Recombinant humanized type I collagen remodels decidual immune microenvironment at maternal-fetal interface by modulating Th17/Treg imbalance.

Disruption of the extracellular matrix and dysregulation of the balance between Th17 and regulatory T cells are recognized as risk factors for recurrent spontaneous abortion (RSA). However, the interaction between matrix components and the Th17/Treg axis remains poorly elucidated. The result of this study revealed that the absence of type I collagen in the decidua is linked to Th17/Treg imbalance in RSA. Furthermore, we discovered that biomaterial recombinant humanized type I collagen (rhCOLI) promoted T cell differentiation into Tregs by inhibition the Notch1/Hes1 signaling pathway and enhanced the immunosuppressive function of Tregs, as indicated by increased secretion level of IL-10 and TGF-ß. Importantly, this study is the first to demonstrate that rhCOLI can modulate the Th17/Treg imbalance, reduce embryo resorption rates, reshape the immune microenvironment at the maternal-fetal interface, and improve fertility in an RSA mouse model. Collectively, these findings suggest that type I collagen deficiency may contribute to, rather than result from, RSA, and propose a potential intervention for RSA using rhCOLI.

Evaluation of ex vivo drug combination optimization platform in recurrent high grade astrocytic glioma: An interventional, non-randomized, open-label trial protocol.

INTRODUCTION: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients. METHODS: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time. TRIAL REGISTRATION: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.

Unraveling the role of hepatitis B virus DNA integration in B-cell lymphomagenesis.

BACKGROUND: Studies have shown that hepatitis B virus (HBV)-associated B-cell non-Hodgkin lymphoma (NHL) constitutes a unique subgroup with distinct clinical features. It still leaves open the question of whether the integration of HBV DNA into the B-cell genome is a causal mechanism in the development of lymphoma. METHODS: Using the hybridisation capture-based next generation sequencing and RNA sequencing, we characterised the HBV integration pattern in 45 HBV-associated B-cell NHL tumour tissues. RESULTS: A total of 354 HBV integration sites were identified in 13 (28.9%) samples, indicating the relatively low integration frequency in B-cell NHLs. High plasma HBV DNA loads were not associated with the existence of HBV integration. The insertion sites distributed randomly across all the lymphoma genome without any preferential hotspot neither at the chromosomal level nor at the genetic level. Intriguingly, most HBV integrations were nonclonal in B-cell NHLs, implying that they did not confer a survival advantage. Analysis of the paired diagnosis-relapse samples showed the unstable status of HBV integrations during disease progression. Furthermore, transcriptomic analysis revealed the limited biological impact of HBV integration. CONCLUSION: Our study provides an unbiased HBV integration map in B-cell NHLs, revealing the insignificant role of HBV DNA integration in B-cell lymphomagenesis.

Spatial and Seasonal Changes in Microbial Community of Hynobius amjiensis Breeding Pools in a Sphagnum-Dominated Peatland.

Peatlands deliver a variety of beneficial ecosystem services, particularly serving as habitats for a diverse array of species. Hynobius amjiensis is a critically endangered amphibian initially discovered in a Sphagnum-dominated peatland in Anji, China. The unique habitat requirements of H. amjiensis make it highly vulnerable to environmental changes. Here, we investigated the different breeding pools of H. amjiensis in the Sphagnum-dominated peatland (the type locality) for a one-year period to evaluate the interactions among the egg sacs present, water quality, and microbial communities (16S and 18S rRNA gene amplicon). The numbers of egg sacs were higher in the breeding pools located at the marginal area than those at the core area of the peatland. Similarly, the α-diversity of bacteria, fungi, and protists were lower in the core region compared to those at the edge of the peatland, perhaps due to water eutrophication. The microbial communities and water quality differed significantly among breeding pools and sampling months. The simpler microbial networks of the breeding pools in the core wetland may impact the numbers and health of the egg sacs. This study contributes to a better understanding of the effect of water quality on biodiversity in peatlands, and it can also guide regulations for wetland conservation and the protection of endangered species.

Multi-Source Feature-Fusion Method for the Seismic Data of Cultural Relics Based on Deep Learning.

The museum system is exposed to a high risk of seismic hazards. However, it is difficult to carry out seismic hazard prevention to protect cultural relics in collections due to the lack of real data and diverse types of seismic hazards. To address this problem, we developed a deep-learning-based multi-source feature-fusion method to assess the data on seismic damage caused by collected cultural relics. Firstly, a multi-source data-processing strategy was developed according to the needs of seismic impact analysis of the cultural relics in the collection, and a seismic event-ontology model of cultural relics was constructed. Additionally, a seismic damage data-classification acquisition method and empirical calculation model were designed. Secondly, we proposed a deep learning-based multi-source feature-fusion matching method for cultural relics. By constructing a damage state assessment model of cultural relics using superpixel map convolutional fusion and an automatic data-matching model, the quality and processing efficiency of seismic damage data of the cultural relics in the collection were improved. Finally, we formed a dataset oriented to the seismic damage risk analysis of the cultural relics in the collection. The experimental results show that the accuracy of this method reaches 93.6%, and the accuracy of cultural relics label matching is as high as 82.6% compared with many kinds of earthquake damage state assessment models. This method can provide more accurate and efficient data support, along with a scientific basis for subsequent research on the impact analysis of seismic damage to cultural relics in collections.

MELD3.0 is superior to MELDNa and MELD for prediction of mortality in patients with cirrhosis: An external validation in a multi-ethnic population.

Background and Aim: The model for end-stage liver disease (MELD) was updated to MELDNa and recently to MELD3.0 to predict survival of cirrhotic patients. We validated the prognostic performance of MELD3.0 and compared with MELDNa and MELD amongst cirrhotic inpatients. Methods: Demographical, clinical, biochemical, and survival data of cirrhotic inpatients in Singapore General Hospital (SGH) from 01 January 2018 to 31 December 2018, were studied retrospectively. Patients were followed up from first admission in 2018 until death or until 01 April 2023. Area under the receiver operating characteristic curves (AUROC) were computed for the discriminative effects of MELD3.0, MELDNa, and MELD to predict 30-, 90-, and 365-day mortalities. AUROC was compared with DeLong's test. The cutoff MELD3.0 score for patients at high risk of 30-day mortality was determined using Youden's Index. Survival curves of patients with MELD3.0 score above and below the cutoff were estimated with Kaplan-Meier method and compared with log-rank analysis. Results: Totally 862 patients were included (median age 71.0 years [interquartile range, IQR: 64.0-79.0], 65.4% males, 75.8% Chinese). Proportion of patients with Child-Turcotte-Pugh classes A/B/C were 55.5%/35.5%/9.0%. Median MELD3.0/MELDNa/MELD scores were 12.2 (IQR: 8.7-18.3)/11.0 (IQR: 8.0-17.5)/10.3 (IQR: 7.8-15.0). Median time of follow-up was 51.9 months (IQR: 8.5-59.6). The proportion of 30-/90-/365-day mortalities was 5.7%/13.2%/26.9%. AUROC of MELD3.0/MELDNa/MELD in predicting 30-, 90-, and 365-day mortalities, respectively, were 0.823/0.793/0.783, 0.754/0.724/0.707, 0.682/0.654/0.644 (P < 0.05). Optimal cutoff to predict 30-day mortality was MELD3.0 > 19 (sensitivity = 67.4%, specificity = 82.4%). Patients with MELD3.0 > 19, compared with patients with MELD3.0 ≤ 19, had shorter median time to death (98.0 days [IQR: 28.8-398.0] vs 390.0 days [IQR: 134.3-927.5]), and higher proportion of 30-day mortality (68.8% vs 43.0%) (P < 0.001). Conclusion: MELD3.0 performs better than MELDNa and MELD in predicting mortality in cirrhotic inpatients. MELD3.0 > 19 predicts higher 30-day mortality.

METTL8 links mt-tRNA m3C modification to the HIF1α/RTK/Akt axis to sustain GBM stemness and tumorigenicity.

Epitranscriptomic RNA modifications are crucial for the maintenance of glioma stem cells (GSCs), the most malignant cells in glioblastoma (GBM). 3-methylcytosine (m3C) is a new epitranscriptomic mark on RNAs and METTL8 represents an m3C writer that is dysregulated in cancer. Although METTL8 has an established function in mitochondrial tRNA (mt-tRNA) m3C modification, alternative splicing of METTL8 can also generate isoforms that localize to the nucleolus where they may regulate R-loop formation. The molecular basis for METTL8 dysregulation in GBM, and which METTL8 isoform(s) may influence GBM cell fate and malignancy remain elusive. Here, we investigated the role of METTL8 in regulating GBM stemness and tumorigenicity. In GSC, METTL8 is exclusively localized to the mitochondrial matrix where it installs m3C on mt-tRNAThr/Ser(UCN) for mitochondrial translation and respiration. High expression of METTL8 in GBM is attributed to histone variant H2AZ-mediated chromatin accessibility of HIF1α and portends inferior glioma patient outcome. METTL8 depletion impairs the ability of GSC to self-renew and differentiate, thus retarding tumor growth in an intracranial GBM xenograft model. Interestingly, METTL8 depletion decreases protein levels of HIF1α, which serves as a transcription factor for several receptor tyrosine kinase (RTK) genes, in GSC. Accordingly, METTL8 loss inactivates the RTK/Akt axis leading to heightened sensitivity to Akt inhibitor treatment. These mechanistic findings, along with the intimate link between METTL8 levels and the HIF1α/RTK/Akt axis in glioma patients, guided us to propose a HIF1α/Akt inhibitor combination which potently compromises GSC proliferation/self-renewal in vitro. Thus, METTL8 represents a new GBM dependency that is therapeutically targetable.

Trends in prevalence of multimorbidity for chronic diseases in China: serial cross-sectional surveys from 2009 to 2018.

BACKGROUND: Multimorbidity, individuals suffering from two or more chronic diseases, has become a major health challenge worldwide, especially in populous and prosperous cities, where studies of this phenomenon in China are limited. We examined the prevalence, trends, patterns, and associated factors of multimorbidity from 2009 to 2018 among community-dwelling adults in Guangzhou, China. METHODS: We conducted serial cross-sectional surveys for chronic diseases in Guangzhou, China, in 2009, 2013, and 2018. General and stratified prevalence were standardized using demographic data. Multivariable logistic regression and hierarchical cluster analysis were applied to identify associated factors and to assess the correlations and patterns of multimorbidity, respectively. RESULTS: This study included 23,284 adults aged 18 and over in 2009, 18,551 in 2013, and 15,727 in 2018. The standardized prevalence of multimorbidity increased substantially, with 12.69% (95% CI: 10.45-15.33) in 2009, 25.44% (95% CI: 23.47-27.52) in 2013, and 35.13% (95% CI:32.64-37.70) in 2018 (P for trend <0.001). The highest bi- and triple-conditions of multimorbidity were dyslipidemia (DP) and overweight or obesity (OO) (12.54%, 95% CI: 11.68-13.46), and DP, OO, and Hypertension (HT) (3.99%, 95% CI: 3.47-4.58) in 2018. From 2009 to 2018, (1) The majority of multimorbidity patterns showed a high prevalence; (2) The percentage of participants with only one chronic condition was found lower, while the percentage with multiple conditions was higher. CONCLUSIONS: The prevalence of chronic disease multimorbidity in Guangzhou China, has increased substantially among adults. Effective policies targeting multimorbidity are urgently needed, especially for the health management of primary medical institutions.

The Association of Malnutrition and Health-Related Factors among 474,467 Older Community-Dwellers: A Population-Based Data Mining Study in Guangzhou, China.

BACKGROUND: This study aimed to examine the prevalence and associated factors of malnutrition in older community-dwellers and explore the interaction between associated factors. METHODS: A total of 474,467 older community-dwellers aged 65 or above were selected in Guangzhou, China. We used a two-step methodology to detect the associated factors of malnutrition and constructed logistic regression models to explore the influencing factors and interactive effects on three patterns of malnutrition. RESULTS: The prevalence of malnutrition was 22.28%. Older adults with both hypertension and diabetes (RERI = 0.13), both meat or fish diet and hypertension (RERI = 0.79), and both meat or fish diet and diabetes (RERI = 0.81) had positive additive interaction effects on the risk of obesity, whereas those on a vegetarian diet with hypertension (RERI = -0.25) or diabetes (RERI = -0.19) had negative additive interaction effects. Moreover, the interactions of physical activity with a meat or fish diet (RERI = -0.84) or dyslipidemia (RERI = -0.09) could lower the risk of obesity. CONCLUSIONS: Malnutrition was influenced by different health factors, and there were interactions between these influencing factors. Pertinent dietary instruction should be given according to different nutritional status indexes and the prevalence of metabolic diseases to avoid the occurrences of malnutrition among older adults.

Successful secukinumab treatment of generalized pustular psoriasis.

Generalized pustular psoriasis is a rare variant of psoriasis. Evidence recommending generalized pustular psoriasis treatment with secukinumab is limited. This report aims to evaluate the use of secukinumab in two patients with generalized pustular psoriasis. The standard treatment regimen for secukinumab was as follows: 300mg subcutaneously once weekly in weeks 0-4, followed by 300mg every four weeks. The efficacy was evaluated by analyzing the psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). One patient had generalized pustular psoriasis, which had developed from palmoplantar pustulosis over 12 years. The second patient was an adolescent with recurrent generalized pustular psoriasis. The first patient achieved PASI-75 response by week 3 and both PASI-90 and a DLQI score of 0 were observed by week 8. The second patient achieved PASI-75 response by week 4 and complete clinical resolution, except for nail changes, and a DLQI of 0 by week 8, without any adverse events.

Inflammation-Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment.

Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly the excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction and MI progression. Herein, a mannan-based nanomedicine, Que@MOF/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti-inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post-MI, in vivo, administration of Que@MOF/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation-targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment.

Triglyceride glucose index combined with body mass index and its 4-year change with the risk of hypertension in middle-aged and older Chinese: A prospective cohort study.

BACKGROUND AND AIM: To explore the association of triglyceride glucose index-body mass index (TyG-BMI) and its dynamic changes with the risk of hypertension among middle-aged and older Chinese adults based on a large-sample prospective cohort study. METHODS AND RESULTS: Participants over 45 years old and without a history of hypertension were included from the China Health and Retirement Longitudinal Study registry. Data were collected in 2011 and followed up in 2015. TyG index and TyG-BMI were calculated as ln (triglyceride∗glucose/2) and TyG index∗BMI, respectively. We performed multivariate logistic regression analysis to identify the relationship between the TyG index, TyG-BMI and their dynamic change and the risk of hypertension. In the analyses, 3885 participants were included. After 4 years of follow-up, 1705 (43.89 %) patients developed hypertension. Logistic regression analysis revealed that after adjustments for all potential confounding factors, the highest tertile of baseline TyG index, baseline TyG-BMI, and the dynamic change in TyG-BMI were each associated with higher hypertension incidence than the lowest tertile: OR,1.38, 95 % CI, 1.17-1.63, OR,1.28, 95 % CI, 1.06-1.56, and OR, 1.26, 95 % CI, 1.07-1.48, respectively, whereas TyG index change was not. Moreover, the risk of hypertension increased with increasing levels of baseline TyG index (P for trend < 0.001), baseline TyG-BMI (P for trend = 0.013), and the dynamic change in TyG-BMI (P for trend = 0.006). CONCLUSIONS: The baseline TyG index, baseline TyG-BMI, and the dynamic changes in TyG-BMI were significantly and positively associated with the risk of hypertension in Chinese adults older than 45 years.

Tumor-infiltrating immune cells and survival in head and neck squamous cell carcinoma: a retrospective computational study.

The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.

Effect of postoperative exercise training on physical function and quality of life of lung cancer patients with chronic obstructive pulmonary disease: A randomized controlled trial.

BACKGROUND: Postoperative rehabilitation programs consisting of exercise training are considered effective for unselected lung cancer patients. However, whether postoperative exercise is beneficial to lung cancer patients comorbid with chronic obstructive pulmonary disease remains unknown. METHODS: Eighty-four patients diagnosed with both lung cancer and chronic obstructive pulmonary disease were randomized into the exercise group and control group. Both groups were given standard postoperative rehabilitation for 1 week. After that, oxygen therapy (if needed) and nebulization were given to the control group, while patients in the exercise group started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as in the control group. The exercise programs consisted of 24 training sessions. RESULTS: In both groups, the functional status and the results of the pulmonary function test decreased from baseline to the endpoint. However, after surgery and the intervention program, both the maximal oxygen consumption in the cardiopulmonary exercise test and walking distance in the 6-minute walk test in the exercise group were significantly better than those in the control group [15.5 (±1.4) mL/kg/min vs 13.1 (±1.3) mL/kg/min, P = 0.016; 437.4 (±48.6) m vs 381.7 (±40.5) m, P = 0.040]. Force vital capacity and forced expiratory volume in the first second in the exercise group were better than those in the control group, but the differences were not statistically significant [1798.1 (±298.9) mL vs 1664.0 (±329.7) mL, P = 0.254; 1155.7 (±174.3) mL vs 967.4 (±219.4) mL, P = 0.497]. The decline in the standard score of the QLQ-C30 (V3.0) was smaller in the exercise group, but the difference did not meet a statistically significant level [61.7 (±5.7) vs 58.4 (±9.3), P = 0.318]. CONCLUSION: This study demonstrates that a short-term postoperative exercise training program can facilitate the recovery of functional capacity in lung cancer patients with comorbidities of chronic obstructive pulmonary disease.

Virtual Reality-Based Training in Chronic Low Back Pain: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Low back pain is one of the most prevalent pain conditions worldwide. Virtual reality-based training has been used for low back pain as a new treatment strategy. Present evidence indicated that the effectiveness of virtual reality-based training for people with chronic low back pain is inconclusive. OBJECTIVE: This study conducted a meta-analysis to evaluate the immediate- and short-term effects of virtual reality-based training on pain, pain-related fear, and disability in people with chronic low back pain. METHODS: We searched the PubMed, Embase, Web of Science, PEDro, CENTRAL, and CINAHL databases from inception until January 2024. Only randomized controlled trials assessing the effects of virtual reality-based training on individuals with chronic low back pain were selected. The outcomes were focused on pain, pain-related fear measured by the Tampa Scale of Kinesiophobia, and disability measured by the Oswestry Disability Index. The immediate term was defined as the immediate period after intervention, and the short term was defined as 3 to 6 months after intervention. The Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach were used to evaluate the quality of the methodology and evidence, respectively. RESULTS: In total, 20 randomized controlled trials involving 1059 patients were eligible for analysis. Virtual reality-based training showed significant improvements in pain (mean difference [MD] -1.43; 95% CI -1.86 to -1.00; I2=95%; P<.001), pain-related fear using the Tampa Scale of Kinesiophobia (MD -5.46; 95% CI -9.40 to 1.52; I2=90%; P=.007), and disability using the Oswestry Disability Index (MD -11.50; 95% CI -20.00 to -3.01; I2=95%; P=.008) in individuals with chronic low back pain immediately after interventions. However, there were no significant differences observed in pain (P=.16), pain-related fear (P=.10), and disability (P=.43) in the short term. CONCLUSIONS: These findings indicated that virtual reality-based training can be used effectively for individuals with chronic low back pain in the immediate term, especially to reduce pain, alleviate pain-related fear, and improve disability. However, the short-term benefits need more high-quality trials to be demonstrated. TRIAL REGISTRATION: PROSPERO CRD42021292633; http://tinyurl.com/25mydxpz.

Impact of vaginal microecological differences on pregnancy outcomes and endometrial microbiota in frozen embryo transfer cycles.

PURPOSE: This prospective study investigates the correlation between vaginal microecology and pregnancy outcomes and explores their impact on endometrial microbiota composition during frozen embryo transfer (FET) cycles. Additionally, the impact of transvaginal Lactobacillus supplementation on reproductive outcomes in patients with previous failed cycles was assessed. METHODS: A total of 379 patients undergoing FET at a reproductive medicine center were categorized into clinical pregnancy (CP), miscarriage (MISC), and non-pregnant (NP) groups. Vaginal specimens were collected for microecological evaluation prior to embryo transfer. Endometrial microbiota samples were obtained during embryo transfer for 16S rRNA gene sequencing analysis to assess endometrial microbiota composition. Vaginal microecological indicators, including pH, Lactobacillus dominance, and leukocyte esterase activity, were measured. Transvaginal Lactobacillus supplementation was investigated in 60 patients with previous failed cycles. RESULTS: Vaginal microecology significantly correlated with pregnancy outcomes, with normal microecology associated with a higher clinical pregnancy rate. Vaginal pH and leukocyte esterase activity were significantly associated with clinical pregnancy. Furthermore, vaginal microecological differences significantly impacted endometrial microbiota composition. However, no significant differences were observed in endometrial microbiota composition among the CP, MISC, and NP groups. Notably, transvaginal Lactobacillus supplementation increased the clinical pregnancy rate without affecting the miscarriage rate. CONCLUSION: This study highlights that normal vaginal microecology, characterized by lower pH and leukocyte esterase negativity, is associated with a higher likelihood of clinical pregnancy following FET. Importantly, vaginal microecological differences influence endometrial microbiota composition. Moreover, transvaginal Lactobacillus supplementation appears promising in improving clinical pregnancy rates in patients with previous failed cycles. These findings contribute to a better understanding of the interplay between vaginal and endometrial microbiota and offer potential interventions to enhance reproductive success in assisted reproductive technologies.

The enhancement of nonlinear optical properties of azulene-based nanographene by N atoms: a finishing touch.

Nonlinear optical (NLO) materials play an increasingly important role in optoelectronic devices, biomedicine, micro-nano processing, and other fields. The development of organic materials with strong second or (and) third NLO properties and a high stability is still challenging due to the unknown strategies for obtaining enhanced high order NLO properties. In the present work, π-conjugated systems are constructed by doping boron or (and) nitrogen atoms in the azulene moiety of azulene-based nanographenes (formed with an azulene chain with two bridging HCCHs at the two sides of the connecting CC bonds between azulenes, A1A2A3), and the NLO properties are predicted with time-dependent density functional theory based methods and a sum-over-states model. The doping of heteroatoms induces charge redistribution, tunes the frontier molecular orbital energy gap, changes the composition of some frontier molecular orbitals, and affects the NLO properties of those nanographenes. Among the designed nanographenes, the azulene-based nanographene with two nitrogen atoms at the two ends has the largest static first hyperpolarizability (91.30 × 10-30 esu per heavy atom), and the further introduction of two N atoms at the two ends of the central azulene moiety of this nanographene results in a large static second hyperpolarizability while keeping the large static first hyperpolarizability.

Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1-KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS.

Bioactive neolignan, iridoid and flavonoid glycosides from the leaves of Vaccinium bracteatum.

Two neolignan glycosides including a new one (1), along with seven iridoid glycosides (3 - 9) and nine flavonoid glycosides (10 - 18), were isolated from the leaves of Vaccinium bracteatum. Their structures were established mainly on the basis of 1D/2D NMR and ESIMS analyses, as well as comparison to known compounds in the literature. The structure of 1 with absolute stereochemistry was also confirmed by chemical degradation and ECD calculation. Selective compounds showed antiradical activity against ABTS and/or DPPH. Moreover, several isolates also suppressed the production of ROS in RAW264.7 cells and exerted neuroprotective effect toward PC12 cells.

Bioactive monoterpenoids and acetophenones from the aerial parts of Eupatorium fortunei.

Thirty-nine thymol and acetophenone derivatives, including eight pairs of enantiomers, were isolated from the aerial parts of Eupatorium fortunei. Their structures were assigned by detailed analyses of spectroscopic data and NMR calculations based on density functional theory, with 18 ones (1a/1b-14) being previously undescribed compounds. While the absolute configurations of 1a/1b, 2a/2b, 4, 6a/6b, 7, 11a/11b and 15a/15b-18a/18b were established by calculations of electronic circular dichroism data, that of 14 was determined by modified Mosher's method. Compounds 1a/1b and 2a/2b represent a previously unreported type of monoterpenoid dimers via an amide linkage, and compound 3 is a monoterpene-phenylpropanoid hybrid connected through an ester bond. Among the known molecules, the formerly mis-assigned structures of 15a/15b and 22 were revised, and pure natural enantiomers of 16a/16b-18a/18b were reported for the first time. Selective compounds showed antiradical and NO production inhibitory activities in the preliminary biological screening. Compound 31 was further demonstrated to alleviate oxidative stress by activating Nrf2 signaling pathway.