Isolation of a facultative methanotroph Methylocystis iwaonis SD4 from rice rhizosphere and establishment of rapid genetic tools for it.

Methanotrophs of the genus Methylocystis are frequently found in rice paddies. Although more than ten facultative methanotrophs have been reported since 2005, none of these strains was isolated from paddy soil. Here, a facultative methane-oxidizing bacterium, Methylocystis iwaonis SD4, was isolated and characterized from rhizosphere samples of rice plants in Nanjing, China. This strain grew well on methane or methanol but was able to grow slowly using acetate or ethanol. Moreover, strain SD4 showed sustained growth at low concentrations of methane (100 and 500 ppmv). M. iwaonis SD4 could utilize diverse nitrogen sources, including nitrate, urea, ammonium as well as dinitrogen. Strain SD4 possessed genes encoding both the particulate methane monooxygenase and the soluble methane monooxygenase. Simple and rapid genetic manipulation methods were established for this strain, enabling vector transformation and unmarked genetic manipulation. Fast growth rate and efficient genetic tools make M. iwaonis SD4 an ideal model to study facultative methanotrophs, and the ability to grow on low concentration of methane implies its potential in methane removal.

3D Laser Writing of Low-Loss Cross-Section-Variable Type-I Optical Waveguide Passive/Active Integrated Devices in Single Crystals.

Optical waveguides fabricated in single crystals offer crucial passive/active optical components for photonic integrated circuits. Single crystals possess inherent advantages over their amorphous counterpart, such as lower optical losses in visible-to-mid-infrared band, larger peak emission cross-section, higher doping concentration. However, the writing of Type-I positive refractive index modified waveguides in single crystals using femtosecond laser technology presents significant challenges. Herein, we introduce a novel femtosecond laser direct writing technique that combines slit-shaping with an immersion oil objective to fabricate low-loss Type-I waveguides in single crystals. This approach allows for precise control of waveguide shape, size, mode-field and refractive index distribution, with a spatial resolution as high as 700 nm and a high positive refractive index variation on the order of 10-2, introducing new degrees of freedom to design and fabricate passive/active optical waveguide devices. As a proof-of-concept, we successfully produced a 7 mm-long circular-shaped gain waveguide (∼10 µm in diameter) in an Er3+-doped YAG single crystal, exhibiting a propagation loss as low as 0.23 dB/cm, a net gain of ∼3 dB and a polarization-insensitive character. The newly-developed technique is theoretically applicable to arbitrary single crystals, holding promising potential for various applications in integrated optics, optical communication, and photonic quantum circuits. This article is protected by copyright. All rights reserved.

Graphitic carbon nitride alleviates cadmium toxicity to soybeans through nitrogen supply.

Graphitic carbon nitride (g-C3N4) is a promising candidate for heavy metal remediation, primarily composed of carbon (C) and nitrogen (N). It has been demonstrated that g-C3N4 adjusts rhizosphere physicochemical conditions, especially N conditions, alleviating the absorption and accumulation of Cadmium (Cd) by soybeans. However, the mechanisms by which g-C3N4 induces N alterations to mitigates plant uptake of Cd remain unclear. This study investigated the impact of g-C3N4-mediated changes in N conditions on the accumulation of Cd by soybeans using pot experiments. It also explored the microbiological mechanisms underlying alterations in soybean rhizospheric N cycling induced by g-C3N4. It was found that g-C3N4 significantly increased N content in the soybean rhizosphere (p < 0.05), particularly in terms of available nitrogen (AN) of nitrate and ammonium. Plants absorbed more ammonium nitrogen (NH4⁺-N), the content of which in the roots showed a significant negative correlation with Cd concentration in plant (p < 0.05). Additionally, g-C3N4 significantly affected rhizospheric functional genes associated with N cycling (p < 0.05) by increasing the ratio of the N-fixation functional gene nifH and decreasing the ratios of functional genes amoA and nxrA involved in nitrification. This enhances soybean's N-fixing potential and suppresses denitrification potential in the rhizosphere, preserving NH4⁺-N. Niastella, Flavisolibacter, Opitutus and Pirellula may play a crucial role in the N fixation and preservation process. In summary, the utilization of g-C3N4 offers a novel approach to ensure safe crop production in Cd-contaminated soils. The results of this study provide valuable data and a theoretical foundation for the remediation of Cd polluted soils.

Integrated transcriptomic, metabolomic, and functional analyses unravel the mechanism of bagging delaying fruit cracking of pomegranate (Punica granatum L.).

The economic impact of fruit cracking in pomegranate products is substantial. In this study, we present the inaugural comprehensive analysis of transcriptome and metabolome in the outermost pericarp of pomegranate fruit in bagging conditions. Our investigation revealed a notable upregulation of differentially expressed genes (DEGs) associated with the calcium signaling pathway (76.92%) and xyloglucan endotransglucosylase/hydrolase (XTH) genes (87.50%) in the fruit peel of non-cracking fruit under bagging. Metabolomic analysis revealed that multiple phenolics, flavonoids, and tannins were identified in pomegranate. Among these, calmodulin-like 23 (PgCML23) exhibited a significant correlation with triterpenoids and demonstrated a marked upregulation under bagging treatment. The transgenic tomatoes overexpressing PgCML23 exhibited significantly higher cellulose content and xyloglucan endotransglucosylase (XET) enzyme activity in the pericarp at the red ripening stage compared to the wild type. Conversely, water-soluble pectin content, polygalacturonase (PG), and ß-galactosidase (ß-GAL) enzyme activities were significantly lower in the transgenic tomatoes. Importantly, the heterologous expression of PgCML23 led to a substantial reduction in the fruit cracking rate in tomatoes. Our findings highlight the reduction of fruit cracking in bagging conditions through the manipulation of PgCML23 expression.

Portable and Flexible Hydrogel Sensor for On-Site Atrazine Assay on Agricultural Products.

There is growing attention focused toward the problems of ecological sustainability and food safety raised from the abuse of herbicides, which underscores the need for the development of a portable and reliable sensor for simple, rapid, and user-friendly on-site analysis of herbicide residues. Herein, a novel multifunctional hydrogel composite is explored to serve as a portable and flexible sensor for the facile and efficient analysis of atrazine (ATZ) residues. The hydrogel electrode is fabricated by doping graphite-phase carbon nitride (g-C3N4) into the aramid nanofiber reinforced poly(vinyl alcohol) hydrogel via a simple solution-casting procedure. Benefiting from the excellent electroactivity and large specific surface area of the solid nanoscale component, the prepared hydrogel sensor is capable of simple, rapid, and sensitive detection of ATZ with a detection limit down to 0.002 ng/mL and per test time less than 1 min. After combination with a smartphone-controlled portable electrochemical analyzer, the flexible sensor exhibited satisfactory analytical performance for the ATZ assay. We further demonstrated the applications of the sensor in the evaluation of the ATZ residues in real water and soil samples as well as the user-friendly on-site point-of-need detection of ATZ residues on various agricultural products. We envision that this flexible and portable sensor will open a new avenue on the development of next-generation analytical tools for herbicide monitoring in the environment and agricultural products.

ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway.

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

Design, Synthesis, and Biological Evaluation of Novel Cinnamide Derivatives as Neuroprotective Agents for the Treatment of Cerebral Ischemia.

BACKGROUND: Ischemic stroke, the most common type of cerebrovascular accident, is a major cause of severe disability among adults worldwide. Although there has been progress in interventions for ischemic stroke in the past decades, there is no effective treatment to prevent brain damage in acute ischemic stroke. Therefore, it is urgent to develop novel neuroprotective agents with a wide therapeutic time window to provide a better prognosis for ischemic stroke patients. OBJECTIVE: The current study aimed to synthesize novel derivatives with substituent cinnamide scaffolds, evaluate biological activity, and obtain neuroprotective agents. METHODS: The target compounds were synthesized using classical methods of medicinal chemistry. The neuroprotective effects in vitro against Glu-induced neurotoxicity injury were evaluated in PC12 cells by MTT assay. The cell apoptosis was analyzed by flow cytometer. The proteins were detected by western blotting. The neuroprotective activities in vivo were determined in two in vivo models of global and focal cerebral ischemia. RESULTS: Among the title compounds, 9t, 9u, 9y, and 9z exhibited good neuroprotection in vivo and in vitro, which were selected and further studied to determine their mechanism of action. 9t, 9u, 9y and 9z protected PC12 cells against glutamate-induced apoptosis in a dose-dependent manner via caspase-3 pathway. Moreover, the four compounds significantly reduced brain infarct area and exhibited excellent neuroprotective activities in the in vivo MCAO model. CONCLUSION: Compounds 9t, 9u, 9y, and 9z, as potent neuroprotective agents with anti- neurotoxicity activity in vitro and anticerebral infarction efficacy in vivo, might serve as a useful molecular tool for further physiology and pathophysiology function studies, leading to potential clinical therapeutic agents for ischemic injury.

Atrial Cardiomyopathy Predicts the Functional Outcome and Mortality in Stroke Patients.

AIM: Atrial cardiomyopathy (ACM) is characterized by atrial dysfunction. This study aims to assess the prognostic significance of ACM in patients with noncardioembolic stroke (NCS). METHODS: Patients with NCS within seven days of onset were prospectively enrolled between January 2019 and December 2020. ACM was defined as either an N-terminal pro-brain natriuretic peptide (NT-pro BNP) ＞250 pg/ml or a P-terminal force in precordial lead V1 (PTFV1) ≥ 5000µV·ms. A poor functional outcome was determined as a score of 3-6 on the modified Rankin Scale (mRS) within a 2-year follow-up period. Logistic regression and Cox regression analyses were employed to examine the relationship between ACM and the long-term prognosis of patients with NCS. RESULTS: A total of 1,346 patients were enrolled, of whom 299 (22.2%) patients were diagnosed with ACM. A total of 207(15.4%) patients experienced a poor functional outcome, and 58 (4.3%) patients died. A multivariate logistic regression analysis indicated that ACM was significantly associated with a poor functional outcome in NCS patients [adjusted odds ratio (aOR): 2.01; 95% confidence interval (CI): 1.42-2.87; p＜0.001]. Additionally, a multivariate Cox regression analysis showed that an NT-pro BNP ＞250 pg/ml was significantly associated with an increased risk of all-cause mortality [adjusted hazard ratio (aHR), 2.51; 95% CI: 1.42-4.43; p=0.001]. CONCLUSIONS: ACM may serve as a novel predictor of a poor long-term functional outcome in patients with NCS. Elevated NT-pro BNP levels (＞250 pg/ml) were found to be associated with a higher risk of all-cause mortality. These findings warrant further validation in multicenter studies.

Long-term exposure to ambient air pollution and risk of microvascular complications among patients with type 2 diabetes: a prospective study.

BACKGROUND: Patients with type 2 diabetes (T2D) may disproportionately suffer the adverse cardiovascular effects of air pollution, but relevant evidence on microvascular outcome is lacking. We aimed to examine the association between air pollution exposure and the risk of microvascular complications among patients with T2D. METHODS: This prospective study included 17 995 participants with T2D who were free of macro- and micro-vascular complications at baseline from the UK Biobank. Annual average concentrations of particulate matter (PM) with diameters <2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were assessed using land use regression models. Cox proportional hazards regression was used to estimate the associations of air pollution exposure with incident diabetic microvascular complications. The joint effects of the air pollutant mixture were examined using quantile-based g-computation in a survival setting. RESULTS: In single-pollutant models, the adjusted hazard ratios (95% confidence intervals) for composite diabetic microvascular complications per interquartile range increase in PM2.5, PM10, NO2 and NOx were 1.09 (1.04-1.14), 1.06 (1.01-1.11), 1.07 (1.02-1.12) and 1.04 (1.00-1.08), respectively. Similar significant results were found for diabetic nephropathy and diabetic neuropathy, but not for diabetic retinopathy. The associations of certain air pollutants with composite microvascular complications and diabetic nephropathy were present even at concentrations below the World Health Organization limit values. Multi-pollutant analyses demonstrated that PM2.5 contributed most to the elevated risk associated with the air pollutant mixture. In addition, we found no interactions between air pollution and metabolic risk factor control on the risk of diabetic microvascular complications. CONCLUSIONS: Long-term individual and joint exposure to PM2.5, PM10, NO2 and NOx, even at low levels, was associated with an increased risk of diabetic microvascular complications, with PM2.5 potentially being the main contributor.

[Distribution of usual vitamin intake and prevalence of inadequate intake among Chinese adults in 2015].

OBJECTIVE: To estimate the usual vitamin intake and the prevalence of inadequate intakes among Chinese adults in 2015, and to provide a scientific basis for developing nutrition intervention strategies and measures for target populations. METHODS: Data was drawn from the Chinese Nutrition and Health Surveillance 2015-2017, a nationally representative cross-sectional study. The multistage stratified whole-group random sampling method was used to draw participants from 298 surveillance sites in 31 provinces(autonomous regions and municipalities). Participants with no available information or abnormal energy intake were excluded, and finally, a total of 72 231 participants aged 18 years and older were included in the current study. The dietary data of the participants were collected by the 24-hour dietary recall method combined with the condiment weighing method for three consecutive days. The National Cancer Institute method was used to estimate the distribution of the usual intake of vitamin B_1(thiamine), vitamin B_2(riboflavin), niacin, vitamin C(ascorbic acid), and vitamin E(tocopherol), and the prevalence of inadequate intake was evaluated based on estimated average requirement or adequate intake from the Chinese Dietary Reference Intakes 2023. RESULTS: The usual intake of vitamin E, vitamin C, vitamin B_1, vitamin B_2 and niacin were 27.93 mg/d, 77.67 mg/d, 0.78 mg/d, 0.62 mg/d and 13.15 mg/d, respectively. The prevalence of inadequate intake was, in descending order, vitamin B_2(95.98%), vitamin B_1(86.73%), vitamin C(63.70%), niacin(39.81%), and vitamin E(21.17%). The prevalence of inadequate vitamin E, vitamin C, vitamin B_1 and niacin intake among females was higher than among males(P<0.01). Overall, the prevalence of inadequate vitamin intake increased with age. Rural residents had a higher prevalence of inadequate intake of vitamin C, vitamin B_2 and niacin than urban residents(P<0.01). Except for vitamin E, the prevalence of inadequate intake of vitamins decreased with increasing education levels. The prevalence of inadequate intake of these five vitamins was higher among participants with lower income levels than those with middle or high income(P<0.01). Participants with normal weight had a higher prevalence of inadequate intake of vitamin E than those with overweight or obesity and had a higher prevalence of inadequate intake of vitamin C than those with obesity. However, participants with normal weight had a higher prevalence of inadequate intake of vitamin E than those with overweight or obesity, with the differences being statistically significant(P<0.01). Except for vitamin E, the prevalence of inadequate intake of vitamins decreased with increasing physical activity intensity. CONCLUSION: In 2015, the usual intake of dietary vitamins of Chinese adults was low. There are differences in usual intakes of vitamins and prevalence of inadequate vitamin intake for adults aged 18 years and above in males and females, different age groups, urban and rural areas, education levels, household income levels, body mass index and physical activity intensity.

Circulating cell-free DNA methylation-based multi-omics analysis allows early diagnosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 7.2% in China. However, effective approaches for diagnosis of PDAC are limited. Tumor-originating genomic and epigenomic aberration in circulating free DNA (cfDNA) have potential as liquid biopsy biomarkers for cancer diagnosis. Our study aims to assess the feasibility of cfDNA-based liquid biopsy assay for PDAC diagnosis. In this study, we performed parallel genomic and epigenomic profiling of plasma cfDNA from Chinese PDAC patients and healthy individuals. Diagnostic models were built to distinguish PDAC patients from healthy individuals. Cancer-specific changes in cfDNA methylation landscape were identified, and a diagnostic model based on six methylation markers achieved high sensitivity (88.7% for overall cases and 78.0% for stage I patients) and specificity (96.8%), outperforming the mutation-based model significantly. Moreover, the combination of the methylation-based model with carbohydrate antigen 19-9 (CA19-9) levels further improved the performance (sensitivity: 95.7% for overall cases and 95.5% for stage I patients; specificity: 93.3%). In conclusion, our findings suggest that both methylation-based and integrated liquid biopsy assays hold promise as non-invasive tools for detection of PDAC.

Urolithin A inhibits breast cancer progression via activating TFEB-mediated mitophagy in tumor macrophages.

INTRODUCTION: Urolithin A (UA) is a naturally occurring compound that is converted from ellagitannin-like precursors in pomegranates and nuts by intestinal flora. Previous studies have found that UA exerts tumor-suppressive effects through antitumor cell proliferation and promotion of memory T-cell expansion, but its role in tumor-associated macrophages remains unknown. OBJECTIVES: Our study aims to reveal how UA affects tumor macrophages and tumor cells to inhibit breast cancer progression. METHODS: Observe the effect of UA treatment on breast cancer progression though in vivo and in vitro experiments. Western blot and PCR assays were performed to discover that UA affects tumor macrophage autophagy and inflammation. Co-ip and Molecular docking were used to explore specific molecular mechanisms. RESULTS: We observed that UA treatment could simultaneously inhibit harmful inflammatory factors, especially for InterleuKin-6 (IL-6) and tumor necrosis factor α (TNF-α), in both breast cancer cells and tumor-associated macrophages, thereby improving the tumor microenvironment and delaying tumor progression. Mechanistically, UA induced the key regulator of autophagy, transcription factor EB (TFEB), into the nucleus in a partially mTOR-dependent manner and inhibited the ubiquitination degradation of TFEB, which facilitated the clearance of damaged mitochondria via the mitophagy-lysosomal pathway in macrophages under tumor supernatant stress, and reduced the deleterious inflammatory factors induced by the release of nucleic acid from damaged mitochondria. Molecular docking and experimental studies suggest that UA block the recognition of TFEB by 1433 and induce TFEB nuclear localization. Notably, UA treatment demonstrated inhibitory effects on tumor progression in multiple breast cancer models. CONCLUSION: Our study elucidated the anti-breast cancer effect of UA from the perspective of tumor-associated macrophages. Specifically, TFEB is a crucial downstream target in macrophages.

Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis.

Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.

Population-based screening for colorectal cancer in Wuhan, China.

Fecal DNA test has emerged as a non-invasive alternative for colorectal cancer (CRC) screening in average-risk population. However, there is currently insufficient evidence in China to demonstrate the effectiveness of population-based CRC screening using fecal DNA based test. Here, a large-scale real-world study for CRC screening was implemented in Wuhan, Hubei province, China. A total of 98,683 subjects aged between 45 and 60 years were screened by a fecal DNA test (ColoTect®) which detected methylation status of SDC2, ADHFE1, and PPP2R5C. Participants who tested positive were advised to receive diagnostic colonoscopy. 4449 (4.5%) subjects tested positive for fecal DNA test, and 3200 (71.9%) underwent colonoscopy. Among these, 2347 (73.3%) had abnormal colonoscopy findings, of which 1330 (56.7%) subjects received pathological diagnosis. Detection rates for CRC and advanced precancerous lesions were 1.3% and 2.3%, respectively. Detection rates for nonadvanced adenomas and polyps were 14.0% and 21.6%, respectively. 28.0% of all colonoscopies showed colorectal neoplasm but lack pathological diagnosis. 6.1% showed other abnormalities such as enteritis. In conclusion, preliminary real-world evidence suggested that fecal DNA tests had promising diagnostic yield in population-based CRC screening. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=192838, identifier ChiCTR2300070520.

A single-cell atlas of Drosophila trachea reveals glycosylation-mediated Notch signaling in cell fate specification.

The Drosophila tracheal system is a favorable model for investigating the program of tubular morphogenesis. This system is established in the embryo by post-mitotic cells, but also undergoes remodeling by adult stem cells. Here, we provide a comprehensive cell atlas of Drosophila trachea using the single-cell RNA-sequencing (scRNA-seq) technique. The atlas documents transcriptional profiles of tracheoblasts within the Drosophila airway, delineating 9 major subtypes. Further evidence gained from in silico as well as genetic investigations highlight a set of transcription factors characterized by their capacity to switch cell fate. Notably, the transcription factors Pebbled, Blistered, Knirps, Spalt and Cut are influenced by Notch signaling and determine tracheal cell identity. Moreover, Notch signaling orchestrates transcriptional activities essential for tracheoblast differentiation and responds to protein glycosylation that is induced by high sugar diet. Therefore, our study yields a single-cell transcriptomic atlas of tracheal development and regeneration, and suggests a glycosylation-responsive Notch signaling in cell fate determination.

New Horizons in Probiotics: Unraveling the Potential of Edible Microbial Polysaccharides through In Vitro Digestion Models.

In vitro digestion models, as innovative assessment tools, possess advantages such as speed, high throughput, low cost, and high repeatability. They have been widely applied to the investigation of food digestion behavior and its potential impact on health. In recent years, research on edible polysaccharides in the field of intestinal health has been increasing. However, there is still a lack of systematic reviews on the application of microbial-derived edible polysaccharides in in vitro intestinal models. This review thoroughly discusses the limitations and challenges of static and dynamic in vitro digestion experiments, while providing an in-depth introduction to several typical in vitro digestion models. In light of this, we focus on the degradability of microbial polysaccharides and oligosaccharides, with a particular emphasis on edible microbial polysaccharides typically utilized in the food industry, such as xanthan gum and gellan gum, and their potential impacts on intestinal health. Through this review, a more comprehensive understanding of the latest developments in microbial polysaccharides, regarding probiotic delivery, immobilization, and probiotic potential, is expected, thus providing an expanded and deepened perspective for their application in functional foods.

Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease.

BACKGROUND: Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD). METHODS: In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women. RESULTS: Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs [95% CIs] of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (95% CI: 1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age (P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7-18.6%) for their additive interaction in women. CONCLUSIONS: Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Yeast Bxi1/Ybh3 mediates conserved mitophagy and apoptosis in yeast and mammalian cells: convergence in Bcl-2 family.

The process of degrading unwanted or damaged mitochondria by autophagy, called mitophagy, is essential for mitochondrial quality control together with mitochondrial apoptosis. In mammalian cells, pan-Bcl-2 family members including conical Bcl-2 members and non-conical ones are involved in and govern the two processes. We have illustrated recently the BH3 receptor Hsp70 interacts with Bim to mediate both apoptosis and mitophagy. However, whether similar pathways exist in lower eukaryotes where conical Bcl-2 members are absent remained unclear. Here, a specific inhibitor of the Hsp70-Bim PPI, S1g-10 and its analogs were used as chemical tools to explore the role of yeast Bxi1/Ybh3 in regulating mitophagy and apoptosis. Using Om45-GFP processing assay, we illustrated that yeast Ybh3 mediates a ubiquitin-related mitophagy pathway in both yeast and mammalian cells through association with Hsp70, which is in the same manner with Bim. Moreover, by using Bax/Bak double knockout MEF cells, Ybh3 was identified to induce apoptosis through forming oligomerization to trigger mitochondrial outer membrane permeabilization (MOMP) like Bax. We not only illustrated a conserved ubiquitin-related mitophagy pathway in yeast but also revealed the multi-function of Ybh3 which combines the function of BH3-only protein and multi-domain Bax protein as one.

Analyzing prehospital delays in recurrent acute ischemic stroke: Insights from interpretable machine learning.

OBJECTIVE: This study investigates prehospital delays in recurrent Acute Ischemic Stroke (AIS) patients, aiming to identify key factors contributing to these delays to inform effective interventions. METHODS: A retrospective cohort analysis of 1419 AIS patients in Shenzhen from December 2021 to August 2023 was performed. The study applied the Extreme Gradient Boosting (XGBoost) algorithm and SHapley Additive exPlanations (SHAP) for identifying determinants of delay. RESULTS: Living with others and lack of stroke knowledge emerged as significant risk factors for delayed hospital presentation in recurrent AIS patients. Key features impacting delay times included residential status, awareness of stroke symptoms, presence of conscious disturbance, diabetes mellitus awareness, physical weakness, mode of hospital presentation, type of stroke, and presence of coronary artery disease. CONCLUSION: Prehospital delays are similarly prevalent among both recurrent and first-time AIS patients, highlighting a pronounced knowledge gap in the former group. This discovery underscores the urgent need for enhanced stroke education and management. PRACTICE IMPLICATION: The similarity in prehospital delay patterns between recurrent and first-time AIS patients emphasizes the necessity for public health initiatives and tailored educational programs. These strategies aim to improve stroke response times and outcomes for all patients.

Unveiling the critical pH values triggering the unfolding of soy 7S and 11S globulins and enhancing their encapsulation efficiency.

The pH-shifting process is an effective encapsulation method, and it is typically performed at extreme alkaline pH, which severely limits the application. In this study, we found that there were critical pH for the unfolding proteins during pH-shifting from 7 to 12, and upon the critical pH, physiochemical characteristics of protein greatly changed, leading to a sharp increase of encapsulation of hydrophobic actives. Firstly, the critical pH for ß-conglycinin (7S) or Glycinin (11S) unfolding was determined by multispectral technology. The critical pH for 7S and 11S were 10.5 and 10.3, respectively. The encapsulation efficiency (EE) obtained by ß-conglycinin-curcumin nanocomposite (7S-Cur) (88.80 %) and Glycinin-curcumin nanocomposite (11S-Cur) (88.38 %) at critical pH was significantly higher than that obtained by pH 7 (7S-Cur = 16.66 % and 11S-Cur = 15.78 %), and both values were close to EE obtained by at 12 (7S-Cur = 95.16 % and 11S-Cur = 94.63 %). The large-scale application of hydrophobic functional compounds will be enhanced by the experimental results.