Toxoplasma gondii, an obligate intracellular pathogen, has a strong affinity for the nervous system. TgCtwh3, a representative Chinese 1 Toxoplasma strain prevalent in China, has the polymorphic features of the effectors ROP16I/III with type I and GRA15II with type II Toxoplasma strains. The interaction of this atypical strain with host cells remains extremely elusive.

Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown.

The human enhancer of filamentation 1 (HEF1) is a multi-domain docking protein of the p130 Cas family. Research reports on the mechanism of HEF1 in gastric cancer (GC) differentiation are limited. In this study, we reveal that HEF1 plays an essential role in regulating of differentiation in human GC. HEF1 was found to be highly expressed in GC tissues. Besides, In GC tissues or cells, cellular level of HEF1 negatively correlated with tumor differentiation. In addition, we showed that upregulation of HEF1 increased Wnt5a expression and the nuclear translocation of β-catenin, thereby resulting in poor differentiation in GC. Notably, GC patients with a higher expression of HEF1 showed significantly poorer disease-free and overall survival. Thus, our findings suggest that HEF1 reduces differentiation through the Wnt5a/β-catenin signaling pathway and that HEF1 is an independent unfavorable prognostic death factor in GC.

Environmental assessment of eutrophication or heavy metals in urban lakes is an important reference for identifying the pollution degree and formulating pollution prevention strategies. At present, the most research on lake health states is often evaluated from a single angle for toxic metals pollution or eutrophication using the standard comparison method for both, the comprehensive trophic level index (TLI), and the health risk assessment for toxic metals. Moreover, the above deterministic methods probably lead to biased or unreliable assessment due to the randomness and fuzziness in environment system caused by natural change and human activities. In this paper, a fuzzy comprehensive lake health assessment method (FCLHAM) was established to evaluate comprehensive lake health states more comprehensively and accurately, which integrates quantitative eutrophication and health risk considerations. To test and verify FCLHAM, 21 lakes, scientifically selected from the total 143 lakes in the Chinese Wuhan city as study case, were investigated and analyzed for their state of eutrophication and the health risk posed by heavy metals. According to the FCLHAM, the average comprehensive lake health state decreased in the sequence of L20 (considerate risk level) > L1⁻L17, L19, L21 (moderate risk level) > L18 (low risk level). Based on the result, lakes were classified into three categories: general management (L18), enhanced management (L1⁻L17, L19, L21), and priority management (L20). If the 143 lakes in Wuhan were classified by the "area-region-function" classification, they would be assigned to the same category as the representative lakes of the same type. At this point, we will attribute all of Wuhan's lakes to the three types. Depending on the characteristics of each type, a targeted approach to different types of management for each type of lake is a more efficient way to manage many of Wuhan's lakes. This management mode also serves as an effective reference for the environmental management of urban lakes both at home and abroad. In other words, according to the FCLHAM, a hierarchical management system based on lake characteristics classification was obtained.

MicroRNAs (miRNA) regulate fundamental biological processes, including neuronal plasticity, stress response, and survival. Here, we describe a neuroprotective function of miR-132, the miRNA most significantly downregulated in neurons in Alzheimer's disease. We demonstrate that miR-132 protects primary mouse and human wild-type neurons and more vulnerable Tau-mutant neurons against amyloid β-peptide (Aβ) and glutamate excitotoxicity. It lowers the levels of total, phosphorylated, acetylated, and cleaved forms of Tau implicated in tauopathies, promotes neurite elongation and branching, and reduces neuronal death. Similarly, miR-132 attenuates PHF-Tau pathology and neurodegeneration, and enhances long-term potentiation in the P301S Tau transgenic mice. The neuroprotective effects are mediated by direct regulation of the Tau modifiers acetyltransferase EP300, kinase GSK3β, RNA-binding protein Rbfox1, and proteases Calpain 2 and Caspases 3/7. These data suggest miR-132 as a master regulator of neuronal health and indicate that miR-132 supplementation could be of therapeutic benefit for the treatment of Tau-associated neurodegenerative disorders.

The aim of this study was to elucidate the effects of regulator of G-protein signaling 5 (Rgs5), a negative regulator of G protein-mediated signaling, on atrial repolarization and tachyarrhythmia (ATA) in mice.

Myeloid differentiation protein 1 (MD1) has been implicated in numerous pathophysiological processes, including immune regulation, obesity, insulin resistance, and inflammation. However, the role of MD1 in cardiac remodelling remains incompletely understood. We used MD1-knockout (KO) mice and their wild-type littermates to determine the functional significance of MD1 in the regulation of aortic banding (AB)-induced left ventricular (LV) structural and electrical remodelling and its underlying mechanisms. After 4 weeks of AB, MD1-KO hearts showed substantial aggravation of LV hypertrophy, fibrosis, LV dilation and dysfunction, and electrical remodelling, which resulted in overt heart failure and increased electrophysiological instability. Moreover, MD1-KO-AB cardiomyocytes showed increased diastolic sarcoplasmic reticulum (SR) Ca2+ leak, reduced Ca2+ transient amplitude and SR Ca2+ content, decreased SR Ca2+-ATPase2 expression, and increased phospholamban and Na+/Ca2+-exchanger 1 protein expression. Mechanistically, the adverse effects of MD1 deletion on LV remodelling were related to hyperactivated CaMKII signalling and increased impairment of intracellular Ca2+ homeostasis, whereas the increased electrophysiological instability was partly attributed to exaggerated prolongation of cardiac repolarisation, decreased action potential duration alternans threshold, and increased diastolic SR Ca2+ leak. Therefore, our study on MD1 could provide new therapeutic strategies for preventing/treating heart failure.

To explore the potential protective effect of Tanshinone ⅡA on myocardial cell apoptosis and elucidate the underlying molecular mechanisms. The rat heart cell H9c2 was treated by either H2O2 or doxorubicin (DOX) to mimic oxidative stress and DNA damage conditions in vivo. Cell growth was monitored by optical microscope observation or CCK-8 counting kit. The relative expression of miR-133 and U6 snoRNA was semi-quantitated by RT-PCR or real-time PCR. Cell apoptosis was analyzed by flow cytometry with Annexin V/PI double staining. The microRNA binding sites were predicted by online bioinformatics tools. The regulatory effect of miR-133 on caspase-9 was measured by luciferase reporter assay. Apoptosis pathway factors were analyzed by immunoblotting. Our data demonstrated that Tanshinone ⅡA significantly ameliorated myocardial apoptosis induced by either H2O2 or DOX. The protective effect was likely mediated by up-regulation of miR-133. We further identified Caspase-9 as the target of miR-133. Tanshinone ⅡA treatment significantly reversed down-regulation of miR-133 under harsh conditions and in turn suppressed evoking of Caspase-9 and related apoptotic effectors, which consequently contributed to the improvement of myocardial injury. In conclusion, Tanshinone ⅡA ameliorated myocardial apoptosis via restoration of miR-133 and suppression Caspase-9 signaling cascade, which underlies its well-proven clinical benefit and warrants larger scale clinical applications.

Several lines of evidence suggest that the human 5-HT(7) receptor may be involved in the pharmacodynamics of risperidone and may influence clinical response of the drug. A pharmocogenetics study of this receptor may therefore be useful in developing individualized therapy. But few studies about it have been done. In this study, we genotyped ten single nucleotide polymorphisms (SNPs) distributed throughout the HTR7 gene and analyzed six of them for association with the reduction of Brief Psychiatric Rating Scale (BPRS) scores in drug-naive Chinese schizophrenia patients, following an eight-week period of risperidone monotherapy. The confounding effects of nongenetic factors were estimated and the baseline symptom score as well as the duration of illness were included as covariates for adjustment. No significant correlation of HTR7 with antipsychotic efficacy was detected in either genotype or haplotype analysis. These results demonstrate that variations in the HTR7 gene may not be good genetic markers for predicting the therapeutic efficacy of risperidone.

Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein reported as an anti-inflammatory adipocytokine. Evidences from clinical and experimental studies revealed that brain inflammation plays important roles in epileptogenesis and seizure. Interestingly, closely relationship between ZAG and many important inflammatory mediators has been proven. Our previous study identified ZAG in neurons and found that ZAG is decreased in epilepsy and interacts with TGFβ and ERK. This study aimed to investigate the role of ZAG in seizure and explore its effect on seizure-related neuroinflammation.

Elevated intracellular Ca2+ ([Ca2+] i ) level could lead to [Ca2+] i overload and promote apoptosis via different pathways. In our previously study, up-regulated expression of transient receptor potential canonical channel (TRPC5) was proven to increase [Ca2+] i level, and resulted in chemoresistance whereas not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent homeostatic maintenance of resting [Ca2+] i should be important in this process. Increased glycolysis was found to be an important adenosine triphosphate (ATP) source in cancer. This study aimed to explore the potential mechanism of aerobic glycolysis in transient receptor potential channel TRPC5 induced chemoresistance.

Chronic kidney disease (CKD) is one of the major causes of renal damage. Shenyan Fangshuai Recipe (SFR), a modified prescription of traditional medicine in China, showed potent effects in alleviating edema, proteinuria, and hematuria of CKD in clinical practices. In this study, we aimed to investigate scientific evidence-based efficacy as well as metabolic regulations of SFR in CKD treatment.

The application prospect of biodegradable materials is being studied extensively. However, the high corrosion rate and its alloys in body fluids have been major limitations of the application of pure Mg (magnesium). To improve corrosion resistance of biodegradable AZ31 Mg alloy, we adopted microarc fluorination within a voltage range of 100-300 V in 46% hydrofluoric acid. To obtain morphologies, chemical compositions, and structural characteristics, field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) were performed, respectively. Results showed that the coating was mainly composed of MgF2. Electrochemical corrosion and immersion tests proved that the corrosion resistance of MAF-treated AZ31 Mg alloy was significantly improved compared with untreated AZ31 Mg alloy in HBSS (Hank's Balanced Salt Solution). Current densities of AZ31, MAF100, MAF150, MAF200, MAF250, and MAF300 were 342.4, 0.295, 0.228, 0.177, 0.199, and 0.212 μA/cm2, respectively. The roughness test indicated that samples under MAF treatment of 200 V, 250 V, and 300 V had large surface roughness. Meanwhile, the contact angle measurement and surface free energy test suggested that those samples had smaller contact angle and higher SFE than Ti. Thus, MAF-treated AZ31 Mg alloy might have promising application in various fields.

Vestigial like family member 3 (VGLL3) is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma, but its role in gastric cancer (GC) is unclear.

Small extracellular vesicles (sEVs) play a key role in intercellular communication. Cargo molecules carried by sEVs may affect the phenotype and function of recipient cells. Epithelial cancer cell-derived sEVs, particularly those enriched in CD151 or tetraspanin8 (TSPAN8) and associated integrins, promote tumour progression. The mechanism of binding and modulation of sEVs to recipient cells remains elusive. Here, we used genetically engineered breast cancer cells to derive TSPAN8-enriched sEVs and evaluated the impact of TSPAN8 on target cell membrane's diffusion and transport properties. The single-particle tracking technique showed that TSPAN8 significantly promoted sEV binding via confined diffusion. Functional assays indicated that the transgenic TSPAN8-sEV cargo increased cancer cell motility and epithelial-mesenchymal transition (EMT). In vivo, transgenic TSPAN8-sEV promoted uptake of sEVs in the liver, lung, and spleen. We concluded that TSPAN8 encourages the sEV-target cell interaction via forced confined diffusion and significantly increases cell motility. Therefore, TSPAN8-sEV may serve as an important direct or indirect therapeutic target.

Buffalo is an important livestock species. Here, we present a comprehensive metagenomic survey of the microbial communities along the buffalo digestive tract. We analysed 695 samples covering eight different sites in three compartments (four-chambered stomach, intestine, and rectum). We mapped ~85% of the raw sequence reads to 4,960 strain-level metagenome-assembled genomes (MAGs) and 3,255 species-level MAGs, 90% of which appear to correspond to new species. In addition, we annotated over 5.8 million nonredundant proteins from the MAGs. In comparison with the rumen microbiome of cattle, the buffalo microbiota seems to present greater potential for fibre degradation and less potential for methane production. Our catalogue of microbial genomes and the encoded proteins provides insights into microbial functions and interactions at distinct sites along the buffalo digestive tract.

Our previous study showed that interferon gamma (IFN-γ) might enhance the immunosuppressive properties of mesenchymal stem cells (MSCs) by upregulating the expression of indoleamine 2,3-dioxygenease. Therefore, we treated experimental autoimmune encephalomyelitis (EAE) mice, an animal model of multiple sclerosis (MS), with IFN-γ-primed human umbilical cord MSCs (IFN-γ-hUCMSCs). This study aimed to investigate the potential therapeutic effects of IFN-γ-hUCMSCs transplantation and to identify the biological pathways involved in EAE mice. Firstly, the body weights and clinical scores of EAE mice were recorded before and after treatment. Then, the inflammatory cytokine levels in splenic cell supernatants were quantified by enzyme-linked immunosorbent assay. Finally, the mRNA expression levels of signal transducer and activator of transduction 3 (STAT3), retinoic acid-related orphan receptor gamma t (ROR-γt), and forkhead box P3 (Foxp3) were detected by quantitative reverse transcription polymerase chain reaction. We observed that IFN-γ-hUCMSCs transplantation significantly alleviated body weight loss and decreased the clinical scores of mice. Additionally, IFN-γ-hUCMSCs transplantation could regulate the production of inflammatory cytokines, interleukin (IL)-10 and IL-17, thereby showing more potent treatment efficacy than human umbilical cord MSCs (hUCMSCs) transplantation (p < 0.05). Compared with the EAE group, the expressions of STAT3 and ROR-γt in the transplantation groups were significantly decreased, but the expression of Foxp3 was significantly upregulated in the IFN-γ-hUCMSCs transplantation group compared to that in the hUCMSCs transplantation group. We assumed that IFN-γ-hUCMSCs may affect the balance of T helper 17 (Th17) cells/regulatory T cells (Tregs) through the Foxp3/ROR-γt/STAT3 signaling pathway to reduce the inflammatory response, thereby improving the clinical symptoms of EAE mice. Our study demonstrated that transplantation of IFN-γ-hUCMSCs could reduce inflammation in EAE mice via the Foxp3/ROR-γt/STAT3 signaling pathway, highlighting the therapeutic effects of IFN-γ-hUCMSCs in patients with MS.

Maintaining a moist and sterile environment is conducive to accelerating wound healing. To develop a natural wound dressing with good water retention capacity and antibacterial activity, we prepared a novel natural multifunctional hydrogel for infected wound healing, which combines the advantages of Aloe polysaccharide (AP) and honey. AP was extracted from Aloe barbadensis, and its structure was characterized by fourier transform infra-red (FT-IR) spectoscopy and nuclear magnetic resonance (NMR) spectroscopy. AP is an acetylated mannan composed of (1 → 4)β-Manp, which is acetylated at C-2, C-3 and C-6 positions. AP/Honey@PVA hydrogel was prepared by cross-linking AP, honey, PVA with borax, which has good mechanical strength and excellent biocompatibility for blood cells, NIH-3T3 cells and L929 cells. The hydrogels showed significant inhibitory effect on Staphylococcus aureus, Escherichia coli and Candida albicans, as well as accelerated the healing of infected full-thickness wound. This study reveals the structure of AP and proves that AP and honey composite hydrogel has potential application prospect in the therapy of infected wounds.

miR-10b is silenced in normal neuroglial cells of the brain but commonly activated in glioma, where it assumes an essential tumor-promoting role. We demonstrate that the entire miR-10b-hosting HOXD locus is activated in glioma via the cis-acting mechanism involving 3D chromatin reorganization and CTCF-cohesin-mediated looping. This mechanism requires two interacting lncRNAs, HOXD-AS2 and LINC01116, one associated with HOXD3/HOXD4/miR-10b promoter and another with the remote enhancer. Knockdown of either lncRNA in glioma cells alters CTCF and cohesin binding, abolishes chromatin looping, inhibits the expression of all genes within HOXD locus, and leads to glioma cell death. Conversely, in cortical astrocytes, enhancer activation is sufficient for HOXD/miR-10b locus reorganization, gene derepression, and neoplastic cell transformation. LINC01116 RNA is essential for this process. Our results demonstrate the interplay of two lncRNAs in the chromatin folding and concordant regulation of miR-10b and multiple HOXD genes normally silenced in astrocytes and triggering the neoplastic glial transformation.

Exposure to particulate matter air pollution is associated with an increased risk of cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not yet understood. Enhanced platelet and pro-thrombotic activity in COPD patients may explain their increased cardiovascular risk. We aim to explore whether short-term exposure to ambient particulate matter is associated with pro-thrombotic changes in adults with and without COPD, and investigate the underlying biological mechanisms in a longitudinal panel study. Serum concentration of thromboxane (Tx)B2 was measured to reflect platelet and pro-thrombotic activity. Lipoxygenase-mediated lipid peroxidation products (hydroxyeicosatetraenoic acids [HETEs]) and inflammatory biomarkers (interleukins [ILs], monocyte chemoattractant protein-1 [MCP-1], tumour necrosis factor alpha [TNF-α], and macrophage inflammatory proteins [MIPs]) were measured as potential mediating determinants of particle-associated pro-thrombotic changes.