The Immune Regulatory Functions in B Cells Are Restored by CpG to Reduce Experimental Food Allergy.

Dysfunctional immune regulation contributes to the pathogenesis of food allergy (FA). The mechanism behind regulatory B-cell dysfunction is unclear. CpG has immune regulatory functions. The purpose of this study is to use CpG to recover the immune suppressive functions of B cells in mice with FA. An FA mouse model was created using ovalbumin as the specific antigen. Flow cytometry was used to isolate B cells from the intestinal tissues. The immune regulatory functions of B cells were assessed using immunological approaches. The results showed that the FA response was linked to low IL-10 levels in gut lavage fluids of FA mice. FA mouse intestinal B cells produced lower amounts of IL-10 as compared with B cells isolated from naïve control mice. Impaired immune suppressive functions were observed in B cells isolated from the FA mouse intestine. The inducibility of the Il10 expression in naïve B cells of the intestine of FA mice was defective. The induction of Il10 expression in FA B cells could be restored by CpG through regulating the methylation status of the Cmip promoter. CpG promoted the therapeutic efficacy of allergen specific immunotherapy by restoring the induction of IL-10+ B cells in the intestine. The expression of Il10 in B cells of the FA mouse intestine was impaired. Administration of CpG could restore the expression of Il10 in B cells in the intestine and promote immunotherapy for FA.

An injectable self-lubricating supramolecular polymer hydrogel loaded with platelet lysate to boost osteoarthritis treatment.

Globally, osteoarthritis (OA) is the most prevalent joint disease and is characterized by infiltration of M1 macrophages in the synovium, anabolic-catabolic imbalance of the extracellular matrix (ECM), increased articular shear force and overproduction of reactive oxygen species (ROS). Disease-modifying OA drugs are not yet available, and treatments for OA focus solely on reducing pain and inflammation and have limited therapeutic effect. Herein, we developed an injectable self-lubricating poly(N-acryloyl alaninamide) (PNAAA) hydrogel loaded with platelet lysate (PL) (termed "PNAAA@PL") for treating OA. Tribological and drug release tests revealed suitable lubrication properties and sustained release of bioactive factors in PNAAA@PL. In vitro experiments showed that PNAAA@PL alleviated interleukin-1ß (IL-1ß)-induced anabolic-catabolic imbalance of chondrocytes and repolarized pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype via intracellular ROS scavenging. Additionally, the PNAAA@PL hydrogel enhanced the migratory capacity and chemotaxis ability of stem cells, which are essential for chondrogenesis. In vivo, the functionalized PNAAA@PL hydrogel acted like synovial fluid following intra-articular injection into a rat OA model with anterior cruciate ligament transection, ultimately attenuating cartilage degeneration and synovitis. According to molecular mechanism studies, PNAAA@PL repairs cartilage in the OA model by inhibiting the NF-ĸB pathway. Overall, this self-lubricating PNAAA@PL hydrogel offers a comprehensive strategy for preventing OA progression by engineering a biophysiochemical microenvironment to generate high-quality hyaline cartilage.

Intranasal administration of Clostridium butyricum and its derived extracellular vesicles alleviate LPS-induced acute lung injury.

Acute lung injury (ALI) is associated with high morbidity and mortality rates. However, its clinical treatment is limited. Currently, the treatment of lung diseases by regulating the lung microbiota has become a research hotspot. In this study, we investigated the protective effects of the intranasal administration of Clostridium butyricum and its derived extracellular vesicles (EVs) against lipopolysaccharide (LPS)-induced ALI. The results demonstrated that compared with the LPS group, the pre-treatment group with C. butyricum and its EVs reduced the expression of pro-inflammatory cytokines and alleviated the symptoms in ALI mice by inhibiting the TLR4/MyD88 signaling pathway. Moreover, C. butyricum and its derived EVs inhibited the expression of apoptosis-related proteins and increased the expression of lung barrier proteins. Additionally, the intervention of C. butyricum changed the composition of the pulmonary microbiota. At the species level, LPS significantly increased the relative abundance of Acinetobacter johnsonii, while C. butyricum reversed this effect. In conclusion, these data demonstrate that intranasal administration of C. butyricum and its EVs can prevent LPS-induced ALI by reducing inflammation, inhibiting apoptosis, and improving lung barrier function. Additionally, C. butyricum regulated the pulmonary microbiota of mice to alleviate LPS-induced ALI.IMPORTANCEThe disorder of pulmonary microbiota plays an important role in the progression of acute lung injury (ALI). However, very few studies have been conducted to treat ALI by modulating pulmonary microbiota. In this study, the diversity and composition of pulmonary microbiota were altered in lipopolysaccharide (LPS)-induced ALI mice, but the ecological balance of the pulmonary microbiota was restored by intranasal administration of Clostridium butyricum. Moreover, the study reported the mechanism of C. butyricum and its derived extracellular vesicles for the treatment of LPS-induced ALI. These results reveal the importance of pulmonary microbiota in ALI disease. It provides a new approach for the treatment of ALI with new-generation probiotics.

Discovery of a urea-based hit compound as a novel inhibitor of transforming growth factor-ß type 1 receptor: in silico and in vitro studies.

Transforming growth factor ß type 1 receptor (TGFßR1), a crucial serine-threonine kinase, is central to the TGFß/Smad signaling pathway, governing cellular processes like growth, differentiation, apoptosis, and immune response. This pathway is closely linked to the epithelial-mesenchymal transition (EMT) process, which plays an important role in the metastasis of hepatocellular carcinoma (HCC). To date, only limited inhibitors targeting TGFßR1 have entered clinical trials, yet they encounter challenges, notably high toxicity, in clinical applications. Herein, an efficient virtual screening pipeline was developed. Eighty compounds were screened from a pool of over 17 million molecules based on docking scores and binding free energy. Four compounds were manually selected with the assistance of enhanced sampling method BPMD (binding pose metadynamics). The binding stability of these four compounds complexed with TGFßR1 was subsequently studied through long-timescale conventional molecular dynamics simulations. The three most promising compounds were subjected to in vitro bioactivity assays. Cpd272 demonstrated moderate inhibitory activity against TGFßR1, with an IC50 value of 1.57 ± 0.33 µM. Moreover, it exhibited cytotoxic effects on human hepatocellular carcinoma cell line Bel-7402. By shedding light on the binding mode of the receptor-ligand complexes, Cpd272 was identified as a hit compound featuring a novel urea-based scaffold capable of effectively inhibiting TGFßR1.

Effects of Different Defatting Methods of Black Soldier Fly (Hermetia illucens) Larvae Meal on the Metabolic Energy and Nutrient Digestibility in Young Laying Hens.

This study aimed to investigate the effects of different defatting methods of black soldier fly (Hermetia illucens) larvae meal (BSFM) on the metabolic energy and nutrient digestibility in laying hens. Sixty young laying hens (Hy-Line W-36) aged 63 days were randomly divided into two groups (G1 and G2), each with five replicates of six hens housed in individual cages. Group G1 was fed 25% pressed black soldier fly meal (BSFMp) and 75% basal diet, and Group G2 was fed 25% extracted black soldier fly meal (BSFMe) and a 75% basal diet. Both diets included 5 g/kg chromium oxide as an external marker. A 7-day preliminary trial was followed by a 4-day experimental period. The results indicate that pressing and extracting significantly affected the digestibility of crude fat and total energy in BSFM, with BSFMp showing significantly higher crude fat digestibility than BSFMe. Similarly, total energy digestibility was also significantly higher in BSFMp. However, there were no significant differences in dry matter, organic matter, and crude protein digestibility between the two processing methods. The apparent metabolic energy values of BSFMp and BSFMe were 16.34 and 12.41 MJ/kg, respectively, showing a significant difference. The nitrogen-corrected metabolic energy values were 15.89 MJ/kg in BSFMp and 11.93 MJ/kg in BSFMe, indicating a highly significant difference. The digestibility of arginine and leucine in BSFMp was significantly higher than in BSFMe, while differences in lysine, cystine, threonine, tryptophan, and isoleucine were not significant. In conclusion, both defatting methods of BSFM had no adverse effects on the metabolic energy and nutrient digestibility in young laying hens, but BSFMp demonstrated better effects on the digestibility of metabolic energy and nutrients in the feed for young laying hens.

Apple polysaccharide improves age-matched cognitive impairment and intestinal aging through microbiota-gut-brain axis.

The Apple polysaccharides (AP), extracted from the fruit of apple, has been used to treat multiple pathological diseases. In this study, we evaluated the effects of AP on cognitive impairment and intestinal aging in naturally aging mice. As a result, it was found that AP could improve spatial learning and memory impairment in aging mice through the Morris water maze experiment. Additionally, AP intervention can upregulate the expression of nerve growth factor (BDNF), postsynaptic marker (PSD95), and presynaptic marker (SYP) proteins. Moreover, AP can enhance total antioxidant capacity, reduce the level of pro-inflammatory cytokine, and inhibit the activation of the NF-κB signaling pathway, exerting anti-inflammatory and antioxidant functions. And the administration of AP restored intestinal mucosal barrier function, reduced the expression of aging and apoptosis related proteins. The administration of AP also altered the gut microbiota of mice. At the genus level, AP decreased the abundance of Helicobacter and Bilophila, while increased the abundance of Lactobacillus and Bacteroides. In summary, these data demonstrate that AP treatment can alleviate cognitive impairment, oxidative stress, and inflammatory reactions, repair the intestinal mucosal barrier, reduce intestinal aging, and alter specific microbial characteristics, ultimately improving the health of the elderly.

hPMSCs prevent erythrocytes dysfunction caused by graft versus host disease via promoting GSH synthesis.

BACKGROUND: Oxidative stress is increased in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients and leads to the development of graft versus host disease (GVHD). Mesenchymal stromal cells (MSCs) can ameliorate GVHD by regulating the function of T cells. However, whether MSCs can modulate erythrocyte antioxidant metabolism and thus reduce GVHD is not known. METHODS: Forty female BALB/c mice were randomly assigned to four groups: the control, GVHDhigh, hPMSC, and PBS groups. A hypoxanthine/xanthine oxidase system was used to steadily and gradually produce superoxide in an in vitro experiment. A scanning microscope was used to examine the ultrastructure of erythrocytes. Laser diffraction analyses were used to analyze erythrocyte deformability. Western blotting was used to measure the expression of the erythrocyte membrane skeleton proteins Band 3 and ß-Spectrin. Corresponding kits were used to assess the levels of oxidative damage and the activity of antioxidant enzymes. RESULTS: Morphological and deformability defects were significantly increased in erythrocytes from GVHD patients. Band 3 and ß-Spectrin expression was also reduced in GVHD patients and model mice. Furthermore, we observed significantly increased oxidative stress-induce injury and decreased antioxidant capability in erythrocytes from both GVHD patients and model mice. Subsequent research showed that human placenta-derived MSC (hPMSC) therapy decreased the GVHD-induced redox imbalance in erythrocytes. Furthermore, our findings suggested that upregulating glucose metabolism promoted both the de novo synthesis and recycling of GSH, which is the primary mechanism by which hPMSCs mediate the increase in antioxidant capacity in erythrocytes. CONCLUSION: Together, our findings suggest that hPMSCs can increase antioxidant capacity by increasing erythrocyte GSH production and thus ameliorate GVHD.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

The Unprecedented Biodegradable Polyzwitterion: A Removal-Free Patch for Accelerating Infected Diabetic Wound Healing.

Zwitterionic polymers have emerged as an important class of biomaterials to construct wound dressings and antifouling coatings over the past decade due to their excellent hydrophilicity. However, all the reported zwitterionic polymers as wound dressings are nondegradable because of noncleavable carbon─carbon bonding backbones, and must be removed periodically after treatment to avoid hypoxia in the wound, thus leading to potential secondary injury. In this work, a biodegradable polyzwitterion patch is fabricated for the first time by ring-opening polymerization of carboxybetaine dithiolane (CBDS), which is self-crosslinked via inter-amide hydrogen bonds and zwitterionic dipole-dipole interactions on the side chains. The unprecedented polyCBDS (PCBDS) patch demonstrates enough ductility owing to the intermolecular physical interactions to fully cover irregular wounds, also showing excellent biodegradability and antifouling performance resulted from the existence of disulfide bonds and carboxybetaine groups. Besides, the PCBDS degradation-induced released CBDS owns potent antioxidant and antibacterial activities. This PCBDS patch is used as a diabetic wound dressing, inhibiting bacterial adhesion on the external surface, and its degradation products can exactly kill bacteria and scavenge excessive reactive oxygen species (ROS) at the wound site to regulate local microenvironment, including regulation of cytokine express and macrophage polarization, accelerating infected diabetic wound repair, and also avoiding the potential secondary injury.

Protective effect of esculentoside A against myocardial infarction via targeting C-X-C motif chemokine receptor 2.

Myocardial infarction (MI) is the primary cause of cardiac mortality. Esculentoside A (EsA), a triterpenoid saponin, has anti-inflammatory and antioxidant activities. However, its effect on MI remains unknown. In this study, the protective effect and mechanisms of EsA against MI were investigated. EsA significantly alleviated hypoxia-induced HL-1 cell injury, including increasing cell viability, inhibiting reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) and lactate dehydrogenase (LDH) leakage. In mouse MI model by left coronary artery (LAD) ligating, EsA obviously restored serum levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI), superoxide dismutase (SOD) and malondialdehyde (MDA). In addition, the cardioprotective effect of EsA was further confirmed by infarct size, electrocardiogram and echocardiography. Mechanistically, the targeted binding relationship between EsA and C-X-C motif chemokine receptor 2 (CXCR2) was predicted by molecular docking and dynamics, and validated by small molecule pull-down and surface plasmon resonance tests. EsA inhibited CXCR2 level both in vitro and in vivo, correspondingly alleviated oxidative stress by suppressing NOX1 and NOX2 and relieved inflammation through inhibiting p65 and p-p65. It demonstrated that EsA could play a cardioprotective role by targeting CXCR2. However, the effect of EsA against MI was abolished in combination with CXCR2 overexpression both in vitro and in vivo. This study revealed that EsA showed excellent cardioprotective activities by targeting CXCR2 to alleviate oxidative stress and inflammation in MI. EsA may function as a novel CXCR2 inhibitor and a potent candidate for the prevention and intervention of MI in the future.

Low hysteresis zwitterionic supramolecular polymer ion-conductive elastomers with anti-freezing properties, high stretchability, and self-adhesion for flexible electronic devices.

The fabrication of stretchable ionic conductors with low hysteresis and anti-freezing properties to enhance the durability and reliability of flexible electronics even at low temperatures remains an unmet challenge. Here, we report a facile strategy to fabricate low hysteresis, high stretchability, self-adhesion and anti-freezing zwitterionic supramolecular polymer ion-conductive elastomers (ICEs) by photoinitiated polymerization of aqueous precursor solutions containing a newly designed zwitterionic monomer carboxybetaine ureido acrylate (CBUIA) followed by solvent evaporation. The resultant poly(carboxybetaine ureido acrylate) (PCBUIA) ICEs are highly stretchable and self-adhesive owing to the presence of strong hydrogen bonds between ureido groups and dipole-dipole interactions of zwitterions. The zwitterion groups on the polymer side chains and loaded-lithium chloride endow PCBUIA ICEs with excellent anti-freezing properties, demonstrating mechanical flexibility and ionic transport properties even at a low temperature (-20 °C). Remarkably, the PCBUIA ICEs demonstrate a low hysteresis (≈10%) during cyclic mechanical loading-unloading (≤500%), and are successfully applied as wearable strain sensors and triboelectric nanogenerators (TENGs) for energy harvesting and human motion monitoring. In addition, the PCBUIA ICE-based TENG was used as a wireless sensing terminal for Internet of Things smart devices to enable wireless sensing of finger motion state detection.

Gut microbiome-based thiamine metabolism contributes to the protective effect of one acidic polysaccharide from Selaginella uncinata (Desv.) Spring against inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a serious disorder, and exploration of active compounds to treat it is necessary. An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata (Desv.) Spring, which contained galacturonic acid, galactose, xylose, arabinose, and rhamnose with the main chain structure of →4)-α-d-GalAp-(1→ and →6)-ß-d-Galp-(1→ and the branched structure of →5)-α-l-Araf-(1→ . Animal experiments showed that compared with Model group, SUSP-4 significantly improved body weight status, disease activity index (DAI), colonic shortening, and histopathological damage, and elevated occludin and zonula occludens protein 1 (ZO-1) expression in mice induced by dextran sulfate sodium salt (DSS). 16S ribosomal RNA (rRNA) sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes. Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism, which was further confirmed by a targeted metabolism study. Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice. A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B (p-NF-κB) and cyclooxygenase-2 (COX-2) and elevating NF-E2-related factor 2 (Nrf2) levels compared with Model group. In conclusion, SUSP-4 affected thiamine metabolism by regulating Akkermania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD. This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD, showing great potential for in-depth research and development applications.

A chemo/chemodynamic nanoparticle based on hyaluronic acid induces ferroptosis and apoptosis for triple-negative breast cancer therapy.

Triple-negative breast cancer (TNBC) poses a serious threat to women's life and health due to its high malignancy, strong invasiveness, and propensity for early recurrence and metastasis. Therefore, there is an urgent need to develop a highly effective and low-toxic TNBC treatment scheme to enhance the anti-cancer efficacy and prolong the survival of patients. In this work, we designed and synthesized a chemodynamic therapy (CDT) agent (HA-Fc-Mal). The chemo/chemodynamic (CT/CDT) nanoparticle (HCM@DOX) based on hyaluronic acid induces ferroptosis and apoptotic for TNBC therapy was constructed via self-assembled of HA-Fc-Mal and doxorubicin (DOX). HCM@DOX orderly realized the TNBC targeting, controlled DOX release, GSH depletion and induce ROS erupt. In vivo and in vitro experiments confirmed that HCM@DOX inhibited the growth of 4 T1 tumors through ferroptosis and apoptosis, and the tumor inhibition rate was as high as 81.87 %. In addition, HCM@DOX significantly inhibited lung metastasis and exhibited excellent biosafety. Overall, our findings offer a new strategy for TNBC therapy using a CT/CDT nanoparticle that induces ferroptosis and apoptosis.

Apigenin-7-glucoside-loaded nanoparticle alleviates intestinal ischemia-reperfusion by ATF3/SLC7A11-mediated ferroptosis.

Intestinal ischemia reperfusion injury (II/R injury) is a common and intractable pathophysiological process in critical patients, for which exploring new treatments and mechanisms is of great importance to improve treatment outcomes. Apigenin-7-O-Glucoside (AGL) is a sugar derivative of apigenin natural product with various pharmacological activities to protect against intestinal diseases. In this study, we synthesized two amphiphilic molecules, namely DTPA-N10-10 and mPEG-TK-DA, which can scavenge free radicals and reactive oxygen species (ROS). They were successfully encapsulated AGL through self-assembly, resulting in the formation of multi-site ROS scavenging nanoparticles called PDN@AGL. In vitro and in vivo experiments demonstrated that PDN@AGL could protect intestinal tissues by reducing lipid peroxidation, lowering ROS levels and inhibiting ferroptosis during II/R injury. Furthermore, our study revealed, for the first time, that the regulation of the ATF3/SLC7A11 pathway by PDN@AGL may play a crucial role in mitigating II/R injury. In conclusion, our study confirmed the beneficial effects of PDN@AGL in combating II/R injury through the ATF3/SLC7A11-mediated regulation of ferroptosis and oxidative stress. These findings lay the groundwork for the potential application of PDN@AGL in the treatment of II/R injury.

Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis.

Introduction: "Probiotic therapy" to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases. Methods: In this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis. Results: We confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis. Conclusion: Therefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics.

Molecular generation strategy and optimization based on A2C reinforcement learning in de novo drug design.

MOTIVATION: In the field of pharmacochemistry, it is a time-consuming and expensive process for the new drug development. The existing drug design methods face a significant challenge in terms of generation efficiency and quality. RESULTS: In this paper, we proposed a novel molecular generation strategy and optimization based on A2C reinforcement learning. In molecular generation strategy, we adopted transformer-DNN to retain the scaffolds advantages, while accounting for the generated molecules' similarity and internal diversity by dynamic parameter adjustment, further improving the overall quality of molecule generation. In molecular optimization, we introduced heterogeneous parallel supercomputing for large-scale molecular docking based on message passing interface communication technology to rapidly obtain bioactive information, thereby enhancing the efficiency of drug design. Experiments show that our model can generate high-quality molecules with multi-objective properties at a high generation efficiency, with effectiveness and novelty close to 100%. Moreover, we used our method to assist shandong university school of pharmacy to find several candidate drugs molecules of anti-PEDV. AVAILABILITY AND IMPLEMENTATION: The datasets involved in this method and the source code are freely available to academic users at https://github.com/wq-sunshine/MomdTDSRL.git.

Circular RNA as new serum metabolic biomarkers in patients with premature ovarian insufficiency.

OBJECTIVE: Quantitative real-time PCR (qPCR) is used to detect the differential expression of circular RNAs in patients of premature ovarian insufficiency (POI), to explore the new biomarkers of POI that can be detected from blood as soon as possible. METHODS: The study collected plasma samples from 30 patients in POI group and 30 normal people group who meet the inclusion criteria, who visited the gynecology clinic of The First Affiliated Hospital of Guangzhou University of Chinese Medicine from July 2019 to December 2020. Then, circRNAs in plasma were extracted for qPCR validation. RESULTS: 1. qPCR technology was performed on hsa_circRNA_008901 and hsa_circRNA_403959, and it was found that the levels of both were considerably downregulated in POI group. Clinical evaluation showed that both hsa_circRNA_008901 and hsa_circRNA_403959 have good diagnostic value for POI. 2. According to miRNA Regulatory Element (MRE) analysis, the predicted target miRNAs of hsa_circRNA_008901 are: hsa-miR-548c-3p, hsa-miR-924, hsa-miR-4677-5p, hsa-miR-6786-3p and hsa-miR-7974; the predicted target miRNAs of hsa_circRNA_403959 are: hsa-miR-1207-5p, hsa-miR-4691-5p, hsa-miR-4763-3p, hsa-miR-6807-5p and hsa-miR-7160-5p. CONCLUSION: Compared with the normal group, the expression levels of hsa_circRNA_008901 and hsa_circRNA_403959 in the POI group were downregulated, suggesting that these two circRNAs may be potential biomarkers of POI. Bioinformatics analysis indicated that hsa_circRNA_008901 and hsa_circRNA_403959 may regulate their binding miRNA through the action form of "molecular sponge", and then regulate the signaling pathway regulated by miRNA, and ultimately affect the disease progression of POI.

Self-healing, flame-retardant, and antimicrobial chitosan-based dynamic covalent hydrogels.

This study reports the fabrication of chitosan-based hydrogels with potential to be applied as a flame-retardant coating on skin or other surfaces. These hydrogels possess remarkable antimicrobial properties that are highly desirable for the protection of epidermises. Hydrogels in this study were prepared via the cross-linking reaction of chitosan with a vanillin-based cross linker containing flame-retarding moieties through Schiff's base reaction. The synthesized hydrogels possess imine linkages enabling them to self-heal at room temperature. Self-healing abilities offered these hydrogels the ability to protect the skin for a longer time. One flame retarding mechanism of these hydrogels was by retaining the water in their polymeric network; thus, the role of bound and unbound water molecules was studied using DSC and Raman spectroscopy. The hydrogels synthesized in this study retained their flame-retarding properties even after drying due to the charring process that inhibited the pyrolysis process. Therefore, these chitosan-based hydrogels are able to prolong the protection time against fire.

Chlorogenic Acid Ameliorates Post-Infectious Irritable Bowel Syndrome by Regulating Extracellular Vesicles of Gut Microbes.

Post-infectious irritable bowel syndrome (PI-IBS) occurs after acute infectious diarrhea, and dysbiosis can be involved in its pathogenesis. Here, the role of chlorogenic acid (CGA) is investigated, a natural compound with several pharmacological properties, in alleviating PI-IBS in rats. It is elucidated that the gut microbiota plays a key role in PI-IBS pathogenesis and that rectal administration of CGA alleviated PI-IBS by modulating the gut microbiota and its metabolites. CGA supplementation significantly increased fecal Bacteroides acidifaciens abundance and glycine levels. Glycine structurally altered B. acidifaciens extracellular vesicles (EVs) and enriched functional proteins in the EVs; glycine-induced EVs alleviated PI-IBS by reducing inflammation and hypersensitivity of the intestinal viscera and maintaining mucosal barrier function. Moreover, B. acidifaciens EVs are enriched in the brain tissue. Thus, CGA mediates the mitigation of PI-IBS through the gut microbiota and its metabolites. This study proposes a novel mechanism of signal exchange between the gut microenvironment and the host.