Protective effect of soluble dietary fiber from Rosa roxburghii Tratt residue on dextran sulfate sodium-induced ulcerative colitis by regulating serum metabolism and NF-κB pathway in mice.

BACKGROUND: Ulcerative colitis (UC) refers to an idiopathic chronic inflammatory bowel disease that start with inflammation of the intestinal mucosa. Dietary fiber plays a crucial role in maintaining the normal architecture of the intestinal mucosa. In this study, the protective effect and potential mechanism of soluble dietary fiber from Rosa roxburghii Tratt residue (SDFR) on dextran sulfate sodium (DSS)-induced UC mice were explored. RESULTS: The results revealed that SDFR could ameliorate the body weight loss and pathological injury, improve the structure and crypt destruction in colon in DSS-induced mice. Moreover, the levels of NO, IL-1ß, TNF-α, MPO, and protein expression of iNOS and COX-2 were decreased after administration of SDFR. Notably, nontargeted metabolomics analysis indicated that there were significant differences in 51 potential metabolites in serum between the DSS and control groups. SDFR intervention could regulate aberrant alterations of these metabolites and mitigate UC via regulating metabolic pathway, including arachidonic acid and glycerophospholipid metabolism. CONCLUSION: This study provides novel evidence that SDFR could be used as a potential modulator to relieve the UC, and also the results provide theoretical basis for the utilization of by-products in Rosa roxburghii Tratt fruit processing. This article is protected by copyright. All rights reserved.

ZMIZ1 Regulates Proliferation, Autophagy and Apoptosis of Colon Cancer Cells by Mediating Ubiquitin-Proteasome Degradation of SIRT1.

There are nearly 1.15 million new cases of colon cancer, as well as 586,858 deaths from colon cancer worldwide in 2020. The aim of this study is to reveal whether ZMIZ1 can control the fate of colon cancer cells and the mechanism by which it functions. Specific shRNA transfection was used to knock down the expression of ZMIZ1 in colon cancer cell lines (HCT116 and HT29), and cell proliferation was detected using EdU and CCK-8 reagents, apoptosis by flow cytometry, and autophagy by western blot. The interaction of ZMIZ1 and SIRT1 was analyzed. Knockdown of ZMIZ1 significantly inhibited autophagy and proliferation, and induced apoptosis of HCT116 and HT29 cells. The mRNA level of SIRT1 was not affected by ZMIZ1 knockdown, but the protein level of SIRT1 was significantly decreased and the protein level of the SIRT1-specific substrate, acetylated FOXO3a, was reduced. Immunoprecipitation assays identified the interaction between SIRT1 and ZMIZ1 in HCT116 and HT29 cells. ZMIZ1 increased intracellular ubiquitination of SIRT1. Knockdown or pharmacological inhibition of SIRT1 neutralized the effects of ZMIZ knockdown on proliferation, autophagy and apoptosis in HCT116 and HT29 cells. ZMIZ1 may control the fate of colon cancer cells through the SIRT1/FOXO3a axis. Targeting ZMIZ1 would be beneficial for the treatment of colon cancer.

Exploring the effect of Anshen Dingzhi prescription on hippocampal mitochondrial signals in single prolonged stress mouse model.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Anshen Dingzhi prescription (ADP), which was first published in the masterpiece of traditional Chinese Medicine in the Qing Dynasty, "Yi Xue Xin Wu" (1732 CE), is documented to interrupt panic-related disorders. However, the mechanism of its action is still not clear. AIM OF THE STUDY: This study aims to investigate the effects of ADP on post-traumatic stress disorder (PTSD)-like behaviors and explore the mechanism from perspective of sirtuin1 (SIRT1)-peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α)-dependent mitochondrial function. MATERIALS AND METHODS: The changes of SIRT1-PGC-1α signal and mitochondrial function were evaluated in the hippocampus of mice receiving single prolonged stress (SPS). Later, the roles of this signaling pathway played in fear memory generalization and anxiety-like behavior in SPS mice was investigated using two agonists of this signaling pathway. On this basis, the effects of ADP (36.8 mg/kg) with definite therapeutic effects, on mitochondrial function were investigated and further confirmed by a SIRT1 inhibitor. Finally, the possible components of ADP targeting PGC-1α were monitored through bioinformatics. RESULTS: Compared with control mice, SIRT1-PGC-1α signal in the hippocampus was impaired in SPS mice, accompanied with dysfunction of mitochondria and abnormal expression of synaptic proteins. The agonists of SIRT1-PGC-1α signal, ZLN005, as well as resveratrol improved the behavioral changes of mice caused by SPS, reversed the decline of proteins in SIRT1-PGC-1α signal, mitochondrial dysfunction, and the abnormal expression of synaptic proteins. The fingerprint was established for the quality control of ADP. At a dose of 36.8 mg/kg, ADP could prevent fear memory generalization and anxiety-like behavior in SPS mice. Mechanically, ADP promoted SIRT1-PGC-1α signal and repaired mitochondrial function. Importantly, SIRT1 inhibitor, selisistat eliminated the ameliorative effects of ADP on behavioral and mitochondrial function. Through molecular docking simulation, the brain-entering components of ADP, including malkangunin, Rg5, fumarine, frutinone A, celabenzine, and inermin had high binding energy with PGC-1α. CONCLUSION: Dysfunction of SIRT1-PGC-1α-dependent mitochondrial function is attributed to SPS-triggered fear generalization and anxiety-like behavior, and ADP could improve PTSD-like behaviors likely through activating this signaling pathway.

Highly efficient identification of nucleocytoplasmic O-glycosylation by the TurboID-based proximity labeling method in living cells.

Glycosylation is a ubiquitous posttranslational modification and plays an important role in many processes, such as protein stability, folding, processing, and trafficking. Among glycosylation types, O-glycosylation is difficult to analyze due to the complex glycan composition, low abundance and lack of glycosidases to remove the O-glycans. Many methods have been applied to analyze the O-glycosylation of membrane glycoproteins and secreted glycoproteins since the synthesis of O-glycosylation occurred in the Golgi apparatus. In recent years, some O-glycosylation has been reported in the nucleus. In this work, we present a proximity labeling strategy based on TurboID by combining core 1 ß1-3 galactosyltransferase (C1GalT1), which has been reported in the nucleus, to characterize nucleocytoplasmic O-glycosylation in living HeLa cells. The O-glycosylated protein C1GalT1 was biotinylated by the proximity labeling method in living HeLa cells overexpressing C1GalT1 fused by TurboID and enriched by streptavidin-coated beads. Following digestion with trypsin and mass spectrometry analysis, 68 high-confidence and 298 putative O-glycosylated sites were identified on 366 peptides mapped to 267 proteins. These results indicated that the proximity labeling method is a highly efficient technique to identify O-glycosylation. Furthermore, the finding of abundant O-glycosylation from nucleocytoplasmic proteins indicates a new pathway of O-glycosylation synthesis in cells.

A comparative study of treatment of cervical low-grade squamous intraepithelial lesions (LSIL).

BACKGROUND AND AIMS: Low-grade squamous intraepithelial lesion (LSIL) is one of two categories of cervical intraepithelial lesions. Given that controversy exists regarding its management, this comparative study aimed to evaluate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating LSIL of the high-risk human papillomavirus (HR-HPV)-infected cervix. METHODS: A total of 218 patients (25-45 years old) with cervical LSIL associated with HR-HPV who underwent ALA-PDT, loop electrosurgical excision procedure (LEEP), or observation only were included. The clearance rates of cervical LSIL and HR-HPV between the ALA-PDT, LEEP, and observation groups were compared at 6 and 12 months follow-up. Adverse reactions were also compared. The factors affecting the clearance on ALA-PDT of cervical LSIL were evaluated. RESULTS: There were no statistically significant differences in lesion and HR-HPV clearance rates between the ALA-PDT and LEEP groups at 6 and 12 months. However, the lesion and HR-HPV clearance rates were significantly higher in the ALA-PDT group than that in the observation group. The adverse reaction rate was significantly lower in the ALA-PDT group than in the LEEP group. CONCLUSION: For patients with cervical LSIL, the lesion and HR-HPV clearance rates after ALA-PDT were close to those after LEEP and significantly higher than in the observation group. Moreover, the adverse reaction rate for ALA-PDT was much lower than that for LEEP. Therefore, ALA-PDT provides a new option for the minimally invasive treatment of cervical LSIL.

A systematic review and meta-analysis of prognostic indicators in patients with head and neck malignancy treated with immune checkpoint inhibitors.

INTRODUCTION: Tumor immunotherapy has recently emerged as a crucial focal point in oncology treatment research. Among tumor immunotherapy approaches, tumor immune checkpoint inhibitors (ICIs) have attracted substantial attention in clinical research. However, this treatment modality has benefitted only a limited number of patients. We conducted a meta-analysis of various biomarkers to decipher their prognostic implications in patients with head and neck squamous cell carcinoma (HNSCC) who are treated with ICIs, and thus identify predictive markers with practical clinical relevance. METHODS: A systematic search of electronic databases was conducted to identify clinical studies that examined the correlation between biomarkers and treatment outcomes in the HNSCC patients. The included articles were screened and analyzed to extract data regarding overall survival (OS) and progression-free survival (PFS). RESULTS: The relationship between the biomarkers included in the summary and prognosis was as follows: HPV positivity was associated with improved OS (HR = 0.76, 95% CI = 0.58-1.99), PFS (HR = 1.16, 95% CI = 0.81-1.67), and response (OR = 1.67, 95% CI = 1.37-2.99). PD-L1 positivity was associated with OS (HR = 0.71, 95% CI = 0.59-0.85), PFS (HR = 0.56 95% CI = 0.43-0.73), and response (OR = 2.16, 95% CI = 1.51-3.10). Neither HPV positivity nor PD-L1 positivity was associated with DCR. The following markers were collected for OS and PFS data and were associated with longer OS: lower Glasgow prognostic score (GPS/mGPS) grading, lower PS grading, high body mass index (BMI), low neutrophil-to-lymphocyte ratio (NLR), low platelet-to-lymphocyte ratio (PLR), high albumin (Alb), low lactate dehydrogenase (LDH). Factors associated with better PFS were lower GPS/mGPS grading, lower PS grading, high BMI, low NLR, high absolute lymphocyte count, and low LDH. Hyperprogressive disease was associated with worse OS and PFS. Fewer clinical studies have been completed on the tumor microenvironment and hypoxia, microsatellite instability/DNA mismatch repair, and microbiome and systematic analysis is difficult. CONCLUSION: In our meta-analysis, different immune checkpoint factors were associated with different prognoses in HNSCC patients receiving immunotherapy. HPV, PD-L1, BMI, Alb, HPD, PS, GPS/mGPS, LDH, NLR, and PLR predicted the ICI outcome in HNSCC patients.

Identification of an APOE ε4-specific blood-based molecular pathway for Alzheimer's disease risk.

INTRODUCTION: The precise apolipoprotein E (APOE) ε4-specific molecular pathway(s) for Alzheimer's disease (AD) risk are unclear. METHODS: Plasma protein modules/cascades were analyzed using weighted gene co-expression network analysis (WGCNA) in the Alzheimer's Disease Neuroimaging Initiative study. Multivariable regression analyses were used to examine the associations among protein modules, AD diagnoses, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), and brain glucose metabolism, stratified by APOE genotype. RESULTS: The Green Module was associated with AD diagnosis in APOE ε4 homozygotes. Three proteins from this module, C-reactive protein (CRP), complement C3, and complement factor H (CFH), had dose-dependent associations with CSF p-tau and cognitive impairment only in APOE ε4 homozygotes. The link among these three proteins and glucose hypometabolism was observed in brain regions of the default mode network (DMN) in APOE ε4 homozygotes. A Framingham Heart Study validation study supported the findings for AD. DISCUSSION: The study identifies the APOE ε4-specific CRP-C3-CFH inflammation pathway for AD, suggesting potential drug targets for the disease.Highlights: Identification of an APOE ε4 specific molecular pathway involving blood CRP, C3, and CFH for the risk of AD.CRP, C3, and CFH had dose-dependent associations with CSF p-Tau and brain glucose hypometabolism as well as with cognitive impairment only in APOE ε4 homozygotes.Targeting CRP, C3, and CFH may be protective and therapeutic for AD onset in APOE ε4 carriers.

Pioneering Enhanced Corrosion Resistance along the Normal Plane of an Ultra-Light Mg-Li Extruded Sheet.

The microstructure and corrosion anisotropy of the Mg-5Li extruded sheet were investigated in this work. Three distinct samples cut from the normal plane (A), longitudinal plane (B), and cross-sectional plane (C) of the as-extruded sheet were prepared. The microstructure was analyzed using optical microscopy (OM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The corrosion resistance and behaviors of the three samples in a 0.1 mol/L NaCl solution were evaluated by employing hydrogen evolution, mass loss testing, electrochemical assessments, and corrosion morphology analyses. The results revealed that sample A displayed a distinctive bimodal (0002) basal texture, along with clearly distinguishably larger grain sizes than the other samples. The effect of grain size and crystallographic orientation on the corrosion resistance was highlighted, indicating the pioneering corrosion resistance of sample A and the lowest corrosion resistance of sample C. Furthermore, all three samples exhibited the characteristic filiform corrosion during the initial stages of corrosion, progressing into the formation of corrosion pits, with sample C displaying pronounced susceptibility.

ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids.

Neuron-derived extracellular vesicles (NDEVs) are potential biomarkers of neurological diseases although their reliable molecular target is not well established. Here, we demonstrate that ATPase Na+/K+ transporting subunit alpha 3 (ATP1A3) is abundantly expressed in extracellular vesicles (EVs) isolated from induced human neuron, brain, cerebrospinal fluid, and plasma in comparison with the presumed NDEV markers NCAM1 and L1CAM by using super-resolution microscopy and biochemical assessments. Proteomic analysis of immunoprecipitated ATP1A3+ brain-derived EVs shows higher enrichment of synaptic markers and cargo proteins relevant to Alzheimer's disease (AD) compared to NCAM1+ or LICAM+ EVs. Single particle analysis shows the elevated amyloid-ß positivity in ATP1A3+ EVs from AD plasma, providing better diagnostic prediction of AD over other plasma biomarkers. Thus, ATP1A3 is a reliable target to isolate NDEV from biofluids for diagnostic research.

Comprehensive characterization of human brain-derived extracellular vesicles using multiple isolation methods: Implications for diagnostic and therapeutic applications.

Extracellular vesicles (EVs) have emerged as critical mediators of intercellular communication and promising biomarkers and therapeutics in the central nervous system (CNS). Human brain-derived EVs (BDEVs) provide a comprehensive snapshot of physiological changes in the brain's environment, however, the isolation of BDEVs and the comparison of different methods for this purpose have not been fully investigated. In this study, we compared the yield, morphology, subtypes and protein cargo composition of EVs isolated from the temporal cortex of aged human brains using three established separation methods: size-exclusion chromatography (SEC), phosphatidylserine affinity capture (MagE) and sucrose gradient ultracentrifugation (SG-UC). Our results showed that SG-UC method provided the highest yield and collected larger EVs compared to SEC and MagE methods as assessed by transmission electron microscopy and nanoparticle tracking analysis (NTA). Quantitative tandem mass-tag (TMT) mass spectrometry analysis of EV samples from three different isolation methods identified a total of 1158 proteins, with SG-UC showing the best enrichment of common EV proteins with less contamination of non-EV proteins. In addition, SG-UC samples were enriched in proteins associated with ATP activity and CNS maintenance, and were abundant in neuronal and oligodendrocytic molecules. In contrast, MagE samples were more enriched in molecules related to lipoproteins, cell-substrate junction and microglia, whereas SEC samples were highly enriched in molecules related to extracellular matrix, Alzheimer's disease and astrocytes. Finally, we validated the proteomic results by performing single-particle analysis using the super-resolution microscopy and flow cytometry. Overall, our findings demonstrate the differences in yield, size, enrichment of EV cargo molecules and single EV assay by different isolation methods, suggesting that the choice of isolation method will have significant impact on the downstream analysis and protein discovery.

Corrigendum: Advanced NSCLC patients with EGFR T790M harbouring TP53 R273C or KRAS G12V cannot benefit from osimertinib based on a clinical multicentre study by tissue and liquid biopsy.

[This corrects the article DOI: 10.3389/fonc.2021.621992.].

Effect of Lankford Coefficients on Springback Behavior during Deep Drawing of Stainless Steel Cylinders.

Accurate prediction of springback is increasingly required during deep-drawing formation of anisotropic stainless steel sheets. The anisotropy of sheet thickness direction is very important for predicting the springback and final shape of a workpiece. The effect of Lankford coefficients (r00, r45, r90) with different angles on springback was investigated using numerical simulation and experiments. The results show that the Lankford coefficients with different angles each have a different influence on springback. The diameter of the straight wall of the cylinder along the 45-degree direction decreased after springback, and showed a concave valley shape. The Lankford coefficient r90 had the greatest effect on the bottom ground springback, followed by r45 and then r00. A correlation was established between the springback of workpiece and Lankford coefficients. The experimental springback values were obtained by using a coordinate-measuring machine and showed good agreement with the numerical simulation results.

FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases.

Forkhead box (FOX) proteins are a wing-like helix family of transcription factors in the DNA-binding region. By mediating the activation and inhibition of transcription and interactions with all kinds of transcriptional co-regulators (MuvB complexes, STAT3, ß-catenin, etc.), they play significant roles in carbohydrate and fat metabolism, biological aging and immune regulation, development, and diseases in mammals. Recent studies have focused on translating these essential findings into clinical applications in order to improve quality of life, investigating areas such as diabetes, inflammation, and pulmonary fibrosis, and increase human lifespan. Early studies have shown that forkhead box M1 (FOXM1) functions as a key gene in pathological processes in multiple diseases by regulating genes related to proliferation, the cell cycle, migration, and apoptosis and genes related to diagnosis, therapy, and injury repair. Although FOXM1 has long been studied in relation to human diseases, its role needs to be elaborated on. FOXM1 expression is involved in the development or repair of multiple diseases, including pulmonary fibrosis, pneumonia, diabetes, liver injury repair, adrenal lesions, vascular diseases, brain diseases, arthritis, myasthenia gravis, and psoriasis. The complex mechanisms involve multiple signaling pathways, such as WNT/ß-catenin, STAT3/FOXM1/GLUT1, c-Myc/FOXM1, FOXM1/SIRT4/NF-κB, and FOXM1/SEMA3C/NRP2/Hedgehog. This paper reviews the key roles and functions of FOXM1 in kidney, vascular, lung, brain, bone, heart, skin, and blood vessel diseases to elucidate the role of FOXM1 in the development and progression of human non-malignant diseases and makes suggestions for further research.

Suppressing Viscous Fingering in Porous Media with Wetting Gradient.

The viscous fingering phenomenon often occurs when a low-viscosity fluid displaces a high-viscosity fluid in a homogeneous porous media, which is an undesirable displacement process in many engineering applications. The influence of wetting gradient on this process has been studied over a wide range of capillary numbers (7.5 × 10-6 to 1.8 × 10-4), viscosity ratios (0.0025 to 0.04), and porosities (0.48 to 0.68), employing the lattice Boltzmann method. Our results demonstrate that the flow front stability can be improved by the gradual increase in wettability of the porous media. When the capillary number is less than 3.5 × 10-5, the viscous fingering can be successfully suppressed and the transition from unstable to stable displacement can be achieved by the wetting gradient. Moreover, under the conditions of high viscosity ratio (M > 0.01) and large porosity (Φ > 0.58), wetting gradient improves the stability of the flow front more significantly.

CD31 as a probable responding and gate-keeping protein of the blood-brain barrier and the risk of Alzheimer's disease.

Several studies have shown that an abnormal vascular-immunity link could increase Alzheimer's disease (AD) risk; however, the mechanism is unclear. CD31, also named platelet endothelial cell adhesion molecule (PECAM), is a surface membrane protein of both endothelial and immune cells and plays important roles in the interaction between the vascular and immune systems. In this review, we focus on research regarding CD31 biological actions in the pathological process that may contribute to AD based on the following rationales. First, endothelial, leukocyte and soluble forms of CD31 play multi-roles in regulating transendothelial migration, increasing blood-brain barrier (BBB) permeability and resulting in neuroinflammation. Second, CD31 expressed by endothelial and immune cells dynamically modulates numbers of signaling pathways, including Src family kinases, selected G proteins, and ß-catenin which in turn affect cell-matrix and cell-cell attachment, activation, permeability, survival, and ultimately neuronal cell injury. In endothelia and immune cells, these diverse CD31-mediated pathways act as a critical regulator in the immunity-endothelia-brain axis, thereby mediating AD pathogenesis in ApoE4 carriers, which is the major genetic risk factor for AD. This evidence suggests a novel mechanism and potential drug target for CD31 in the background of genetic vulnerabilities and peripheral inflammation for AD development and progression.

Peripheral apolipoprotein E proteins and their binding to LRP1 antagonize Alzheimer's disease pathogenesis in the brain during peripheral chronic inflammation.

C-reactive protein (CRP) impacts apolipoprotein E4 (ApoE4) allele to increase Alzheimer's disease (AD) risk. However, it is unclear how the ApoE protein and its binding to LRP1 are involved. We found that ApoE2 carriers had the highest but ApoE4 carriers had the lowest concentrations of blood ApoE in both humans and mice; blood ApoE concentration was negatively associated with AD risk. Elevation of peripheral monomeric CRP (mCRP) reduced the expression of ApoE in ApoE2 mice, while it decreased ApoE-LRP1 binding in the brains of ApoE4 mice that was characterized by Proximity Ligation Assay. Both serum ApoE and brain ApoE-LRP1 binding were positively associated with the expression of pericytes that disappeared after mCRP treatment, and negatively associated with brain tauopathy and neuroinflammation in the presence of mCRP. In ApoE-/- mice, mCRP reduced the brain expression levels of synaptophysin and PSD95 and the positive relationship between ApoE-LRP1 binding and synaptophysin or PSD95 expression disappeared. Our study suggests that blood ApoE protects against AD pathogenesis by binding to LRP1 during peripheral chronic inflammation.

Comparisons of the diagnostic accuracy of the ultrasonic sign-score method and MRI for PA, PI and PP in high-risk gravid women: a retrospective study.

Background: The diagnosis and management of placenta accrete spectrum (PAS) is a great challenge to obstetricians. Ultrasound (US) and magnetic resonance imaging (MRI) are two main methods to detect PAS. MRI has high resolution, but the examination fee is expensive. US machine and examination fee is cheap, but the resolution is relatively low. Balancing the cost and accuracy for PAS diagnosis is very important. Methods: The ultrasonic sign-score method and MRI findings for 49 pregnant women at high risk of placental implantation were retrospectively analyzed. Inclusion criteria: (I) at high risk for PA as described in the Guidelines to Placenta Accreta Spectrum Disorders issued by the American College of Obstetricians and Gynecologists (ACOG) in 2018; (II) complete records of ultrasonic sign-scoring method and MRI data; (III) cesarean section; (IV) definite surgical and/or pathological findings. The results were validated by the gold-standard surgical or postoperative pathological findings, and the efficacy of the 2 imaging approaches in diagnosing placenta PAS was compared. Kappa test was used to analyze the consistency. Receiver operating characteristic (ROC) curves were used to compare the sensitivity and specificity. Results: The mean maternal age was 32.6±4.4 years. The mean gestational week was 35.9±2.0 weeks. The mean gravidity was 3.3±1.1. The surgical or histopathological findings revealed PA in 26, placenta increta (PI) in 19 and placenta percreta (PP) in 4 of the 49 women. The diagnosis accuracy of PA, PI, and PP was higher using the ultrasonic sign-scoring method than MRI (75.51%, 73.47%, and 97.96% vs. 61.22%, 57.14% and 91.84%, respectively). The areas under the ROC curve for the sensitivity and specificity of the ultrasonic sign-scoring method and MRI in the diagnosis of PA, PI, and PP were 0.757 [95% confidence interval (CI): 0.613, 0.868], 0.725 (95% CI: 0.579, 0.843), 0.989 (95% CI: 0.907, 1.000), and 0.607 (95% CI: 0.457, 0.743), 0.544 (95% CI: 0.395, 0.687), 0.614 (95% CI: 0.464, 0.749), respectively. Conclusions: Although the sensitivity and specificity were lower than 0.8, the ultrasonic sign-scoring method was still superior to MRI in the detection of PI and PP. US can be used to help identify high-risk gravid women.

Quantitative proteomics reveals key pathways in the symbiotic interface and the likely extracellular property of soybean symbiosome.

An effective symbiosis between legumes and rhizobia relies largely on diverse proteins at the plant-rhizobium interface for material transportation and signal transduction during symbiotic nitrogen fixation. Here, we report a comprehensive proteome atlas of the soybean symbiosome membrane (SM), peribacteroid space (PBS), and root microsomal fraction (RMF) using state-of-the-art label-free quantitative proteomic technology. In total, 1759 soybean proteins with diverse functions are detected in the SM, and 1476 soybean proteins and 369 rhizobial proteins are detected in the PBS. The diversity of SM proteins detected suggests multiple origins of the SM. Quantitative comparative analysis highlights amino acid metabolism and nutrient uptake in the SM, indicative of the key pathways in nitrogen assimilation. The detection of soybean secretory proteins in the PBS and receptor-like kinases in the SM provides evidence for the likely extracellular property of the symbiosome and the potential signaling communication between both symbionts at the symbiotic interface. Our proteomic data provide clues for how some of the sophisticated regulation between soybean and rhizobium at the symbiotic interface is achieved, and suggest approaches for symbiosis engineering.

Curculigoside rescues hippocampal synaptic deficits elicited by PTSD through activating cAMP-PKA signaling.

Chronic traumatic stress results in various psychiatric disorders, especially posttraumatic stress disorder (PTSD). Previous study demonstrated that curculigoside (CUR) a component of Rhizoma Curculiginis prevented fear extinction and stress-induced depression-like behaviors. However, its effects on PTSD and the mechanisms are still not completely clear. In this study, we observed typical PTSD-like phenotypes, synaptic deficit, and reduction of BDNF/TrkB signaling pathway in mice receiving modified single prolonged stress and electrical stimulation (SPS&S). By contrast, systemic administration of CUR blocked PTSD-like phenotypes and synaptic deficits, including reduction of BDNF/TrkB signaling pathway, GluA1 and Arc expression. Importantly, CUR reversed the impairment of PKA signaling pathway elicited by PTSD. We further confirmed that the effects of CUR on synaptic function were through PKA signaling pathway, as H-89, an inhibitor of PKA blocked the effect of CUR on behavioral changes and BDNF/TrkB signaling pathway. Thereafter, we verified that CUR on synaptic function were through PKA pathway using direct intracerebral injection of CUR and H-89. Direct intracerebral injection of CUR activated PKA/CREB/BDNF/TrkB, which was blocked by H-89. Additionally, the docking results showed high binding energies of CUR with A2AR, AC, PRKACA, and PRKAR1A, which might indicate that CUR functions through regulating PKA signaling pathway. In conclusion, CUR prevented the behavioral changes and hippocampal synaptic deficits elicited by PTSD through activating cAMP-PKA signaling.

Zn-Sb Bimetallic Electrocatalyst Enhances the Conversion of CO2 to Formate.

It was discovered the bimetallic Zn-Sb nanoparticles supported on carbon nanotubes can electrocatalyze CO2 into formate efficiently, comprising the best performance to date for Sb-based catalysts under moderate overpotential. This project was accomplished by a versatile two-step alcoholysis precipitation strategy with tunable Zn : Sb ratios, and the performance of optimized Zn2.33 Sb0.67 O4 was locked in the electrochemical CO2 reduction reaction. During the subsequent electrolysis, the mixed phases of metallic Zn and Sb served as active centers. The Zn-Sb heterostructure and the electron relocation were confirmed. By means of interactions and possible additional binding sites for reaction intermediate *OCHO, the material displayed different catalytic properties from either Zn or Sb, and was selective for formate up to 92%, which was ca. 6.1 times or 4.6 times than that of each single component. The encouraging results highlight the power of the interaction between binary metallic components to synergistically electrocatalyze CO2 conversion.