Novel Hydrogel Adjuvant of Chinese Medicine External Preparations for Accelerated Healing of Deep Soft Tissue Injuries.

Traditional Chinese medicine external prescriptions have displayed excellent clinical effects for treating deep soft tissue injuries. However, the effects cannot be fully utilized due to the limitations of their dosage forms and usage methods. It is still a challenge to develop a satisfactory adjuvant of traditional Chinese medicine external prescriptions. Herein, a hydrogel adjuvant was prepared based on gallic acid coupled ε-poly-l-lysine and partially oxidized hyaluronic acid. The resulting adjuvant shows great physicochemical properties, low hemolysis rate (still much less than 5% at 5 mg/mL), excellent antibacterial ability (about 95% at 2 mg/mL), strong antioxidant ability (1.687 ± 0.085 mmol FeSO4/(g hydrogel) at 1 mg/mL), as well as outstanding biocompatibility. A clinically used Chinese medicine external preparation was selected as an example to investigate the effectiveness of the adjuvant in treating deep soft tissue injuries. The results show that the prescription can be evenly dispersed in the adjuvant. Moreover, the introduction of the prescription has not significantly changed these advanced properties of the adjuvant. Importantly, the hydrogel adjuvant significantly improves the effectiveness of the prescription in treating deep soft tissue injuries. This work offers an alternative approach to the development of a new-type adjuvant of Chinese medicine external preparations and also provides a new strategy for the combination of traditional Chinese medicine and hydrogel to treat clinical diseases.

Programmable, High-resolution Printing of Spatially Graded Perovskites for Multispectral Photodetectors.

Micro/nanostructured perovskites with spatially graded compositions and bandgaps are promising in filter-free, chip-level multispectral, and hyperspectral detection. However, achieving high-resolution patterning of perovskites with controlled graded compositions is challenging. Here, a programmable mixed electrohydrodynamic printing (M-ePrinting) technique is presented to realize the one-step direct-printing of arbitrary spatially graded perovskite micro/nanopatterns for the first time. M-ePrinting enables in situ mixing and ejection of solutions with controlled composition/bandgap by programmatically varying driving voltage applied to a multichannel nozzle. Composition can be graded over a single dot, line or complex pattern, and the printed feature size is down to 1 µm, which is the highest printing resolution of graded patterns to the knowledge. Photodetectors based on micro/nanostructured perovskites with halide ions gradually varying from Br to I are constructed, which successfully achieve multispectral detection and full-color imaging, with a high detectivity and responsivity of 3.27 × 1015 Jones and 69.88 A W-1, respectively. The presented method provides a versatile and competitive approach for such miniaturized bandgap-tunable perovskite spectrometer platforms and artificial vision systems, and also opens new avenues for the digital fabrication of composition-programmable structures.

Association of Serum AGR With All-Cause and Cause-Specific Mortality Among Individuals With Diabetes.

BACKGROUND: There is insufficient data to support a link between serum AGR and mortality in individuals with diabetes. This prospective study sought to investigate the relationship between serum AGR and all-cause and cause-specific mortality in adult diabetics. METHODS: This study included 8508 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using weighted Cox proportional hazards models. RESULTS: 2415 all-cause deaths, including 688 cardiovascular deaths and 413 cancer deaths, were recorded over an average of 9.61 years of follow-up. After multivariate adjustment, there was a significant and linear relationship between higher serum AGR levels and reduced all-cause and cause-specific mortality in a dose-response manner. The multivariate-adjusted HR and 95% CI for all-cause mortality (Ptrend<0.0001), cardiovascular mortality (Ptrend<0.001), and cancer mortality (Ptrend<0.01) were 0.51(0.42,0.60), 0.62(0.46,0.83), and 0.57(0.39,0.85), respectively, for individuals in the highest AGR quartile. There was a 73% decreased risk of all-cause death per one-unit rise in natural log-transformed serum AGR, as well as a 60% and 63% decreased risk of mortality from CVD and cancer, respectively (all P<0.001). Both the stratified analysis and the sensitivity analyses revealed the same relationships. CONCLUSIONS: AGR is a promising biomarker in risk predictions for long-term mortality in diabetic individuals, particularly in those under age 60 and heavy drinker.

Lineage-specific gene duplication and expansion of DUF1216 gene family in Brassicaceae.

Proteins containing domain of unknown function (DUF) are prevalent in eukaryotic genome. The DUF1216 proteins possess a conserved DUF1216 domain resembling to the mediator protein of Arabidopsis RNA polymerase II transcriptional subunit-like protein. The DUF1216 family are specifically existed in Brassicaceae, however, no comprehensive evolutionary analysis of DUF1216 genes have been performed. We performed a first comprehensive genome-wide analysis of DUF1216 proteins in Brassicaceae. Totally 284 DUF1216 genes were identified in 27 Brassicaceae species and classified into four subfamilies on the basis of phylogenetic analysis. The analysis of gene structure and conserved motifs revealed that DUF1216 genes within the same subfamily exhibited similar intron/exon patterns and motif composition. The majority members of DUF1216 genes contain a signal peptide in the N-terminal, and the ninth position of the signal peptide in most DUF1216 is cysteine. Synteny analysis revealed that segmental duplication is a major mechanism for expanding of DUF1216 genes in Brassica oleracea, Brassica juncea, Brassica napus, Lepidium meyneii, and Brassica carinata, while in Arabidopsis thaliana and Capsella rubella, tandem duplication plays a major role in the expansion of the DUF1216 gene family. The analysis of Ka/Ks (non-synonymous substitution rate/synonymous substitution rate) ratios for DUF1216 paralogous indicated that most of gene pairs underwent purifying selection. DUF1216 genes displayed a specifically high expression in reproductive tissues in most Brassicaceae species, while its expression in Brassica juncea was specifically high in root. Our studies offered new insights into the phylogenetic relationships, gene structures and expressional patterns of DUF1216 members in Brassicaceae, which provides a foundation for future functional analysis.

Exosomes derived from mesenchymal stem cells in diabetes and diabetic complications.

Diabetes, a group of metabolic disorders, constitutes an important global health problem. Diabetes and its complications place a heavy financial strain on both patients and the global healthcare establishment. The lack of effective treatments contributes to this pessimistic situation and negative outlook. Exosomes released from mesenchymal stromal cells (MSCs) have emerged as the most likely new breakthrough and advancement in treating of diabetes and diabetes-associated complication due to its capacity of intercellular communication, modulating the local microenvironment, and regulating cellular processes. In the present review, we briefly outlined the properties of MSCs-derived exosomes, provided a thorough summary of their biological functions and potential uses in diabetes and its related complications.

Effects of ESPCS mode nursing on the surgical tolerance, gastrointestinal tract recovery and self­management efficacy of patients with colon cancer.

Colon cancer is a common gastrointestinal malignant tumor. In addition to conventional treatment, thoughtful and comprehensive aftercare should be given to patients. The present study aimed to explore the effects of explain-simulate-practice-communication-support (ESPCS) model nursing on the surgical tolerance, gastrointestinal recovery and self-management efficacy of patients with colon cancer. The clinical data of 136 patients with colon cancer diagnosed and treated at the Second Affiliated Hospital of Harbin Medical University (Harbin, China) from June 2020 to April 2022 were retrospectively analyzed and a total of 84 patients met the inclusion criteria. A total of 42 patients who underwent conventional nursing were included in the conventional nursing group and 42 patients who underwent ESPCS model nursing were included in the ESPCS model nursing group. Surgical tolerance, gastrointestinal recovery, self-management efficacy (Cancer Self-Management Efficacy Scale), quality of life (Comprehensive Quality of Life Inventory-74) and nursing satisfaction were analyzed. Slightly higher proportions of excellent and good surgical tolerance were found in the ESPCS model nursing group (97.62%) compared with those in the conventional nursing group (85.71%); however, no significant difference was shown (P>0.05). Compared with the conventional nursing group, the time needed for gastric tube removal, bowel sound recovery, anal exhaust, first defecation, general food intake and the time until getting out of bed was significantly shorter in the ESPS model nursing group (all P<0.05). Before the intervention, no statistically significant difference was found between the indicators in the Cancer Self-Management Efficacy Scale of the two groups (all P>0.05). After the intervention, the ESPCS model nursing group had significantly higher scores for positive attitude, stress relief and self-determination than the conventional nursing group (all P<0.05). Before intervention, there was no statistically significant difference in the indicators of CQOLI-74 between the two groups (P>0.05). After the intervention, the ESPCS model nursing group also had significantly higher scores for social function, psychological function, life state and somatic function compared with the conventional nursing group (all P<0.05). Higher satisfaction of patients was found in the ESPCS mode group (95.24%) compared with that in the conventional nursing group (78.57%) (P<0.05). Overall, ESPCS mode nursing could effectively elevate the surgical tolerance of patients with colon cancer, promote the recovery of gastrointestinal function, increase self-management efficacy, and improve the quality of life and nursing satisfaction, which is certainly worthy of clinical promotion.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

ETV2 regulating PHD2-HIF-1α axis controls metabolism reprogramming promotes vascularized bone regeneration.

The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration. Adequate energy production forms the cornerstone supporting new bone formation. ETS variant 2 (ETV2) has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis. In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells (DPSCs) by regulating the ETV2- prolyl hydroxylase 2 (PHD2)- hypoxia-inducible factor-1α (HIF-1α)- vascular endothelial growth factor A (VEGFA) axis. Notably, ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis, thus fulfilling the energy requirements essential to expedite osteogenic differentiation. Furthermore, decreased α-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction. Additionally, we engineered hydroxyapatite/chitosan microspheres (HA/CS MS) with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation. Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration. In summary, this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.

Computational-aided analysis of the pathway and mechanism of dichloroacetonitrile formation from phenylalanine upon chloramination.

Dichloroacetonitrile (DCAN) is an emerging disinfection by-product (DBP) that is widespread in drinking water. However, the pathway for DCAN formation from aromatic amino acids remains unclear, leading to a lack of an understanding of its explicit fate during chloramination. In this study, we investigated the specific formation mechanism of DCAN during the chloramination of phenylalanine based on reaction kinetics and chemical thermodynamics. The reason for differences between aldehyde and decarboxylation pathways was explained, and kinetic parameters of the pathways were obtained through quantum chemistry calculations. The results showed that the reaction rate constant of the rate-limiting step of the aldehyde pathway with 1.9 × 10-11 s-1 was significantly higher than that of decarboxylation (3.6 × 10-16 s-1 M-1), suggesting that the aldehyde pathway is the main reaction pathway for DCAN formation during the chloramination of phenylalanine to produce DCAN. Subsequently, theoretical calculations were performed to elucidate the effect of pH on the formation mechanism, which aligned well with the experimental results. Dehydrohalogenation was found to be the rate-limiting step under acidic conditions with reaction rate constants higher than those of the rate-limiting step (expulsion of amines) under neutral conditions, increasing the rate of DCAN formation. This study highlights the differences in DCAN formation between the decarboxylation and aldehyde pathways during the chloramination of precursors at both molecular and kinetic levels, contributing to a comprehensive understanding of the reaction mechanisms by which aromatic free amino acids generate DCAN.

Construction of an infectious clone for enterovirus A89 and mutagenesis analysis of viral infection and cell binding.

Enterovirus A89 (EV-A89) is an unconventional strain belonging to the Enterovirus A species. Limited research has been conducted on EV-A89, leaving its biological and pathogenic properties unclear. Developing reverse genetic tools for EV-A89 would help to unravel its infection mechanisms and aid in the development of vaccines and anti-viral drugs. In this study, an infectious clone for EV-A89 was successfully constructed and recombinant enterovirus A89 (rEV-A89) was generated. The rEV-A89 exhibited similar characteristics such as growth curve, plaque morphology, and dsRNA expression with parental strain. Four amino acid substitutions were identified in the EV-A89 capsid, which were found to enhance viral infection. Mechanistic studies revealed that these substitutions increased the virus's cell-binding ability. Establishing reverse genetic tools for EV-A89 will significantly contribute to understanding viral infection and developing anti-viral strategies.IMPORTANCEEnterovirus A species contain many human pathogens and have been classified into conventional cluster and unconventional cluster. Most of the research focuses on various conventional members, while understanding of the life cycle and infection characteristics of unconventional viruses is still very limited. In our study, we constructed the infectious cDNA clone and single-round infectious particles for the unconventional EV-A89, allowing us to investigate the biological properties of recombinant viruses. Moreover, we identified key amino acids residues that facilitate EV-A89 infection and elucidate their roles in enhancing viral binding to host cells. The establishment of the reverse genetics system will greatly facilitate future study on the life cycle of EV-A89 and contribute to the development of prophylactic vaccines and anti-viral drugs.

Network pharmacology and molecular docking to explore the mechanism of a clinical proved recipe for external use of clearing heat and removing dampness in the treatment of immune-related cutaneous adverse events.

Immune-related cutaneous adverse events (ircAEs) will undermine the patients' quality of lives, and interrupt the antitumor therapy. A clinical proved recipe for external use of clearing heat and removing dampness (Qing-Re-Li-Shi Formula, hereinafter referred to as "QRLSF") is beneficial to the treatment of ircAEs in clinical practice. Our study will elucidate the mechanism of QRLSF against ircAEs based on network pharmacology and molecular docking. The active components and corresponding targets of QRLSF were collected through traditional Chinese medicine systems pharmacology database. GeneCards, online Mendelian inheritance in man, and pharmacogenomics knowledgebase were used to screen the targets of ircAEs. The intersecting targets between drug and disease were acquired by venn analysis. Cytoscape software was employed to construct "components-targets" network. Search tool for the retrieval of interacting genes/proteins database was applied to establish the protein-protein interaction network and then its core targets were identified. Gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed to predict the mechanism. The molecular docking verification of key targets and related phytomolecules was accomplished by AutoDock Vina software. Thirty-nine intersecting targets related to QRLSF against ircAEs were recognized. The analysis of network clarified 5 core targets (STAT3, RELA, TNF, TP53, and NFKBIA) and 4 key components (quercetin, apigenin, luteolin, and ursolic acid). The activity of QRLSF against ircAEs could be attributed to the regulation of multiple biological effects via multi-pathways (PI3K-Akt pathway, cytokine-cytokine receptor interaction, JAK-STAT pathway, chemokine pathway, Th17 cell differentiation, IL-17 pathway, TNF pathway, and Toll-like receptor pathway). The binding activities were estimated as good level by molecular docking. These discoveries disclosed the multi-component, multi-target, and multi-pathway characteristics of QRLSF against ircAEs, providing a new strategy for such medical problem.

CircRNA: a rising therapeutic strategy for lung injury induced by pulmonary toxicants.

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.

Facile Solid-State Chemical Synthesis of CoMoO4 Nanorods for High-Performance Supercapacitors.

The development of electrode materials with excellent performance serves as the key for researchers to enhance the energy density of supercapacitors. Cobalt molybdate (CoMoO4) nanomaterials have been regarded as one of the most prospective electrode materials for supercapacitors due to their high theoretical capacitance and excellent electrical conductivity. In this paper, three kinds of CoMoO4 nanorods were prepared directly via simple and environmentally friendly solid-phase chemical reactions with solid inorganic salts as raw materials. According to X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) test results, different reagents had certain effects on the size and morphology of CoMoO4, and these affected its electrochemical performance. In particular, the samples prepared with Co(NO3)2·6H2O as raw material took on a more uniform micromorphology, with a better crystallinity. Simultaneously, electrochemical test results showed that the samples synthesized with Co(NO3)2·6H2O presented relatively good electrical conductivity and a large specific capacitance (177 F g-1). This may be due to the nitrates reacting more slowly during the reaction and the crystals having difficulty aggregating during growth. Therefore, the structure of the prepared CoMoO4 nanomaterial was more uniform, and it was resistant to collapse during the charging and discharging process; thus, the capacitor presents the best performance.

Integration of HiBiT into enteroviruses: A universal tool for advancing enterovirus virology research.

The utilization of enteroviruses engineered with reporter genes serves as a valuable tool for advancing our understanding of enterovirus biology and its applications, enabling the development of effective therapeutic and preventive strategies. In this study, our initial attempts to introduce a NanoLuc luciferase (NLuc) reporter gene into recombinant enteroviruses were unsuccessful in rescuing viable progenies. We hypothesized that the size of the inserted tag might be a determining factor in the rescue of the virus. Therefore, we inserted the 11-amino-acid HiBiT tag into the genomes of enterovirus A71 (EV-A71), coxsackievirus A10 (CVA10), coxsackievirus A7 (CVA7), coxsackievirus A16 (CVA16), namely EV-A71-HiBiT, CVA16-HiBiT, CVA10-HiBiT, CVA7-HiBiT, and observed that the HiBiT-tagged viruses exhibited remarkably high rescue efficiency. Notably, the HiBiT-tagged enteroviruses displayed comparable characteristics to the wild-type viruses. A direct comparison between CVA16-NLuc and CVA16-HiBiT recombinant viruses revealed that the tiny HiBiT insertion had minimal impact on virus infectivity and replication kinetics. Moreover, these HiBiT-tagged enteroviruses demonstrated high genetic stability in different cell lines over multiple passages. In addition, the HiBiT-tagged viruses were successfully tested in antiviral drug assays, and the sensitivity of the viruses to drugs was not affected by the HiBiT tag. Ultimately, our findings provide definitive evidence that the integration of HiBiT into enteroviruses presents a universal, convenient, and invaluable method for advancing research in the realm of enterovirus virology. Furthermore, HiBiT-tagged enteroviruses exhibit great potential for diverse applications, including the development of antivirals and the elucidation of viral infection mechanisms.

Preparation and Peculiar Magnetic Properties at Low Temperatures of La1.85Sr0.15CuO4 Nanofibers.

Herein, the preparation process, morphology, structure, and magnetic properties of La1.85Sr0.15CuO4 (LSCO) cobweb-like nanofibers are reported. LSCO nanofibers with a regular grain size distribution are successfully prepared via electrospinning, followed by calcination. We conducted morphology analysis and elemental distribution using electron microscopy and energy-dispersive X-ray spectroscopy (EDS), respectively. Additionally, magnetic property testing was performed using a vibrating sample magnetometer (VSM) to confirm the superconducting properties of the samples. Interestingly, our samples exhibited a superconducting transition temperature, Tc, of 25.21 K, which showed some disparity compared to similar works. Furthermore, we observed a ferromagnetic response at low temperatures in the superconducting nanofibers. We attribute these phenomena to the effects generated by surface states of nanoscale superconducting materials.

Hydrogen peroxide sulfenylates and inhibits the photorespiratory enzyme PGLP1 to modulate plant thermotolerance.

Climate change is resulting in more frequent and rapidly changing temperatures at both extremes that severely affect the growth and production of plants, particularly crops. Oxidative stress caused by high temperatures is one of the most damaging factors for plants. However, the role of hydrogen peroxide (H2O2) in modulating plant thermotolerance is largely unknown, and the regulation of photorespiration essential for C3 species remains to be fully clarified. Here, we report that heat stress promotes H2O2 accumulation in chloroplasts and that H2O2 stimulates sulfenylation of the chloroplast-localized photorespiratory enzyme 2-phosphoglycolate phosphatase 1 (PGLP1) at cysteine 86, inhibiting its activity and promoting the accumulation of the toxic metabolite 2-phosphoglycolate. We also demonstrate that PGLP1 has a positive function in plant thermotolerance, as PGLP1 antisense lines have greater heat sensitivity and PGLP1-overexpressing plants have higher heat-stress tolerance than the wild type. Together, our results demonstrate that heat-induced H2O2 in chloroplasts sulfenylates and inhibits PGLP1 to modulate plant thermotolerance. Furthermore, targeting CATALASE2 to chloroplasts can largely prevent the heat-induced overaccumulation of H2O2 and the sulfenylation of PGLP1, thus conferring thermotolerance without a plant growth penalty. These findings reveal that heat-induced H2O2 in chloroplasts is important for heat-caused plant damage.

Enniatin B1 induces damage to Leydig cells via inhibition of the Nrf2/HO-1 and JAK/STAT3 signaling pathways.

Enniatin B1 (ENN B1) is a mycotoxin that can be found in various foods. However, whether ENN B1 is hazardous to the reproductive system is still elusive. Leydig cells are testosterone-generating cells that reside in the interstitial compartment between seminiferous tubules. Dysfunction of Leydig cells could result in male infertility. This study aimed to examine the toxicological effects of ENN B1 against TM3 Leydig cells. ENN B1 significantly inhibited cell viability in a dose-dependent manner. ENN B1 treatment also decreased the expression of functional genes in Leydig cells. Moreover, ENN B1 induced Leydig cells apoptosis and oxidative stress. Mechanistically, ENN B1 leads to the upregulation of Bax and downregulation of Bcl-2 in Leydig cells. In addition, ENN B1 inhibited the Nrf2/HO-1 pathway, which is critical for the induction of oxidative stress. Additionally, ENN B1 treatment repressed the JAK/STAT3 signaling pathway in Leydig cells. Rescue experiments showed that activation of STAT3 resulted in alleviation of ENN B1-induced damage in Leydig cells. Collectively, our study demonstrated that ENN B1 induced Leydig cell dysfunction via multiple mechanisms.

L-arginine attenuates Streptococcus uberis-induced inflammation by decreasing miR155 level.

L-arginine, as an essential substance of the immune system, plays a vital role in innate immunity. MiR155, a multi-functional microRNA, has gained importance as a regulator of homeostasis in immune cells. However, the immunoregulatory mechanism between L-arginine and miR155 in bacterial infections is unknown. Here, we investigated the potential role of miR155 in inflammation and the molecular regulatory mechanisms of L-arginine in Streptococcus uberis (S. uberis) infections. And we observed that miR155 was up-regulated after infection, accompanying the depletion of L-arginine, leading to metabolic disorders of amino acids and severe tissue damage. Mechanically, the upregulated miR155 mediated by the p65 protein played a pro-inflammatory role by suppressing the suppressor of cytokine signaling 6 (SOCS6)-mediated p65 ubiquitination and degradation. This culminated in a violently inflammatory response and tissue damage. Interestingly, a significant anti-inflammatory effect was revealed in L-arginine supplementation by reducing miR155 production via inhibiting p65. This work firstly uncovers the pro-inflammatory role of miR155 and an anti-inflammatory mechanism of L-arginine in S.uberis infection with a mouse mastitis model. Collectively, we provide new insights and strategies for the prevention and control of this important pathogen, which is of great significance for ensuring human food health and safety.

Phenazine biosynthesis protein MoPhzF regulates appressorium formation and host infection through canonical metabolic and noncanonical signaling function in Magnaporthe oryzae.

Microbe-produced secondary metabolite phenazine-1-carboxylic acid (PCA) facilitates pathogen virulence and defense mechanisms against competitors. Magnaporthe oryzae, a causal agent of the devastating rice blast disease, needs to compete with other phyllosphere microbes and overcome host immunity for successful colonization and infection. However, whether M. oryzae produces PCA or it has any other functions remains unknown. Here, we found that the MoPHZF gene encodes the phenazine biosynthesis protein MoPhzF, synthesizes PCA in M. oryzae, and regulates appressorium formation and host virulence. MoPhzF is likely acquired through an ancient horizontal gene transfer event and has a canonical function in PCA synthesis. In addition, we found that PCA has a role in suppressing the accumulation of host-derived reactive oxygen species (ROS) during infection. Further examination indicated that MoPhzF recruits both the endoplasmic reticulum membrane protein MoEmc2 and the regulator of G-protein signaling MoRgs1 to the plasma membrane (PM) for MoRgs1 phosphorylation, which is a critical regulatory mechanism in appressorium formation and pathogenicity. Collectively, our studies unveiled a canonical function of MoPhzF in PCA synthesis and a noncanonical signaling function in promoting appressorium formation and host infection.

Diagnostic value of liver stiffness measurement combined with risk scores for esophagogastric variceal bleeding in patients with hepatitis B cirrhosis.

PURPOSE: To assess the predictive value of liver stiffness measurement (LSM) and three bleeding risk scoring systems for esophagogastric varices bleeding (EGVB) in patients with hepatitis B cirrhosis during hospitalization. METHODS: In this study, 210 patients who had hepatitis B cirrhosis were selected as the subjects. They were categorized into two groups based on whether EGVB occurred during hospitalization: a bleeding group (70 cases) and a non-bleeding group (140 cases). Logistic regression was used to analyze the factors related to the occurrence of EGVB, and the diagnostic performance was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: Significant differences were observed between the two groups in systolic blood pressure, platelet count, albumin, urea nitrogen, LSM, pre-endoscopic Rockall score (PRS), Glasgow-Blatchford score (GBS), and AIMS65 score (P < 0.05). The correlation analysis showed that LSM had significant positive relationship with PRS, GBS and AIMS65 score. Logistic regression analysis revealed that LSM and GBS score were independent risk factors for EGVB occurrence during hospitalization. ROC curve analysis showed that the combined prediction model of LSM and GBS score had the best prediction performance for EGVB occurrence, with an ROC curve area of 0.811, which was significantly better than the three risk scoring systems (P < 0.05), but similar to the predicted value of LSM (P = 0.335). CONCLUSIONS: The combination of LSM and GBS score can significantly improve the predictive efficacy of EGVB occurrence in patients with hepatitis B cirrhosis during hospitalization, which has important clinical significance for patients' prognosis.