One New Quinazoline-Containing Diketopiperazine Isolated from the Marine-Sponge-Derived Fungus Penicillium sp. SCSIO41043.

One new quinazoline-containing diketopiperazine (1), along with 24 known compounds including nine alkaloids (2-9, and 25), thirteen lactones (10-22), aspterric acid (23), and catechol (24), were isolated from the marine sponge-derived Penicillium sp. SCSIO41043. Their planar structures were unequivocally elucidated by spectroscopic analysis. The absolute configuration of 1 was determined by a comparison of reported and experimental electronic circular dichroism (ECD) spectra. Compound 16 was found to notably inhibit the growth of five pathogenic bacteria and fungi with MIC values ranging from 0.5-16.0 µg/mL. Compounds 7, 17, 20, and 22 demonstrated moderate activity against Micrococcus luteus with MIC values ranging from 35.6 to 71.1 µg/mL. Moreover, 1-3 displayed different degrees of antioxidant activity with EC50 values of 0.98, 0.60, 0.46 mg/mL, respectively.

Association of blood isobutyronitrile with infertility among reproductive-aged women: Results from the NHANES cohort.

Isobutyronitrile finds extensive application in organic synthesis for the production of the insecticide diazinon. Apart from occupational exposure, cigarette smoking may also expose the general population to isobutyronitrile. However, to date, the association between isobutyronitrile and female infertility has not been explored in a population-based study. Hence, we analysed data from 1254 women, aged 18-44, with blood isobutyronitrile results and infertility questionnaires, from National Health and Nutrition Examination Survey (NHANES) 2015-2016 and NHANES 2017-March 2020. To compare differences, weighted chi-square tests were conducted for categorical variables and weighted regression models were performed for continuous variables. Logistic regression and generalized linear models were applied to examine the associations. Each standard deviation increment (SD=0.026) of isobutyronitrile increased the risk of infertility by 24 % after adjusting for potential confounders in logistic regression model (aOR=1.24; 95 % CI: 1.06-1.46). In women who had been pregnant and gave birth, the results exhibited a consistent linear relationship. The participants were classified into two groups, namely positive and negative, using an isobutyronitrile cut-off value that exceeded 0.040 ng/mL. The positive group did not demonstrate a statistically significant correlation (aOR=1.55; 95 % CI: 0.66-3.65). According to smooth curve fitting, isobutyronitrile and infertility was linearly related across the entire range, and no threshold effect was found. Particularly, non-Hispanic Black women had a significantly stronger association with isobutyronitrile exposure and infertility (aOR=4.27; 95 % CI: 1.32-13.83). In conclusion, our study was the first report of an independent association of isobutyronitrile with infertility, especially in non-Hispanic Black women. Additional fundamental research on nonhuman primates, along with comprehensive clinical studies, are necessary to fully elucidate the intricate mechanisms underlying isobutyronitrile activity.

Unveiling the therapeutic potential of airpotato yam rhizome against colorectal cancer: a network pharmacology approach.

Objective: The objective of this investigation was to elucidate the key active compounds and molecular mechanisms underlying the therapeutic potential of airpotato yam rhizome (AYR) in colorectal cancer (CRC) treatment. Methods: By utilizing network pharmacology and molecular docking, key targets and signaling pathways of AYR against CRC were predicted and subsequently validated in cellular and mouse xenograft models. Results: This study initially predicted that quercetin was the primary compound in AYR that might have potential efficacy against CRC and that EGFR and AKT1 could be the main targets of AYR, with the EGF/EGFR-induced PI3K/AKT signaling pathway potentially playing a crucial role in the anti-CRC effects of AYR. Molecular docking analysis further indicated a strong binding affinity between quercetin and EGFR, primarily through hydrogen bonds. Additionally, the AYR-derived drug-containing serum was found to inhibit the PI3K/AKT signaling pathway, as demonstrated by decreased levels of p-PI3K, p-AKT, and BCL2, which ultimately led to enhanced apoptosis of HCT116 and HT29 cells. The potential antitumor effects of AYR were investigated in nude mouse xenograft models of human HCT116 and HT29 cells, in which AYR was found to induce tumor cell apoptosis and inhibit tumor formation. Conclusion: AYR may promote CRC cell apoptosis by suppressing the PI3K/AKT signaling pathway, which provides a basis for further research on the safe and effective use of AYR for the treatment of CRC.

Release of exosomes from injectable silk fibroin and alginate composite hydrogel for treatment of myocardial infarction.

Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-ß1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI.

Dual routes of chunking social interaction: Insights from grouping two agent actions in working memory.

Humans have evolved the sophisticated ability to extract social relations embedded in interactive entities. One typical demonstration is a social chunking phenomenon wherein the cognitive system chunks individual actions into a unified episode basing on perceived interactive actions. However, the mechanisms underlying social chunking remain to be elucidated. Most studies have adopted static images and manipulated interactions through agents' facingness (face-to-face vs. back-to-back). Connecting agents via directed contingent actions is crucial in forming real-life social interaction. Hence, we employed dynamic actions as stimuli, separated physical- and communicative-contingency interactive actions, and predicted that domain-general physical regularities and domain-specific social relationships are crucial in social interactions, respectively. We tested this prediction by using an involuntary chunking effect in working memory, wherein two individual actions are involuntarily chunked when containing task-irrelevant interactive information. We found that involuntary chunking occurred for both types of upright interactive actions (Experiments 1, 3, 5, and 6). Inverting actions erased the chunking of communicative- but not physical-contingency actions (Experiments 2, 4, and 5). The facingness of dyads did not participate in chunking physical-contingency actions but was a prerequisite for chunking communicative-contingency actions (Experiments 3 and 6). These results reveal the dual routes of chunking interactive actions. Moreover, they suggest that the chunking mechanisms of dynamic social interaction are distinct from those of static images, highlighting the importance of using dynamic stimuli to explore the mechanisms of social interaction in emerging people-watching interdisciplinarity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Anti-PD-1 treatment protects against seizure by suppressing sodium channel function.

AIMS: Although programmed cell death protein 1 (PD-1) typically serves as a target for immunotherapies, a few recent studies have found that PD-1 is expressed in the nervous system and that neuronal PD-1 might play a crucial role in regulating neuronal excitability. However, whether brain-localized PD-1 is involved in seizures and epileptogenesis is still unknown and worthy of in-depth exploration. METHODS: The existence of PD-1 in human neurons was confirmed by immunohistochemistry, and PD-1 expression levels were measured by real-time quantitative PCR (RT-qPCR) and western blotting. Chemoconvulsants, pentylenetetrazol (PTZ) and cyclothiazide (CTZ), were applied for the establishment of in vivo (rodents) and in vitro (primary hippocampal neurons) models of seizure, respectively. SHR-1210 (a PD-1 monoclonal antibody) and sodium stibogluconate (SSG, a validated inhibitor of SH2-containing protein tyrosine phosphatase-1 [SHP-1]) were administrated to investigate the impact of PD-1 pathway blockade on epileptic behaviors of rodents and epileptiform discharges of neurons. A miRNA strategy was applied to determine the impact of PD-1 knockdown on neuronal excitability. The electrical activities and sodium channel function of neurons were determined by whole-cell patch-clamp recordings. The interaction between PD-1 and α-6 subunit of human voltage-gated sodium channel (Nav1.6) was validated by performing co-immunostaining and co-immunoprecipitation (co-IP) experiments. RESULTS: Our results reveal that PD-1 protein and mRNA levels were upregulated in lesion cores compared with perifocal tissues of surgically resected specimens from patients with intractable epilepsy. Furthermore, we show that anti-PD-1 treatment has anti-seizure effects both in vivo and in vitro. Then, we reveal that PD-1 blockade can alter the electrophysiological properties of sodium channels. Moreover, we reveal that PD-1 acts together with downstream SHP-1 to regulate sodium channel function and hence neuronal excitability. Further investigation suggests that there is a direct interaction between neuronal PD-1 and Nav1.6. CONCLUSION: Our study reveals that neuronal PD-1 plays an important role in epilepsy and that anti-PD-1 treatment protects against seizures by suppressing sodium channel function, identifying anti-PD-1 treatment as a novel therapeutic strategy for epilepsy.

Association between waist circumference and female infertility in the United States.

BACKGROUND: Obesity has significant implications for fertility and reproductive health. However, evidences linking abdominal obesity to female infertility were limited and inconclusive. Our objective was to figure out the potential relationship between waist circumference (WC) and infertility among women of childbearing age in the United States using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Our cross-sectional study included 3239 female participants aged 18-45 years. To explore the independent relationship between WC and female infertility, the weighted multivariable logistic regression and smoothed curve fitting were performed. Interaction and subgroup analyzes were then conducted for secondary analysis. RESULTS: WC was positively associated with female infertility independent of BMI after adjusting for BMI and other potential confounders. In fully adjusted model, for every 1cm increase in waist circumference, the risk of infertility increased by 3% (OR = 1.03, 95% CI: 1.01-1.06). When WC was divided into five equal groups, women in the highest quintile had 2.64 times risk of infertility than that in the lowest quintile (OR = 2.64, 95% CI: 1.31-5.30). Smooth curve fitting revealed a non-linear but positively dose-dependent relationship between WC and female infertility. Furthermore, we found an inverted U-shaped relationship (turning point: 113.5 cm) between WC and female infertility in participants who had moderate recreational activities and a J-shaped relationship (turning point: 103 cm) between WC and female infertility in participants who had deficient recreational activities. CONCLUSIONS: Waist circumference is a positive predictor of female infertility, independent of BMI. Moderate recreational activities can lower the risk of female infertility associated with abdominal obesity.

Mood congruency affects physiological synchrony but not empathic accuracy in a naturalistic empathy task.

Empathy is a crucial aspect of our daily lives, as it enhances our wellbeing and is a proxy for prosocial behavior. It encompasses two related but partially distinct components: cognitive and affective empathy. Both are susceptible to context, biases and an individual's physiological state. Few studies have explored the effects of a person's mood on these empathy components, and results are mixed. The current study takes advantage of an ecological, naturalistic empathy task - the empathic accuracy (EA) task - in combination with physiological measurements to examine and differentiate between the effects of one's mood on both empathy components. Participants were induced with positive or negative mood and presented videos of targets narrating autobiographical negative stories, selected from a Chinese empathy dataset that we developed (now publicly available). The stories were conveyed in audio-only, visual-only and full-video formats. Participants rated the target's emotional state while watching or listening to their stories, and physiological measures were taken throughout the process. Importantly, similar measures were taken from the targets when they narrated the stories, allowing a comparison between participants' and targets' measures. We found that in audio-only and visual-only conditions, participants whose moods were congruent with the target showed higher physiological synchrony than those with incongruent mood, implying a mood-congruency effect on affective empathy. However, there was no mood effect on empathic accuracy (reflecting cognitive empathy), suggesting a different influence of mood on the two empathy components.

Bisabolane-type sesquiterpenoids and bacillibactin from the marine-derived fungus Aspergillus sydowii SCSIO 41041 and their enzyme inhibiting activity.

Twelve compounds, including eleven bisabolane-type sesquiterpenoids (1 - 11), and one bacillibactin (12) were identified from marine-derived fungus Aspergillus sydowii SCSIO 41041 isolated from Creseis acicula. The chemical structures were elucidated by the basis of spectroscopic evidences, including HRESIMS, NMR and optical rotation. Biologically, all compounds were evaluated for their acetyl cholin-esterase (AChE) enzyme, pancreatic lipase (PL) enzyme, neuraminidase (NA) and phosphodiesterase 4 (PDE4) inhibitory activities. Compound 12 displayed significant inhibitory activity against neuraminidase (NA) with an IC50 value of 24.0 µM, which was equivalent to the positive drug oseltamivir phosphate (IC50 value of 20.0 µM). And the NA inhibitory activity was confirmed by molecular docking analysis.

Pure total flavonoids from citrus alleviate oxidative stress and inflammation in nonalcoholic fatty liver disease by regulating the miR-137-3p/NOXA2/NOX2 pathway.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become a global health issue owing to its large disease population and high morbidity. We previously reported that the improvement in oxidative stress (OS) using pure total flavonoids from citrus (PTFC), flavonoids isolated from the peel of Citrus changshan-huyou Y.B. Chan, is a crucial strategy for NAFLD treatment. However, OS-associated intervention pathways in NAFLD remain unclear. METHODS: In this study, we used microRNA (miR)- and mRNA-sequencing to identify the pathway by which PTFC improve OS in NAFLD. Clinical data, mimic/inhibitor assays, and a dual-luciferase reporter assay were selected to verify the regulatory relationships of this pathway. Moreover, in vivo and in vitro experiments were used to confime the regulatory effect of PTFC on this pathway. RESULTS: miR-seq, mRNA-seq, and bioinformatics analyses revealed that the miR-137-3p/neutrophil cytosolic factor 2 (NCF2, also known as NOXA2)/cytochrome b-245 beta chain (CYBB, also known as NOX2) pathway may be a target pathway for PTFC to improve OS and NAFLD. Additionally, bivariate logistic regression analysis combining the serum and clinical data of patients revealed NOX2 and NOXA2 as risk factors and total antioxidant capacity (indicator of OS level) as a protective factor for NAFLD. miR-137-3p mimic/inhibitor assays revealed that the upregulation of miR-137-3p is vital for improving cellular steatosis, OS, and inflammation. Dual-luciferase reporter assay confirmed that NOXA2 acts as an miR-137-3p sponge. These results co-determined that miR-137-3p/NOXA2/NOX2 is an essential pathway involved in NAFLD pathogenesis, including lipid accumulation, OS, and inflammation. In vivo and in vitro experiments further confirmed that the miR-137-3p/NOXA2/NOX2 pathway is regulated by PTFC. CONCLUSION: PTFC alleviates OS and inflammation in NAFLD by regulating the miR-137-3p/NOXA2/NOX2 pathway.

Construction of the machine learning-based live birth prediction models for the first in vitro fertilization pregnant women.

BACKGROUND: This study was to conduct prediction models based on parameters before and after the first cycle, respectively, to predict live births in women who received fresh or frozen in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for the first time. METHODS: This retrospective cohort study population consisted of 1,857 women undergoing the IVF cycle from 2019 to 2021 at Huizhou Municipal Central Hospital. The data between 2019 and 2020 were completely randomly divided into a training set and a validation set (8:2). The data from 2021 was used as the testing set, and the bootstrap validation was carried out by extracting 30% of the data for 200 times on the total data set. In the training set, variables are divided into those before the first cycle and after the first cycle. Then, predictive factors before the first cycle and after the first cycle were screened. Based on the predictive factors, four supervised machine learning algorithms were respectively considered to build the predictive models: logistic regression (LR), random forest (RF), extreme gradient boosting (XGBoost), and light gradient boosting machine (LGBM). The performances of the prediction models were evaluated by the area under the receiver operator characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. RESULTS: Totally, 851 women (45.83%) had a live birth. The LGBM model showed a robust performance in predicting live birth before the first cycle, with AUC being 0.678 [95% confidence interval (CI): 0.651 to 0.706] in the training set, 0.612 (95% CI: 0.553 to 0.670) in the validation set, 0.634 (95% CI: 0.511 to 0.758) in the testing set, and 0.670 (95% CI: 0.626 to 0.715) in the bootstrap validation. The AUC value in the training set, validation set, testing set, and bootstrap of LGBM to predict live birth after the first cycle was 0.841 (95% CI: 0.821 to 0.861), 0.816 (95% CI: 0.773 to 0.859), 0.835 (95% CI: 0.743 to 0.926), and 0.839 (95% CI: 0.806 to 0.871), respectively. CONCLUSION: The LGBM model based on the predictive factors before and after the first cycle for live birth in women showed a good predictive performance. Therefore, it may assist fertility specialists and patients to adjust the appropriate treatment strategy.

Network pharmacology-based approach to explore the underlying mechanism of sinomenine on sepsis-induced myocardial injury in rats.

Background: Sepsis, a systemic disease, usually induces myocardial injury (MI), and sepsis-induced MI has become a significant contributor to sepsis-related deaths in the intensive care unit. The objective of this study is to investigate the role of sinomenine (SIN) on sepsis-induced MI and clarify the underlying mechanism based on the techniques of network pharmacology. Methods: Cecum ligation and puncture (CLP) was adopted to induce sepsis in male Sprague-Dawley (SD) rats. Serum indicators, echocardiographic cardiac parameters, and hematoxylin and eosin (H&E) staining were conducted to gauge the severity of cardiac damage. The candidate targets and potential mechanism of SIN against sepsis-induced MI were analyzed via network pharmacology. Enzyme-linked immunosorbent assay was performed for detecting the serum concentration of inflammatory cytokines. Western blot was applied for evaluating the levels of protein expression. Terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling assay was applied to assess cardiomyocyte apoptosis. Results: SIN significantly improved the cardiac functions, and attenuated myocardial structural damage of rats as compared with the CLP group. In total, 178 targets of SIN and 945 sepsis-related genes were identified, and 33 overlapped targets were considered as candidate targets of SIN against sepsis. Enrichment analysis results demonstrated that these putative targets were significantly associated with the Interleukin 17 (IL-17) signal pathway, inflammatory response, cytokines-mediated signal pathway, and Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) pathway. Molecular docking suggested that SIN had favorable binding affinities with Mitogen-Activated Protein Kinase 8 (MAPK8), Janus Kinase 1 (JAK1), Janus Kinase 2 (JAK2), Signal Transducer and Activator of Transcription 3 (STAT3), and nuclear factor kappa-B (NF-κB). SIN significantly reduced the serum concentration of Tumor Necrosis Factor-α (TNF-α), Interleukin 1 Beta (IL-1ß), Interleukin 6 (IL-6), Interferon gamma (IFN-γ), and C-X-C Motif Chemokine Ligand 8 (CXCL8), lowered the protein expression of phosphorylated c-Jun N-terminal kinase 1 (JNK1), JAK1, JAK2, STAT3, NF-κB, and decreased the proportion of cleaved-caspase3/caspase3. In addition, SIN also significantly inhibited the apoptosis of cardiomyocytes as compared with the CLP group. Conclusion: Based on network pharmacology analysis and corresponding experiments, it was concluded that SIN could mediate related targets and pathways to protect against sepsis-induced MI.

Isoflurane impairs olfaction by increasing neuronal activity in the olfactory bulb.

AIM: General anesthesia can induce cognitive deficits in both humans and rodents, correlating with pathological alterations in the hippocampus. However, whether general anesthesia affects olfactory behaviors remains controversial as clinical studies have produced inconsistent results. Therefore, we aimed to investigate how olfactory behaviors and neuronal activity are affected by isoflurane exposure in adult mice. METHODS: The olfactory detection test, olfactory sensitivity test, and olfactory preference/avoidance test were used to examine olfactory function. In vivo electrophysiology was performed in awake, head-fixed mice to record single-unit spiking and local field potentials in the olfactory bulb (OB). We also performed patch-clamp recordings of mitral cell activity. For morphological studies, immunofluorescence and Golgi-Cox staining were applied. RESULTS: Repeated exposure to isoflurane impaired olfactory detection in adult mice. The main olfactory epithelium, the first region exposed to anesthetics, displayed increased proliferation of basal stem cells. In the OB, a crucial hub for olfactory processing, repeated isoflurane exposure increased the odor responses of mitral/tufted cells. Furthermore, the odor-evoked high gamma response was decreased after isoflurane exposure. Whole-cell recordings further indicated that repeated isoflurane exposure increased the excitability of mitral cells, which may be due to weakened inhibitory input in isoflurane-exposed mice. In addition, elevated astrocyte activation and glutamate transporter-1 expression in the OB were observed in isoflurane-exposed mice. CONCLUSIONS: Our findings indicate that repeated isoflurane exposure impairs olfactory detection by increasing neuronal activity in the OB in adult mice.

Evaluation of serum anti-pertussis toxin IgA antibodies for the diagnosis of Bordetella pertussis infection in young children.

BACKGROUND: The determination of serum anti-pertussis toxin (PT) IgG antibodies is recommended for the diagnosis and surveillance of pertussis. However, the diagnostic power of anti-PT IgG can be hampered by possible interference from previous vaccinations. We aim to assess if anti-PT IgA antibodies can be well induced by Bordetella pertussis (B. pertussis) infections in children, and their capacity to improve pertussis serodiagnosis. METHODS: Serum samples from 172 hospitalized children younger than 10 years old with confirmed pertussis were tested. Pertussis was confirmed by culture, PCR and/or serology. Anti-PT IgA antibodies were determined with commercial ELISA kits. RESULTS: Sixty-four (37.2 %) subjects had anti-PT IgA antibodies greater than or equal to 15 IU/ml, and 52 (30.2 %) of them had anti-PT IgA antibodies greater than or equal to 20 IU/ml. No children with negative anti-PT IgG (less than 40 IU/ml) were observed to have anti-PT IgA antibodies greater than or equal to 15 IU/ml. Of patients younger than one year of age, about 50 % had an IgA antibody response. Moreover, the proportion of subjects with anti-PT IgA antibodies greater than or equal to 15 IU/ml among PCR negative subjects was significantly higher than that among PCR positive subjects (76.9 % vs 35.5 %). CONCLUSIONS: The determination of anti-PT IgA antibodies does not seem to have added value for the serodiagnosis of pertussis in children older than one year of age. However, for infants, determination of serum anti-PT IgA antibodies appears to be useful for the diagnosis of pertussis especially when PCR and culture are negative. The results should be interpreted with caution as the number of subjects included in this study was limited.

Analysis of the prevalence and related factors of primary hypertension among adolescents and children in the Taicang area.

OBJECTIVE: To investigate the prevalence of hypertension in adolescents and children in the Taicang area and analyse related factors to provide a theoretical basis for the prevention and control of hypertension in this region. METHODS: A total of 1,000 students who were visited and surveyed in primary schools in the Taicang area in 2021 were selected for statistical testing using a cluster random sampling method, and a survey was conducted on their dietary habits. dietary habits, such as the consumption of meals that included protein-rich animal products, beans and dairy products, vegetables and fruits, salty foods and fried food, was taken into consideration, along with physical fitness indices, waist-to-height ratio and waist circumference. RESULTS: Of the 1,000 adolescents and children surveyed, 222 were classified into the hypertensive group and 778 into the normotensive group. There were 138 boys (a prevalence rate of 6.3%) and 84 girls (a prevalence rate of 4.1%) in the hypertensive group. The physical fitness indices of the hypertensive group were significantly higher than those of the normotensive group. Concerning dietary structure, the frequency of cereal intake between the two groups was comparable, while the hypertensive group's intake of vegetables, fruits, beans and dairy products was significantly lower than that of the normotensive group. Finally, a logistic multivariate regression analysis of related factors was carried out, and it was concluded that waist-to-height ratio, waist circumference and salty and fried food intake were positively correlated with the prevalence of hypertension. CONCLUSION: The prevalence of hypertension among adolescents and children in the Taicang area is high. Body weight and dietary structure can be used as reference indicators for the prevalence of hypertension in this age group.

Association between serum Chlamydia trachomatis antibody levels and infertility among reproductive-aged women in the U.S.

Introduction: Chlamydia trachomatis infection, the most prevalent sexually transmitted bacterial infection worldwide, is a significant cause of infertility. Many countries have introduced the widespread use of serologic assays for IgG seropositivity to chlamydial plasmid gene product 3 (Pgp3). However, data on the association between the level of Pgp3-IgG in the multiplex bead array assay (Pgp3AbMBA) and female infertility are still scarce. Methods: This cross-sectional analysis included 1,425 women from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016. Results: In the fully adjusted logistic regression model, each standard deviation increments of Pgp3AbMBA (SD = 17,079.63) led to a 28% increase in the risk of infertility. The relationship remained consistent in women who had been pregnant and women who gave birth. Smooth curve fitting revealed that the association was linear across the entire range of Pgp3AbMBA. Subgroup analysis suggested that the association was significantly stronger in women who had ever used marijuana and lived in poverty. Conclusions: This study revealed a linear and independent association between the level of Pgp3AbMBA and self-reported infertility in U.S. women. Furthermore, we found that women who had ever used marijuana and lived in poverty were at the highest risk of infertility upon chlamydial infection.

Integrated analysis reveals important differences in the gut and oropharyngeal microbiota between children with mild and severe hand, foot, and mouth disease.

Little is known about alternation and difference in gut microbiota between patients with mild and severe hand, foot, and mouth disease (HFMD). We investigated the differences in gut and oropharynx microbiota between mild and severe HFMD in young children and changes in bacterial profiles as the disease progresses from acute to convalescent phase. Forty-two patients with confirmed HFMD were studied, among which 32 had severe HFMD and 10 had mild HFMD. First rectal swabs were collected from all patients at an average of 2 days (acute phase) after the onset of symptoms, and second rectal swabs were collected from 8 severe patients at day 9 (convalescent phase) after the onset. Oropharyngeal swabs were obtained from 10 patients in the acute phase and 6 in the convalescent phase. 16S rRNA sequencing was performed for all 70 samples. Compared with mild HFMD, severe HFMD exhibited significantly decreased diversity and richness of gut microbiota. Gut microbiota bacterial profiles observed in the acute and convalescent phases resembled each other but differed from those in mild cases. Additionally, 50% of patients with severe HFMD in the acute phase harboured a dominant pathobiontic bacterial genus. However, none of the patients with mild HFMD had such bacteria. Similar bacterial compositions in oropharynx microbiota were detected between mild and severe cases. Our findings indicate that severe HFMD exhibits significantly impaired diversity of gut microbiota and frequent gut and oropharyngeal inflammation-inducing bacteria. However, the results should be interpreted with caution as the number of subjects was limited.

The IDI1/SREBP2 axis drives intrahepatic cholestasis and is a treatment target of San-Huang-Cai-Zhu formula identified by sequencing and experiments.

San-Huang-Chai-Zhu formula (SHCZF), originates from Da-Huang-Xiao-Shi decoction (DHXSD) for the treatment of jaundice as recorded in the Chinese traditional Chinese medicine book Jin Gui Yao Lue. In the clinic, SHCZF has been used to treat cholestasis-related liver disease by improving intrahepatic cholestasis, but the treatment mechanism has not been elucidated. In this study, 24 Sprague-Dawley (SD) rats were randomly assigned to the normal, acute intrahepatic cholestasis (AIC), SHCZF, and ursodeoxycholic acid (UDCA) groups. In addition, 36 SD rats were divided into dynamic groups, namely, normal 24 h, AIC 24 h, normal 48 h, AIC 48 h, normal 72 h, and AIC 72 h groups. Alpha-naphthylisothiocyanate (ANIT) was used to induce an AIC rat model. Serum biochemical indices and hepatic pathology were detected. Part of the hepatic tissues was used for sequencing, and others were used for subsequent experiments. Sequencing data combined with bioinformatics analysis were used to screen target genes and identify the mechanisms of SHCZF in treating AIC rats. Quantitative real-time PCR (qRT-PCR) and Western blotting (WB) were used to detect the RNA/Protein expression levels of screened genes. Rats in the dynamic group were used to determine the sequence of cholestasis and liver injury. High-performance liquid chromatography (HPLC) was used to determine the representative bioingredients of SHCZF. Sequencing and bioinformatics analysis suggested that IDI1 and SREBP2 are hub target genes of SHCZF to ameliorate ANTI-induced intrahepatic cholestasis in rats. The treatment mechanism is associated with the regulation of lipoprotein receptor (LDLr) to reduce cholesterol intake and 3-Hydroxy-3-Methylglutaryl-CoA reductase (HMGCR), and 3-Hydroxy-3-Methylglutaryl-CoA synthase 1 (HMGCS1) to decrease cholesterol synthesis. Animal experiments showed that SHCZF significantly reduced the expression levels of the above genes and proinflammatory cytokine lipocalin 2 (LCN2), inflammatory cytokines interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α), thereby improving intrahepatic cholestasis and inflammation and liver injury.

Diagnostic value of peripheral TiM-3, NT proBNP, and Sestrin2 testing in left-to-right shunt congenital heart disease with heart failure.

BACKGROUND: Left-to-right shunt congenital heart disease is more likely to induce recurrent respiratory infections in the patients which exacerbate pulmonary hypertension and thereby impairs cardiac function. It is urgent to explore a non-invasive and accurate diagnostic method that can show the cardiac anatomy and associated malformations in clinical research. OBJECTIVE: To determine the diagnostic value of peripheral mucin domain protein-3 (Tim-3), N-terminal pro-brain natriuretic peptide (NT proBNP), sestrin2 testing in patients with the left-to-right shunt congenital heart disease and heart failure. METHODS: Fifty-two neonates with with left to right shunt congenital heart disease and 30 healthy neonates were enrolled. Blood samples were collected within 24 h of admission from newborns for determining the content of TiM-3, NT proBNP, and Sestrin2. Analyzing the ROC curve provided insight into the diagnostic accuracy. Both a Spearman's rank correlation test and a logistic regression analysis were carried out. RESULTS: TiM-3, NT proBNP, and Sestrin2 levels in peripheral blood were statistically different in the three groups (P < 0.05). There were significant differences in LVEF and LVFS among the three groups (P < 0.05). When used to diagnose heart failure in conjunction with left-to-right shunt congenital heart disease, TiM-3, NT proBNP, and Sestrin2 exhibited sensitivity of 58.3, 58.3, and 83.3%, respectively, and specificity of 85.0, 72.5, and 70.0%. ROC curve analysis showed that the AUCs of Tim-3, NT proBNP, and sestrin2 in predicting the outcome of left-to-right shunted congenital heart disease combined with heart failure were 0.744 (95% CI, 0.580 to 0.908), 0.608 (95% CI, 0.359 to 0.857), respectively 0.744 (95% CI 0.592 to 0.896). CONCLUSION: Tim-3, NT proBNP, and sestrin2 can accurately differentiate heart failure from non-combined heart failure from left-to-right shunt congenital heart disease.

Deficit of PKHD1L1 in the dentate gyrus increases seizure susceptibility in mice.

Epilepsy is a chronic neurological disorder featuring recurrent, unprovoked seizures, which affect more than 65 million people worldwide. Here, we discover that the PKHD1L1, which is encoded by polycystic kidney and hepatic disease1-like 1 (Pkhd1l1), wildly distributes in neurons in the central nervous system (CNS) of mice. Disruption of PKHD1L1 in the dentate gyrus region of the hippocampus leads to increased susceptibility to pentylenetetrazol-induced seizures in mice. The disturbance of PKHD1L1 leads to the overactivation of the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK)-Calpain pathway, which is accompanied by remarkable degradation of cytoplasmic potassium chloride co-transporter 2 (KCC2) level together with the impaired expression and function of membrane KCC2. However, the reduction of membrane KCC2 is associated with the damaged inhibitory ability of the vital GABA receptors, which ultimately leads to the significantly increased susceptibility to epileptic seizures. Our data, thus, indicate for the first time that Pkhd1l1, a newly discovered polycystic kidney disease (PKD) association gene, is required in neurons to maintain neuronal excitability by regulation of KCC2 expression in CNS. A new mechanism of the clinical association between genetic PKD and seizures has been built, which could be a potential therapeutic target for treating PKD-related seizures.