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Bacteria exist everywhere and pose a threat to human health. Reactive oxygen species (ROS), as a highly reactive chemical substance, can effectively oxidize and break lipids, DNA, protein and other bioactive molecules, leading to the death of bacteria. Modification of manganese oxide on the surface of silicon nanowire arrays deposited with polydopamine (SN@PDA@MnOX) can significantly increase the yield of ROS in a short period of time, which provides SN@PDA@MnOX with a strong chemodynamic antibacterial effect. Both manganese ions and manganese oxides in the reaction system promote the generation of ROS, and their mechanisms of action can be synergistic with each other. The results show that SN@PDA@MnOX can achieve a 99.99% antibacterial effect by using the ROS generated by chemodynamic reactions within 1 hour. SN@PDA@MnOX has great potential as a novel antibacterial material.

During a screening for novel and useful actinobacteria in desert animal, a new actinomycete was isolated and designated strain TRM63209T. The strain was isolated from in vivo of a Blattella germanica in Tarim University in Alar City, Xinjiang, north-west China. The strain was found to exhibit an inhibitory effect on biofilm formation by Candida albicans ATCC 18,804. The strain was observed to form abundant aerial mycelium, occasionally twisted and which differentiated into spiral spore chains. Spores of TRM63209T were observed to be oval-shaped, with a smooth surface. Strain TRM63209T was found to grow optimally at 28 °C, pH 8 and in the presence of 1% (w/v) NaCl. The whole-cell sugars of strain TRM63209T were rhamnose ribose, xylose, mannose, galactose and glucose, and the principal polarlipids were found to be diphosphatidylglycerol, phos-phatidylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, phosphatidylinositol and an unknown phospholipid(L). The diagnostic cell wall amino acid was identified as LL-diaminopimelic acid. The predominant menaquinone was found to be MK-9(H6) (14.64%), MK-9(H2) (19.65%), MK-9(H8) (22.34%), MK-10(H2) (25.37%). The major cellular fatty acids were identified as iso-C16:0, 16:0, anteiso-C15:0, anteiso-C17:0, iso-C15:0 and Sum in Feature 3. Analysis of the 16S rRNA sequence showed that strain TRM63209T exhibits high sequence similarity to Streptomyces bungoensis strain DSM 41781T 98.20%. A multi-locus sequence analysis of five house-keeping genes (atpD, gyrB, rpoB, recA and trpB) and phylogenomic analysis also illustrated that strain TRM63209T should be assigned to the genus Streptomyces. The DNA G + C content of the strain was determined to be 70.2 mol%. Average nucleotide identity (ANI) between strain TRM63209T and S. bungoensis DSM 41781T, Streptomyces phyllanthi PA1-07T, Streptomyces longwoodensis DSM 41677T and Streptomyces caeruleatus NRRL B-24802T were 82.76%, 82.54%, 82.65%, 84.02%, respectively. Digtal DNA-DNA (dDDH) hybridization were 26.30%, 25.10%, 26.20%, 29.50%, respectively. Therefore, it is concluded that strain TRM63209T represents a novel species of the genus Streptomyces, for which the name Streptomyces blattelae is proposed. The type strain is TRM63209T (CCTCC AA 2018093T = LMG 31,403 = TRM63209T).

Methyl jasmonate (MeJA) has been widely used to improve the biosynthesis of secondary metabolites such as triterpenoid saponins in medicinal plants. However, the underlying molecular mechanisms remain poorly understood. Differing from roots that accumulate protopanaxatriol-type saponins, Panax notoginseng leaves with a lower biomass mainly contain protopanaxadiol (PPD)-type saponins. Therefore, it is interesting to explore whether MeJA can activate the biosynthesis of PPD-type saponins in P. notoginseng leaves. In this study, we found MeJA could effectively induce the accumulation of PPD-type saponins, including ginsenoside Rb1, Rc, Rb2, Rb3 and notoginsenoside Fa, Fe in P. notoginseng leaves based on a newly established high-performance liquid chromatography method. Transcriptome analysis showed that differentially expressed genes (DEGs) induced by MeJA were mainly enriched in “terpenoid backbone biosynthesis”, “biosynthesis of unsaturated fatty acids”, “sesquiterpenoid and triterpenoid biosynthesis”, “fatty acid metabolism”, and “phenylpropanoid biosynthesis”. Furthermore, the expression profile and quantitative real-time PCR analysis of DEGs showed that MeJA could positively induce the molecular response of endogenous jasmonic acid (JA) signaling pathway, and increased PPD-type saponins mediated by MeJA in P. notoginseng leaves may be related to the high expression of FPS, SS, SE, DS and UGTs, and the low expression of CYP716A53v2 and β-AS. The results provide a molecular understanding for MeJA-elicited biosynthesis of triterpenoid saponins and facilitate the further characterization of the genes responsible for biosynthesis of PPD-type saponins in P. notoginseng leaves.

Autophagy plays a critical role in cancer, since it can either suppress tumorigenesis by inhibiting cancer cell survival, or facilitate tumorigenesis by promoting cancer cell proliferation and tumor growth. However, the role of genetic variants of autophagy-regulated key genes for bladder cancer risk remained unclear. Here, we aimed to explore the association of bladder cancer with genetic variants on genes involved in autophagy pathway. Gene-based analysis was performed with multi-marker analysis of genomic annotation (MAGMA) in 580 bladder cancer cases and 1101 controls. The logistic regression model was used to calculate the SNP effects on bladder cancer susceptibility. Expression quantitative trait loci (eQTL) analysis was conducted by the genotype-tissue expression (GTEx) project. Gene expression was evaluated based on the Cancer Genome Atlas (TCGA) database. Three potentially functional SNPs RPS6KB1 rs1292038, PIK3R1 rs34303, and rs56352616 were demonstrated to be associated with risk of bladder cancer (OR = 0.71, 95% CI = 0.61–0.82, P = 7.88 × 10−6 for rs1292038; OR = 1.25, 95% CI = 1.09–1.45, P = 2.11 × 10−3 for rs34303; OR = 0.74, 95% CI = 0.62–0.90, P = 2.47 × 10−3 for rs56352616). An increasing number of risk genotypes of these three SNPs were associated with a higher risk of developing bladder cancer. Besides, rs1292038 exhibited an eQTL effect for RPS6KB1 in whole blood (P = 3.90 × 10−7). Furthermore, the higher expression of RPS6KB1 and lower expression of PIK3R1 were both significantly associated with bladder cancer risk. Our findings indicated that genetic variants in autophagy pathway genes RPS6KB1 and PIK3R1 confer bladder cancer susceptibility.

Two previously undescribed 3(4), 8(9), 9(10)-trisecocycloartane triterpene dilactones with a featured eleven-membered ring, pseudoladilactones A and B (1-2), together with three known ones (4-5), were isolated from the 80 % ethanol extract of the cones of Pseudolarix amabilis. The structures of compounds 1 and 2 were determined on the basis of analysis of 1D- and 2D-NMR spectroscopic data. The absolute configuration of pseudoladilactones A (1) was elucidated by single crystal X-ray diffraction (CuKα). All isolates were tested for cytototoxicity against four human tumor cell lines A549, HCT116, SK-BR-3, and HepG2.

ComX can improve bacterial competence by modulating global gene expression. Although competence induction may also be a protective mechanism under stress, this has not been investigated in detail. Here, we demonstrated that ComX improved the acid tolerance and nisin yield of Lactococcus lactis, which is an important gram-positive bacterium increasingly used in modern biotechnological applications. We found that overexpression of comX could improve the survival rate up to 36.5% at pH 4.0, compared with only 5.4% and 1.1% with the wild-type and comX knockout strains, respectively. Moreover, quantitative real-time PCR results indicated that comX overexpression stimulated the expression of late competence genes synergistically with exposure to acid stress. Finally, electrophoretic mobility shift assay demonstrated the binding of purified ComX to the cin-box in the promoters of these genes. Taken together, our results reveal a regulation mechanism by which ComX and acid stress can synergistically modulate the expression of late competence genes to enhance cells' acid tolerance and nisin yield.

Follicular helper T (TFH) cells are a specialized subset of CD4+ T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of TFH cell survival remains unclear. Here we report that TFH cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation. Glutathione peroxidase 4 (GPX4) is the major lipid peroxidation scavenger and is necessary for TFH cell survival. The deletion of GPX4 in T cells selectively abrogated TFH cells and germinal center responses in immunized mice. Selenium supplementation enhanced GPX4 expression in T cells, increased TFH cell numbers and promoted antibody responses in immunized mice and young adults after influenza vaccination. Our findings reveal the central role of the selenium–GPX4–ferroptosis axis in regulating TFH homeostasis, which can be targeted to enhance TFH cell function in infection and following vaccination. T follicular helper (TFH) cells are important for the generation of effective antibody responses. Yu and colleagues find that TFH cells are exceptionally sensitive to death by ferroptosis and that this process is regulated by the activity of the selenoenzyme GPX4.

Toddalia asiatica (L.) Lam., belonging to Toddalia genus of Rutaceae family, is a folk medicine in China used for hundreds of years. The whole plant can be used as medicine, especially the root that used to be applied in the folk. In recent decades, with the in-depth research from domestic and foreign researchers, it has gradually been discovered that the chemical components in T. asiatica are mainly coumarins and alkaloids. Its pharmacological effects are manifested in anti-inflammatory and analgesic, hemostatic coagulation, anti-tumor, treatment of cardiovascular diseases, etc. It has a wide range of clinical applications and significant effects on rheumatism, pain, wound bleeding, and bruises. Due to its important research value, in this article, the chemical compositions and pharmacological effects of T. asiatica are comprehensively expounded in recent years in order to provide a reference for the related research and application of this medicinal material, which were carried out through a bibliometric search using the Science Citation Index- Expanded (SCIE) database, web of science, Google scholar and Chinese National Knowledge Infrastructure (CNKI) and all that.

The duration of natural immunity in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of some debate in the literature at present. For example, in a recent publication characterizing SARS-CoV-2 immunity over time, the authors fit pooled longitudinal data, using fitted slopes to infer the duration of SARS-CoV-2 immunity. In fact, such approaches can lead to misleading conclusions as a result of statistical model-fitting artifacts. To exemplify this phenomenon, we reanalyzed one of the markers (pseudovirus neutralizing titer) in the publication, using mixed-effects modeling, a methodology better suited to longitudinal datasets like these. Our findings showed that the half-life was both longer and more variable than reported by the authors. The example selected by us here illustrates the utility of mixed-effects modeling in provide more accurate estimates of the duration and heterogeneity of half-lives of molecular and cellular biomarkers of SARS-CoV-2 immunity.

Anthocyanin plays an important role in wine color and quality. The anthocyanin concentration in grapes depends on the variety and is influenced by environmental factors, such as temperature, sunlight, soil, and grapevine practice. In this study, the anthocyanin profiles of two varieties, namely Cabernet Sauvignon and Merlot, from five regions (11 plots) in Xinjiang were examined. The climatic parameters performed noticeable difference between northern and southern of Xinjiang region. Result showed that northern of Xinjiang possessed the relatively lower humidity and higher average temperature in comparison with southern area. In addition, the total anthocyanin profiles of Cabernet sauvignon, which in Changji, Wushitala, Heshuo respectively, were higher than of other plots. This result might be caused by which those have relatively higher altitude than in other plots. For merlot, the higher anthocyanin concentrations performed in southern of Xinjiang, which could be contributed to the lower average temperature and higher relative humidity. Comparing Cabernet sauvignon and Merlot, the latter was easily affected by environment factors, and the anthocyanin composition and concentration of Merlot showed significant differences in different regions.

Salt marshes provide crucial ecological functions and services and are experiencing rapid losses and degradation under global climate changes and high-intensity human activities in coastal zone. However, mapping salt marsh distributions and compositions with high accuracy on the national or global scale remains challenging. Here, we used Sentinel-1 time-series data and knowledge-based automatic decision tree classifiers to produce a 10-m map of the salt marshes in China coastal zones. We established annual synthetic aperture radar (SAR) composite features to address seasonal variations and tidal dynamics in salt marshes and created five partitioned-region classifiers according to the climatic and environmental characteristics. In total, 1729 Sentinel-1 images in 2019 and 3418 in situ sites were included for the classification. The results showed that (1) the annual mean SAR composite is more stable and practical than the seasonal composite for salt marsh classification along the China coastal zones in terms of these features addressing variations in tidal fluctuation, climate zones, and salt marsh compositions; (2) SAR surface roughness can effectively separate salt marshes into sparse density and red phenotype salt marshes; (3) the total area of Chinese coastal salt marshes was 127,477.37 ha with an overall accuracy of 87.30%, it included 48.30% Spartina alterniflora, 29.19% Phragmites australis, 13.76% Suaeda spp. and 8.75% Scirpus spp., and more than 85% of salt marshes were distributed from Shandong Province to Zhejiang Province. This study showed the potential application of time-series Sentinel-1 SAR data, annual composite data and knowledge-based classifiers for large-scale coastal zones, and these data will be valuable for coastal ecological restoration and sustainability management.

Abstract Four new 3,4-secocycloartane triterpenoids, pseudolactones A–D (1–4), were isolated from the ethanol extract of the cones of Pseudol arixamabilis. Their structures were established by extensive 1D- and 2D-NMR experiments. The cones of P. arixamabilis are enriched in the ring-expanded or cleaved cycloartane triterpenoids. This work provides new insight into cycloartane triterpenoids from the cones of P. arixamabilis. Graphic Abstract

Two new prenylated flavonoids named 4',1”-dihydroxy-3'-methoxy-6,7-furanflavanone (1), 5,3',4'-trihydroxy-1”-methoxy-6,7-furanbavachalcone (2), together with six known compounds (3-8), were isolated from the seeds of Psoralea corylifolia. The chemical structures were elucidated on the basis of spectroscopic analyses including MS and NMR spectrometry. All isolates were evaluated for in vitro inhibitory activity against α-glucosidase. And compound 1 showed moderate inhibitory activity on α-glucosidase with IC50 value of 53.1 μM, compared with the 214.5 μM of positive control acarbose.

Severe RSV infection is the main cause of hospitalization to children under the age of five. The regulation of miRNAs on the severity of RSV infection is unclear. The aim of the study was to identify the critical differential expression miRNAs (DE miRNAs) that can regulate the pathological response in RSV‐infected airway epithelial cells. In this study, miRNA and mRNA chips of RSV‐infected airway epithelia from Gene Expression Omnibus (GEO) were screened and analysed, separately. DE miRNAs‐targeted genes were performed for further pathway and process enrichment analysis. DE miRNA‐targeted gene functional network was constructed on the basis of miRNA‐mRNA interaction. The screened critical miRNA was also investigated by bioinformatics analysis. Then, RSV‐infected human bronchial epithelial cells (HBECs) were constructed to verify the expression of the DE miRNAs. Finally, specific synthetic DE miRNAs mimics were used to confirm the effect of DE miRNAs on the RSV‐infected HBECs. 45 DE miRNAs were identified from GEO62306 dataset. Our results showed that hsa‐mir‐34b‐5p and hsa‐mir‐34c‐5p decreased significantly in HBECs after RSV infection. Consistent with the biometric analysis, hsa‐mir‐34b/c‐5p is involved in the regulation of mucin expression gene MUC5AC. In RSV‐infected HBECs, the inducement of MUC5AC production by decreased hsa‐mir‐34b/c‐5p was partly mediated through activation of c‐Jun. These findings provide new insights into the mechanism of mucus obstruction after RSV infection and represent valuable targets for RSV infection and airway obstruction treatment.

Background Integrin β4 (ITGB4) is a hemi-desmosome protein which is downregulated in the airway epithelial cells of asthma patients. The proximal promoters and exons of ITGB4 contain CpG islands or multiple CpG sites both in human and mice, which indicated the possible methylation regulation of ITGB4 in airway epithelial cells. Objective We sought to unveil that DNA methylation regulates the decreased ITGB4 during the pathogenesis of asthma. Methods Mice were exposed to house dust mite (HDM) extracts to construct an asthma model. 5-Aza-2'-deoxycytidine (5-AZA) or dexamethasone (DEX) were added in the last two weeks. Besides, the primary human bronchial epithelial (HBE) cells were incubated for the detection of ITGB4 expression and methylation status after HDM stress. Furthermore, DNA methylation of ITGB4 in peripheral blood was measured in asthma patients. Logistic regression was employed to evaluate the association between methylation sites and asthma patients' ages in the control of potential confounders. Moreover, the correlations between differentially methylated sites (DMSs) and clinical parameters in asthma patients were assessed. Finally, the ability of candidate DMSs to predict asthma was evaluated by receiver operating characteristic (ROC) analysis and principal component analysis (PCA). Results We found that in HDM-stressed asthma model, DNA methylation regulated the reduced ITGB4 expression in airway epithelial cells. Moreover, alteration in the specific CpG sites (chr17:73717720 and chr17:73717636) of ITGB4 may regulate ITGB4 expression and further may be associated with the clinically phenotypic of asthma. The specific DMSs of ITGB4 in peripheral blood can distinguish asthma patients from healthy controls (HCs) effectively. Conclusions and clinical relevance This study confirmed that DNA methylation regulates the decreased expression of ITGB4 in the airway epithelial cells of asthma patients. These results supply some useful insights to the mechanism of the decreased ITGB4 in asthmatic airway epithelial and provide possible targets for early prediction and screening of asthma.

Background Type I Helicobacter pylori (H. pylori) infection causes severe gastric inflammation and is a predisposing factor for gastric carcinogenesis. However, its infection status in stepwise gastric disease progression in this gastric cancer prevalent area has not been evaluated; it is also not known its impact on commonly used epidemiological gastric cancer risk markers such as gastrin-17 (G-17) and pepsinogens (PGs) during clinical practice. Aim To explore the prevalence of type I and type II H. pylori infection status and their impact on G-17 and PG levels in clinical practice. Methods Thirty-five hundred and seventy-two hospital admitted patients with upper gastrointestinal symptoms were examined, and 523 patients were enrolled in this study. H. pylori infection was confirmed by both 13C-urea breath test and serological assay. Patients were divided into non-atrophic gastritis (NAG), non-atrophic gastritis with erosion (NAGE), chronic atrophic gastritis (CAG), peptic ulcers (PU) and gastric cancer (GC) groups. Their serological G-17, PG I and PG II values and PG I/PG II ratio were also measured. Results A total H. pylori infection rate of 3572 examined patients was 75.9%, the infection rate of 523 enrolled patients was 76.9%, among which type I H. pylori infection accounted for 72.4% (291/402) and type II was 27.6%; 88.4% of GC patients were H. pylori positive, and 84.2% of them were type I infection, only 11.6% of GC patients were H. pylori negative. Infection rates of type I H. pylori in NAG, NAGE, CAG, PU and GC groups were 67.9%, 62.7%, 79.7%, 77.6% and 84.2%, respectively. H. pylori infection resulted in significantly higher G-17 and PG II values and decreased PG I/PG II ratio. Both types of H. pylori induced higher G-17 level, but type I strain infection resulted in an increased PG II level and decreased PG I/PG II ratio in NAG, NAGE and CAG groups over uninfected controls. Overall PG I levels showed no difference among all disease groups and in the presence or absence of H. pylori; in stratified analysis, its level was increased in GC and PU patients in H. pylori and type I H. pylori-positive groups. Conclusion Type I H. pylori infection is the major form of infection in this geographic region, and a very low percentage (11.6%) of GC patients are not infected by H. pylori. Both types of H. pylori induce an increase in G-17 level, while type I H. pylori is the major strain that affects PG I and PG IIs level and PG I/PG II ratio in stepwise chronic gastric disease. The data provide insights into H. pylori infection status and indicate the necessity and urgency for bacteria eradication and disease prevention in clinical practice.

Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.

Acid-and-ethanol tolerance plays an important role in the cell viability of Oenococcus oeni and affects the enological characteristics of malolactic fermentation in wine. To reveal the mechanism of the response to acid-and-ethanol in O. oeni, we analyzed the changes to its gene expression profile after acid-and-ethanol shock for the first time using RNA-Seq. Some physiological indicators related to this stress response were also characterized. Bioinformatic and physiological analyses showed that the O. oeni strengthened the biosynthesis of peptidoglycan as a response to ethanol toxicity, and the cell membranes altered their fatty acid compositions for keeping the acidic H+ outside when the cells were shocked with acid-and-ethanol. When H+ entered the cytoplasm, the F0F1-ATPase system began discharging H+ (producing ATP), and the cells increased their expression of recN and mutT genes for minimizing the DNA damage. The cells also used two-component systems to communicate between same-species cells for improving the overall population survival rate. Genes encoding spermidine and putrescine transport were also upregulated to increase resistance to the acid-and-ethanol environment. This study fills important gaps in the current understanding of the bacterial acid-and-ethanol stress response mechanism, and it may be beneficial to screen more robust O. oeni strains in future works.

Approximately 20–40% of patients with cancer will experience brain metastasis (BM), which has a great impact on the quality of life and survival rates of patients. Whole brain radiotherapy (WBRT) is an effective method for the treatment of BM. However, it cannot be ignored that WBRT might induce a series of neuropsychiatric side effects, including cognitive dysfunction (CD). Accumulating evidence shows that the gut microbiota and the gut-microbiota–brain axis may play a vital role in the pathogenesis of CD. We adopted WBRT to mimic CD after a hierarchical cluster analysis of the Morris water maze test (MWMT) results. In addition, we observed the effects of antibiotics and prebiotics on WBRT-induced CD. Variations were revealed via the 16S rRNA sequencing analysis at different levels. The 16S rRNA sequencing analysis revealed an altered composition of gut microbiota between CD and non-CD phenotypes. Furthermore, we observed a decrease in the levels of Phylum-Bacteroidete, Class-Bacteroidia, and Order-Bacteroidales in the CD group and an increase in the Genus-Allobaculum level after WBRT. Pretreatment with antibiotics caused a significant decrease in the level of Phylum-TM7 01, whereas an increase in the levels of Class-Gammaproteobacteria, Order-Enterobacteriales, and Species-Escherichia coli. After pretreatment with probiotics, the levels of Phylum-Cyanobacteria, Class-4C0d-2, and Order-YS2 were decreased, while the levels of Family-Bacteroidaceae, Genus-Bacteroides, and Species-Parabacteroides distasonis were increased. WBRT-induced CD might be highly related to abnormal composition of gut microbiota. Strategies improving the composition of the gut microbiota may provide beneficial effects on CD in individuals exposed to WBRT.

To explore the relationship between fruit developmental periods and the protein datasets of Alpinia oxyphylla, a label-free quantitative proteomic profiling analysis of the A. oxyphylla fruits sampled at the Earlystage, Metaphase and Advanced stage was carried out using the liquid chromatography combined with tandem mass spectrometry. A total of 19,219 peptide fragments and 4946 quantitative proteins were obtained. Annotation and enrichment analysis of these peptides and proteins were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases with bioinformatics software. The results showed that the differentially expressed proteins were mainly involved in metabolic and cellular processes, cellular component organization or biogenesis and response to the stimulus. Three significantly enriched metabolic pathways were non-alcoholic fatty liver disease, vibrio cholera infection and valine, leucine and isoleucine degradation. The significantly enriched proteins were NADH dehydrogenase, putative vacuolar proton translocation ATPase and putative acyltransferase component. The proteomic profiles of the fruit samples from the Advanced and the Metaphase stages differed little, while the difference in proteomic components between the Earlystage and the Advanced groups was significant. This study should lay the theoretical foundation for the effective utilization of A. oxyphylla germplasm resource in the treatment of human diseases.

Hierodula jianfenglingensis sp. nov. (Ledong, Hainan) is described as a new species. Its related taxa, Hierodula chinensis Werner, 1929, is revised herein based on some confusions that exist in pre...

A novel Streptomyces strain, designated TRM43335T, was isolated from the Taklimakan desert in Alar City, Xinjiang, north-west China. The strain was found to exhibit an inhibitory effect on biofilm formation by Candida albicans and Staphylococcus epidermidis. A polyphasic approach was used to determine its taxonomic status. The strain was observed to form abundant aerial mycelium, occasionally twisted and which differentiated into spiral spore chains. Spores of TRM43335T were observed to be oval-shaped, with a smooth surface. Strain TRM43335T was found to grow optimally at 37 °C, pH 8 and in the presence of 1% (w/v) NaCl. The major sugars were identified as ribose, xylose, glucose, mannose and galactose, and the principal phospholipids were found to be diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol mannoside and phosphatidylinositol. The diagnostic cell wall amino acid was identified as LL-diaminopimelic acid. The predominant menaquinone was found to be MK-9(H6). The major cellular fatty acids were identified as iso-C16:1 H, anteiso-C15:0, iso-C16:0, anteiso-C17:0, anteiso-C17:1 w9c and iso-C15:0. Analysis of the 16S rRNA sequence showed that strain TRM43335T exhibits high sequence similarity to Streptomyces desertarenae SYSU D8023T 98.69%. A multilocus sequence analysis of five house-keeping genes (atpD, gyrB, rpoB, recA and trpB) also illustrated that strain TRM43335T should be assigned to the genus Streptomyces. The DNA G + C content of the strain was determined to be 72.8 mol%. The average nucleotide identity relatedness between strain TRM43335T and the phylogenetically related strain S. desertarenae SYSU D8023T was found to be 89.23%, and the in silico DNA-DNA hybridization value to be 36.70%. Therefore, it is concluded that strain TRM43335T represents a novel species of the genus Streptomyces, for which the name Streptomyces taklimakanensis sp. nov is proposed. The type strain is TRM43335T (CCTCC AA 2018052 T = KCTC 49254 T).

A novel actinobacterium, designated TRM68348T, was isolated from the silt collected from the Tailan River in Xinjiang Province, north-west China. The strain was aerobic and Gram-stain-positive. The aerial mycelium was densely straight or tortuous, with a few branches of hyphae and no spores. The whole-cell sugar pattern of strain TRM68348T consisted of ribose and glucose. The diagnostic diamino was ll-diaminopimelic acid. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, phosphatidylinositol mannose and an unidentified phospholipid. The predominant menaquinones were MK-9 (H10), MK-9 (H6) and MK-9 (H2). The major fatty acids (>5 %) were iso-C14 : 0, iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0, C16 : 0 and summed feature 6. The G+C content of the genomic DNA was 69.93 mol%. Phylogenetic analysis showed that strain TRM68348T shared 16S rRNA gene sequence similarity of 98.14 % to the closest described species Streptomyces capitiformicae 1H-SSA4T. Strain TRM68348T had a relatively low DNA–DNA relatedness value with S. capitiformicae 1H-SSA4T as determined by calculating the average nucleotide identity value (92.78 %). Strain TRM68348T could also be differentiated from S. capitiformicae 1H-SSA4T based on morphological and physiological characteristics. On the basis of the evidence from this polyphasic study, the strain is concluded to represent a novel species of the genus Streptomyces , for which the name Streptomyces tailanensis sp. nov. is proposed. The type strain is TRM68348T (=CCTCC AA 2018086T=KCTC 49274T).

The retinoic acid-related orphan receptors alpha (RORa) are members of the steroid/thyroid nuclear receptor super-family and core components of the circadian timing system. In the present study, we continue to investigate the role of RORas in human breast cancer. Assays using the RORa response element (RORE)-tk-luciferase reporter demonstrate the functionality of the RORa1 in MCF-7 breast cancer cells and that over-expression of RORa1 stimulates MCF-7 human breast cancer cell proliferation. Genomic analysis revealed that RORα1 over-expression regulated the transcription of numerous genes in MCF-7 breast cancer cells including increasing the expression of connexin 43 (CX43), aldo-keto reductases 1C1 (AKR1C1), and AKR1C3. Furthermore, administration of the pineal hormone melatonin represses RORa1 induction of CX43, AKR1C1, and AKR1C3 in MCF-7 cells. AKR1C3 has been reported to impact in intra-tumoral production of androgens and estrogens and thus, might promote Tamoxifen resistance in breast cancer. Over-expression of RORa1 and subsequently AKR1C3 does promote Tamoxifen resistance, which can be inhibited by melatonin administration.

The exotic species Spartina alterniflora (S. alterniflora) seriously threatens the stability and functioning of saltmarsh ecosystems in the Yangtze Estuary. Ambitious efforts have been undertaken to control this species, but subsequent re-invasion is frequent, presenting a significant barrier to restoration. The complexity and high cost of integrated physical control programs has necessitated a shift in focus, leading to considerable attention being paid to the potential of herbicides to control S. alterniflora. To find a strategy for emergency control of small and scattered patches of re-invading S. alterniflora, an in situ field experiment using Gallant (Haloxyfop-R-methyl) herbicide was conducted. The growth parameters of plant density and height were used to evaluate the control efficiency of different treatment dosages and times and sediment samples were taken for environmental toxicity analysis. The results show the following: (1) the control efficacy of the maximum proposed application dose (2.70 g/m2) was 92% for continuous swards and 100% for small patches, while those of other dosages (0.45 g/m2, 0.90 g/m2, and 1.35 g/m2) were lower than 40%; (2) the appropriate implementation time was July to August with 100% mortality resulting from a single application, while S. alterniflora was shown to be capable of recovering rapidly after treatment in May; and (3) there were no significant differences in the community structure of meiofauna among the herbicide treatments and the control, and no herbicide residues were detected in sediment samples collected from treatment areas. This chemical control method was implemented in the Shanghai Chongming Dongtan National Bird Nature Reserve (CDNR). The results of this study indicate that Gallant is an environmentally friendly herbicide with high efficiency, which can be adopted for emergency control of re-invading S. alterniflora.

Osteonecrosis of the femoral head (ONFH) is a pathological process that initially occurs in the weight-bearing field of the femoral head. Due to the unknown pathogenesis, this study was for the investigation of the effect of microRNA-141 (miR-141) targeting transforming growth factor-β2 (TGF-β2) on regulating osteoblast activity and osteoclast activity in steroid-induced ONFH. Tissues of ONFH and normal femoral head were collected for detecting the expression of miR-141 and TGF-β2. A rat model of ONFH was constructed by injection of hormones, and transfected with miR-141 inhibitors and overexpressed TGF-β2. The apoptosis of bone cells was detected by TUNEL staining. The expression of osteoprotegerin (OPG), osteoprotegerin ligand (OPGL), Bcl-2, Bax, Runx2, BMP2 and RANK were detected. Highly expressed miR-141 and lowly expressed TGF-β2 existed in femoral head tissues in ONFH. Inhibited miR-141 resulted in elevated TGF-β2 in femoral head tissues in ONFH of rats. Depressed miR-141 or overexpressed TGF-β2 inhibited the apoptosis of bone cells of rats with ONFH and induced elevated OPG, Bcl-2, BMP2, Runx2 and declined OPGL, Bax and RANK expression in the femoral head tissues of rats with ONFH. Altogether, we find that down-regulated miR-141 promotes osteoblast activity and inhibits osteoclast activity to ameliorate ONFH via up-regulated TGF-β2 expression.

Lung immune responses to respiratory pathogens and allergens are initiated in early life which will further influence the later onset of asthma. The airway epithelia form the first mechanical physical barrier to allergic stimuli and environmental pollutants, which is also the key regulator in the initiation and development of lung immune response. However, the epithelial regulation mechanisms of early‐life lung immune responses are far from clear. Our previous study found that integrin β4 (ITGB4) is decreased in the airway epithelium of asthma patients with specific variant site. ITGB4 deficiency in adult mice aggravated the lung Th2 immune responses and enhanced airway hyper‐responsiveness (AHR) with a house dust mite (HDM)‐induced asthma model. However, the contribution of ITGB4 to the postnatal lung immune response is still obscure. Here, we further demonstrated that ITGB4 deficiency following birth mediates spontaneous lung inflammation with ILC2 activation and increased infiltration of eosinophils and lymphocytes. Moreover, ITGB4 deficiency regulated thymic stromal lymphopoietin (TSLP) production in airway epithelial cells through EGFR pathways. Neutralization of TSLP inhibited the spontaneous inflammation significantly in ITGB4‐deficient mice. Furthermore, we also found that ITGB4 deficiency led to exaggerated lung allergic inflammation response to HDM stress. In all, these findings indicate that ITGB4 deficiency in early life causes spontaneous lung inflammation and induces exaggerated lung inflammation response to HDM aeroallergen.

According to the government of China, reported cases of pertussis have increased remarkably and are still increasing. To determine the genetic relatedness of Bordetella pertussis strains, we compared multilocus variable-number tandem-repeat analysis (MLVA) results for isolates from China with those from Western countries. Among 335 isolates from China, the most common virulence-associated genotype was ptxA1/ptxC1/ptxP1/prn1/fim2-1/fim3A/tcfA2, which was more frequent among isolates from northern than southern China. Isolates of this genotype were highly resistant to erythromycin. We identified 36 ptxP3 strains mainly harboring ptxA1 and prn2 (35/36); ptxP3 strains were sensitive to erythromycin and were less frequently from northern China. For all isolates, the sulfamethoxazole/trimethoprim MIC was low, indicating that this drug should be recommended for patients infected with erythromycin-resistant B. pertussis. MLVA of 150 clinical isolates identified 13 MLVA types, including 3 predominant types. Our results show that isolates circulating in China differ from those in Western countries.

Background Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. Methods The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin β1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. Results Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin β1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin β1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. Conclusion A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin β1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.

During a woman's reproductive period, the endometrial tissue is shed and regenerated every month to prepare for pregnancy or for the next cycle. The aim of the present study was to isolate, culture and characterize human endometrial cells (ECs) derived from menstrual blood (MB) and the endometrium (E). MB-derived ECs (MB-ECs) were isolated from women's MB. E-derived ECs (E-ECs) were isolated from women's endometrial tissues. The present study investigated the epithelial cell marker cytokeratin 18 (CK18) in MB-ECs and E-ECs. Cell proliferation analyses indicated that E-ECs (population doubling time, 20.85 h) grew faster than MB-ECs (population doubling time, 22.05 h; P

Dendritic spines are the postsynaptic structure to mediate signal transduction in neural circuitry, whose function and plasticity are regulated by organization of their molecular architecture and by the expression of target genes and proteins. EphB2, a member of the Eph receptor tyrosine kinase family, potentiates dendritic spine maturation through cytoskeleton reorganization and protein trafficking. However, the transcriptional mechanisms underlying prolonged activation of EphB2 signaling during dendritic spine morphogenesis are unknown. Herein, we performed transcriptional profiling by stimulating EphB2 signaling and identified differentially expressed genes implicated in pivotal roles at synapses. Notably, we characterized an F-actin binding protein, Annexin A1, whose expression was induced by EphB2 signaling; the promotor activity of its coding gene Anxa1 is regulated by the activity of CREB (cAMP-response element-binding protein). Knockdown of Annexin A1 led to a significant reduction of mature dendritic spines without an obvious deficit in the complexity of dendrites. Altogether, our findings suggest that EphB2-induced, CREB-dependent Annexin A1 expression plays a key role in regulating dendritic spine morphology.

SHORT VEGETATIVE PHASE (SVP) genes are members of the well-known MADS-box gene family that play a key role in regulating vital developmental processes in plants. Hemerocallis are perennial herbs that exhibit continuous flowering development and have been extensively used in landscaping. However, there are few reports on the regulatory mechanism of flowering in Hemerocallis. To better understand the molecular basis of floral formation of Hemerocallis, we identified and characterized the SVP-like gene HkSVP from the Hemerocallis cultivar ‘Kanai Sensei’. Quantitative RT-PCR (qRT-PCR) indicated that HkSVP transcript was mainly expressed in the vegetative growth stage and had the highest expression in leaves, low expression in petals, pedicels and fruits, and no expression in pistils. The HkSVP encoded protein was localized in the nucleus of Arabidopsis protoplasts and the nucleus of onion epidermal cells. Yeast two hybrid assay revealed that HKSVP interacted with Hemerocallis AP1 and TFL1. Moreover, overexpression of HkSVP in Arabidopsis resulted in delayed flowering and abnormal phenotypes, including enriched trichomes, increased basal inflorescence branches and inhibition of inflorescence formation. These observations suggest that the HkSVP gene may play an important role in maintaining vegetative growth by participating in the construction of inflorescence structure and the development of flower organs.

Background: Although thousands of alternative splicing related single nucleotide polymorphisms (AS-SNPs) have been uncovered in human tumors, the potential function of AS-SNPs involved in bladder cancer is rarely reported. Here we identified bladder cancer risk-associated AS-SNPs and revealed its underlying causal mechanism in bladder carcinogenesis.Methods: Variants with annotation of “splice-3” or “splice-5” were extracted as AS-SNPs through the database of Single Nucleotide Polymorphism (dbSNP). Two-stage case-control studies comprising 1,630 cases and 2,504 controls were conducted to assess the association between the AS-SNPs and bladder cancer risk. A series of experiments including luciferase reporter assays, RNA immunoprecipitation, and malignant phenotype were performed to comprehensively investigate the genetic and epigenetic biological effects of AS-SNPs in the development of bladder cancer.Results: We identified the potential causal variant rs558814 A>G located in intron of lncRNA BCLET (Bladder Cancer Low-Expressed Transcript) was significantly associated with a reduced risk of bladder cancer [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.76 to 0.92, P = 3.26 × 10−4]. The SNP rs558814 exerted transcriptional activity regulatory effect and thus facilitated the expression of BCLET transcripts including BCLET-long and BCLET-short. In addition, both BCLET transcripts overexpression remarkably inhibited in vitro and in vivo bladder cancer phenotypes including cell proliferation, clone formation, invasion, migration and apoptosis. Mechanistically, lncRNA BCLET bound to MSANTD2 mRNA, masked splicing site of MSANTD2 mRNA, and thereby facilitated the expression of MSANTD2-004 transcript, which lacks the first exon and remarkably inhibited the progression of bladder cancer.Conclusions: Our findings not only revealed the important role of AS related genetic variants rs558814 and its associated gene BCLET in bladder cancer progression, but also provided the perspective to understand the etiology and pathology of cancers from the alternative splicing regulation mechanism.

Objective The benefit of Se supplementation in rheumatoid arthritis (RA) has been tested in clinical trials, but results remain inconclusive. The objective of this study was to specifically investigate the potential benefit of supranutritional Se by examining human samples from an area with supranutritional Se intake and testing a mouse model of RA. Methods Peripheral blood mononuclear cells (PBMCs) from RA patients (N = 57) and healthy controls (HC, N = 71) from an area of supranutritional Se intake (Enshi, Hubei, China) were analysed by flow cytometry. Serum cytokine and Se levels were measured by cytometric beads array (CBA) and inductively coupled plasma mass spectrometry (ICP‐MS), respectively. With sufficient or supranutritional selenium intake, mice were induced with collagen‐induced arthritis (CIA) and examined for disease activity and immunopathology. The influence of Se supplementation in the generation of RANKL‐expressing osteoclastogenic CD4+ T cells was investigated by in vitro assays. Results In Enshi city, HC showed the above‐normal concentrations of serum Se concentrations while RA patients were enriched in the normal range (70–150 ng mL−1) or below. RA patients with higher Se levels demonstrated milder disease and lower levels of C‐reactive protein, IL‐6, RANKL and Th17 cells. In the mouse CIA model, supranutritional Se supplementation delayed disease onset, ameliorated joint pathology and reduced CD4+CD44+RANKL+ T cells. Se supplementation could suppress RANKL expression in cultured mouse Th17 cells. Conclusion Supranutritional Se suppresses RANKL‐expressing osteoclastogenic CD4+ T cells and could be beneficial to RA, which warrants formal testing in randomised clinical trials., In this study, we found that supranutritional selenium (Se) was associated with improved disease activities in patients with rheumatoid arthritis and also ameliorated collagen‐induced arthritis in mice. Se attenuated the production of reactive oxygen species (ROS) and thus suppressed ROS‐mediated induction of RANKL expression in activated CD4+ T cells.

The objective of this study was to explore the therapeutic effects of berberine on necrotic enteritis (NE) in broilers caused by Clostridium perfringens. A total of 240 1-day-old Arbor Acres chicks were divided into four groups, as negative controls (NC), positive controls (PC), berberine- (BER-) treated, or lincomycin- (LMY-) treated groups. Broilers were challenged with C. perfringens at 15-21 days of age, followed by BER or LMY supplied in drinking water for 7 days. Experimental results showed that C. perfringens infection significantly decreased growth performance and increased intestinal necrosis index and the number of C. perfringens present to 6.45 Log10CFU/g ( P < 0.001 ). Proinflammatory cytokines in the ileum were significantly increased, but the expression of ileal tight junction proteins occludin and claudin-1 was significantly reduced. Both BER and LMY ameliorated some of these observations. Compared with the PC group, the number of C. perfringens in the cecum was significantly decreased following treatment ( P < 0.001 ), and growth performance and small intestine morphology were similar to those of the NC group ( P > 0.05 ). IL-1β, IL-6, and TNF-α levels as well as occludin and claudin-1 expression were also significantly improved ( P < 0.05 ). BER has the potential to replace antibiotics for NE caused by C. perfringens.

Background Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson’s and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a “prion-like” manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail. Methods Three strains of preformed α-syn fibrils (PFFs) were generated in different buffer conditions which varied in pH and ionic concentrations. The α-syn PFFs were intramuscularly (IM) injected into a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses wild-type human α-syn, and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated. Results The three strains of α-syn PFFs triggered distinct propagation patterns. The fibrils generated in mildly acidic buffer led to the most severe α-syn pathology, degeneration of motor neurons and microgliosis in the spinal cord. Conclusions The different α-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS, which further supports the view that α-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.

The development of an effective vaccine against SARS-CoV-2, the causative agent of pandemic coronavirus disease-2019 (COVID-19), is a global priority. Here, we present three chimpanzee adenovirus vaccines that express either the full-length spike (ChAdTS-S), or receptor-binding domain (RBD) with two different signal sequences (ChAdTS-RBD and ChAdTS-RBDs). Single-dose intranasal or intramuscular immunization induced robust and sustained neutralizing antibody responses in BALB/c mice, with ChAdTS-S being superior to ChAdTS-RBD and ChAdTS-RBDs. Intranasal immunization appeared to induce a predominately Th2-based response whereas intramuscular administration resulted in a predominately Th1 response. The neutralizing activity against several circulating SARS-CoV-2 variants remained unaffected for mice serum but reduced for rhesus macaque serum. Importantly, immunization with ChAdTS-S via either route induced protective immunity against high-dose challenge with live SARS-CoV-2 in rhesus macaques. Vaccinated macaques demonstrated dramatic decreases in viral RNA in the lungs and nasal swabs, as well as reduced lung pathology compared to the control animals. Similar protective effects were also found in a golden Syrian hamster model of SARS-CoV-2 infection. Taken together, these results confirm that ChAdTS-S can induce protective immune responses in experimental animals, meriting further development toward a human vaccine against SARS-CoV-2.

Anthocyanins are vital components of plant secondary metabolites, and are also the most important coloring substances in wine. Teinturier cultivars are rich in anthocyanins. However, the differences in anthocyanin accumulation and profiles between teinturier and non-teinturier cultivars have not been reported. In this study, Yan 73 and Dunkelfelder were selected as the experimental materials, and three non-teinturier cultivars were used for comparison. LC-MS and qRT-PCR were used to determine the individual anthocyanin contents and the relative gene expression. The results show that the total anthocyanin content of the teinturier cultivars was considerably higher than that in non-teinturier cultivars, and the levels of individual anthocyanins increased gradually during ripening. Lower ratios of modified anthocyanins were found in the teinturier cultivars, which was not only due to the high expression level of VvUFGT and VvGST4, but also due to the relatively low expression of VvOMT in these cultivars. Cluster analysis of gene expression and anthocyanin accumulation showed that VvUFGT is related to anthocyanin accumulation, and that AM1 is related to the synthesis and transport of methylated anthocyanins. Our results will be useful for further clarifying the pathways of anthocyanin synthesis, modification, and transport in teinturier cultivars.

The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme complex that regulates many fundamental cellular processes. PP2A is involved in tumorigenesis because mutations in the scaffold subunit, PPP2R1B, were found in several types of cancers. However, the biological function of PPP2R1B remains largely unknown. We report here that homozygous deletion of Ppp2r1b in Mus musculus impairs meiotic recombination and causes meiotic arrest in spermatocytes. Consistently, male mice lacking Ppp2r1b are characterized with infertility. Furthermore, heterozygous missense mutations in the Homo sapiens PPP2R1B gene, which encodes PPP2R1B, are identified in azoospermia patients with meiotic arrest. We found that PPP2R1B mutants are susceptible to degradation by an E3 ligase CRL4ADCAF6 , and resistant to de-polyubiquitylation by ubiquitin-specific protease 5 (USP5). In addition, heterozygous mutations in PPP2R1B reduce stability of the wild-type PPP2R1B. Our results demonstrate an essential role of PPP2R1B in spermatogenesis and identify upstream regulators of PPP2R1B.

ObjectiveOsteoporosis is a common metabolic bone disease mainly involving bone remodeling and blood vessels. The current study aimed to explore the suppressive role of interleukin (IL)-35 in nuclear factor kappa-B ligand receptor activator (RANKL) and macrophage colony stimulating factor (M-CSF)-induced osteoclastogenesis and angiogenesis in osteoclasts.MethodsOsteoclasts differentiation were induced by incubation of mouse leukemic monocyte/macrophage cell line RAW264.7 cells in the presence of RANKL and M-CSF and was assessed with tartrate-resistant acid phosphatase (TRAP) staining assay. The viability and apoptosis of RAW264.7 was measured using CCK-8 assay and flow cytometry, respectively. The expression of angiogenic genes and proteins were measured using RT-PCR, Western blots and ELISA. The inhibition of Th17/IL-17 axis was examined using plumbagin, which was demonstrated as an IL-17A related signaling pathway inhibitor.ResultsIL-35 inhibited the viability of RAW264.7 cells and promoted the apoptosis of RAW264.7 cells in a dose-dependent manner. Furthermore, IL-35 dose-dependently suppressed the expression of angiogenic markers including VEGF and its receptor. The suppressive effect of IL-35 was confirmed through the activation of Th17/IL-17 axis.ConclusionsWe demonstrated for the first time the immuno-suppressive function of IL-35 on RANKL and M-CSF-induced osteoclastogenesis and angiogenesis through Th17/IL-17 axis. Therapeutic approach involving augmentation of IL-35 regulatory response may serve as a novel treatment option for osteoporosis, especially by suppressing bone resorption and angiogenesis.

In horticulture, continuous flowering (CF) is a popular trait introduced into a wide range of cultivated varieties. To explore the mechanism of continuous flowering, this study first cloned the continuous flowering gene, named HkTFL1, from Hemerocallis fulva ‘H2006001’. Based on real-time PCR, HkTFL1 was expressed higher in the vegetative growth phase than in the reproductive growth phase, and the expression level was greatest in the shoot apex, followed by the leaf and pedicel. With Hemerocallis ‘Golden Doll’ and ‘H2006001’ as the core parents, their hybrid offspring showed that the expression level of the HkTFL1 gene in the continuous flowering population was lower than that in the single flowering (SF) population. Subcellular localization of onion and tobacco epidermal cells showed that HkTFL1 was located in the cytoplasm. The expression level of HkTFL1 was highest in the petal differentiation stage and then decreased gradually. In addition, the heterologous expression of HkTFL1 in Arabidopsis thaliana resulted in delayed flowering, increased rosette number, increased basal inflorescence branch number, inhibition of inflorescence formation, and failure to form a normal inflorescence. HkTFL1 is not only involved in flowering time and floral meristem differentiation but also regulates inflorescence architecture.

Histone demethylase KDM7A regulates neuronal differentiation and development in mammals. In this study, we found that KDM7A was also required for breast cancer stem cells (BCSCs) maintenance. Silencing KDM7A significantly reduced the BCSCs population and mamosphere formation in vitro, and inhibited breast tumor growth in vivo. Restoring KDM7A expression rescued the defect in stem cell maintenance. Our mechanism analysis suggested that KDM7A upregulated the stemness-associated factors KLF4 and c-MYC for BCSCs maintenance. In addition, KDM7A knockdown promoted apoptosis through decreasing BCL2 expression and BAD phosphorylation in breast cancer (BrCa). Furthermore, restoring KDM7A and BCL2 expression rescued apoptosis inhibition in breast cancer, suggesting that KDM7A inhibited apoptosis by upregulating the BCL2 level in breast cancer. In conclusion, KDM7A promotes cancer stem cell maintenance and apoptosis inhibition in breast cancer.

Background Gallbladder cancer (GBC) is the most malignant cancer occurring in the biliary tract cancer featured with undesirable prognosis, in which most patients die within a year of cholecystectomy. Long noncoding RNAs (lncRNAs) function as critical regulators of multiple stages of cancers. Herein, the mechanism of lncRNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in GBC is investigated. Methods Microarray-based analysis initially provided data suggesting that the expression of MALAT1 was up-regulated while that of the ABI family member 3 binding protein (ABI3BP) was down-regulated in GBC tissues and cell lines. Kaplan-Meier method was then adopted to analyze the relationship between the MALAT1 expression and overall survival and disease-free survival of patients with GBC. A set of in vitro and in vivo experiments were conducted by transducing ABI3BP-vector or sh-MALAT1 into GBC cells. Results The results confirmed that the cancer prevention effects triggered by restored ABI3BP and depleted MALAT1 as evidenced by suppressed cell growth and enhanced cell senescence. MALAT1 was observed to down-regulate ABI3BP expression through recruitment of the enhancer of zeste homolog 2 (EZH2) to the ABI3BP promoter region while the silencing of MALAT1 or suppression of H3K27 methylation was observed to promote the expression of ABI3BP. Furthermore, GBC patients with high expression of MALAT1 indicated poor prognosis. Conclusion The current study clarifies that MALAT1 silencing and ABI3BP elevation impede the GBC development through the H3K27 methylation suppression induced by EZH2, highlighting a promising competitive paradigm for therapeutic approaches of GBC.

An environmentally synchronized circadian clock is important for plant growth and developments. In the genus Hemerocallis, plants can be divided into diurnal (open between 3:00-15:00) and nocturnal (open between 15:00-3:00) flowering. The duration of each single flower is no more than 24 h. Hybrids obtained through crossing between diurnal and nocturnal flowers are fertile and show different daily flowering rhythms from their parents. Therefore, to enhance our understanding of daily circadian flowering rhythms in Hemerocallis, we studied inheritance by observing flowering processes among species, cultivars and F1 hybrids. Daily flowering rhythm was a relatively stable character that could be influenced through a breeding program. In F1 generations of crosses between daylilies and nightlilies, there was an obvious tendency toward nocturnal opening. Opening times showed a negatively skewed and leptokurtic distribution with a single peak. Closure times showed a normal distribution (peak times were 12:41–13:53, almost the mid-parent value). Variation increased when cultivars were used as parents, especially in closure times. Observations over 4 years showed subtle differences with a similar trend. Our results suggest that in Hemerocallis, opening is characterized by mixed major loci and polygenic inheritance, with dominant nocturnal opening. Closure was controlled by multiple genetic loci. Inheritance of opening and closure is controlled by different nuclear circadian clock genes and perhaps photoreceptor-binding motifs. By manipulating cultivar diversity, single flower duration could be prolonged effectively through hybridization. In addition, it was assumed that daily flowering rhythm was not a completely conserved character, and could be partly affected by environment.

Exosomes, which are lipid bilayer membrane vesicles, have been implicated as carriers of biological macromolecules. In recent years, the functions of exosomes in the spreading of pathological conversion of proteins among neurons have drawn particular attention in Parkinson's disease research. Extracellular α-synuclein is proven to be associated with exosomes in vivo and in vitro. The contents of these exosomes may be altered during the pathological and clinical processes, serving as a potential target for biomarker development in Parkinson's disease. This Review highlights the current understanding of biogenesis and pathophysiological roles of exosomes. Meanwhile, exosomes are promising delivery vehicles. Artificial exosomes can be loaded with defined therapeutically active molecules, such as drugs, small interfering RNAs, long noncoding RNAs, and proteins to the brain, ensuring the site-specific targeting strategy to the recipient cells. Therefore, we will also discuss the potential applications of exosomes in developing modified exosome-based drug carrier systems to halt the pathologic propagation of Parkinson's disease.

The continuing emergence of antibiotic-resistant bacteria due to the excessive use of antibiotics has produced a strong demand for novel strategies and new materials that do not lead to bacterial resistance. In the present work silicon nanowire arrays modified with gold-silver alloy nanoparticles (SN-Au/Ag) was investigated as a photo-induced antibacterial material. It was shown that SN-Au/Ag can kill bacteria with high efficiency under sunlight in times of the order of a few minutes, and this is achieved through synergism between photothermal and photocatalytic effects. It appears that the combined effect of heat and reactive oxygen species (ROS) causes bacteria killing through damage to the cell membrane and leakage of cytoplasm contents. Both gold and silver in the alloy nanoparticles are required for the observed bactericidal action. Moreover, the SN-Au/Ag material can be "recycled" without loss of bactericidal activity. It is concluded that the silicon nanowire arrays modified with gold-silver alloy nanoparticles developed in this work has promise as an antibacterial nanomaterial for the development of novel antibiotics.

Vitamin C (Vc) is an important antioxidant that helps turtles tolerating stressful environment. This work quantified changes in tissue Vc levels during winter hibernation in the soft-shelled turtle Pelodiscus sinensis, to reveal the stress response pattern of tissue Vc during hibernation and contribute basic data for turtle culture. We sampled juvenile soft-shelled turtles at pre-hibernation (17.0°C mud temperature; MT), during hibernation (5.8°C MT) and after arousal (20.1°C MT) in the field. The transcript levels of the gene encoding L-gulonolactone oxidase (GLO), the key enzyme for Vc synthesis, decreased significantly during hibernation. However, GLO activity did not match the GLO transcription patterns and remained stable during hibernation, and showed temperature-dependent kinetic characteristics. Vitamin C levels in the brain, liver, kidney, and spleen (but not muscle) all decreased significantly during hibernation, but recovered to pre-hibernation levels or even higher levels after arousal. The soft-shelled turtle endured 5 months of hibernation with no significant oxidative damage in most tissues, except in the spleen. Splenic Vc was nearly exhausted during hibernation, accompanied by a significantly elevated malonaldehyde (MDA) level. Although the high level of oxidative damage quickly decreased after arousal, the potential tissue damage in the spleen during hibernation might account for the weakened immune capacity of turtles after hibernation.

The worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing, and this metabolic disorder has been recognized as a severe threat to human health. A variety of chemical drugs have been approved for treating NAFLD, however, they always has serious side effects. Chinese herbal medicines (CHMs) have been widely used for preventing and treating a range of metabolic diseases with satisfactory safety and effective performance in clinical treatment of NAFLD. Recent studies indicated that imbanlance of the intestinal microbiota was closely associated with the occurrence and development of NAFLD, thus, the intestinal microbiota has been recognized as a promising target for treatment of NAFLD. In recent decades, a variety of CHMs have been reported to effectively prevent or treat NAFLD by modulating intestinal microbiota to further interfer the gut-liver axis. In this review, recent advances in CHMs for the treatment of NAFLD via rebuilding the intestinal microecology were systematically reviewed. The key roles of CHMs in the regulation of gut microbiota and the gut-liver axis along with their mechanisms (such as modulating intestinal permeability, reducing the inflammatory response, protecting liver cells, improving lipid metabolism, and modulating nuclear receptors), were well summarized. All the knowledge and information presented here will be very helpful for researchers to better understand the applications and mechanisms of CHMs for treatment of NAFLD.