Artificial Microglia Nanoplatform Loaded With Anti-RGMa in Acoustic/Magnetic Feld for Recanalization and Neuroprotection in Acute Ischemic Stroke.

Ischemic stroke is a leading cause of death and disability worldwide, and the main goals of stroke treatment are to destroy the thrombus to recanalize blood vessels and protect tissue from ischemia/reperfusion injury. However, current recanalization therapies have serious limitations and there are few neuroprotection methods. Hence, an artificial nanoplatform loaded with anti-Repulsive Guidance Molecule a monoclonal antibody (anti-RGMa) and coated with microglia membrane (MiCM) is reported for stroke treatment, namely MiCM@PLGA/anti-RGMa/Fe3O4@PFH (MiCM-NPs). Tail vein injection of MiCM-NPs targeted the ischemia-damaged endothelial cells because of the MiCM, then superparamagnetic iron oxide (Fe3O4) and anti-RGMa are released after external low-intensity focused ultrasound (LIFU) exposure. The thrombus is destroyed by LIFU-induced "liquid-to-gas" phase transition and cavitation of perfluorohexane (PFH) as well as Fe3O4 movements induced by an external magnetic field. Anti-RGMa protected the ischemic region from ischemia/reperfusion injury. The nanoplatform enabled visualization of the thrombus by ultrasound/photoacoustic imaging when the clot is in an extracranial artery. Importantly, in vivo animal studies revealed good safety for MiCM-NPs treatment. In conclusion, this nanoplatform shows promise as an ischemic stroke treatment strategy combining targeted delivery, recanalization, and neuroprotection.

SLL-1A-16 suppresses proliferation and induces autophagy in non-small-cell lung cancer cells via the AKT/mTOR signaling pathway.

Non-small-cell lung cancer (NSCLC), which accounts for approximately eighty-five percent of lung cancer diagnoses worldwide, is a malignancy with high incidence and mortality rates. Among the various antitumor compounds, organic selenium-containing compounds have emerged as a promising class of therapeutic agents for cancer treatment. In the present study, SLL-1A-16, a new organoselenium small molecule, was discovered to exhibit antiproliferative activity against NSCLC both in vitro and in vivo. Treatment with SLL-1A-16 significantly inhibited NSCLC cell proliferation and induced apoptosis and autophagy. Mechanistically, SLL-1A-16 inhibited cell proliferation through G1-S phase arrest by reducing cyclin D1 and CDK4 expression. Additionally, SLL-1A-16 significantly induced apoptosis by upregulating cleaved caspase 3 and Bax expression, while downregulating Bcl-2 levels. Our study also demonstrated that SLL-1A-16 induced autophagy in NSCLC cells by inhibiting the Akt/mTOR pathway. Overall, our findings suggest that SLL-1A-16 could induce cell cycle arrest, apoptosis and autophagy in NSCLC cells by inhibiting the Akt/mTOR signaling pathways, providing a theoretical basis for the potential clinical application of SLL-1A-16 as a chemotherapeutic agent in NSCLC treatment.

Investigation of Human Milk as a Biological System in a Multicenter Mother-Infant Cohort: Protocol Design and Cohort Profile of the Phoenix Study.

Breastfeeding and human milk are the gold standard for infant feeding. Studying human milk with a systems biology approach in a large longitudinal cohort is needed to understand its complexity and health implications. The Phoenix study is a multicenter cohort study focusing on the interactions of maternal characteristics, human milk composition, infant feeding practices, and health outcomes of Chinese mothers and infants. A total of 779 mother-infant dyads were recruited from November 2021 to September 2022, and 769 mother-infant dyads were enrolled in the study. Scheduled home visits took place at 1, 4, 6, and 12 months postpartum, and 696 dyads (90.5% participants) completed the 12-month visit. At each visit, maternal and infant anthropometry was assessed. Questionnaires were administered to collect longitudinal information on maternal characteristics and lifestyle, infant feeding, and health. Digital diaries were used to record maternal dietary intake, infant feeding, and stool character. Human milk, maternal feces, infant feces, and infant saliva were collected. An external pharmaceutical-level quality assurance approach was implied to ensure the trial quality. Multi-omics techniques (including glycomics, lipidomics, proteomics, and microbiomics) and machine learning algorithms were integrated into the sample and data analysis. The protocol design of the Phoenix study provides a framework for prospective cohort studies of mother-infant dyads and will provide insights into the complex dynamics of human milk and its interplay with maternal and infant health outcomes in the Chinese population.

Characteristics of Myocardial Structure and Central Carbon Metabolism during the Early and Compensatory Stages of Cardiac Hypertrophy.

Cardiac hypertrophy is a classical forerunner of heart failure and myocardial structural and metabolic remodeling are closely associated with cardiac hypertrophy. We aim to investigate the characteristics of myocardial structure and central carbon metabolism of cardiac hypertrophy at different stages. Using echocardiography and pathological staining, early and compensatory cardiac hypertrophy were respectively defined as within 7 days and from 7 to 14 days after transverse aortic constriction (TAC) in mice. Among mass-spectrometry-based metabolomics, we identified 45 central carbon metabolites. Differential metabolite analysis showed that six metabolites, including citrate, cis-aconitate and so on, decreased significantly on day 1 after TAC. Ten metabolites, including l-lactate, (S)-2-hydroxyglutarate and so on, were obviously changed on days 10 and 14. Pathway analysis showed that these metabolites were involved in seven metabolic pathways, including carbohydrates, amino acids and so on. Western blot showed the expression of ATP-citrate lyase, malate dehydrogenase 1 and lactate dehydrogenase A in myocardium changed markedly on day 3, while the phosphorylation level of AMP-activated protein kinase did not show significantly difference. We hope our research will promote deeper understanding and early diagnosis of cardiac hypertrophy in clinical practice. All raw data were deposited in MetaboLights (MTBLS10555).

Associations of the EAT-Lancet reference diet with metabolic dysfunction-associated steatotic liver disease and its severity: A multicohort study.

BACKGROUND AND AIMS: The EAT-Lancet Commission devised a globally sustainable dietary pattern to jointly promote human health and sustainability. However, the extent to which this diet supports metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been assessed. This study aimed to investigate the association between the EAT-Lancet diet and the risk of MASLD and its severity. APPROACH AND RESULTS: This prospective multicohort study included 15,263 adults from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort, 1137 adults from the Guangzhou Nutrition and Health Study (GNHS) cohort, and 175,078 adults from the UK Biobank. In addition, 228 Chinese adults from the Prospective Epidemic Research Specifically of Non-alcoholic Steatohepatitis (PERSONS) with biopsy-proven MASLD were included. An EAT-Lancet diet index was created to reflect adherence to the EAT-Lancet reference diet. The TCLSIH cohort recorded 3010 MASLD cases during 53,575 person-years of follow-up, the GNHS cohort documented 624 MASLD cases during 6454 person-years of follow-up, and the UK Biobank developed 1350 MASLD cases during 1,745,432 person-years of follow-up. In multivariable models, participants in the highest tertiles of the EAT-Lancet diet index had a lower risk of MASLD compared with those in the lowest tertiles (TCLSIH: HR = 0.87, 95% CI: 0.78, 0.96; GNHS: HR = 0.79, 95% CI: 0.64, 0.98; UK Biobank: HR = 0.73, 95% CI: 0.63, 0.85). Moreover, liver-controlled attenuation parameter decreased with increasing the diet index in individuals with biopsy-proven MASLD (ß = -5.895; 95% CI: -10.014, -1.775). CONCLUSIONS: Adherence to the EAT-Lancet reference diet was inversely associated with the risk of MASLD as well as its severity.

Application of Bimetallic Hydroxide/Graphene Composites in Wastewater Treatment.

The increasing discharge of antibiotic wastewater leads to increasing water pollution. Most of these antibiotic wastewaters are persistent, strongly carcinogenic, easy to bioaccumulate, and have other similar characteristics, seriously jeopardizing human health and the ecological environment. As a commonly used wastewater treatment technology, non-homogeneous electro-Fenton technology avoids the hazards of H2O2 storage and transportation as well as the loss of desorption and reabsorption. It also facilitates electron transfer on the electrodes and the reduction of Fe3+ on the catalysts, thereby reducing sludge production. However, the low selectivity and poor activity of electro-synthesized H2O2, along with the low concentration of its products, combined with the insufficient activity of electrically activated H2O2, results in a low ∙OH yield. To address the above problems, composites of layered bimetallic hydroxides and carbon materials were designed and prepared in this paper to enhance the performance of electro-synthesized H2O2 and non-homogeneous electro-Fenton by changing the composite mode of the materials. Three composites, NiFe layered double hydroxides (LDHs)/reduced graphene oxide (rGO), NiMn LDHs/rGO, and NiMnFe LDHs/rGO, were constructed by the electrostatic self-assembly of exfoliated LDHs with few-layer graphene. The LDHs/rGO was loaded on carbon mats to construct the electro-Fenton cathode materials, and the non-homogeneous electro-Fenton oxidative degradation of organic pollutants was realized by the in situ electrocatalytic reduction of O2 to ∙OH. Meanwhile, the effects of solution pH, applied voltage, and initial concentration on the performance of non-homogeneous electro-Fenton were investigated with ceftazidime as the target pollutant, which proved that the cathode materials have an excellent electro-Fenton degradation effect.

The chromatin accessibility and transcriptomic landscape of the aging mice cochlea and the identification of potential functional super-enhancers in age-related hearing loss.

BACKGROUND: Presbycusis, also referred to as age-related hearing loss (ARHL), is a condition that results from the cumulative effects of aging on an individual's auditory capabilities. Given the limited understanding of epigenetic mechanisms in ARHL, our research focuses on alterations in chromatin-accessible regions. METHODS: We employed assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) in conjunction with unique identifier (UID) mRNA-seq between young and aging cochleae, and conducted integrated analysis as well as motif/TF-gene prediction. Additionally, the essential role of super-enhancers (SEs) in the development of ARHL was identified by comparative analysis to previous research. Meanwhile, an ARHL mouse model and an aging mimic hair cell (HC) model were established with a comprehensive identification of senescence phenotypes to access the role of SEs in ARHL progression. RESULTS: The control cochlear tissue exhibited greater chromatin accessibility than cochlear tissue affected by ARHL. Furthermore, the levels of histone 3 lysine 27 acetylation were significantly depressed in both aging cochlea and aging mimic HEI-OC1 cells, highlighting the essential role of SEs in the development of ARHL. The potential senescence-associated super-enhancers (SASEs) of ARHL were identified, most of which exhibited decreased chromatin accessibility. The majority of genes related to the SASEs showed obvious decreases in mRNA expression level in aging HCs and was noticeably altered following treatment with JQ1 (a commonly used SE inhibitor). CONCLUSION: The chromatin accessibility in control cochlear tissue was higher than that in cochlear tissue affected by ARHL. Potential SEs involved in ARHL were identified, which might provide a basis for future therapeutics targeting SASEs related to ARHL.

Circulating free DNA as a diagnostic marker for echinococcosis: a systematic review and meta-analysis.

Introduction: Echinococcosis is a chronic zoonotic disease caused by tapeworms of the genus Echinococcus. The World Health Organization (WHO) has identified encapsulated disease as one of 17 neglected diseases to be controlled or eliminated by 2050. There is no accurate, early, non-invasive molecular diagnostic method to detect echinococcosis. The feasibility of circulating free DNA as a diagnostic method for echinococcosis has yielded inconclusive results in a number of published studies. However, there has been no systematic evaluation to date assessing the overall performance of these assays. We report here the first meta-analysis assessing the diagnostic accuracy of cfDNA in plasma, serum, and urine for echinococcosis. Methods: We systematically searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WeiPu databases up to 17 January 2024, for relevant studies. All analyses were performed using RevMan 5.3, Meta-DiSc 1.4, Stata 17.0, and R 4.3.1 software. The sensitivity, specificity, and other accuracy indicators of circulating free DNA for the diagnosis of echinococcosis were summarized. Subgroup analyses and meta-regression were performed to identify sources of heterogeneity. Results: A total of 7 studies included 218 patients with echinococcosis and 214 controls (156 healthy controls, 32 other disease controls (non-hydatid patients), and 26 non-study-targeted echinococcosis controls were included). Summary estimates of the diagnostic accuracy of cfDNA in the diagnosis of echinococcosis were as follows: sensitivity (SEN) of 0.51 (95% CI: 0.45-0.56); specificity (SPE) of 0.99 (95% CI: 0.97-0.99); positive likelihood ratio (PLR) of 11.82 (95% CI: 6.74-20.74); negative likelihood ratio (NLR) of 0.57 (95% CI: 0.41-0.80); diagnostic ratio (DOR) of 36.63 (95% CI: 13.75-97.59); and area under the curve (AUC) value of 0.98 (95% CI: 0.96-1.00). Conclusion: Existing evidence indicates that the combined specificity of circulating cfDNA for echinococcosis is high. However, the combined sensitivity performance is unsatisfactory due to significant inter-study heterogeneity. To strengthen the validity and accuracy of our findings, further large-scale prospective studies are required.Systematic review registrationThe systematic review was registered in the International Prospective Register of Systematic Reviews PROSPERO [CRD42023454158]. https://www.crd.york.ac.uk/PROSPERO/.

Molecular and Cytological Identification of Wheat-Thinopyrum intermedium Partial Amphiploid Line 92048 with Resistance to Stripe Rust and Fusarium Head Blight.

Thinopyrum intermedium (2n = 6x = 42, EeEeEbEbStSt or JJJsJsStSt) contains a large number of genes that are highly adaptable to the environment and immune to a variety of wheat diseases, such as powdery mildew, rust, and yellow dwarf, making it an important gene source for the genetic improvement of common wheat. Currently, an important issue plaguing wheat production and breeding is the spread of pests and illnesses. Breeding disease-resistant wheat varieties using disease-resistant genes is currently the most effective measure to solve this problem. Moreover, alien resistance genes often have a stronger disease-resistant effect than the resistance genes found in common wheat. In this study, the wheat-Th. intermedium partial amphiploid line 92048 was developed through hybridization between Th. intermedium and common wheat. The chromosome structure and composition of 92048 were analyzed using ND-FISH and molecular marker analysis. The results showed that the chromosome composition of 92048 (Octoploid Trititrigia) was 56 = 42W + 6J + 4Js + 4St. In addition, we found that 92048 was highly resistant to a mixture of stripe rust races (CYR32, CYR33, and CYR34) during the seedling stage and fusarium head blight (FHB) in the field during the adult plant stage, suggesting that the alien or wheat chromosomes in 92048 had disease-resistant gene(s) to stripe rust and FHB. There is a high probability that the gene(s) for resistance to stripe rust and FHB are from the alien chromosomes. Therefore, 92048 shows promise as a bridge material for transferring superior genes from Th. intermedium to common wheat and improving disease resistance in common wheat.

Robust reactive oxygen species modulator hitchhiking yeast microcapsules for colitis alleviation by trilogically intestinal microenvironment renovation.

Ulcerative colitis (UC) is characterized by chronic inflammatory processes of the intestinal tract of unknown origin. Current treatments lack understanding on how to effectively alleviate oxidative stress, relieve inflammation, as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously. In this study, a novel drug delivery system based on a metal polyphenol network (MPN) was constructed via metal coordination between epigallocatechin gallate (EGCG) and Fe3+. Curcumin (Cur), an active polyphenolic compound, with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN. The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical (O2•-) as well as hydroxyl radical (·OH). By hitchhiking yeast microcapsule (YM), Cur-MPN was then encapsulated into YM to obtain CM@YM. Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon. When administered orally, CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS, reducing pro-inflammatory cytokines, and regulating the polarization of macrophages to M1, thus restoring barrier function and maintaining intestinal homeostasis. Importantly, CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids (SCFA) (such as acetic acid, propionic acid, and butyric acid). Collectively, with excellent biocompatibility, our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.

Circadian disruption during fetal development promotes pathological cardiac remodeling in male mice.

Disruption of circadian rhythms during fetal development may predispose mice to developing heart disease later in life. Here, we report that male, but not female, mice that had experienced chronic circadian disturbance (CCD) in utero were more susceptible to pathological cardiac remodeling compared with mice that had developed under normal intrauterine conditions. CCD-treated males showed ventricular chamber dilatation, enhanced myocardial fibrosis, decreased contractility, higher rates of induced tachyarrhythmia, and elevated expression of biomarkers for heart failure and myocardial remodeling. In utero CCD exposure also triggered sex-dependent changes in cardiac gene expression, including upregulation of the secretoglobin gene, Scgb1a1, in males. Importantly, cardiac overexpression of Scgb1a1 was sufficient to induce myocardial hypertrophy in otherwise naive male mice. Our findings reveal that in utero CCD exposure predisposes male mice to pathological remodeling of the heart later in life, likely as a consequence of SCGB1A1 upregulation.

The use of breast milk iodine concentration in the first week of lactation as a biomarker of iodine status in breast-feeding women.

Breast milk iodine concentration (BMIC) is a promising indicator of iodine status in lactating women. However, there are limited data on its usefulness to reflect maternal iodine deficiency. Therefore, the aim of our study was to assess iodine concentration in breast milk and urine samples in exclusively breast-feeding women. Eligible pregnant women undergoing routine antenatal care in a large hospital in Shaanxi Province, China, were followed up from the third trimester of pregnancy until the first week of lactation. Urine samples (20 ml) were collected during pregnancy and lactation. Iodine concentration in samples was measured based on Sandell-Kolthoff reaction. Breast milk samples (5 ml) were provided during lactation. A receiver operating curve (ROC) was constructed to determine the diagnostic performance of BMIC. An iodine-specific FFQ was completed twice during pregnancy and lactation. A total of 200 women completed the study. The overall median BMIC was 89 µg/l, indicating iodine sufficiency (i.e. BMIC reference range between 60 and 465 µg/l). Women reported similar median urinary iodine concentration (UIC) during pregnancy and lactation (112 and 113 µg/l, respectively), but their iodine status differed - mild-to-moderate iodine deficiency during pregnancy and iodine sufficiency during lactation. The ROC for BMIC using UIC as a reference standard was 0·755 (95 % CI: 0·644, 0·866). In conclusion, this study demonstrated that women were iodine sufficient in the first week of lactation as assessed by UIC, which was consistent with BMIC. These findings suggested that BMIC is a useful biomarker to assess iodine status in lactating women.

Spleen-dedicated stiffness measurement performed well to rule out high-risk varices in HBV-related hepatocellular carcinoma: Screening for high-risk varices in HCC.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is required to screen for high-risk varices (HRV) in patients with hepatocellular carcinoma (HCC), especially since overall survival rates have dramatically improved with new systemic therapies. AIM: To assess the Baveno VI and Baveno VII algorithms' ability to rule out HRV in hepatitis B virus (HBV)-related HCC METHODS: We prospectively enrolled consecutive patients with HBV related, compensated cirrhosis and newly diagnosed HCC who underwent liver stiffness measurement, spleen stiffness measurement (SSM) using a 100-Hz shear wave frequency, and EGD. RESULTS: From September 2021 to August 2023, we enrolled 219 patients with HCC, with 107 (48.9%) Barcelona Clinic Liver Cancer (BCLC) A, 28 (12.8%) BCLC B and 84 (38.3%) BCLC C, respectively. HRV prevalence was 28.8% (63/219). Baveno VI criteria safely (HRV missing rate, 3.2%) avoided 27.4% unnecessary EGDs, while the Baveno VII algorithm avoided 49.3% with HRV missing rate at 7.9% (5/63). The SSM ≤40 kPa avoided 47.5% of EGDs safely (HRV missing rate, 4.8%), significantly better than the Baveno VI criteria (p < 0.001) and comparable to the Baveno VII algorithm (p = 0.390). The SSM ≤40 kPa safely avoided EGDs in patient subgroups within Milan criteria, with portal vein tumour thrombosis or BCLC B/C or candidates for systemic therapy. CONCLUSIONS: We validated that the SSM ≤40 kPa using a 100-Hz probe could safely eliminate more unnecessary EGDs than the Baveno VI criteria in patients with HBV-related HCC. However, the efficacy of the Baveno VII algorithm in patients with HCC requires further investigation.

Impact of Epicardial Adipose Tissue on Right Cardiac Function and Prognosis in Pulmonary Arterial Hypertension.

BACKGROUND: Although epicardial adipose tissue (EAT) is linked to effects on survival in left-sided heart failure, the association between EAT and right-sided heart failure caused by pulmonary arterial hypertension (PAH) remains unknown. RESEARCH QUESTION: What are the potential impacts of EAT volume (EATV) on right ventricular function, biomarkers of myocardial injury, and long-term prognosis in patients with PAH?. STUDY DESIGN AND METHODS: A total of 135 age- and BMI-matched patients with PAH and 49 control subjects were included in this study. EATV was quantified by using cardiac magnetic resonance and was related to clinical correlates, N-terminal pro-brain natriuretic peptide, and cardiac function. Levels of EATV associated with the risk of clinical worsening were evaluated on a continuous scale (restricted cubic splines) and by previously defined centile categories with Cox proportional hazards regression models and Kaplan-Meier survival estimates. RESULTS: Compared with the control subjects, patients with PAH had a lower EATV (ln [EATV], 3.2 ± 0.8 mL vs 3.5 ± 0.7 mL; P = .034). The association of EATV with right ventricular end-diastolic volume (Pnonlinear = .001), right ventricular end-diastolic volume index (P < .001), right ventricular cardiac output (P = .003), N-terminal pro-brain natriuretic peptide (P = .030), and the risk of clinical worsening (P = .014) was U shaped. Compared with individuals with middle-level EATV, multivariable-adjusted hazard ratio for clinical worsening was 6.0 (95% CI, 1.3-27.8) for the individuals with low-level EATV and 6.8 (95% CI, 1.5-30.2) for high-level EATV in patients with PAH. INTERPRETATION: Patients with PAH had a decreased EATV compared with control subjects. EATV exhibited a U-shaped association with right ventricular function and biomarkers of myocardial injury in patients with PAH. Low and high levels of EATV might reduce long-term event-free survival in patients with PAH. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; No. ChiCTR2100049804; www.chictr.org.cn.

Pre-pregnancy body mass index and glycated-hemoglobin with the risk of metabolic diseases in gestational diabetes: a prospective cohort study.

Background: Metabolic diseases during pregnancy result in negative consequences for mothers. Pre-pregnancy body mass index (BMI) and late-pregnancy glycated-hemoglobin (HbA1c) are most important factors independently affecting the risk of gestational diabetes mellitus (GDM). However how both affect the combined risk of other metabolic diseases in women with GDM is unclear. The study aims to investigate the influence of pre-pregnancy BMI and pregnancy glycemic levels on other gestational metabolic diseases in women with GDM. Methods: Pregnancies with GDM from January 2015 to December 2018 in the Xi'an longitudinal mother-child cohort study (XAMC) were retrospectively enrolled. Those without other metabolic diseases by the time of oral glucose tolerance test (OGTT) detection were finally recruited and divided into four groups by pre-pregnancy BMI (Underweight <18.5kg/m2; Normal weight 18.5-23.9 kg/m2; Overweight 24.0-27.9 kg/m2; Obesity ≥28.0 kg/m2, respectively) or two groups by HbA1c in late pregnancy (normal HbA1c<5.7%; high HbA1c≥5.7%). Multivariate logistic regression analysis was used to identify risk factors. Interaction between pre-pregnancy BMI (reference group 18.5-23.9 kg/m2) and HbA1c (reference group <5.7%) was determined using strata-specific analysis. Results: A total of 8928 subjects with GDM were included, 16.2% of which had a composite of metabolic diseases. The pre-pregnancy overweight and obesity, compared with normal BMI, were linked to the elevated risk of the composite of metabolic diseases, particularly pre-eclampsia (both P <0.001) and gestational hypertension (both P <0.001). Meanwhile, patients with high HbA1c had an obvious higher risk of pre-eclampsia (P< 0.001) and gestational hypertension (P= 0.005) compared to those with normal HbA1c. In addition, there were significant interactions between pre-pregnancy BMI and HbA1c (P< 0.001). The OR of pre-pregnancy BMI≥ 28 kg/m2 and HbA1c≥ 5.7% was 4.46 (95% CI: 2.85, 6.99; P< 0.001). The risk of other metabolic diseases, except for pre-eclampsia (P= 0.003), was comparable between the two groups of patients with different HbA1c levels at normal pre-pregnancy BMI group. However, that was remarkably elevated in obese patients (P= 0.004), particularly the risk of gestational hypertension (P= 0.004). Conclusion: Pre-pregnancy overweight/obesity and late-pregnancy high HbA1c increased the risk of other gestational metabolic diseases of women with GDM. Monitoring and controlling late-pregnancy HbA1c was effective in reducing metabolic diseases, particularly in those who were overweight/obese before conception.

Analysis of relationship between P wave dispersion and diagnosis of pulmonary arterial hypertension and risk stratification.

BACKGROUND: The aim of this study was to measure the P-wave dispersion(PWD) in the ECG of patients with pulmonary arterial hypertension(PAH). METHODS: A total of 103 PAH patients were collected, including 55 patients related with congenital heart disease(CHD) and 44 patients with idiopathic pulmonary arterial hypertension(IPAH). In addition, 30 CHD patients without PAH (nPAH-CHD group) and 30 healthy controls (HCG group) were collected as control. Patients in the PAH group were categorized into the low-risk group (30 cases), moderate-risk group (53 cases) and high-risk group (20 cases), followed by comparison of PWD difference between groups. The ROC curve was used to evaluate the diagnostic efficacy of PWD on PAH-CHD and IPAH. RESULTS: The levels of PWD and maximum P wave duration(Pmax) in PAH-CHD and IPAH group were significantly higher than those in nPAH-CHD and HCG group (P < 0.05). PWD level was positively correlated with right ventricular end-diastolic diameter(RVD), right atrial end-systolic diameter(RAS), mean pulmonary arterial pressure(mPAP), pulmonary vascular resistance(PVR)(r = 0.407, 0.470, 0.477, 0.423, P < 0.001), and was negatively correlated with systolic displacement of tricuspid valve annulus(TAPSE) level (r = -0.551, P < 0.001). After risk quantification in 103 PAH patients, we found that PWD was significantly different among the low-risk, moderate-risk and high-risk groups (43.89 ± 9.91 vs. 51.29 ± 6.61, 62.15 ± 10.44, P < 0.001). CHD-PAH and IPAH were identified by PWD with a cut off value of 41.5 ms (P < 0.001), and a cut off value of 41.45 ms (P < 0.001), respectively. CONCLUSIONS: PWD might be an effective ECG indicator for PAH, which might be used as a relatively economical indicator for PAH patients to assist in early diagnosis, disease severity assessment and prognosis evaluation.

Metabolomics and metatranscriptomics reveal the influence mechanism of endogenous microbe (Staphylococcus succinus) inoculation on the flavor of fermented chili pepper.

This study integrated metabolomic and metatranscriptomic techniques to examine how the endogenous microbe, Staphylococcus succinus, influenced the essential flavor of fermented chili peppers. The mechanisms governing spontaneous fermentation and S. succinus-inoculated fermentation were also elucidated. Esters (e.g., ethyl undecanoate, isoamyl acetate, and methyl salicylate), terpenes (e.g., terpinen-4-ol), and alcohols (e.g., α-terpineol, linalool, and 4-methyl-3-heptanol) were found to be the key aroma-active compounds, aspartic acid (Asp) and glutamic acid (Glu) were identified as primary flavoring free amino acids. Notably, during the early stages of S. succinus-inoculated fermentation, the production of these essential metabolites was abundant, while their gradual increase over time was observed in the case of spontaneous fermentation. Metatranscriptomic analysis revealed that S. succinus inoculation could up-regulate genes related to glycolysis, amino acid metabolism, and aroma compound synthesis. These changes sequentially boosted the production of sweet and umami free amino acids, enhanced organic acid levels, increased unique aroma compound generation, and further improved the flavor and quality of the fermented chili peppers. Therefore, S. succinus inoculation can augment the sensory quality of fermented chili peppers, making this strain a promising candidate for Sichuan pickle fermentation starters.

Integrated Analysis of Immune Infiltration and Hub Pyroptosis-Related Genes for Multiple Sclerosis.

Purpose: Studies on overall immune infiltration and pyroptosis in patients with multiple sclerosis (MS) are limited. This study explored immune cell infiltration and pyroptosis in MS using bioinformatics and experimental validation. Methods: The GSE131282 and GSE135511 microarray datasets including brain autopsy tissues from controls and MS patients were downloaded for bioinformatic analysis. The gene expression-based deconvolution method, CIBERSORT, was used to determine immune infiltration. Differentially expressed genes (DEGs) and functional enrichments were analyzed. We then extracted pyroptosis-related genes (PRGs) from the DEGs by using machine learning strategies. Their diagnostic ability for MS was evaluated in both the training set (GSE131282 dataset) and validation set (GSE135511 dataset). In addition, messenger RNA (mRNA) expression of PRGs was validated using quantitative real-time polymerase chain reaction (qRT-PCR) in cortical tissue from an experimental autoimmune encephalomyelitis (EAE) model of MS. Moreover, the functional enrichment pathways of each hub PRG were estimated. Finally, co-expressed competitive endogenous RNA (ceRNA) networks of PRGs in MS were constructed. Results: Among the infiltrating cells, naive CD4+ T cells (P=0.006), resting NK cells (P=0.002), activated mast cells (P=0.022), and neutrophils (P=0.002) were significantly higher in patients with MS than in controls. The DEGs of MS were screened. Analysis of enrichment pathways showed that the pathways of transcriptional regulatory mechanisms and ion channels associating with pyroptosis. Four PRGs genes CASP4, PLCG1, CASP9 and NLRC4 were identified. They were validated in both the GSE135511 dataset and the EAE model by using qRT-PCR. CASP4 and NLRC4 were ultimately identified as stable hub PRGs for MS. Single-gene Gene Set Enrichment Analysis showed that they mainly participated in biosynthesis, metabolism, and organism resistance. ceRNA networks containing CASP4 and NLRC4 were constructed. Conclusion: MS was associated with immune infiltration. CASP4 and NLRC4 were key biomarkers of pyroptosis in MS.

Evaluating the role of serum uric acid in the risk stratification and therapeutic response of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD).

Background: Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease that negatively impacts quality of life, exercise capacity, and mortality. This study sought to investigate the relationship between serum uric acid (UA) level and the disease severity and treatment response of patients with PAH and congenital heart disease (PAH-CHD). Methods: This study included 225 CHD patients and 40 healthy subjects. Serum UA was measured in all patients, and UA levels and haemodynamic parameters were re-evaluated in 20 patients who had received PAH-specific drug treatment for at least 7 ± 1 month. Results: Serum UA levels were significantly higher in PAH-CHD patients than in CHD patients with a normal pulmonary artery pressure and normal subjects (347.7 ± 105.7 µmol/L vs. 278.3 ± 84.6 µmol/L; 347.7 ± 105.7 µmol/L vs. 255.7 ± 44.5 µmol/L, p < 0.05). UA levels in the intermediate and high risk groups were significantly higher than those in the low-risk group (365.6 ± 107.8 µmol/L vs. 311.2 ± 82.8 µmol/L; 451.6 ± 117.6 µmol/L vs. 311.2 ± 82.8 µmol/L, p < 0.05). Serum UA levels positively correlated with mean pulmonary arterial pressure, WHO functional class, pulmonary vascular resistance, and NT-proBNP (r = 0.343, 0.357, 0.406, 0.398; p < 0.001), and negatively with mixed venous oxygen saturation (SvO2) and arterial oxygen saturation (SaO2) (r = -0.293, -0.329; p < 0.001). UA significantly decreased from 352.7 ± 97.5 to 294.4 ± 56.8 µmol/L (p = 0.001) after PAH-specific drug treatment for at least 6 months, along with significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance and increases in cardiac index and mixed SvO2. Conclusion: Serum UA can be used as a practical and economic biomarker for risk stratification and the evaluation of PAH-specific drug treatment effects for patients with PAH-CHD.