TFAP2A Activates S100A2 to Mediate Glutamine Metabolism and Promote Lung Adenocarcinoma Metastasis.

BACKGROUND: Lung adenocarcinoma (LUAD) is a fatal disease with metabolic abnormalities. The dysregulation of S100 calcium-binding protein A2 (S100A2), a member of the S100 protein family, is connected to the development of various cancers. The impact of S100A2 on the LUAD occurrence and metastasis, however, has not yet been reported. The functional mechanism of S100A2 on LUAD cell metastasis was examined in this article. METHODS: The expression of TFAP2A and S100A2 in LUAD tissues and cells was analyzed by bioinformatics and qRT-PCR, respectively. The enrichment pathway analysis was performed on S100A2. Bioinformatics analysis determined the binding relationship between TFAP2A and S100A2, and their interaction was validated through dual-luciferase and chromatin immunoprecipitation experiments. Cell viability was determined using cell counting kit-8 (CCK-8). A transwell assay was performed to analyze the invasion and migration of cells. Immunofluorescence was conducted to obtain vimentin and E-cadherin expression, and a western blot was used to detect the expression of MMP-2, MMP-9, GLS, and GLUD1. The kits measured the NADPH/NADP ratio, glutathione (GSH)/glutathione disulfide (GSSG) levels, and the contents of glutamine, α-KG, and glutamate. RESULTS: S100A2 was upregulated in LUAD tissues and cells, and S100A2 mediated glutamine metabolism to induce LUAD metastasis. Additionally, the transcriptional regulator TFAP2A was discovered upstream of S100A2, and TFAP2A expression was upregulated in LUAD, which indicated that TFAP2A promoted the S100A2 expression. The rescue experiment found that upregulation of S100A2 could reverse the inhibitory effects of silencing TFAP2A on glutamine metabolism and cell metastasis. CONCLUSION: In conclusion, by regulating glutamine metabolism, the TFAP2A/S100A2 axis facilitated LUAD metastasis. This suggested that targeting S100A2 could be beneficial for LUAD treatment.

A facile electrochemical aptasensor for chloramphenicol detection based on synergistically photosensitization enhanced by SYBR Green I and MoS2.

This study reports the development of a photocatalytic electrochemical aptasensor for the purpose of detecting chloramphenicol (CAP) antibiotic residues in water by utilizing SYBR Green I (SG) and chemically exfoliated MoS2 (ce-MoS2) as synergistically signal-amplification platforms. The Au nanoparticles (AuNPs) were electrodeposited onto the surface of an indium tin oxide (ITO) electrode. After that, the thiolate-modified cDNA, also known as capture DNA, was combined with the aptamer. Subsequently, photosensitized SG molecules and ce-MoS2 nanomaterial were inserted into the groove of the resultant double-stranded DNA (dsDNA). The activation of the photocatalytic process upon exposure to light resulted in the generation of singlet oxygen. The singlet oxygen effectively split the dsDNA, resulting in significant enhancement in the current of [Fe(CN)6]3-/4-. When the CAP was present, both SG molecules and ce-MoS2 broke away from the dsDNA, which turned off the photosensitization response, leading to significant reduction in the current of [Fe(CN)6]3-/4-. Under the optimal conditions, the aptasensor exhibited a linear relationship between the current of [Fe(CN)6]3-/4- with logarithmic concentrations of CAP from 20 to 1000 nM, with a detection of limit (3σ) of 3.391 nM. The aptasensor also demonstrated good selectivity towards CAP in the presence of interfering antibiotics, such as tetracycline, streptomycin, levofloxacin, ciprofloxacin, and sulfadimethoxine. Additionally, the results obtained from the analysis of natural water samples using the proposed aptasensor were consistent with the findings acquired through the use of a liquid chromatograph-mass spectrometer. Therefore, with its simplicity and high selectivity, this aptasensor can potentially detect alternative antibiotics in environmental water samples by replacing the aptamers based on photosensitization.

Inhibiting Hepatocyte Uric Acid Synthesis and Reabsorption Ameliorates Acetaminophen-Induced Acute Liver Injury in Mice.

BACKGROUND & AIMS: Acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury worldwide. Uric acid (UA) is involved in sterile inflammation in many organs, but its role in APAP-induced liver injury remains elusive. METHODS: We quantified the concentration of UA in the serum and liver tissues of APAP-overdosed mice and explored the changes in proteins involved in UA synthesis, absorption, and degeneration on APAP stimulation. We also examined the effects of inhibiting hepatocyte UA synthesis or reabsorption on APAP-induced liver injury in mice. Furthermore, we explored the process of UA clearance by peripheral macrophages. RESULTS: APAP overdose significantly increased intrahepatic UA contents, which occurred earlier than apparent hepatocyte injury in APAP-overdosed mice. APAP overdose induced significant DNA leakage and may thereby increase the substrate of UA synthesis. APAP overdose also significantly increased the enzymatic activity of xanthine oxidase and urate oxidase and decreased the expression of the UA reabsorption transporter GLUT9 in hepatocytes. Inhibiting hepatocyte UA synthesis by febuxostat or reabsorption by hepatic-specific knockout of GLUT9 alleviated APAP-induced liver injury. Further experiments showed that monosodium urate but not soluble UA may be a major form of UA mediating hepatocyte injury. Additionally, monosodium urate further recruited circulating macrophages into the liver and then aggravated inflammation by increasing the levels of inflammatory factors and reactive oxygen species. Deletion of macrophages significantly ameliorated APAP-induced liver injury in mice. CONCLUSIONS: APAP overdose induces excessive UA production and leads to local high concentrations in the liver, which further injures cells and induces liver inflammation. Inhibiting the production of UA may be a potential therapeutic option for treating APAP-induced liver injury.

Mineralization of Few-Layer Graphene Made It Bioavailable in Chlamydomonas reinhardtii.

Numerous studies have emphasized the toxicity of graphene-based nanomaterials to algae, however, the fundamental behavior and processes of graphene in biological hosts, including its transportation, metabolization, and bioavailability, are still not well understood. As photosynthetic organisms, algae are key contributors to carbon fixation and may play an important role in the fate of graphene. This study investigated the biological fate of 14C-labeled few-layer graphene (14C-FLG) in Chlamydomonas reinhardtii (C. reinhardtii). The results showed that 14C-FLG was taken up by C. reinhardtii and then translocated into its chloroplast. Metabolomic analysis revealed that 14C-FLG altered the metabolic profiles (including sugar metabolism, fatty acid, and tricarboxylic acid cycle) of C. reinhardtii, which promoted the photosynthesis of C. reinhardtii and then enhanced their growth. More importantly, the internalized 14C-FLG was metabolized into 14CO2, which was then used to participate in the metabolic processes required for life. Approximately 61.63%, 25.31%, and 13.06% of the total radioactivity (from 14CO2) was detected in carbohydrates, lipids, and proteins of algae, respectively. Overall, these results reveal the role of algae in the fate of graphene and highlight the potential of available graphene in bringing biological effects to algae, which helps to better assess the environmental risks of graphene.

The impact of boarding schools on the development of cognitive and non-cognitive abilities in adolescents.

BACKGROUND: Since China adopted a policy to eliminate rural learning centers, boarding has become an important feature of the current rural student community. However, there is a lack of consensus on the impact of boarding schools on students' cognitive and non-cognitive development. This study investigates the effect of boarding schools on the development of cognitive and non-cognitive abilities of junior high school students in rural northwest China. METHODS: Using a sample of 5,660 seventh-grade students from 160 rural junior high schools across 19 counties, we identify a causal relationship between boarding and student abilities with the instrumental variables (IV) approach. RESULTS: The results suggest that boarding positively influences memory and attention, while it has no significant effect on other cognitive abilities such as reasoning, transcription speed, and accuracy. Furthermore, we find no significant association between boarding and the development of non-cognitive skills. CONCLUSIONS: Given the widespread prevalence of boarding schools in rural regions, our study highlights the growing importance of improving school management to promote the development of students' cognitive abilities and integrating the development of non-cognitive or social-emotional abilities into students' daily routines.

Genetic Predictors of Ibrutinib-related Cardiovascular Side Effects in Patients with Chronic Lymphocytic Leukemia.

PURPOSE: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSE). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton tyrosine kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. EXPERIMENTAL DESIGN: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least 6 months. CVSEs, primarily atrial fibrillation and hypertension, occurred in 10 patients (20%), of whom 4 discontinued therapy. DNA was isolated from buccal swabs of all 50 patients and genotyped for 40 SNPs in GATA4, SGK1, KCNQ1, KCNA4, NPPA, and SCN5A using a customized next-generation sequencing panel. Univariate and multivariate logistic regression analysis were performed to determine genetic and clinical factors associated with the incidence of ibrutinib-related CVSEs. RESULTS: GATA4 rs804280 AA (P = 0.043), KCNQ1 rs163182 GG (P = 0.036), and KCNQ1 rs2237895 AA (P = 0.023) genotypes were univariately associated with ibrutinib-related CVSEs. On the basis of multivariate analysis, a high genetic risk score, defined as the presence of at least two of these genotypes, was associated with 11.5-fold increased odds of CVSEs (P = 0.019; 95% confidence interval, 1.79-119.73). CONCLUSIONS: Our findings suggest possible genetic determinants of ibrutinib-related CVSEs in CLL. If replicated in a larger study, pretreatment pharmacogenetic testing for GATA4 and KCNQ1 polymorphisms may be a useful clinical tool for personalizing treatment selection for CLL and/or instituting early risk mitigation strategies.

Research progress of implantation materials and its biological evaluation.

With the development of modern material science, life science and medical science, implantation materials are widely employed in clinical fields. In recent years, these materials have also evolved from inert supports or functional substitutes to bioactive materials able to trigger or promote the regenerative potential of tissues. Reasonable biological evaluation of implantation materials is the premise to make sure their safe application in clinical practice. With the continual development of implantation materials and the emergence of new implantation materials, new challenges to biological evaluation have been presented. In this paper, the research progress of implantation materials, the progress of biological evaluation methods, and also the characteristics of biocompatibility evaluation for novel implantation materials, like animal-derived implantation materials, nerve contact implantation materials, nanomaterials and tissue-engineered medical products were reviewed in order to provide references for the rational biological evaluation of implantable materials.

Genetic Evolution of Hepatitis E Virus.

Comparative analysis of the genomic sequences of multiple hepatitis E virus (HEV) isolates has revealed extensive genomic diversity among them. Recently, a variety of genetically distinct HEV variants have also been isolated and identified from large numbers of animal species, including birds, rabbits, rats, ferrets, bats, cutthroat trout, and camels, among others. Furthermore, it has been reported that recombination in HEV genomes takes place in animals and in human patients. Also, chronic HEV infection in immunocompromised individuals has revealed the presence of viral strains carrying insertions from human genes. This paper reviews current knowledge on the genomic variability and evolution of HEV.

Olfactomedin-4 deletion exacerbates DSS-induced colitis through a matrix metalloproteinase-9-dependent mechanism.

Background and Aims: Olfactomedin-4 is a glycoprotein that is upregulated in inflamed gastrointestinal tissues. This study aimed to investigate the role and underlying mechanisms of olfactomedin-4 in ulcerative colitis. Methods: C57BL/6 mice and olfactomedin-4 knockout mice were fed dextran sulfate sodium in drinking water to establish a colitis model. An in vitro inflammation model was constructed in HCT116 and NCM460 cells stimulated with lipopolysaccharide. The expression of olfactomedin-4 was detected by Western blotting, immunohistochemistry staining, and qRT‒PCR. The differences in the severity of colitis between olfactomedin-4 knockout mice and wild-type mice were compared, and the underlying mechanisms were explored. Results: Olfactomedin-4 expression was significantly upregulated in colonic tissues of active ulcerative colitis patients and in cellular and mouse models of colitis. Compared with wild-type littermates, olfactomedin-4 knockout mice were more susceptible to dextran sulfate sodium-induced colitis and produced higher levels of proinflammatory cytokines and chemokines. In addition, olfactomedin-4 deficiency significantly promoted intestinal epithelial cell apoptosis and increased intestinal permeability, which was mediated by the p53 pathway. Moreover, olfactomedin-4 directly interacted with and negatively regulated matrix metalloproteinase-9. Inhibiting matrix metalloproteinase-9 significantly decreased colonic p53 expression and ameliorated experimental colitis in olfactomedin-4 knockout mice, while overexpression of matrix metalloproteinase-9 aggravated colitis. Further experiments showed that matrix metalloproteinase-9 regulated p53 through the Notch1 signaling pathway to promote ulcerative colitis progression. Conclusions: Olfactomedin-4 is significantly upregulated in ulcerative colitis and may protect against colitis by directly inhibiting matrix metalloproteinase-9 and further decreasing p53-mediated apoptosis via Notch1 signaling.

Evaluation of the effectiveness of alginate-based hydrogels in preventing peritoneal adhesions.

Infertility and intestinal blockage are just two examples of the postoperative consequences that can arise from peritoneal damage, which can also result in severe peritoneal fibrosis and peritoneal adhesions. Peritoneal adhesions are still not effectively treated, and both pharmaceutical therapy and biomaterial barriers have only had modest preventative effects. In this work, we looked into the effectiveness of in-place injectable sodium alginate hydrogel for peritoneal adhesion prevention. The findings demonstrated that sodium alginate hydrogel promoted human peritoneal mesothelial cell proliferation and migration, prevented peritoneal fibrosis by suppressing the production of transforming growth factor-ß1, and, most importantly, promoted mesothelium self-repair. These findings imply that this brand-new sodium alginate hydrogel is a good candidate material for peritoneal adhesion prevention.

Identifying the distinct spectral dynamics of laminar-specific interhemispheric connectivity with bilateral line-scanning fMRI.

Despite extensive efforts to identify interhemispheric functional connectivity (FC) with resting-state (rs-) fMRI, correlated low-frequency rs-fMRI signal fluctuation across homotopic cortices originates from multiple sources. It remains challenging to differentiate circuit-specific FC from global regulation. Here, we developed a bilateral line-scanning fMRI method to detect laminar-specific rs-fMRI signals from homologous forepaw somatosensory cortices with high spatial and temporal resolution in rat brains. Based on spectral coherence analysis, two distinct bilateral fluctuation spectral features were identified: ultra-slow fluctuation (<0.04 Hz) across all cortical laminae versus Layer (L) 2/3-specific evoked BOLD at 0.05 Hz based on 4 s on/16 s off block design and resting-state fluctuations at 0.08-0.1 Hz. Based on the measurements of evoked BOLD signal at corpus callosum (CC), this L2/3-specific 0.05 Hz signal is likely associated with neuronal circuit-specific activity driven by the callosal projection, which dampened ultra-slow oscillation less than 0.04 Hz. Also, the rs-fMRI power variability clustering analysis showed that the appearance of L2/3-specific 0.08-0.1 Hz signal fluctuation is independent of the ultra-slow oscillation across different trials. Thus, distinct laminar-specific bilateral FC patterns at different frequency ranges can be identified by the bilateral line-scanning fMRI method.

Pesticin-Like Effector VgrG3cp Targeting Peptidoglycan Delivered by the Type VI Secretion System Contributes to Vibrio cholerae Interbacterial Competition.

Vibrio cholerae can utilize a type VI secretion system (T6SS) to increase its intra- and interspecies competition. However, much still remains to be understood about the underlying mechanism of this intraspecies competition. In this study, we isolated an environmental V. cholerae strain E1 that lacked the typical virulence factors toxin-coregulated pilus and cholera toxin and that encoded a functional T6SS. We identified an evolved VgrG3 variant with a predicted C-terminal pesticin-like domain in V. cholerae E1, designated VgrG3cp. Using heterologous expression, protein secretion, and peptidoglycan-degrading assays, we demonstrated that VgrG3cp is a T6SS-dependent effector harboring cell wall muramidase activity and that its toxicity can be neutralized by cognate immunity protein TsiV3cp. Site-directed mutagenesis proved that the aspartic acid residue at position 867 is crucial for VgrG3cp-mediated antibacterial activity. Bioinformatic analysis showed that genes encoding VgrG3cp-like homologs are distributed in Vibrio species, are linked with T6SS structural genes and auxiliary genes, and the vgrG3cp-tsiV3cp gene pair of V. cholerae probably evolved from Vibrio anguillarum and Vibrio fluvialis via homologous recombination. Through a time-lapse microscopy assay, we directly determined that cells accumulating VgrG3cp disrupted bacterial division, while the cells continued to increase in size until the loss of membrane potential and cell wall breakage and finally burst. The results of the competitive killing assay showed that VgrG3cp contributes to V. cholerae interspecies competition. Collectively, our study revealed a novel T6SS E-I pair representing a new T6SS toxin family which allows V. cholerae to gain dominance within polymicrobial communities by T6SS. IMPORTANCE The type VI secretion system used by a broad range of Gram-negative bacteria delivers toxic proteins to target adjacent eukaryotic and prokaryotic cells. Diversification of effector proteins determines the complex bacterium-bacterium interactions and impacts the health of hosts and environmental ecosystems in which bacteria reside. This work uncovered an evolved valine-glycine repeat protein G3, carrying a C-terminal pesticin-like domain (VgrG3cp), which has been suggested to harbor cell wall hydrolase activity and is able to affect cell division and the integrity of cell wall structure. Pesticin-like homologs constitute a family of T6SS-associated effectors targeting bacterial peptidoglycan which are distributed in Vibrio species, and genetic loci of them are linked with T6SS structural genes and auxiliary genes. T6SS-delivered VgrG3cp mediated broad-spectrum antibacterial activity for several microorganisms tested, indicating that VgrG3cp-mediated antimicrobial activity is capable of conferring bacteria a competitive advantage over competitors in the same niches.

Cerebrovascular Gi Proteins Protect Against Brain Hypoperfusion and Collateral Failure in Cerebral Ischemia.

Cerebral hypoperfusion and vascular dysfunction are closely related to common risk factors for ischemic stroke such as hypertension, dyslipidemia, diabetes, and smoking. The role of inhibitory G protein-dependent receptor (GiPCR) signaling in regulating cerebrovascular functions remains largely elusive. We examined the importance of GiPCR signaling in cerebral blood flow (CBF) and its stability after sudden interruption using various in vivo high-resolution magnetic resonance imaging techniques. To this end, we induced a functional knockout of GiPCR signaling in the brain vasculature by injection of pertussis toxin (PTX). Our results show that PTX induced global brain hypoperfusion and microvascular collapse. When PTX-pretreated animals underwent transient unilateral occlusion of one common carotid artery, CBF was disrupted in the ipsilateral hemisphere resulting in the collapse of the cortically penetrating microvessels. In addition, pronounced stroke features in the affected brain regions appeared in both MRI and histological examination. Our findings suggest an impact of cerebrovascular GiPCR signaling in the maintenance of CBF, which may be useful for novel pharmacotherapeutic approaches to prevent and treat cerebrovascular dysfunction and stroke.

Biglycan promotes hepatic fibrosis through activating heat shock protein 47.

BACKGROUND: Biglycan (BGN) is a small leucine-rich proteoglycan that participates in the production of excess extracellular matrix (ECM) and is related to fibrosis in many organs. However, the role of BGN in liver fibrosis remains poorly understood. This study aimed to investigate the role and mechanism of BGN in liver fibrosis. METHODS: Human liver samples, Bgn-/0 (BGN KO) mice and a human LX-2 hepatic stellate cells (HSCs) model were applied for the study of experimental fibrosis. GEO data and single-cell RNA-seq data of human liver tissue were analysed as a bioinformatic approach. Coimmunoprecipitation, immunofluorescence staining, western blotting and qRT-PCR were conducted to identify the regulatory effects of BGN on heat shock protein 47 (HSP47) expression and liver fibrosis. RESULTS: We observed that hepatic BGN expression was significantly increased in patients with fibrosis and in a mouse model of liver fibrosis. Genetic deletion of BGN disrupted TGF-ß1 pathway signalling and alleviated liver fibrosis in mice administered carbon tetrachloride (CCl4 ). siRNA-mediated knockdown of BGN significantly reduced TGF-ß1-induced ECM deposition and fibroblastic activation in LX-2 cells. Mechanistically, BGN directly interacted with and positively regulated the collagen synthesis chaperon protein HSP47. Rescue experiments showed that BGN promoted hepatic fibrosis by regulating ECM deposition and HSC activation by positively regulating HSP47. CONCLUSION: Our data indicate that BGN promotes hepatic fibrosis by regulating ECM deposition and HSC activation through an HSP47-dependent mechanism. BGN may be a new biomarker of hepatic fibrosis and a novel target for disease prevention and treatment.

Information Exchange between Cortical Areas: The Visual System as a Model.

As nearly all brain functions, perception, motion, and higher-order cognitive functions require coordinated neural information processing within distributed cortical networks. Over the past decades, new theories and techniques emerged that advanced our understanding of how information is transferred between cortical areas. This review surveys critical aspects of interareal information exchange. We begin by examining the brain's structural connectivity, which provides the basic framework for interareal communication. We then illustrate information exchange between cortical areas using the visual system as an example. Next, well-studied and newly proposed theories that may underlie principles of neural communication are reviewed, highlighting recent work that offers new perspectives on interareal information exchange. We finally discuss open questions in the study of the neural mechanisms underlying interareal information exchange.

In Vitro and In Vivo Investigation on the Effectiveness of Alginate-Based Gastric Mucosal Protective Gel.

Objective: To investigate the feasibility and effectiveness of an alginate-based gastric mucosal protective gel on the gastric ulcer. Methods: (1) In the physical protection model, after GES-1 cell attachment add the gel to transwell chamber, add different concentrations of HCl to the gel. Absorbance was measured to assess proliferation and images of the cells migrating into the wound were taken; then the migration rate of the cells was quantified by comparing images. (2) In the gastric ulcer model, excise the gastric mucosal of SD rats; the gel and fixative were applied on the artificial ulcer immediately. Dissect rats after 10 days, and calculate the wound healing rate and analyzed histology changes. Results: The effect of hydrochloric acid on cells in the lower layer was significantly reduced after the use of gastric mucosal protection gel. The protective gel had an isolation effect on different concentrations of acid. A number of GES-1 were significantly higher than those in the control group at 24 h to 72 h (P < 0.01). The migration was observed compared with the control group. The average healing rate of ulcer in the gel group was about 50%, and the control group was about 30%. Inflammation occurred in all wound regions after ten days. In the gel group, inflammatory infiltration depth was lower than that of the control, and part of SD rats' new muscle layer appeared without inflammatory infiltration. The connective tissue proliferation promoted tissue repair. In the control group, necrosis marginal, mucosal hyperplasia, marginal lymphocyte aggregation, and bleeding were observed. Conclusion: This novel gel mainly has an isolating and shielding effect to prevent the wound from being exposed to gastric acid for a long time, and it can reduce the inflammatory reaction on the wounds to promote the healing of the ulcer. The gastric mucosal protective gel cannot only promote the speed of wound healing but also improve the quality of wound healing.

Umbilical Cord Mesenchymal Stem Cells Seeded on Small Intestinal Submucosa to Repair the Uterine Wall Injuries.

Objective: The effectiveness of tissue engineering materials combining porcine small intestine submucosa (SIS) and umbilical cord mesenchymal stem cells (UC-MSCs) on uterine injury in female rat after full-thickness uterine resection was evaluated as a basis for clinical treatment of postoperative uterine injury. Methods: After complex culture with SIS and UC-MSCs, cell adhesion, growth, and proliferation were assessed. Before the implantation, a surgical procedure of bilateral full-thickness uterine resection (0.5-2.0 cm long and 0.3 cm wide) was performed to obtain the rat uterine injury model, while the sham-operated rats were used as controls. Hematoxylin-eosin (H&E) staining results and fertility of female rats in each group were assessed to determine the critical resection length of the full-thickness uterine resection. Then SIS or UC-MSCs-SIS were implanted into the female rats from the uterine injury group, followed by assessments of H&E staining, the expression of ki67, α-SMA, and leukemia inhibitory factor (LIF), and fertility to determine the effectiveness of SIS and UC-MSCs-SIS on uterine injury in female rat. Results: At 24, 48, and 72 h, the cells grew progressively on the SIS material. In the 1.5 cm and 2.0 cm groups, the pregnancy rate, proportion of the uterus supporting live embryo growth, number of live embryos, and proportion of live embryos were all significantly less than those in the 0.5 cm and sham-operated groups. In the 2.0 cm group, there was little tissue regeneration at the center of the injury and not conducive to subsequent assessment. The UC-MSCs-SIS and SIS groups were better on morphological development, cell proliferation, LIF expression, and fertility than the control group. Conclusions: UC-MSCs show good adhesion, growth, and proliferation on the SIS scaffold material. The optimal resection length in full-thickness uterine resection on female rat is 1.5 cm. UC-MSCs-SIS is the effective treatment for repairing a injury after the full-thickness resection of the uterus in this research. Impact Statement The acquired severe uterus injury is a serious condition, which prone to uterine adhesions. Postoperative endometrial repairment and prevention of intrauterine adhesion recurrence are two major clinical challenges. Fortunately, the development of tissue engineering technology makes repairing a uterine injury possible. There are two main contributions from this study. First, due to ethical requirements, it is difficult to assess the repairing effect on uterus by invasive experiments in a clinical practice. Therefore, we constructed a full-thickness uterine injury rat model, which allows us to assess the repairing effect of treatments after severe uterine injuries in vivo. Second, it explored the effect of using a combination of and umbilical cord mesenchymal stem cells and small intestine submucosa materials on improving uterine repairments, providing a potential possibility for a future clinical practice.

The regulation effect of GLUT9/SLC2A9 on intrahepatic uric acid level and metabolic associated fatty liver disease.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. The important role of urid acid (UA) in MAFLD has been widely investigated. Our previous studies unveiled the elevation of serum UA levels independently predicts an increased risk of incident MAFLD. However, the role of intrahepatic UA in MAFLD has not been investigated yet. Glucose transporter 9 (GLUT9) is a key transporter that mediates the uptake of UA in hepatocytes. METHODS: In this study, we first explored the clinical association between GLUT9 polymorphism and MAFLD. Blood samples of 247 male Chinese (127 were MAFLD patients) were collected and tested for the blood UA levels and genotype of the single nucleotide polymorphism (SNP) of GLUT9 (rs1014290). Next, Glut9 hepatic-specific knockout mice (Glut9Hep-ko) were generated to investigate the role of hepatic GLUT9 in MAFLD in male mice. RESULTS: We found that the GA/AA genotypes (rs1014290) were associated with elevated serum UA levels in MAFLD patients. Meanwhile, we found that Glut9Hep-ko mice displayed lower intrahepatic UA levels, down-regulated lipogenesis genes expressions, and attenuated MAFLD symptoms after 12 weeks of high-fat diet feeding, compared with Glut9Fl/Fl littermates. However, Glut9Hep-ko mice and wild-type littermates showed no significant difference on hepatic fatty acid oxidation or inflammation. CONCLUSIONS: Our results suggested that GLUT9 polymorphism was significantly associated with MAFLD, and hepatic-specific knockout of Glut9 significantly decreased intrahepatic contents and ameliorated diet-induced MAFLD in mice.

Pre-treatment with phages achieved greater protection of mice against infection with Shiga toxin-producing Escherichia coli than post-treatment.

Shiga toxin-producing Escherichia coli (STEC) is a group of pathogen that can cause various diseases in both humans and animals, such as watery diarrhea, hemorrhagic colitis, and uremia syndrome. Due to the serious situation of antibiotic resistance, phage therapy is considered to have a great potential in combating bacterial diseases. In this study, three phages (NJ-10, NJ-20, and NJ-38) with strong abilities to lyse virulent STEC strain CVCC193 cells in vitro were isolated. Subsequently, the therapeutic effects of the three phages were investigated in mice infected with CVCC193 cells. The results showed that the survival rates of mice injected with the phages at 3 h after challenge with CVCC193 cells were 40%-50%, while the survival rates of mice injected with the phages at 24 h before challenge were 80%-100%, indicating that pre-treatment with phages had better therapeutic effects than post-treatment. Pathological changes, bacterial loads in different organs, and serum levels of inflammatory factors of the infected mice were also detected. The results showed that the mice injected with the phages at 3 h after or 24 h before challenge with CVCC193 cells had significantly decreased organ lesions, bacterial loads, and serum levels of inflammatory factors as compared to infected mice without phage treatment. These results suggested that phages NJ-10, NJ-20, and NJ-38 can potentially protect against STEC infections.

Preliminary evaluation of different methods to detect and quantify Taenia eggs in sludge and water samples: A spiking experiment to assess recovery efficiency.

An improved understanding of the environmental transmission of Taenia spp. is key to control of the parasite. Methods to detect and quantify Taenia eggs in different environmental matrices, including sludge and water, currently lack performance validation with regard to the recovery efficiency and process ease of use. Therefore, this study aimed to assess the recovery efficiency and process duration of commonly used methods for the detection of Taenia eggs in sludge and water samples. Ten detection methods for Taenia spp. eggs were selected from a systematic review. Sludge and water samples were spiked with a high dose of Taenia saginata eggs, i.e., around 200 eggs/g sludge and 50 eggs/ml water, and were tested using five methods each. The two methods with the highest egg recovery efficiencies were selected per matrix for assessment with a lower spiking dose, i.e., 4 eggs/g sludge and 1 egg/ml water. Each time five replicates were used. Recovery efficiency was defined as the proportion of the number of eggs recovered to the total number of eggs spiked. Using the high spiking dose, all samples tested positive for all the methods. The mean egg recovery efficiency varied from 4% to 69% for sludge samples and from 3% to 68% for water samples. Using the lower spiking dose, one of the methods performed on sludge samples was able to detect all replicates, whereas only one replicate was positive using the other method. For water, all low dose samples tested positive using both methods. In conclusion, most methods performed inadequately in recovering Taenia eggs from sludge and water, with half of the methods performed on the high dose samples having a mean egg recovery efficiency of approximately 10% or less. The assessed recovery methods were generally time-consuming and labourious. A more thorough validation of existing recovery methods and improvement of method protocols to increase recovery efficiency is thus urgently needed.