochondria. In this paper, we found that DIP2A was involved in superoxide dismutase (SOD)-mediated antioxidative reactions. In mice, DIP2A knockout inhibited SOD activity and increased reactive oxygen species (ROS) levels in the cerebral cortex. In vitro gain-of-function experiments further confirmed the positive role of DIP2A in scavenging ROS upon oxidative stress. Moreover, DIP2A knockout caused irregular mitochondrial morphology in the cerebral cortex and impaired mitochondrial metabolism with an over consumption of lipids for energy supply. Taken together, these results revealed unrecognized functions of DIP2A in antioxidative protection, providing another possible explanation for DIP2A-mediated ASD pathophysiology.

Insecticide overuse in crop production systems often results in detrimental effects on predators and parasitoids, which regulate important insect pests. The natural enemies are also unable to survive in monocrop landscapes with the absence of shelter or food sources. Diversified vegetation, especially with flowering plants, can enhance natural enemy abundance and diversity, thus strengthening biological control, enabling farmers to reduce insecticides. In this study, we conserved bund vegetation and manipulated the existing rice landscapes with flowering plants to provide food and shelter for the biological control agents. Our study revealed significant positive relationships between predator densities and bund plant diversity. The abundance of predators significantly increased in the eco-engineered plots, especially at the flowering peaks compared to the insecticide-treated and control plots, while parasitoids were more diverse in both the eco-engineered and control plots. There were no significant differences in planthopper and leafhopper densities among the treatments during the rice early and maximum tillering stages, suggesting effective natural control of these herbivore pests in the eco-engineered plots at the early rice-growing season. However, at the heading stage relatively higher planthopper and leafhopper populations in the control and eco-engineered plots than in the insecticide-sprayed plots were recorded, suggesting perhaps the need for insecticide interventions if exceeding the threshold at this time. Our study indicates that manipulating the habitats surrounding the rice fields to enhance natural enemies is a sustainable practice in rice production as it can enhance the natural suppression of pests and thus reducing the need for insecticide.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00376-w.

Anaerobic digestion is promising for waste activated sludge (WAS) degradation. However, conventional processes were generally stuck with limited hydrolysis and poor pathogen destruction. Hyperthermophilic digestion at 70 °C has drawn attention in overcoming those issues at a relatively low energy requirement and operating difficulties. In order to illuminate its operation characteristics, a single-stage hyperthermophilic digester was controlled at 70 °C and operated continuously to degrade WAS. 88.7 mL/g VSadded of methane yield could be achieved in the hyperthermophilic system, fourfold higher than that in the mesophilic system. Kinetic analysis revealed that hyperthermophilic digestion was advantageous in converting the non-degradable fraction. Consequently, hydrolysis under the hyperthermophilic condition was able to be significantly improved. Above 10 d was necessary for the hyperthermophilic system to gain such a high methane production. In the case of stability, the organic loading of higher than 10.2 g VS/L/d resulted in increasing limitation from methanogenesis and accumulation of propionic, butyric and valeric acids. In addition to the dominant acetoclastic genus Methanothrix for methane production in the hyperthermophilic system, two hydrogenotrophic methanogens Methanospirillum and Methanothermobacter reached 18.84% and 8.31%, respectively. The genus Coprothermobacter, affiliated with the phylum Firmicutes, made more contribution to protein hydrolysis in the hyperthermophilic digester.

Background Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome comprise a rare genodermatosis associated with biallelic (homozygous or compound heterozygous) mutations in the DSG1 (desmoglein-1) gene, or heterozygous mutations in the DSP (desmoplakin) gene. To date, while many patients with SAM syndrome have been described, the number of cases with SAM syndrome with deep-intronic variants, together its genetic aetiology, remain limited. Objectives We report the case of a five-year-old Chinese boy with atypical SAM syndrome. Materials & methods Relevant blood specimens from the family were collected. DNA isolation, RNA isolation and cDNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the pathogenic gene. To test the functional consequences and pathogenic mechanism of the deep-intronic mutation in vitro, a mini gene strategy was constructed. Results A heterozygous DSG1 deletion (c.2437_2450delACCTATCCCTCGGG: p.Tyr814Trpfs*6) and a deep-intronic (c.1688-30A > T) variant were identified. The identified intronic variant was shown to create an alternative splice site, leading to nonsense-mediated mRNA decay of the aberrant transcript. Conclusion This is the first study to demonstrate a causal role for a deep-intronic DSG1 mutation in a patient with SAM syndrome. Our findings underline the need to analyse the intronic regions of DSG1 in patients with SAM syndrome. Improved diagnosis and a better understanding of prognosis will lead to clearer a picture of the concept of atypical SAM syndrome.

Background: Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver. Methods: Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People's Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines. Results: The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues (P = 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, P = 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells. Conclusions: Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.

Recent large-scale integrative analyses (including Transcriptome-Wide Association Study [TWAS] and Summary-data-based Mendelian Randomization [SMR]) have identified multiple genes whose cis-regulated expression changes may confer risk of schizophrenia. Nevertheless, expression quantitative trait loci (eQTL) data and genome-wide associations used for integrative analyses were mainly from populations of European ancestry, resulting in potential missing of pivotal biological insights in other continental populations due to population heterogeneity. Here we conducted TWAS and SMR integrative analyses using blood eQTL (from 162 subjects) and GWAS data (22 778 cases and 35 362 controls) of schizophrenia in East Asian (EAS) populations. Both TWAS (P = 2.89 × 10–14) and SMR (P = 6.04 × 10–5) analyses showed that decreased TMEM180 mRNA expression was significantly associated with risk of schizophrenia. We further found that TMEM180 was significantly down-regulated in the peripheral blood of schizophrenia cases compared with controls (P = 8.63 × 10–4 in EAS sample), and its expression was also significantly lower in the brain tissues of schizophrenia cases compared with controls (P = 1.87 × 10–5 in European sample from PsychENCODE). Functional explorations suggested that Tmem180 knockdown affected neurodevelopment, ie, proliferation and differentiation of neural stem cells. RNA sequencing showed that pathways regulated by Tmem180 were significantly enriched in brain development and synaptic transmission. In conclusion, our study provides convergent lines of evidence for the involvement of TMEM180 in schizophrenia, and highlights the potential and importance of resource integration and sharing at this big data era in bio-medical research.

Cavernous malformations affecting the CNS occur in ∼0.16–0.4% of the general population. The majority (85%) of cavernous malformations are in a sporadic form, but the genetic background of sporadic cavernous malformations remains enigmatic. Of the 81 patients, 73 (90.1%) patients were detected carrying somatic missense variants in two genes: MAP3K3 and PIK3CA by whole-exome sequencing. The mutation spectrum correlated with lesion size (P = 0.001), anatomical distribution (P

Clarifying the signaling pathway associated with nitric oxide (NO) and glutathione (GSH) in cardiovascular disease therapy is important for understanding its physiological and pathological processes but is challenging due to the lack of efficient analytical techniques. Herein, we report a BODIPY-based fluorescent probe for recognition of NO and GSH in sequence with high sensitivity and selectivity. The probe exhibits turn-on fluorescence triggered by NO, followed by red-shifted emission in the presence of GSH. The sequentially activated mechanism allows the visualization of NO-induced GSH upregulation in drug-treated endothelial cells and zebrafish for the first time, revealing a signal pathway during the therapy. We hope that it can be used as a convenient and efficient tool for the study of the interplay between NO and GSH and for the screening of effective drugs for cardiovascular disease therapy.

Autoimmune hepatitis (AIH) is characterized by interface hepatitis, elevated serum alanine aminotransferase and aspartate aminotransferase levels, circulating autoantibodies, and elevated predominantly immunoglobulin G (IgG) levels. The goal in the treatment of autoimmune hepatitis (AIH) is complete disease remission. Here we took advantage of a large cohort of AIH patients to clarify predictors associated with biochemical and histological remission. Of 705 patients with complete follow-up, 569 (80.7%) patients achieved complete biochemical remission. Lower IgG levels (17.8 vs. 25 g/L, p

Failed neuroprotection leads to the initiation of several diseases. SOX1 plays many roles in embryogenesis, oncogenesis, and male sex determination, and can promote glioma stem cell proliferation, invasion, and migration due to its high expression in glioblastoma cells. The functional versatility of the SOX1 gene in malignancy, epilepsy, and Parkinson's disease, as well as its adverse effects on dopaminergic neurons, makes it an interesting research focus. Hence, we collate the most important discoveries relating to the neuroprotective effects of SOX1 in brain cancer and propose hypothesis worthy of SOX1's role in the survival of senescent neuronal cells, its roles in fibroblast cell proliferation, and cell fat for neuroprotection, and the discharge of electrical impulses for homeostasis. Increase in electrical impulses transmitted by senescent cells affects the synthesis of neurotransmitters, which will modify the brain cell metabolism and microenvironment.

The high plasticity of root morphology, physiology, and function influences root-associated microbiomes. However, the variation in root-associated microbiome diversity and structures in response to root diameter at different root depths remains poorly understood. Here, we selected black locust (Robinia pseudoacacia L.) as a model plant to investigate the selection and network interactions of rhizospheric and root endophytic bacterial microbiomes associated with roots of different diameters (1, 1-2, and > 2 mm) among root depths of 0-100 cm via the Illumina sequencing of the 16S rRNA gene. The results showed that the alpha diversity of the root-associated bacterial communities decreased with increasing root diameters among different root depths; fewer orders with higher relative abundance, especially in the endosphere, were enriched in association with coarse roots (> 2 mm) than fine roots among root depths. Furthermore, the variation in the enriched bacterial orders associated with different root diameters was explained by bulk soil properties. Higher co-occurrence network complexity and stability emerged in the rhizosphere microbiomes of fine roots than those of coarse roots, in contrast to the situation in the endosphere microbiomes. In particular, the endosphere of roots with a diameter of 1-2 mm exhibited the lowest network complexity and stability and a high proportion of keystone taxa (e.g., Cytophagia, Flavobacteriia, Sphingobacteriia, β-Proteobacteria, and γ-Proteobacteria), suggesting a keystone taxon-reliant strategy in this transitional stage. In summary, this study indicated that root diameter at different root depths differentially affects rhizospheric and endophytic bacterial communities, which implies a close relationship between the bacterial microbiome, root function, and soil properties.

Objectives Liver cirrhosis (LC) is the end-stage of fibrosis in chronic liver diseases, non-invasive early detection of liver fibrosis (LF) is particularly essential for therapeutic decision. Aberrant glycosylation of glycoproteins has been demonstrated to be closely related to liver abnormalities. Methods This study was designed to enroll a total of 1,565 participants with LC/LF, chronic hepatitis virus (CHB) and healthy controls. Fibrosis was confirmed by liver biopsy. Using capillary electrophoresis N-glycan fingerprint (NGFP) analysis, we developed a nomogram algorithm (FIB-G) to discriminate LC from non-cirrhotic subjects. Results The FIB-G demonstrated good diagnostic performances in identifying LC with the area under the curve (AUC) 0.895 (95%CI: 0.857–0.915). Furthermore, the diagnostic efficiencies of FIB-G were superior to that of log (P2/P8), procollagen III N-terminal (PIIINP), type IV collage (IV-C), laminin (LN), hyaluronic acid (HA), aspartate transaminase to platelets ratio index (APRI), and FIB-4 when detecting significant fibrosis (S0–1 vs. S2–4, AUC: 0.787, 95%CI: 0.701–0.873), severe fibrosis (S0–2 vs. S3–4, AUC: 0.844, 95%CI: 0.763–0.924), and LC (S0–3 vs. S4, AUC: 0.773, 95%CI: 0.667–0.880). Besides, changes of FIB-G were associated well with the regression of fibrosis and liver function Child–Pugh classification. Conclusions FIB-G is an accurate multivariant N-glycomic algorithm for LC prediction and fibrosis progression/regression monitoring. The high throughput feasible NGFP using only 2 μL of serum could help physicians make the more precise non-invasive staging of LF or cirrhosis and reduce the need for invasive liver biopsy.

Obsessive-compulsive disorder (OCD) represents a heterogeneous collection of diseases with diverse levels of phenotypic, genetic, and etiologic variability, making it difficult to identify the underlying genetic and biological mechanisms in humans. Domestic dogs exhibit several OCD-like behaviors. Using continuous circling as a representative phenotype for OCD, we screened two independent dog breeds, the Belgian Malinois and Kunming Dog and subsequently sequenced ten circling dogs and ten unaffected dogs for each breed. Using population differentiation analyses, we identified 11 candidate genes in the extreme tail of the differentiated regions between cases and controls. These genes overlap significantly with genes identified in a genome wide association study (GWAS) of human OCD, indicating strong convergence between humans and dogs. Through gene expressional analysis and functional exploration, we found that two candidate OCD risk genes, PPP2R2B and ADAMTSL3, affected the density and morphology of dendritic spines. Therefore, changes in dendritic spine may underlie some common biological and physiological pathways shared between humans and dogs. Our study revealed an unprecedented level of convergence in OCD shared between humans and dogs, and highlighted the importance of using domestic dogs as a model species for many human diseases including OCD.

Three new monoterpenoid coumarins, zantholin A (3), altissimacoumarin P-Q (5, 6), two new monoterpenoid phenylpropanoids, altissmaphenylpropanoids A-B (2, 4), along with two known compounds (7, 8), were obtained from aqueous EtOH extracts of the root bark of Ailanthus altissima. The assignments of their structures were conducted via extensive analyses of the spectroscopic data. The evidence for the reassignment of the relative configuration in compound 1 was obtained from acetonide analysis, which was also used for assigning the relative configuration of compounds 2 and 6. The utility of statistical procedure (DP4+) was assessed for the relative stereochemistry of compounds 3 and 4. The relative configuration of compound 5 was verified utilizing NOE differential spectroscopy and computational methods. A combination of Mosher's method, optical rotation calculations and a plausible biosynthetic pathway was used to confirm the absolute configuration of compounds 1–6. Moreover, the compounds were tested for their anti-tumor effects against two hepatoma carcinoma cell lines (HepG2 and Hep3B).

Four-and-a-half LIM domain protein 1 (FHL1) is a member of the FHL protein family that serves as a scaffold protein to maintain normal cellular structure and function. Its mutations have been implicated in multiple muscular diseases. These FHL1 related myopathies are characterized by symptoms such as progressive muscle loss, rigid or bent spine, even cardiac or respiratory failure in some patients, which implies pathological problems not only in muscles, but also in the nervous system. Moreover, decreased FHL1 protein level has been found in patients with FHL1 mutations, indicating the protein loss-of-function as a pathological cause of such diseases. These findings suggest the significance of understanding the systemic role of FHL1 in the homeostasis of nervous system and muscle. Here we reported that Fhl1 loss in C2C12 myotubes obscured acetylcholine receptor (AChR) clustering in addition to myotube fusion, which was associated with impaired MuSK phosphorylation. Mechanistically, myostatin-SMAD2/3 signaling was enhanced, whereas IGF-PI3K-AKT signaling was suppressed in Fhl1-/- C2C12 myotubes. Reversion of these molecular alterations rescued AChR clustering and differentiation deficits. These data outline a systemic regulation of AChR clustering and myotube fusion by FHL1, which may offer clues for mechanism study and development of therapeutic strategies to treat FHL1 related myopathies.

Microsporidia are a group of unicellular and opportunistic intestinal parasites in which Enterocytozoon bieneusi is a frequent species causing microsporidial infections in humans. Many domesticated and wild animals have been shown to be hosts of E. bieneusi and other microsporidia. The role of hedgehogs in the ecology of microsporidia is unclear; therefore, we investigated the prevalence and genetic diversity of E. bieneusi, Cryptosporidium, and Blastocystis spp. in hedgehogs (Erinaceus amurensis) collected from Hubei Province in Central China. PCR amplification of the internal transcribed spacer region of the ribosomal DNA indicated that 9.8% (4/41) hedgehogs were positive to E. bieneusi, but none (0/41) was positive to Cryptosporidium and Blastocystis spp. Phylogenetic analysis showed the strains detected from the hedgehogs belong to four novel genotypes (EA1-EA4), which were most closely related to type IV of group 1c. This study demonstrated that hedgehogs are hosts of E. bieneusi and may play a role in the transmission of E. bieneusi to humans in the process of being caught and slaughtered.

(±)-Pinnatifidaones A–C (1–3), three enantiomeric pairs of highly modified spirocyclohexenone neolignans, along with a pair of biogenetically related enantiomers (±)-pinnatifidaones D (4), were isolated from Crataegus pinnatifida. Pinnatifidaones A (1) and B (2) share an unprecedented 5/6/6 tricyclic ring system with a rare 2-oxaspiro[4.5]deca-6-en-8-one motif, while 3 features a unique 2-oxaspiro[4.5]deca-6-en-8-one 5/5/6/6 tetracyclic framework. Their structures including absolute configurations were established by spectroscopic analysis, X-ray diffraction, and application of Snatzke's method, as well as NMR and ECD calculations. Moreover, (+)-3 possessed cytotoxicity against Hep3B cells by inducing cell apoptosis.

Cytochrome P450 (CYP) enzymes are one of the main sources of variability in drug metabolic clearance. Information on their abundance levels is therefore crucial to optimize scaling factors for in vitro–in vivo extrapolation (IVIVE) to predict metabolic clearance. This study aims to quantify the abundance data of hepatic drug-metabolizing CYP enzymes in East Asian subjects reported from various sources in the literature using meta-analysis. We conducted a meta-analysis on the abundance of drug-metabolizing CYP enzymes in the liver of East Asian adults. Eligible reports were identified based on predefined criteria—(1) individual liver microsomal samples, and (2) absolute protein abundance data from normal tissues of East Asian adult subjects. Subgroup and sensitivity analyses were also performed. Among the 11 CYP isoforms analyzed in East Asian subjects, CYP3A5 and CYP3A4 had the highest protein levels. In particular, the number of studies and the liver sample used to quantify the abundance of CYP3A4 were the largest. Of the isoforms involved, CYP2J2 and CYP2B6 had the lowest abundance level, i.e.

Due to pollution in the process of chemical treatments, wool textile industry has been remarkably changed to use eco-friendly reagents in preparatory and finishing operations. We previously isolate...

Chiral β-amino alcohols are privileged scaffolds frequently found in pharmaceutically active molecules and natural products. Aminohydroxylation of olefins is one of the most powerful strategies to access chiral vicinal amino alcohols. However, the direct regio- and stereoselective aminohydroxylation of olefins to unprotected enantioenriched β-amino alcohols remains a long-standing challenge. Herein, we report that a novel one-pot four-enzyme [styrene monooxygenase (SMO)/epoxide hydrolase (EH)/alcohol dehydrogenase (ADH)/ω-transaminase (TA)] biocatalytic cascade efficiently catalyzes the direct transformation of readily available styrenyl olefins into unprotected 2-amino-2-phenyl ethanols in good yields and excellent enantioselectivity. In vitro cascade biocatalysis aminohydroxylation of styrenyl olefins was first investigated by the combined four enzymes (SMO/EH/ADH/TA) with a trace amount of NADH (0.02 mM) and pyridoxal-5′-phosphate (0.1 mM), affording both enantiomers of β-amino alcohols 5a–j in 13.9–98.7% conversions and 86–99% ee. Whole-cell-based cascade biocatalysis was achieved by using the constructed recombinant Escherichia coli pairwise combinations and single tailor-made whole-cell biocatalyst without an additional NADH cofactor; (R)- and (S)-β-amino alcohols 5a–j could be obtained in 14.6–99.7% conversions and 86–99% ee. Moreover, the preparative experiments of this new cascade biocatalysis were demonstrated by the single tailor-made whole-cell biocatalyst [E. coli (CGS-DEM) and E. coli (CGS-DEB)] with the substrates 1a–b and 1h in an aqueous-organic two-phase system, affording chiral β-amino alcohols [(R)- or (S)-5a–b, h] in good yields (50.9–64.3%) and excellent ee (>99%).

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Purpose Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment. Our previous studies demonstrated that Huaier enhanced chemotherapy sensitivity and restrained HCC proliferation. This study aimed to identify differentially expressed proteins with Huaier treatment in HCC cells, providing molecular targets for future targeted therapy of HCC. Materials and Methods The effects of Huaier on the cell cycle were determined by flow cytometry and Western blot (WB). Xenograft models were used to verify the effects of Huaier on tumor growth. Then, proteomics was performed to identify the potential proteins regulated by Huaier. The enrichment analysis of GO and KEGG was performed for the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were used to detect the levels of proteins after Huaier treatment. After that the correlation of differentially expressed proteins with pathological stages was analyzed via the GEPIA database. We also analyzed candidate expression after Huaier treatment in HCC cells by WB and qRT-PCR. Furthermore, siRNA was performed to verify the targeted regulation of Huaier on candidate proteins. Results First, the proteomics data showed that a total of 160 proteins were identified as differentially expressed proteins, among which six minichromosome maintenance (MCM) family members were enriched in the tumor-associated pathways after Huaier treatment. Moreover, MCM proteins were highly expressed in HCC and closely correlated with the survival of HCC patients. Finally, we confirmed that MCM proteins were targets of Huaier treatment in HCC cells. Conclusion Huaier treatment was closely associated with the activation and inhibition of cancer-related pathways, and the MCM family was identified as a potential target in the antitumor process of Huaier. This study is helpful in understanding the molecular alterations and clinical relevance of HCC after Huaier treatment, which is beneficial for finding new targets and designing effective chemotherapy regimens for the future treatment of HCC.

20–40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Plasma-derived exosomal microRNAs had been isolated and sequenced of total 30 non-small cell lung cancer (NSCLC) patients including 16 with bone metastasis and 14 without bone metastasis. Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients with (BM +) or without (BM−) BM. Weight Co-expression network of miRNAs (WGCNA) analyses identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Three differentially expressed miRNAs between BM + and BM− patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/β-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote epithelial-mesenchymal transition (EMT) and bone metastasis. Electronic supplementary material The online version of this article (10.1007/s10585-020-10062-y) contains supplementary material, which is available to authorized users.

Understanding the violence behaviors in schizophrenia patients has always been the focus of forensic psychiatry. Although many studies show gut microbiota could regulate behavior, to our knowledge, no studies have profiled the gut microbiota structure in schizophrenia patients with violence. We profiled the characteristics of gut microbiota structure in 26 schizophrenia patients with violence (V.SCZ) by comparing with that of 16 schizophrenia patients without violence (NV.SCZ) under the control of confounders, and found the differences of gut microbiota structure between the two groups. Violence was assessed by the MacArthur Community Violence Instrument. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale. The 16S rRNA gene sequencing was used to identify and relatively quantify gut microbial composition. Bioinformatics analysis was used to find differential gut microbial composition between the V.SCZ and NV.SCZ groups. Fifty-nine differential microbial taxonomic compositions were found between the two groups. Fifteen gut microbial compositions were the key microbial taxonomic compositions responsible for the differences between the V.SCZ and NV.SCZ groups, including five enriched microbial taxonomic compositions (p_Bacteroidetes, c_Bacteroidia, o_Bacteroidales, f_Prevotellaceae, s_Bacteroides_uniformis), and ten impoverished microbial taxonomic compositions (p_Actinobacteria, c_unidentified_Actinobacteria, o_Bifidobacteriales, f_ Enterococcaceae, f_Veillonellaceae, f_Bifidobacteriaceae, g_Enterococcus, g_Candidatus_Saccharimonas, g_Bifidobacterium, and s_Bifidobacterium_pseudocatenulatum). This study profiled the differences of gut microbiota between schizophrenia patients with violence and without violence. These results could enrich the etiological understanding of violence in schizophrenia and might be helpful to violence management in the future.

Methane metabolism in deep subsurface petroleum reservoirs is of paramount interest in the global biogeochemical cycle of carbon. Methanogenesis in such habitats is driven mostly by methanogens in ...

A missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system. MATR3 S85C knock-in mice recapitulate behavioral and neuropathological features of early-stage ALS including motor impairment, muscle atrophy, neuromuscular junction defects, Purkinje cell degeneration and neuroinflammation in the cerebellum and spinal cord. Our neuropathology data reveals a loss of MATR3 S85C protein in the cell bodies of Purkinje cells and motor neurons, suggesting that a decrease in functional MATR3 levels or loss of MATR3 function contributes to neuronal defects. Our findings demonstrate that the MATR3 S85C mouse model mimics aspects of early-stage ALS and would be a promising tool for future basic and preclinical research., MATR3 is an ALS-linked gene. Here the authors describe a mutant MATR3 knockin mouse, which mimics some aspects of early-stage ALS.

Eleven triterpenoids, including a new tirucallane-type triterpenoid and a new natural product, were isolated from Picrasma quassioides. Their structures were elucidated by extensive spectroscopic analysis. All isolates were evaluated for their cytotoxic activities against Hep3B and HepG2 cell lines. Compounds 1 and 4 showed moderate cytotoxic activities toward the HepG2 cell at 50 μM, and 1 and 4 displayed equivalent effect to the positive control on Hep3B cell.