LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.

Pruritus is often accompanied with bacterial infections, but the underlying mechanism is not fully understood. Although previous studies revealed that lipopolysaccharides (LPS) could directly activate TRPV4 channel and TRPV4 is involved in the generation of both acute itch and chronic itch, whether and how LPS affects TRPV4-mediated itch sensation remains unclear. Here, we showed that LPS-mediated TRPV4 sensitization exacerbated GSK101-induced scratching behaviour in mice. Moreover, this effect was compromised in TLR4-knockout mice, suggesting LPS acted through a TLR4-dependent mechanism. Mechanistically, LPS enhanced GSK101-evoked calcium influx in mouse ear skin cells and HEK293T cells transfected with TRPV4. Further, LPS sensitized TRPV4 channel through the intracellular TLR4-PI3K-AKT signalling. In summary, our study found a modulatory role of LPS in TRPV4 function and highlighted the TLR4-TRPV4 interaction in itch signal amplification.

Characterization of the CsCENH3 protein and centromeric DNA profiles reveal the structures of centromeres in cucumber.

Centromeres in eukaryotes mediate the accurate segregation of chromosomes during cell division. They serve as essential functional units of chromosomes and play a core role in the process of genome evolution. Centromeres are composed of satellite repeats and highly repetitive centromeric retrotransposons (CRs), which vary greatly even among closely related species. Cucumber (Cucumis sativus) is a globally cultivated and economically important vegetable and the only species in the Cucumis genus with seven pairs of chromosomes. Therefore, studying the centromeres of the Cucumis subgenus may yield valuable insights into its genome structure and evolution. Using chromatin immunoprecipitation (ChIP) techniques, we isolated centromeric DNA from cucumber reference line 9930. Our investigation into cucumber centromeres uncovered the centromeric satellite sequence, designated as CentCs, and the prevalence of Ty1/Copia long terminal repeat retrotransposons. In addition, active genes were identified in the CsCENH3 nucleosome regions with low transcription levels. To the best of our knowledge, this is the first time that characterization of centromeres has been achieved in cucumber. Meanwhile, our results on the distribution of CentCs and CsCRs in the subgenus Cucumis indicate that the content of centromeric repeats in the wild variants was significantly reduced compared with the cultivated cucumber. The results provide evidence for centromeric DNA amplification that occurred during the domestication process from wild to cultivated cucumber. Furthermore, these findings may offer new information for enhancing our understanding of phylogenetic relationships in the Cucumis genus.

Association between Triglyceride-Glucose Index and risk of all-cause and cardiovascular mortality in adults with prior cardiovascular disease: a cohort study using data from the US National Health and Nutrition Examination Survey, 2007-2018.

OBJECTIVE: The association between the Triglyceride-Glucose (TyG) Index and mortality rates in patients with cardiovascular disease (CVD) remains unclear. This study investigates the association between the TyG index and the incidence of all-cause and CVD-specific mortality among individuals with a history of CVD. DESIGN: Population-based cohort study. SETTING: Data were sourced from the US National Health and Nutrition Examination Survey (2007-2018) and linked mortality data, with follow-up continuing until 31 December 2019. PARTICIPANTS: The study population comprised 3422 individuals aged 20 years or older with a documented history of CVD. OUTCOME MEASURES: We examined the association between the TyG index and the risk of all-cause and cardiovascular mortality. RESULTS: Over a median follow-up of 5.79 years, 1030 deaths occurred, including 339 due to CVD. Cox regression analysis, adjusted for multiple confounders, showed that individuals in the highest TyG index quartile, compared with those in the lowest, had HRs of 0.76 (95% CI: 0.60 to 0.96) for all-cause mortality and 0.58 (95% CI: 0.39 to 0.89) for CVD mortality. There was a significant inverse relationship between higher TyG index levels and lower mortality risks. For each unit increase in the TyG index, the adjusted HRs for all-cause and CVD mortality decreased by 18% (HR 0.82; 95% CI: 0.71 to 0.94) and 27% (HR 0.73; 95% CI: 0.57 to 0.92), respectively. CONCLUSIONS: TyG index values are negatively associated with all-cause and CVD mortality risks among individuals with previous CVD. Further interventional studies are needed to clarify the impact of TyG levels on cardiovascular health.

IL-18BP Therapy Ameliorates Reproductive and Metabolic Phenotypes in a PCOS Mouse Model by Relieving Inflammation, Fibrosis and Endoplasmic Reticulum Stress.

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice.

Polydopamine modified colloidal gold nanotag-based lateral flow immunoassay platform for highly sensitive detection of pathogenic bacteria and fast evaluation of antibacterial agents.

Bacterial infection is a great threat to human health. Lateral flow immunoassays (LFIAs) with the merits of low cost, quick screening, and on-site detection are competitive technologies for bacteria detection, but their detection limits depend on the optical performance of the adopted nanotags. Herein, we presented a LFIA platform for bacteria detection using polydopamine (PDA) functionalized Au nanoparticles (denoted as Au@PDA) as the nanotag. The introduction of PDA could provide enhanced light absorption of Au, as well as numerous functional groups for conjugation. Small recognition molecules i.e. vancomycin (Van) and p-mercaptophenylboronic acid (PMBA) were covalently anchored to Au@PDA, and selected as the specific probes towards Gram-positive (G+) and Gram-negative (G-) bacteria, respectively. Taken Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) as the representative targets of G+ and G- bacteria, two LFA strips were successfully constructed based on the immuno-sandwich principle. They could quantitatively detect S. aureus and E. coli both down to 102 cfu/mL, a very competitive detection limit in comparison with other colorimetric or luminescent probes-based LFIAs. Furthermore, the proposed two strips were applied for the quantitative, accurate, and rapid detection of S. aureus and E. coli in food and human urine samples with good analytical results obtained. In addition, they were integrated as a screening platform for quick evaluation of diverse antibacterial agents within 3 h, which is remarkably shortened compared with that of the two traditional methods i.e. bacterial culture and plate-counting.

Superior nitrate and chromium reduction synergistically driven by multiple electron donors: Performance and the related biochemical mechanism.

Nitrate and Cr(VI) are the typical and prevalent co-contaminants in the groundwater, how to synchronously and effectively diminish them has received growing attention. The most problem that currently limits the nitrate and Cr(VI) reduction technology for groundwater remediation is with emphasis on exploring the optimal electron donors. This study investigated the feasibility of utilizing the synergistical effect of inorganic electron donors (pyrite, sulfur) and inherently limited organics to promote synchronous nitrate and Cr(VI) removal, which meets the requirement of naturally low-carbon and eco-friendly technologies. The NO3--N and Cr(VI) removal efficiencies in the pyrite and sulfur involved mixotrophic biofilter (PS-BF: approximately 90.8 ± 0.6% and 99.1 ± 2.1%) were substantially higher than that in a volcanic rock supported biofilter (V-BF: about 49.6% ± 2.8% and 50.0% ± 9.3%), which was consistent with the spatial variations of their concentrations. Abiotic and biotic batch tests directly confirmed the decisive role of pyrite and sulfur for NO3--N and Cr(VI) removal via chemical and microbial pathways. A server decline in sulfate production correlated with decreasing COD consumption revealed that there was sulfur disproportionation induced by limited organics. Metagenomic analysis suggested that chemoautotrophic microbes like Sulfuritalea and Thiobacillus were key players responsible for sulfur oxidation, nitrate and Cr(VI) reduction. The metabolic pathway analysis suggested that genes encoding functional enzymes related to complete denitrification, S oxidation, and dissimilatory sulfate reduction were upregulated, however, genes encoding Cr(VI) reduction enzymes (e.g. chrA, chrR, nemA, and azoR) were downregulated in PS-BF, which further explained the synergistical effect of multiple electron donors. These findings provide insights into their potential cooperative interaction of multiple electron donors on greatly promoting nitrate and Cr(VI) removal and have implications for the remediation technology of nitrate and Cr(VI) co-contaminated groundwater.

Extracellular Vesicle Spherical Nucleic Acids.

Extracellular vesicles (EVs) are naturally occurring vesicles secreted by cells that can transport cargo between cells, making them promising bioactive nanomaterials. However, due to the complex and heterogeneous biological characteristics, a method for robust EV manipulation and efficient EV delivery is still lacking. Here, we developed a novel class of extracellular vesicle spherical nucleic acid (EV-SNA) nanostructures with scalability, programmability, and efficient cellular delivery. EV-SNA was constructed through the simple hydrophobic coassembly of natural EVs with cholesterol-modified oligonucleotides and can be stable for 1 month at room temperature. Based on programmable nucleic acid shells, EV-SNA can respond to AND logic gates to achieve vesicle assembly manipulation. Importantly, EV-SNA can be constructed from a wide range of biological sources EV, enhancing cellular delivery capability by nearly 10-20 times. Compared to artificial liposomal SNA, endogenous EV-SNA exhibited better biocompatibility and more effective delivery of antisense oligonucleotides in hard-to-transfect primary stem cells. Additionally, EV-SNA can deliver functional EVs for immune regulation. As a novel material form, EV-SNA may provide a modular and programmable framework paradigm for EV-based applications in drug delivery, disease treatment, nanovaccines, and other fields.

Gelatin­sodium alginate composite hydrogel doped with black phosphorus@ZnO heterojunction for cutaneous wound healing with antibacterial, immunomodulatory, and angiogenic properties.

Hydrogels with novel antimicrobial properties and accelerated wound healing are of great interest in the field of wound dressings because they not only prevent bacterial infections but also fulfill the essential needs of wound healing. In this study, multifunctional hydrogel dressings consisting of black phosphorus nanosheets(BPNS) surface-modified Zinc oxide (BP@ZnO heterojunction) based on gelatin (Gel), sodium alginate (SA), glutamine transferase (mTG), and calcium ions with a three-dimensional crosslinked network were prepared. The BP@ZnO-Gel/SA hydrogel has excellent mechanical properties, hemocompatibility (hemolysis rate: 3.29 %), swelling rate(832.8 ± 19.2 %), cytocompatibility, photothermal and photodynamic antibacterial properties(Sterilization rate: 96.4 ± 3.3 %). In addition, the hydrogel accelerates wound healing by promoting cell migration, immune regulation and angiogenesis. Thus, this hydrogel achieves the triple effect of antimicrobial, immunomodulation and angiogenesis, and is a tissue engineering strategy with great potential.

Effect of Mn-HA on ARGs and MRGs in nitrogen-culturing sludge.

The simultaneous escalation in ARGs (antibiotic resistance genes) and MRGs (metal resistance genes) further complicates the intricate network of factors contributing to the proliferation of microbial resistance. Manganese, which has been reported to affect the resistance of bacteria to antibiotics and metals, plays a vital role in microbial nitrogen metabolism. Moreover, nitrifying and denitrifying populations are potential hosts for ARGs. In this study, manganese was introduced in its prevalent organic chelated form in the environment (Manganese humus chelates, Mn-HA) to a N metabolism sludge to explore the effect of manganese on MRGs and ARGs dissemination. Metagenomics results revealed that manganese availability enhances nitrogen metabolism, while a decrease in ARGs was noted which may be attributed to the inhibition of horizontal gene transfer (HGT), reflected in the reduced integrase -encoded gene int. Population analysis revealed that nitrifier and denitrifier genus harbor MRGs and ARGs, indicating that nitrifier and denitrifier are hosts of MRGs and ARGs. This raises the question of whether the prevalence of ARGs is always increased in metal-contained environments.

A fully digital workflow for the design and manufacture of a class of metal orthodontic appliances.

Background: Traditional working procedures requires a lot of clinical processes and processing time. Methods: The orthodontic metal appliances were made by applying oral scanners, digital images, computer-aided design and computer-aided manufacturing (CAD-CAM) printers. Results: The computer digital technology simplified the manufacturing process for dental appliances and shorten the duration for clinical operation and technical processing. Conclusions: The technique described in this paper can guarantee the accuracy of orthodontic appliances and bring revolution the field. Clinical significance: The CAD-CAM technology provides a fully digital workflow for manufacturing metal orthodontic appliances, which saves a considerable amount of labor and material costs, and significantly reduces heavy metal pollution in the working environment of dental technicians.

J-shaped relationship between stress hyperglycemia ratio and 90-day and 180-day mortality in patients with a first diagnosis of acute myocardial infarction: analysis of the MIMIC-IV database.

AIMS: The Stress Hyperglycemia Ratio (SHR) potently predicts adverse outcomes in patients with cardiovascular and cerebrovascular diseases. However, the relationship between SHR and short-term mortality risk in patients with a first diagnosis of acute myocardial infarction (AMI) remains contentious. This study sought to understand better the relationship between SHR and short-term mortality risk in patients with a first diagnosis of AMI. METHODS: We conducted a cohort study using data from 1961 patients with a first diagnosis of AMI from the MIMIC-IV (version 2.2) database. Patients were divided into three groups based on SHR tertiles. The Cox proportional hazards model and a two-segmented Cox proportional hazards model were used to elucidate the nonlinear relationship between SHR in patients with a first diagnosis of AMI and mortality. RESULTS: Of the surveyed population, 175 patients (8.92%) died within 90 days, and 210 patients (10.71%) died within 180 days. After multivariate adjustments, elevated SHR levels were significantly and non-linearly associated with a higher risk of 90-day and 180-day mortality in patients with a first diagnosis of AMI, showing a J-shaped correlation with an inflection point at 0.9. Compared to participants with SHR levels below the inflection point, those with higher SHR levels had a fivefold increased risk of 90-day mortality (hazard ratio [HR] 5.74; 95% confidence interval [CI] 3.19, 10.33) and a fourfold increased risk of 180-day mortality (HR 4.56; 95% CI 2.62, 7.95). In the subgroup analysis, patients with pre-diabetes mellitus (pre-DM) and higher SHR levels had increased 90-day (HR 6.90; 95% CI 1.98, 24.02) and 180-day mortality risks (HR 5.30; 95% CI 1.96, 14.27). CONCLUSION: In patients with a first diagnosis of AMI, there is a J-shaped correlation between SHR and 90-day and 180-day mortality, with an adverse prognostic inflection point of SHR at 0.9.

Engineering Yarrowia lipolytica for sustainable Cis-13, 16-docosadienoic acid production.

Cis-13, 16-docosadienoic acid (DDA) is an omega-6 polyunsaturated fatty acid with great potential for application in medicine and health. Using microbial cell factories for DDA production is considered a viable alternative to extracting DDA from plant seeds. In this study, using Yarrowia lipolytica Po1f (Δku70) as a chassis, firstly, the adaptation of three elongases in Po1f (Δku70) were explored. Secondly, the DDA biosynthetic pathway was redesigned, resulting in a DDA content of 0.046 % of total fatty acids (TFAs). Thirdly, through the "push-pull" strategy, the DDA content increased to 0.078 % of TFAs. By enhancing the supply of acetyl-CoA, the DDA production in the engineered strain YL-7 reached 0.391 % of the TFAs (3.19 mg/L). Through optimizing the fermentation conditions, the DDA titer of YL-7 reached 29.34 mg/L. This research achieves the sustainable biological production of DDA in Y. lipolytica.

Formation, characterization, and application of natural bioactive phytosterol-based oleogels: A review.

Oleogels are innovative structured fat systems that can replace detrimental lipids and saturated fats. Among the various gelators used to construct oleogels, phytosterols are regarded as potential oleogelators due to ability to lower blood cholesterol levels and protect patients from cardiovascular illnesses, although little research has been conducted on phytosterols. This article examines the formation, characterization, and application of phytosterol-based oleogels in detail. The oleogelation behaviors of phytosterol-based oleogels are affected by their formulation, which includes phytosterol type, combined oleogelator, proportion, concentration and oil type. These oleogels exhibit potential applications as solid fat substitutes without affecting the texture or sensory properties of food products or as effective delivery vehicles. To encourage the research and implementation of phytosterol-based oleogels, we will ultimately not only highlight problems related to their use in food processing, but also provide a few viewpoints, with the goal of providing fresh insights for advancing trends.

Development of nanoparticle vaccines utilizing designed Fc-binding homo-oligomers and RBD-Fc of SARS-CoV-2.

The Fc-fused receptor binding domain (RBD-Fc) vaccine for SARS-CoV-2 has garnered significant attention for its capacity to provide effective and specific immune protection. However, its immunogenicity is limited, highlighting the need for improvement in clinical application. Nanoparticle delivery has been shown to be an effective method for enhancing antigen immunogenicity. In this study, we developed bivalent nanoparticle recombinant protein vaccines by assembling the RBD-Fc of SARS-CoV-2 and Fc-binding homo-oligomers o42.1 and i52.3 into octahedral and icosahedral nanoparticles. The formation of RBD-Fc nanoparticles was confirmed through structural characterization and cell binding experiments. Compared to RBD-Fc dimers, the nanoparticle vaccines induced more potent neutralizing antibodies (nAb) and stronger cellular immune responses. Therefore, using bivalent nanoparticle vaccines based on RBD-Fc presents a promising vaccination strategy against SARS-CoV-2 and offers a universal approach for enhancing the immunogenicity of Fc fusion protein vaccines.

A Diagnostic Nomogram for Predicting Hypercapnic Respiratory Failure in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: To develop and validate a nomogram for assessing the risk of developing hypercapnic respiratory failure (HRF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: From January 2019 to August 2023, a total of 334 AECOPD patients were enrolled in this research. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to determine independent predictors and develop a nomogram. This nomogram was appraised by the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow goodness-of-fit test (HL test), decision curve analysis (DCA), and clinical impact curve (CIC). The enhanced bootstrap method was used for internal validation. Results: Sex, prognostic nutritional index (PNI), hematocrit (HCT), and activities of daily living (ADL) were independent predictors of HRF in AECOPD patients. The developed nomogram based on the above predictors showed good performance. The AUCs for the training, internal, and external validation cohorts were 0.841, 0.884, and 0.852, respectively. The calibration curves and HL test showed excellent concordance. The DCA and CIC showed excellent clinical usefulness. Finally, a dynamic nomogram was developed (https://a18895635453.shinyapps.io/dynnomapp/). Conclusion: This nomogram based on sex, PNI, HCT, and ADL demonstrated high accuracy and clinical value in predicting HRF. It is a less expensive and more accessible approach to assess the risk of developing HRF in AECOPD patients, which is more suitable for primary hospitals, especially in developing countries with high COPD-related morbidity and mortality.

Remodeling Intestinal Microbiota Alleviates Severe Combined Hyperlipidemia-Induced Nonalcoholic Steatohepatitis and Atherosclerosis in LDLR-/- Hamsters.

Combined hyperlipidemia (CHL) manifests as elevated cholesterol and triglycerides, associated with fatty liver and cardiovascular diseases. Emerging evidence underscores the crucial role of the intestinal microbiota in metabolic disorders. However, the potential therapeutic viability of remodeling the intestinal microbiota in CHL remains uncertain. In this study, CHL was induced in low-density lipoprotein receptor-deficient (LDLR-/-) hamsters through an 8-week high-fat and high-cholesterol (HFHC) diet or a 4-month high-cholesterol (HC) diet. Placebo or antibiotics were administered through separate or cohousing approaches. Analysis through 16S rDNA sequencing revealed that intermittent antibiotic treatment and the cohousing approach effectively modulated the gut microbiota community without impacting its overall abundance in LDLR-/- hamsters exhibiting severe CHL. Antibiotic treatment mitigated HFHC diet-induced obesity, hyperglycemia, and hyperlipidemia, enhancing thermogenesis and alleviating nonalcoholic steatohepatitis (NASH), concurrently reducing atherosclerotic lesions in LDLR-/- hamsters. Metabolomic analysis revealed a favorable liver lipid metabolism profile. Increased levels of microbiota-derived metabolites, notably butyrate and glycylglycine, also ameliorated NASH and atherosclerosis in HFHC diet-fed LDLR-/- hamsters. Notably, antibiotics, butyrate, and glycylglycine treatment exhibited protective effects in LDLR-/- hamsters on an HC diet, aligning with outcomes observed in the HFHC diet scenario. Our findings highlight the efficacy of remodeling gut microbiota through antibiotic treatment and cohousing in improving obesity, NASH, and atherosclerosis associated with refractory CHL. Increased levels of beneficial microbiota-derived metabolites suggest a potential avenue for microbiome-mediated therapies in addressing CHL-associated diseases.

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline.

A new method for the synthesis of heterocyclic systems containing tetrazole and tetrahydroisoquinoline is developed via the performance of one-pot Ugi-azide and Heck cyclization reactions. The integration of the multicomponent and post-condensation reactions in one-pot maximizes the pot-, atom-, and step-economy (PASE).

Ischemic stroke due to stylocarotid artery syndrome: a case report and review.

Stylocarotid artery syndrome (SAS) is a rare variant of Eagle's syndrome that may lead to transient ischemic attack or stroke. The underlying pathophysiological mechanism involves compression of the internal carotid artery by an elongated styloid process (ESP), potentially resulting in vascular occlusion or dissection. An ESP exceeding 2.5 cm is deemed elongated, with a length of 3.0 cm considered clinically significant. Although the prevalence of ESP ranges from 4.0% to 7.3%, symptomatic cases are rare; symptoms are present in only approximately 4.0% of individuals with an ESP. Unlike the typical symptoms of Eagle's syndrome, SAS may not cause pharyngeal discomfort, the sensation of a foreign body in the throat, dysphagia, or facial pain. This absence of characteristic symptoms as well as the development of central nervous system symptoms often leads patients to seek care from neurologists instead of otolaryngologists, increasing the likelihood of misdiagnosis or underdiagnosis. We herein report a unique case of ischemic stroke caused by SAS and present a literature review on cases of SAS-associated ischemic stroke published in the past decade. The reporting of this study conforms to the CARE guidelines.

Insights into the Distinct Behaviors between Bifunctional and Binary Organoborane Catalysts through Terpolymerization of Epoxide, CO2, and Anhydride.

Alkyl borane compounds-mediated polymerizations have expanded to Lewis pair polymerization, free radical polymerization, ionic ring-opening polymerization, and polyhomologation. The bifunctional organoborane catalysts that contain the Lewis acid and ammonium or phosphonium salt in one molecule have demonstrated superior catalytic performance for ring-opening polymerization of epoxides and ring-opening copolymerization of epoxides and CO2 than their two-component analogues, i.e., the blend of organoborane and ammonium or phosphonium salt. To explore the origin of the differences of the one-component and two-component organoborane catalysts, here we conducted a systematic investigation on the catalytic performances of these two kinds of organoborane catalysts via terpolymerization of epoxide, carbon dioxide and anhydride. The resultant terpolymers produced independently by bifunctional and binary organoborane catalyst exhibited distinct microstructures, where a series of gradient polyester-polycarbonate terpolymers with varying polyester content were afforded using the bifunctional catalyst, while tapering diblock terpolymers were obtained using the binary system. The bifunctional catalyst enhances the competitiveness of CO2 insertion than anhydride, which leads to the premature incorporation of CO2 into the polymer chains and ultimately results in the formation of gradient terpolymers. DFT calculations revealed the role of electrostatic interaction and charge distribution caused by intramolecular synergistic effect for bifunctional organoborane catalyst.

Sodium oligomannate's amelioration of reproductive and metabolic phenotypes in a letrozole-induced PCOS-like mouse model depends on the gut microbiome.

It has been well-established that there is a connection between polycystic ovary syndrome (PCOS) pathology and gut microbiome dysbiosis. A marine-derived oligosaccharide, GV-971, has been reported to alter gut microbiota and alleviate Aß amyloidosis. In this study, the effects of GV-971 on PCOS-like mice were explored. Mice were randomly assigned into four groups: control, letrozole, letrozole + GV-971, control + GV-971. Glucose metabolism in PCOS-like mice was ameliorated by GV-971, while the reproductive endocrine disorder of PCOS-like mice was partially reversed. The messenger ribonucleic acid levels of steroidogenic enzymes in ovaries of PCOS-like mice were improved. GV-971 restored the fertility of PCOS-like mice and significantly increase the number of litters. Furthermore, GV-971 treatment effectively mitigated abnormal bile acid metabolism. Notably, after GV-971 intervention, gut microbiota alpha-diversity was considerably raised and the relative abundance of Firmicutes was reduced. In conclusion, the hyperinsulinemia and hyperandrogenemia of PCOS-like mice were alleviated by GV-971 intervention, which was associated with mitigating bile acid metabolism and modulating gut microbiota.