VPS34 Acetylation Controls Its Lipid Kinase Activity and the Initiation of Canonical and Non-canonical Autophagy.

The class III phosphoinositide 3-kinase VPS34 plays a key role in the regulation of vesicular trafficking and macroautophagy. So far, we know little about the molecular mechanism of VPS34 activation besides its interaction with regulatory proteins to form complexes. Here, we report that VPS34 is specifically acetylated by the acetyltransferase p300, and p300-mediated acetylation represses VPS34 activity. Acetylation at K771 directly diminishes the affinity of VPS34 for its substrate PI, while acetylation at K29 hinders the VPS34-Beclin 1 core complex formation. Inactivation of p300 induces VPS34 deacetylation, PI3P production, and autophagy, even in AMPK-/-, TSC2-/-, or ULK1-/- cells. In fasting mice, liver autophagy correlates well with p300 inactivation/VPS34 deacetylation, which facilitates the clearance of lipid droplets in hepatocytes. Thus, p300-dependent VPS34 acetylation/deacetylation is the physiological key to VPS34 activation, which controls the initiation of canonical autophagy and of non-canonical autophagy in which the upstream kinases of VPS34 can be bypassed.

Association of sdLDL-C With Incident Carotid Plaques With Stable and Vulnerable Morphology: A Prospective Cohort Study.

BACKGROUND: Small dense low-density lipoprotein cholesterol (sdLDL-C) particles are more atherogenic than large and intermediate low-density lipoprotein cholesterol (LDL-C) subfractions. We sought to investigate the association of sdLDL-C and the sdLDL-C/LDL-C ratio with incident carotid plaques with stable and vulnerable morphology in rural China. METHODS: This community-based cohort study used data from the RICAS study (Rose Asymptomatic Intracranial Artery Stenosis), which enrolled 887 participants (aged ≥40 years) who were living in Kongcun Town, Pingyin County, Shandong, and free of carotid plaques and had no history of clinical stroke or transient ischemic attack at baseline (2017). Incident carotid plaques and their vulnerability were detected by carotid ultrasound at follow-up (2021). Multivariable logistic regression models were used to explore the association of sdLDL-C or sdLDL-C/LDL-C ratio with incident carotid plaques while adjusting for demographic factors, vascular risk factors, and follow-up time. RESULTS: Of the 887 participants (mean age [SD], 53.89 [8.67%] years; 54.34% women), 179 (20.18%) were detected with incident carotid plaques during an average follow-up of 3.94 years (SD=0.14). Higher sdLDL-C or sdLDL-C/LDL-C ratio, but not LDL-C, was significantly associated with an increased risk of incident carotid plaques. The upper tertile of sdLDL-C (versus lower tertile) was associated with the multivariate-adjusted odds ratio of 2.48 (95% CI, 1.00-6.15; P=0.049; P for linear trend=0.046) for carotid plaques with vulnerable morphology (n=41), and the association remained significant in participants with normal LDL-C (<130 mg/dL; n=693; upper versus lower tertile: odds ratio, 3.38 [95% CI, 1.15-9.90]; P=0.027; P for linear trend=0.025). Moreover, the sdLDL-C/LDL-C ratio was associated with a higher odds ratio of incident carotid plaques in participants without diabetes (P for interaction=0.014). CONCLUSIONS: Higher sdLDL-C was associated with an increased risk of incident carotid plaques, especially carotid plaques with vulnerable morphology, even in participants with normal LDL-C. This suggests the potential of sdLDL-C as a therapeutic target for stroke prevention. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017197.

The Epidemic Characteristics of Stroke Death from 2012 to 2021 in Chongqing, China.

INTRODUCTION: Stroke has become a major disease that threatens the global population's health and is a major public health problem that needs to be solved in China. Therefore, it is essential to analyze the trend of the mortality of stroke and its epidemic characteristic of stroke death. METHODS: Death cases of stroke were reported to the national death registry system by the medical staff of all medical institutions, and the population data every year were obtained from District or County's Statistic Bureau in Chongqing. They were analyzed to calculate the mortality, age-standardized mortality rate by Chinese standardization population (ASMRC), age-specific mortality, proportion, and annual percent of change (APC) according to the ICD-10 code. ASMRC was based on the standard population of the 6th census in China, 2010. The stroke mortality of each subgroup was compared using the χ2 test. Trend analysis was presented by APC. RESULTS: The crude mortality of stroke increased from 96.29 per 100,000 in 2012 to 115.93 per 100,000 significantly, with the APC of 2.02% (t = 2.82, p = 0.022) in Chongqing. ASMRC of stroke was 56.47 per 100,000 in 2012 and 54.70 per 100,000 in 2021, and its trend change was stable (APC = -0.01, t = 0.07, p = 0.947). The crude mortality of stroke in males was higher than that in females every year (p < 0.05). The death proportion of intracerebral hemorrhage dwindled from 60.53% in 2012 to 49.88% in 2021, whereas the death proportion of ischemic stroke increased from 20.92% in 2012 to 39.96% in 2021. The average age of stroke death was delayed from 73.43 years old in 2012 to 76.52 years old in 2021 significantly (t = 18.12, p < 0.001). The percentage of stroke death at home increased from 75.23% in 2012 to 79.23% in 2021, while the percentage of stroke death at hospitals decreased from 17.89% in 2012 to 15.89% in 2021. CONCLUSION: The crude mortality of stroke surged, and intracerebral hemorrhage was the main death cause of all subtypes. The mortality of stroke in males and rural residents was higher than that in females and urban residents. Most stroke deaths occurred at home. Male and rural residents were crucial populations for stroke prevention and control. There should be improved medical resources in rural areas and enhanced capability of stroke diagnosis and treatment.

A study of prehospital EMS response time and influencing factors in the main urban area of Chongqing, China.

Shortening the prehospital emergency medical service (EMS) response time is crucial for saving lives and lowering mortality and disability rates in patients with sudden illnesses. Descriptive analyses of prehospital EMS response time and each component were conducted separately using ambulance trip data from the 120 Dispatch Command Centre in the main urban area of Chongqing in 2021, and then, logistic regression analyses were used to explore the influencing factors. The median prehospital EMS response time in the main urban area of Chongqing was 14.52 min and the mean was 16.14 min. A 44.89% of prehospital EMS response time exceeded 15 min. Response time was more likely to surpass this threshold during peak hours and in high population density areas. Conversely, lower probabilities exceeding 15 min were observed during the night shift, summer, and autumn seasons, and areas with a high density of emergency station. 33.28% of preparation time was >3 min, with the night shift and high population density areas more likely to be >3 min, while for the summer and autumn seasons, high Gross National Product (GDP) per capita areas had a lower likelihood of having preparation time >3 min. 45.52% of travel time was >11 min, with peak hours, summer and autumn, and high GDP per capita areas more likely to have had a travel time >11 min, while night shift and high emergency station density areas had a lower likelihood of travel time >11 min. The primary factors influencing prehospital EMS response time were shifts, traffic scenarios, seasons, GDP per capita, emergency station density, and population density. Relevant departments can devise effective interventions to reduce response time through resource allocation and department coordination, staff training and work arrangement optimisation, as well as public participation and education, thereby enhancing the efficiency of prehospital emergency medical services.

Comprehensive Assessment of Collagen/Sodium Alginate-Based Sponges as Hemostatic Dressings.

In our search for a biocompatible composite hemostatic dressing, we focused on the design of a novel biomaterial composed of two natural biological components, collagen and sodium alginate (SA), cross-linked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) and oxidized sodium alginate (OSA). We conducted a series of tests to evaluate the physicochemical properties, acute systemic toxicity, skin irritation, intradermal reaction, sensitization, cytotoxicity, and in vivo femoral artery hemorrhage model. The results demonstrated the excellent biocompatibility of the collagen/sodium alginate (C/SA)-based dressings before and after crosslinking. Specifically, the femoral artery hemorrhage model revealed a significantly shortened hemostasis time of 132.5 ± 12.82 s for the EDC/NHS cross-linked dressings compared to the gauze in the blank group (hemostasis time of 251.43 ± 10.69 s). These findings indicated that C/SA-based dressings exhibited both good biocompatibility and a significant hemostatic effect, making them suitable for biomedical applications.

The Structural Characteristics and Bioactivity Stability of Cucumaria frondosa Intestines and Ovum Hydrolysates Obtained by Different Proteases.

The study aimed to investigate the effects of alcalase, papain, flavourzyme, and neutrase on the structural characteristics and bioactivity stability of Cucumaria frondosa intestines and ovum hydrolysates (CFHs). The findings revealed that flavourzyme exhibited the highest hydrolysis rate (51.88% ± 1.87%). At pH 2.0, the solubility of hydrolysate was the lowest across all treatments, while the solubility at other pH levels was over 60%. The primary structures of hydrolysates of different proteases were similar, whereas the surface hydrophobicity of hydrolysates was influenced by the types of proteases used. The hydrolysates produced by different proteases were also analyzed for their absorption peaks and antioxidant activity. The hydrolysates of flavourzyme had ß-fold absorption peaks (1637 cm-1), while the neutrase and papain hydrolysates had N-H bending vibrations. The tertiary structure of CFHs was unfolded by different proteases, exposing the aromatic amino acids and red-shifting of the λ-peak of the hydrolysate. The alcalase hydrolysates showed better antioxidant activity in vitro and better surface hydrophobicity than the other hydrolysates. The flavourzyme hydrolysates displayed excellent antioxidant stability and pancreatic lipase inhibitory activity during gastrointestinal digestion, indicating their potential use as antioxidants in the food and pharmaceutical industries.

Association between ambient temperatures and injuries: a time series analysis using emergency ambulance dispatches in Chongqing, China.

BACKGROUND: Global warming and increasing extreme weather have become a severe problem in recent years, posing a significant threat to human health worldwide. Research exploring the link between injury as one of the leading causes of death globally and ambient temperature was lacking. Based on the hourly injury emergency ambulance dispatch (IEAD) records from 2019-2021 in the main urban area of Chongqing, this study explored the role of temperature extremes on the pathogenesis of injury by different mechanisms and identified sensitive populations for different mechanisms of injury. METHODS: In this study, we collected hourly injury emergency ambulance dispatch (IEAD) records from Chongqing Emergency Dispatch Center in the main urban area of Chongqing from 2019 to 2021, and used a distributed lagged nonlinear model (DLNM) with quasi-Poisson distribution to evaluate the association between ambient temperature and IEADs. And the stratified analysis was performed by gender, age and different injury mechanisms to identify susceptible groups. Finally, the attributable burden of ambient extreme temperatures was also investigated. RESULTS: The risk for total IEADs increased significantly at high temperature (32 °C) compared with optimal temperature (9 °C) (CRR: 1.210; 95%CI[1.127,1.300]). The risks of traffic accident injury (CRR: 1.346; 95%CI[1.167,1.552]), beating injury (CRR: 1.508; 95%CI[1.165,1.952]), fall-height injury (CRR: 1.871; 95%CI[1.196-2.926]) and injury of sharp penetration (CRR: 2.112; 95%CI[1.388-3.213]) were significantly increased. At low temperature (7 °C), the risk of fall injury (CRR: 1.220; 95% CI [1.063,1.400]) increased significantly. Lag for 24 hours at extreme low temperature (5 °C), the risk of 18-45 years (RR: 1.016; 95%CI[1.009,1.024]) and over 60 years of age (RR: 1.019; 95%CI[1.011,1.025]) increased significantly. The effect of 0 h delay in extreme high temperature (36 °C) on males aged 18-45 years (RR: 1.115; 95%CI[1.071,1.162]) and 46-59 years (RR: 1.069; 95%CI[1.023,1.115]) had significant impact on injury risk. CONCLUSIONS: This study showed that ambient temperature was significantly related to the risk of injury, and different mechanisms of injury were affected differently by extreme temperature. The increasing risk of traffic accident injury, beating injury, fall-height injury and sharp penetrating injury was associated with extreme heat, while fall injury was associated with extreme cold. The risk of injury in high temperature environment was mainly concentrated in males and young adults. The results of this study can help to identify the sensitive population with different injury mechanisms in extreme temperature environment, and provide reference for public health emergency departments to respond to relevant strategies in extreme temperature environment to minimize the potential risk to the public.

Integrative analysis of transcriptomics and metabolomics to reveal the melanogenesis pathway of muscle and related meat characters in Wuliangshan black-boned chickens.

BACKGROUND: Melanin is an important antioxidant in food and has been used in medicine and cosmetology. Chicken meat with high melanin content from black-boned chickens have been considered a high nutritious food with potential medicinal properties. The molecular mechanism of melanogenesis of skeletal muscle in black-boned chickens remain poorly understood. This study investigated the biological gene-metabolite associations regulating the muscle melanogenesis pathways in Wuliangshan black-boned chickens with two normal boned chicken breeds as control. RESULTS: We identified 25 differentially expressed genes and 11 transcription factors in the melanogenesis pathways. High levels of the meat flavor compounds inosine monophosphate, hypoxanthine, lysophospholipid, hydroxyoctadecadienoic acid, and nicotinamide mononucleotide were found in Wuliangshan black-boned chickens. CONCLUSION: Integrative analysis of transcriptomics and metabolomics revealed the dual physiological functions of the PDZK1 gene, involved in pigmentation and/or melanogenesis and regulating the phospholipid signaling processes in muscle of black boned chickens.

Effect of epicatechin on inflammatory cytokines and MAPK/NF-κB signaling pathway in lipopolysaccharideinduced acute lung injury of BALB/c mice.

This study evaluated the anti-inflammatory effect of epicatechin (EC) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) of tracheal installation in BALB/c mice. It was observed that EC could alleviate not only the histopathological changes but also decrease the wet/dry weight (W/D) ratio of lung tissues. It also suppressed the release of IL-1ß, IL-6, and TNF-α in serum, bronchoalveolar lavage fluid (BALF), and lung tissues, respectively. A quantitative realtime PCR-based study further indicated that EC also inhibited the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA in lung tissues. In addition, the Western blot report suggested that EC was closely involved in the inhibition of phosphorylation of ERK, JNK, p38, p65, and IκB in mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathway. These results provide an experimental and theoretical basis for treating pulmonary inflammation by EC.

The effect of daily mean temperature on hand, foot and mouth disease and the source of regional heterogeneity in Chongqing, China, 2010-2019.

BACKGROUND: Hand, foot and mouth disease (HFMD) is a serious infectious disease which has become a public health problem. A multi-regional study was conducted in this study to explore the relationship between temperature and HFMD in different regions and the source of heterogeneity, and further detect the effect modifiers such as socio-economic factors, medical and health factors and meteorological factors. METHODS: The data on daily reported HFMD cases and meteorological data from 2010 to 2019 in Chongqing were collected. Thirty-eight districts and counties of Chongqing were divided into 6 regions. The distributed lag nonlinear model (DLNM) was applied to assess the effect of daily mean temperature on HFMD at region level with the pooled effect estimates from multivariate meta-regression model analysis. Stratified analyses by gender, age and children's type were also conducted. Potential modifiers were considered in meta regression to explore the source of heterogeneity. RESULTS: There were nonlinear relationships with an inverted V-shape between temperature and HFMD. A maximum cumulative relative risk (CRR) of 1.22 (95% confidence interval (CI): 1.12-1.34) peaked at 23.8 °C, and the risk appeared immediately and lasted for the whole 14 days. Compared with other groups, warm temperature had a stronger effect on children aged 0-1 and scattered children, while cold temperature had a stronger effect on female, children aged 3-6 and childcare children with an M-shape. We found that socio-economic factors, medical health factors and meteorological factors were significantly associated with heterogeneity. Density of medical technical personnel, urbanization rate and density of health care institutions were the main modifiers for explaining heterogeneity of 26.10%, 24.90% and 24.86% respectively which were revealed by meta-analysis. CONCLUSIONS: There was a significant nonlinear correlation between temperature and HFMD. Compared with other groups, children aged 0-1 and scattered children were more susceptible to warm temperature, while female, children aged 3-6 and childcare children were more susceptible to cold temperature. Socio-economic factors, medical health factors and meteorological factors may be the source of the heterogeneity. Therefore, local governments should consider different temperature-HFMD relationships between different regions and populations when formulating appropriate preventive measures.

Lactate: A Novel Signaling Molecule in Synaptic Plasticity and Drug Addiction.

l-Lactate is emerging as a crucial regulatory nexus for energy metabolism in the brain and signaling transduction in synaptic plasticity, memory processes, and drug addiction instead of being merely a waste by-product of anaerobic glycolysis. In this review, the role of lactate in various memory processes, synapse plasticity and drug addiction on the basis of recent studies is summarized and discussed. To this end, three main parts are presented: first, lactate as an energy substrate in energy metabolism of the brain is described; second, lactate as a novel signaling molecule in synaptic plasticity, neural circuits, memory, and drug addiction is described; and third, in light of the above descriptions, it is plausible to speculate that lactate is predominantly a signaling molecule in specific memory processes and partly acts as an energy substrate. The future perspective in lactate signaling involving microglia and associated precise signaling pathways in the brain is highlighted.

Preparation and Modification of Collagen/Sodium Alginate-Based Biomedical Materials and Their Characteristics.

(1) Background: Collagen and sodium alginate are commonly used in the field of biomedical materials due to their excellent biocompatibility. This study focuses on the preparation, modification, and characterization of collagen/sodium alginate (C/SA)-based biomedical materials. (2) Methods: The characteristics, including surface chemistry, mechanical properties, hygroscopicity, and porosity, were analyzed. The hemostatic activity in vitro was measured using a blood clotting assay and dynamic blood clotting assay. (3) Results: The results from microstructure and porosity measurement revealed that all of the sponges exhibited a porosity of more than 95 percent. The sponge cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) showed better tensile strength and lower elongation at break. The sponges cross-linked with EDC/NHS and oxidized sodium alginate (OSA) exhibited the highest hygroscopicity in comparison with the uncross-linked sponge. (4) Conclusions: Our study demonstrated that the C/SA-based material we prepared exhibited a high level of porosity, enabling efficient absorption of tissue exudate and blood. Additionally, the materials revealed excellent hemocompatibility, making them suitable for use as a hemostatic dressing in the field of biomedical materials.

Integrated extraction, structural characterization, and activity assessment of squid pen protein hydrolysates and ß-chitin with different protease hydrolysis.

Squid pen (SP) is a valuable source of protein and ß-chitin. However, current research has primarily focused on extracting ß-chitin from SP. This study innovatively extracted both SP protein hydrolysates (SPPHs) and SP ß-chitin (SPC) simultaneously using protease hydrolysis. The effects of different proteases on their structural characteristics and bioactivity were evaluated. The results showed that SP alcalase ß-chitin (SPAC) had the highest degree of deproteinization (DP, 98.19 %) and SP alcalase hydrolysates (SPAH) had a degree of hydrolysis (DH) of 24.47 %. The analysis of amino acid composition suggested that aromatic amino acids accounted for 17.44 % in SPAH. Structural characterization revealed that SP flavourzyme hydrolysates (SPFH) had the sparsest structure. SPC exhibited an excellent crystallinity index (CI, over 60 %) and degree of acetylation (DA, over 70 %). During simulated gastrointestinal digestion (SGD), the hydroxyl radical scavenging activity, ABTS radical scavenging activity, Fe2+ chelating activity, and reducing power of the SPPHs remained stable or increased significantly. Additionally, SPFC exhibited substantial inhibitory effects on Staphylococcus aureus and Escherichia coli (S. aureus and E. coli), with inhibition circle diameters measuring 2.4 cm and 2.1 cm. These findings supported the potential use of SPPHs as natural antioxidant alternatives and suggested that SPC could serve as a potential antibacterial supplement.

Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: a reconstructed individual patient data meta-analysis.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS (p = 0.042) and OS (p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups (p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV (p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/.

Multifunctional sprayable carboxymethyl chitosan/polyphenol hydrogel for wound healing.

The use of facile methods to synthesize environmentally friendly and multifunctional hydrogel dressings is still a major challenge in development. Herein, Turkish gall extract (TGE) and carboxymethyl chitosan (CMCS) were combined and sprayed using a dual syringe to form a multifunctional TGE-CMCS hydrogel (TC gel) in one step through abundant hydrogen bonding between functional groups as a green approach. TC gel showed rapid gelation at 19.0 ± 2.9 s. Apart from the advantage of being able to adapt to different wound shapes, TC gel retained the antioxidant, antibacterial, hemostatic and anti-inflammatory properties of TGE. In vitro antibacterial experiments showed that TC-gel eliminated 98.27 ± 0.79 % of Staphylococcus aureus and 98.87 ± 1.08 % of Escherichia coli. Compared with TGE or CMCS alone, TC gel accelerates skin wound healing due to its three-dimensional network structure and continuous release of active components at the wound site, enhancing re-epithelialization, improving collagen deposition, and increasing angiogenesis. The wound healing rate of full-thickness skin defect rats treated with TC gel was 93.98 ± 0.63 % on the 10th day. These results suggest that TC gel combined with a facile and scalable manufacturing method is a promising multifunctional wound dressing for clinical wound management.

Association of the High-Sensitivity C-Reactive Protein-to-Albumin Ratio with Carotid Atherosclerotic Plaque: A Community-Based Cohort Study.

Background: The inflammatory response is a pivotal factor in accelerating the progression of atherosclerosis. The high-sensitivity C-reactive protein-to-albumin ratio (CAR) has emerged as a novel marker of systemic inflammation. However, few studies have shown the CAR to be a promising prognostic marker for carotid atherosclerotic disease. This study aimed to analyse the predictive role of the CAR in carotid atherosclerotic disease. Methods: This community-based cohort study recruited 2003 participants from the Rose asymptomatic IntraCranial Artery Stenosis (RICAS) study who were free of stroke or transient ischemic attack. Carotid atherosclerotic plaques and their stability were identified via carotid ultrasound. Logistic regression models were utilized to investigate the association between CAR and the presence of carotid atherosclerotic plaques. Results: The prevalence of carotid atherosclerotic plaques was 38.79% in this study. After adjusting for clinical risk factors, including sex, age, dyslipidemia, hypertension, diabetes mellitus (DM), and smoking and drinking habits, a high CAR-level was independently associated with carotid plaque (odds ratio [OR] of upper: 1.46, 95% confidence interval [CI]: 1.13-1.90, P = 0.004; P for trend = 0.011). The highest CAR tertile was still significantly associated with carotid plaques among middle-aged (40-64 years) or female participants. Notably, an elevated CAR may be an independent risk factor for vulnerable carotid plaques (OR of upper: 2.06, 95% CI: 1.42-2.98, P < 0.001; P for trend <0.001). Conclusion: A high CAR may be correlated with a high risk of carotid plaques, particularly among mildly aged adults (40-64 years) or females. Importantly, the CAR may be associated with vulnerable carotid plaques, suggesting that the CAR may be a new indicator for stroke prevention.

Engineering Corynebacterium glutamicum for the efficient production of N-acetylglucosamine.

N-acetylglucosamine (GlcNAc) is significant functional monosaccharides with diverse applications in medicine, food, and cosmetics. In this study, the GlcNAc synthesis pathway was constructed in Corynebacterium glutamicum and its reverse byproduct pathways were blocked. Simultaneously the driving force of GlcNAc synthesis was enhanced by screening key gene sources and inhibiting the GlcNAc consumption pathway. To maximize carbon flux, some competitive pathways (Pentose phosphate pathway, Glycolysis pathway and Mannose pathway) were weakened and the titer of GlcNAc reached 23.30 g/L in shake flasks. Through transcriptome analysis, it was found that dissolved oxygen was an important limiting factor, which was optimized in a 5 L bioreactor. Employing optimal fermentation conditions and feeding strategy, the titer of GlcNAc reached 138.9 g/L, with the yeild of 0.44 g/g glucose. This study significantly increased the yield and titer of GlcNAc, which lay a solid foundation for the industrial production of GlcNAc in C. glutamicum.

The short-term effect of air pollution on the incidence of pulmonary tuberculosis in Chongqing, China, 2014-2020.

INTRODUCTION: Tuberculosis (TB) is one of the top ten causes of death in the world. The purpose of this study was to explore the relationship between the short-term exposure to air pollutants and the risk of pulmonary TB in Chongqing. METHODOLOGY: A distributed lag nonlinear model was used to explore the effect of short-term exposure to air pollutants on the risk of pulmonary TB. Stratified analysis was used to explore the impact of gender and age on the risk of pulmonary TB. RESULTS: There were 170,934 confirmed cases of pulmonary TB in Chongqing from January 1st, 2014 to December 30th, 2020. There was a positive correlation between the exposure to particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5), particulate matter with aerodynamic diameter less than 10 µm (PM10) ozone (O3) and the incidence risk of TB. The maximum lag-specific relative risk (RR) of pulmonary TB was 1.012 (95% CI: 1.001-1.023, 14 days delay) for each 10 µg/m3 increase in PM2.5; 1.010 (95% CI: 1.003-1.017, 14 days delay) for each 10µg/m3 increase in PM10; and 1.002 (95% CI:1.000-1.004, 2 days delay) for each 10 mg/m3 increase in O3. Stratified analysis showed that the exposure effects of PM2.5, PM10 and O3 were different between different genders and age. CONCLUSIONS: This study suggested that exposure to PM2.5, PM10, and O3 was associated with the risk of pulmonary TB, and the risk was higher for males than females, while the exposure to PM2.5 and PM10 was riskier for people aged 15-60 years.

A Spatio-temporal Bayesian model to estimate risk and influencing factors related to tuberculosis in Chongqing, China, 2014-2020.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease that is one of the leading causes of death worldwide. This study aimed to investigate the spatial and temporal distribution patterns and potential influencing factors of TB incidence risk, and to provide a scientific basis for the prevention and control of TB. METHODS: We collected reported cases of TB in 38 districts and counties in Chongqing from 2014 to 2020 and data on environment, population characteristics and economic factors during the same period. By constructing a Bayesian spatio-temporal model, we explored the spatio-temporal distribution pattern of TB incidence risk and potential influencing factors, identified key areas and key populations affected by TB, compared the spatio-temporal distribution characteristics of TB in populations with different characteristics, and explored the differences in the influence of various social and environmental factors. RESULTS: The high-risk areas for TB incidence in Chongqing from 2014 to 2020 were mainly concentrated in southeastern and northeastern regions of Chongqing, and the overall relative risk (RR) of TB showed a decreasing trend during the study period, while RR of TB in main urban area and southeast of Chongqing showed an increasing trend. The RR of TB was relatively high in the main urban area for the female population and the population aged 0-29 years, and the RR of TB for the population aged 30-44 years in the main urban area and the population aged 60 years or older in southeast of Chongqing had an increasing trend, respectively. For each 1 µg/m3 increase in SO2 and 1% increase in the number of low-income per 1000 non-agricultural households (LINA per 1000 persons), the RR of TB increased by 0.35% (95% CI: 0.08-0.61%) and 0.07% (95% CI: 0.05-0.10%), respectively. And LINA per 1000 persons had the greatest impact on the female population and the over 60 years old age group. Although each 1% increase in urbanization rate (UR) was associated with 0.15% (95% CI: 0.11-0.17%) reduction in the RR of TB in the whole population, the RR increased by 0.18% (95% CI: 0.16-0.21%) in the female population and 0.37% (95% CI: 0.34-0.45%) in the 0-29 age group. CONCLUSION: This study showed that high-risk areas for TB were concentrated in the southeastern and northeastern regions of Chongqing, and that the elderly population was a key population for TB incidence. There were spatial and temporal differences in the incidence of TB in populations with different characteristics, and various socio-environmental factors had different effects on different populations. Local governments should focus on areas and populations at high risk of TB and develop targeted prevention interventions based on the characteristics of different populations.

Improving the Sustainability of Processing By-Products: Extraction and Recent Biological Activities of Collagen Peptides.

Society and consumers are increasingly concerned about food safety and the sustainability of food production systems. A significant amount of by-products and discards are generated during the processing of aquatic animals, which still needs to be fully utilized by the food industry. The management and sustainable use of these resources are essential to avoiding environmental pollution and resource waste. These by-products are rich in biologically active proteins, which can be converted into peptides by enzymatic hydrolysis or fermentation treatment. Therefore, exploring the extraction of collagen peptides from these by-products using an enzymatic hydrolysis technology has attracted a wide range of attention from numerous researchers. Collagen peptides have been found to possess multiple biological activities, including antioxidant, anticancer, antitumor, hypotensive, hypoglycemic, and anti-inflammatory properties. These properties can enhance the physiological functions of organisms and make collagen peptides useful as ingredients in food, pharmaceuticals, or cosmetics. This paper reviews the general methods for extracting collagen peptides from various processing by-products of aquatic animals, including fish skin, scales, bones, and offal. It also summarizes the functional activities of collagen peptides as well as their applications.