Sphingopyxis yananensis sp. nov., a novel 2-nitropropane degrading bacterium isolated from a microbial fermentation bed substrate.

A rod-shaped, Gram-negative staining strain, FBM22T, was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 µm wide, 0.5-0.83 µm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C18:1 ω7c, C16:1 ω7c and/ or C16:1 ω6c, and C14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098T (96.40%). Furthermore, FBM22T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2T and S. terrae subsp. terrae NBRC 15098T). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22T (= KCTC 82290T = CCTC AB2020286T).

Adamgammadex in patients to reverse a moderate rocuronium-induced neuromuscular block.

AIMS: The aim of this study was to investigate the effectiveness, safety and pharmacokinetics of adamgammadex in surgical patients. METHODS: Forty-eight patients aged 18-64 years old were randomized to receive adamgammadex (2, 4, 6, and 8 mg.kg-1 ) or placebo at a ratio of 10:2 for reversal of 0.6 mg.kg-1 rocuronium-induced neuromuscular block. Neuromuscular function was monitored by TOF-Watch® SX. When the T2 of train-of-four (TOF) reappeared at the end of surgery, patients received an intravenous administration of adamgammadex or placebo. RESULTS: The recovery time of the TOF ratio to 0.9 decreased significantly from 39.3 [29.5, 50.2] minutes in the group that received placebo to 3.0 [2.3, 3.9] minutes, P < .0001; 2.1 [1.5, 3.0] minutes, P < .0001; 2.1 [1.8, 3.3] minutes, P < .0001; and 1.8 [1.5, 2.2] minutes, P < .0001 in the 2, 4, 6 and 8 mg.kg-1 adamgammadex groups, respectively. Then, adamgammadex also showed a shortened recovery time for the TOF ratio recovered to 0.8 and 0.7. Adamgammadex was well tolerated, and no cases of anaphylactic reactions, post-operative bleeding, recurarization, abnormal basic vital signs and prolonged QT intervals were observed. The pharmacokinetics of adamgammadex in plasma increased in dose-dependent manner. The 24-hour cumulative fraction of adamgammadex in urine was 65-83%, and that of rocuronium was increased after using adamgammadex from 15% to about 25-30%. CONCLUSION: Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block, and it was safe and well tolerated in patients.

Characterization of algal organic matter as precursors for carbonaceous and nitrogenous disinfection byproducts formation: Comparison with natural organic matter.

Algal organic matter (AOM) and natural organic matter (NOM) from a typical eutrophic lake were comprehensively investigated in terms of their physico-chemical property, components and disinfection byproduct formation potentials (DBPFPs). The relationships between specific chemical properties of AOM and NOM with their corresponding DBPFPs were further evaluated during chlorination. Results indicated that AOM had lower specific UV absorbance (SUVA) but richer organic nitrogen contents than NOM. Fluorescence excitation emission matrix spectroscopy further demonstrated that AOM were chiefly composed of aromatic protein-like and soluble microbial byproduct-like matters, while NOM were mainly contributed from humic acid-like and soluble microbial byproduct-like substances. Although the molecular weight (MW) distribution of AOM and NOM showed no significant difference, size-exclusion chromatography with organic carbon as well as organic nitrogen detection (LC-OCD-OND) revealed that AOM were concentrated with the fraction of building blocks and NOM had higher concentrations of biopolymers and humics (HS). Moreover, AOM displayed higher DBPFPs than NOM, especially for nitrogenous DBPFP (N-DBPFP). MW < 1 kDa fractions both in AOM and NOM contributed the largest proportion to the formation of carbonaceous disinfection byproducts (C-DBPs). In addition, Pearson correlation analysis showed that bulk parameter SUVA was significantly relevant to the formation potentials of trihalomethane both in AOM and NOM, but was ineffective for carbonaceous DBPFP (C-DBPFP) prediction. Dissolved organic nitrogen contents in biopolymer and HS characterized by LC-OCD-OND had strong correlations with N-DBPFPs from AOM and NOM, indicating that LC-OCD-OND quantitative analysis could improve the prediction accuracy of the DBP formation than bulk parameters during NOM and AOM chlorination.

Tracking the interaction of drug molecules with individual mesoporous amorphous calcium phosphate/ATP nanocomposites - an X-ray spectromicroscopy study.

Adenosine triphosphate (ATP) biomolecules play critial roles in the biomineralization process during the formation of amorphous calcium phosphate composites (ACPC), and ACPC is an important drug carrier due to its significant advantages of biocompatibility and biodegradability. Hence, studying the behavior of ACPC nanodrug carriers is crucial to investigate the structural regulation of biomimetic minerals and calcium phosphate (CaP)-based drug delivery systems. However, it is difficult to probe these interactions using traditional characterization methods. In this paper, XANES analysis together with STXM successfully provided a method to reveal the interaction of ATP and drug molecules with individual mesoporous ACPC. We found that the adenosine and phosphate groups of ATP biomolecules coordinated with Ca2+ and played critical roles in the formation of ACPC; drug molecules with the -COOH groups were linked to Ca2+via carboxylic acid groups primarily by electrostatic interactions, and the N-containing ring structures within the drug molecules also coordinated with Ca2+.

Adult Hippocampal Neurogenesis along the Dorsoventral Axis Contributes Differentially to Environmental Enrichment Combined with Voluntary Exercise in Alleviating Chronic Inflammatory Pain in Mice.

Cognitive behavioral therapy, such as environmental enrichment combined with voluntary exercise (EE-VEx), is under active investigation as an adjunct to pharmaceutical treatment for chronic pain. However, the effectiveness and underlying mechanisms of EE-VEx remain unclear. In mice with intraplantar injection of complete Freund's adjuvant, our results revealed that EE-VEx alleviated perceptual, affective, and cognitive dimensions of chronic inflammatory pain. These effects of EE-VEx on chronic pain were contingent on the occurrence of adult neurogenesis in the dentate gyrus in a functionally dissociated manner along the dorsoventral axis: neurogenesis in the ventral dentate gyrus participated in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas neurogenesis in the dorsal dentate gyrus was involved in EE-VEx's cognitive-enhancing effects. Chronic inflammatory pain was accompanied by decreased levels of brain-derived neurotrophic factor (BDNF) in the dentate gyrus, which were reversed by EE-VEx. Overexpression of BDNF in the dentate gyrus mimicked the effects of EE-VEx. Our results demonstrate distinct contribution of adult hippocampal neurogenesis along the dorsoventral axis to EE-VEx's beneficial effects on different dimensions of chronic pain.SIGNIFICANCE STATEMENT Environmental enrichment combined with voluntary exercise (EE-VEx) is under active investigation as an adjunct to pharmaceutical treatment for chronic pain, but its effectiveness and underlying mechanisms remain unclear. In a mouse model of inflammatory pain, the present study demonstrates that the beneficial effects of EE-VEx on chronic pain depend on adult neurogenesis with a dorsoventral dissociation along the hippocampal axis. Adult neurogenesis in the ventral dentate gyrus participates in alleviating perceptual and affective components of chronic pain by EE-VEx, whereas that in the dorsal pole is involved in EE-VEx's cognitive-enhancing effects in chronic pain.

Enzymatic Reaction Generates Biomimic Nanominerals with Superior Bioactivity.

In vivo mineralization is a multistep process involving mineral-protein complexes and various metastable compounds in vertebrates. In this complex process, the minerals produced in the mitochondrial matrix play a critical role in initiating extracellular mineralization. However, the functional mechanisms of the mitochondrial minerals are still a mystery. Herein, an in vitro enzymatic reaction strategy is reported for the generation of biomimic amorphous calcium phosphate (EACP) nanominerals by an alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) in a weakly alkalescent aqueous condition (pH 8.0-8.5), which is partially similar to the mitochondrial environment. Significantly, the EACP nanomineral obviously promotes autophagy and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by activating an AMPK related pathway, and displays a high performance in promoting bone regeneration. These results provide in vitro evidence for the effect of ATP on the formation and stabilization of the mineral in the mineralization process, demonstrating a potential strategy for the preparation of the biomimic mineral for treating bone related diseases.

Porous Nanocomposite Comprising Ultralong Hydroxyapatite Nanowires Decorated with Zinc-Containing Nanoparticles and Chitosan: Synthesis and Application in Bone Defect Repair.

Hydroxyapatite nanowires exhibit a great potential in biomedical applications owing to their high specific surface area, high flexibility, excellent mechanical properties, and similarity to mineralized collagen fibrils of natural bone. In this work, zinc-containing nanoparticle-decorated ultralong hydroxyapatite nanowires (Zn-UHANWs) with a hierarchical nanostructure have been synthesized by a one-step solvothermal method. The highly flexible Zn-UHANWs exhibit a hierarchical rough surface and enhanced specific surface area as compared with ultralong hydroxyapatite nanowires (UHANWs). To evaluate the potential application of Zn-UHANWs in bone regeneration, the biomimetic Zn-UHANWs/chitosan (CS) (Zn-UHANWs/CS) composite porous scaffold with 80 wt % Zn-UHANWs was prepared by incorporating Zn-UHANWs into the chitosan matrix by the freeze-drying process. The as-prepared Zn-UHANWs/CS composite porous scaffold exhibits enhanced mechanical properties, highly porous structure, and excellent water retention capacity. In addition, the Zn-UHANWs/CS porous scaffold has a good biodegradability with the sustainable release of Zn, Ca, and P elements in aqueous solution. More importantly, the Zn-UHANWs/CS porous scaffold can promote the osteogenic differentiation of rat bone marrow derived mesenchymal stem cells and facilitate in vivo bone regeneration as compared with the pure CS porous scaffold or UHANWs/CS porous scaffold. Thus, both the Zn-UHANWs and Zn-UHANWs/CS porous scaffold developed in this work are promising for application in bone defect repair.

Prevalence of Early Childhood Caries Among 2- to 5-year-old Preschoolers in Kindergartens of Weifang City, China: A Cross-sectional Study.

PURPOSE: To assess the prevalence of early childhood caries (ECC) in 2- to 5-year-old preschool children in Weifang City, China, and to investigate the factors related to this condition. MATERIALS AND METHODS: A cross-sectional study was carried out among 2829 children (2-5 years old, including 1601 boys and 1228 girls) in twenty kindergartens in Weifang City, China, in 2014. These children were selected via cluster sampling. First, the percentages of ECC and severe ECC (S-ECC) as well as the mean dmft were compared between different genders and ages, and the tooth distribution pattern of ECC was analysed. Meanwhile, the information regarding feeding and oral hygiene practices was collected by a questionnaire with 14 questions to evaluate their relationships with the percentages of ECC and S-ECC as well as the mean dmft. The chi-squared test, t-test and one-way ANOVA were conducted to evaluate the significant differences. RESULTS: The ECC prevalence of the preschoolers was 53.3%, and the mean dmft was 2.12 ±â€¯2.56. 71.4% of the 1509 children with ECC were identified as S-ECC. Not only the percentages of ECC and S-ECC but also the mean dmft differed statistically significantly according to gender and age (p < 0.05). Furthermore, caries was most common in primary maxillary central incisors. Feeding and oral hygiene practices were shown to be the significant determining factors for caries. CONCLUSIONS: The oral health status of children living in Weifang is very poor. Appropriate strategies must be implemented to promote oral health early on by improving feeding and oral hygiene practices.

Self-rated health and health-related quality of life among Chinese residents, China, 2010.

BACKGROUND: Self-rated health (SRH) and health-related quality of life (HRQOL) are two outcome measures used to assess health status. However, little is known about population-based SRH and HRQOL in China. METHODS: Data from the 2010 China Chronic Disease and Risk Factor Surveillance, a nationally representative sample of 98,658 adults (≥18-year-old) residing in China, were analyzed. SRH was assessed by asking "Would you say that, in general, your health is very good, good, general, poor, or very poor?" HRQOL was assessed by asking "For about how many days during the past 30 days was your health not good due to physical illnesses, injuries, or mental unhealthy?". RESULTS: Overall, 6.3 % of participants rated their health as poor or very poor. The prevalence of poor/very poor health increased with advancing age ranging from 2.0 % in the 18-24 year-olds to 14.9 % in those ≥75 years-old, while it decreased with education levels from 13.0 % in illiterates/those with some primary school education to 2.2 % in college graduates or above. Additionally, women were more likely than men to rate their health as poor or very poor (7.2 % vs. 5.4 %). The reported rate of poor/very poor health was higher in western region residents compared to those in the east (7.4 % vs. 5.3 %). The mean numbers of self-reported physically unhealthy days, injury-caused unhealthy days, or mentally unhealthy days during the past 30 days were 1.48, 0.20, and 0.54, respectively. Older adults had more physically unhealthy days than the younger ones ranging from 2.92 days in those ≥ 75 year-old to 0.95 days in 18-24 year-olds. Women had more physically unhealthy days and mentally unhealthy days than men (1.72 vs. 1.23; 0.62 vs. 0.46, respectively). The highest mean number of physically unhealthy days (2.32) was reported by illiterates or those with some primary school education. The highest mean number of mentally unhealthy days (0.86) reported by college graduates or above. CONCLUSIONS: Substantial variations existed in SRH and HRQOL among age groups, gender groups, education groups, and across regions in China. Considering these disparities will be important when developing health policies and allocating resources.

[Isolation, identification and inhibition activity of endophytes in Fengdan].

Endophytes were isolated and purified from the roots of medicinal plant Fengdan also known as Paeonia suffruticosa from Tongling region, Anhui province, China. Morphology and molecular biology methods were applied to indentify the endophyte strains. And methods of growth rate and filtering paper were also used for studying antibacterial/antifungal effects of the strains. As a result, 129 endophyte strains were isolated. Fifty-eight endophytic fungi strains were identified as 6 species in 4 genera and the dominant genus was Fusarium. Seventy-one endophytic bacteria strains were identified as 9 species in 3 genera and the dominant genus was Bacillus. Inhibitory diameter with endophytic fermenting liquid of Pseudomonas chlororaphis, F. nematophilum and B. megaterium from P. suffruticosa against Staphyloccocus aureus, Escherichia coli and B. subtilis reached 25.0,20.2,24.0 mm respectively. The inhibition rate of endophytic fermenting liquid from F. nematophilum against Penicillium sp. and Colletotrichum dematium reached 90.6% and 83.3%, respectively. The inhibition effect of P. chlororaphis against F. oxysporum f. sp. niveum and Mucor sp. was good and the antifungal rate reached 80.0% and 84.9%, respectively. P. suffruticosa in Tongling region contains abundant endophytes. P. chlororaphis and F. nematophilum are valuable species as starting strain about microbicide.

Gender-related difference in the upper airway dimensions and hyoid bone position in Chinese Han children and adolescents aged 6-18 years using cone beam computed tomography.

OBJECTIVE: To investigate the gender-related differences in upper airway dimensions and hyoid bone position in Chinese Han children and adolescents (6-18 years) using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT-scans of 119 boys and 135 girls were selected and divided into four groups (group 1: 6-9 years; group 2: 10-12 years; group 3: 13-15 years; group 4: 16-18 years). The airway dimensions including the cross-sectional area (CSA), anteroposterior (AP) and lateral (LAT) width, length (L), mean CSA and volume (VOL) of upper airway segmentations and hyoid bone position including 11 linear and three angular measurements were investigated using Materialism's interactive medical image control system (MIMICS) 16.01 software. Gender-related differences were analyzed by two independent sample t-tests. RESULTS: No gender-related difference was found in values of the facial morphology, airway dimensions and hyoid bone position for group 1 (p > 0.05). The children and adolescents in groups 2, 3 and 4 showed significant gender-related differences in the measurement results of facial morphology, airway dimensions and hyoid bone positions (p < 0.05). What's more, the measurement values of boys were obviously larger than those of girls except some measurements in group 2. CONCLUSIONS: The measurements of airway dimensions and hyoid bone positions have gender-related differences in children and adolescents aged 10-18 years. These results could be taken into consideration during orthodontic diagnosis and treatment.

Paenibacillus quercus sp. nov., isolated from rhizosphere of Quercus aliena var. acuteserrata.

A Gram-positive, spore-forming, rod-shaped and motile bacterium, designated strain 1-25(T), was isolated from the rhizosphere of Quercus aliena var. acuteserrata in Taibai Mountain, Shaanxi Province, China. 16S rRNA gene sequence analysis showed that strain 1-25(T) belongs to the genus Paenibacillus. Strain 1-25(T) was found to be closely related to Paenibacillus harenae and Paenibacillus castaneae with 96.0 and 95.9 % 16S rRNA gene sequence similarities, respectively. The strain was observed to grow optimally at 28 °C and pH 7.5. The major isoprenoid quinone was found to be menaquinone-7. The dominant cellular fatty acids were identified as anteiso-C15:0 and iso-C15:0. The diagnostic diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. The DNA G+C content was determined to be 41.6 mol%. On the basis of phenotypic characteristics and molecular properties, strain 1-25(T) is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus quercus sp. nov. is proposed. The type strain is 1-25(T) (=CCTCC AB2013265(T) = KCTC 33194(T)).

Random forest differentiation of Escherichia coli in elderly sepsis using biomarkers and infectious sites.

This study addresses the challenge of accurately diagnosing sepsis subtypes in elderly patients, particularly distinguishing between Escherichia coli (E. coli) and non-E. coli infections. Utilizing machine learning, we conducted a retrospective analysis of 119 elderly sepsis patients, employing a random forest model to evaluate clinical biomarkers and infection sites. The model demonstrated high diagnostic accuracy, with an overall accuracy of 87.5%, and impressive precision and recall rates of 93.3% and 87.5%, respectively. It identified infection sites, platelet distribution width, reduced platelet count, and procalcitonin levels as key predictors. The model achieved an F1 Score of 90.3% and an area under the receiver operating characteristic curve of 88.0%, effectively differentiating between sepsis subtypes. Similarly, logistic regression and least absolute shrinkage and selection operator analysis underscored the significance of infectious sites. This methodology shows promise for enhancing elderly sepsis diagnosis and contributing to the advancement of precision medicine in the field of infectious diseases.

Effect of Placental Transfusion on Long-Term Neurodevelopmental Outcomes in Premature Infants: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The pathophysiology and the potential risks of placental transfusion (PT) differ substantially in preterm infants, necessitating specific studies in this population. This study aimed to evaluate the safety and efficacy of PT in preterm infants from the perspective of long-term neurodevelopmental outcomes. METHODS: We conducted a systematic literature search using placental transfusion, preterm infant, and its synonyms as search terms. Cochrane Central Register of Controlled Trials, Medline, and Embase were searched until March 07, 2023. Two reviewers independently identified, extracted relevant randomized controlled trials, and appraised the risk of bias. The extracted studies were included in the meta-analysis of long-term neurodevelopmental clinical outcomes using fixed-effects models. RESULTS: A total of 5612 articles were identified, and seven randomized controlled trials involving 2551 infants were included in our meta-analysis. Compared with immediate cord clamping (ICC), PT may not impact adverse neurodevelopment events. No clear evidence was found of a difference in the risk of neurodevelopmental impairment (risk ratio [RR]: 0.89, 95% confidence interval [CI]: 0.76 to 1.03, P = 0.13, I2 = 0). PT was not associated with the incidence of cerebral palsy (RR: 1.23, 95% CI: 0.59 to 2.57, P = 0.79, I2 = 0). Analyses showed no differences between the two interventions in cognitive, language, and motor domains of neurodevelopment. CONCLUSIONS: From the perspective of long-term neurodevelopment, PT at preterm birth may be as safe as ICC. Future studies should focus on standardized, high-quality clinical trials and individual participant data to optimize cord management strategies for preterm infants after birth.

The impact of oxygen on metabolic evolution: a chemoinformatic investigation.

The appearance of planetary oxygen likely transformed the chemical and biochemical makeup of life and probably triggered episodes of organismal diversification. Here we use chemoinformatic methods to explore the impact of the rise of oxygen on metabolic evolution. We undertake a comprehensive comparative analysis of structures, chemical properties and chemical reactions of anaerobic and aerobic metabolites. The results indicate that aerobic metabolism has expanded the structural and chemical space of metabolites considerably, including the appearance of 130 novel molecular scaffolds. The molecular functions of these metabolites are mainly associated with derived aspects of cellular life, such as signal transfer, defense against biotic factors, and protection of organisms from oxidation. Moreover, aerobic metabolites are more hydrophobic and rigid than anaerobic compounds, suggesting they are better fit to modulate membrane functions and to serve as transmembrane signaling factors. Since higher organisms depend largely on sophisticated membrane-enabled functions and intercellular signaling systems, the metabolic developments brought about by oxygen benefit the diversity of cellular makeup and the complexity of cellular organization as well. These findings enhance our understanding of the molecular link between oxygen and evolution. They also show the significance of chemoinformatics in addressing basic biological questions.

Effectiveness analysis on the physical activity and the health benefit of a community population based program.

OBJECTIVE: To evaluate the community-based health promotion effect of physical activity. METHODS: The residents aged 18 and above from two communities in Gongshu District of Hangzhou City, Zhejiang province, were randomly selected and recruited for the multi-strategy and comprehensive physical activity intervention. Questionnaire survey, physical check up and blood biochemistry were conducted. RESULTS: After this two-year intervention, the time of the participant spent on weekly physical activity of moderate intensity increased from 464 min to 542 min (P<0.05), with an average increase of 78 min. Time spent in walking every week increased from 533 min to 678 min (P<0.05), with an average increase of 145 min. The body weight, waistline, blood pressure and heart rate all reduced significantly (P<0.05); the vital capacity increased significantly (P<0.05); and the related biochemical indicators were also improved. CONCLUSION: Comprehensive and evidence-based physical activity interventions targeting community population can improve the levels of physical activity, related body measurement and biochemical indicators.

Construction and results of a comprehensive index for gastrointestinal health monitoring in China: a nationwide study.

Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

A universal molecular clock of protein folds and its power in tracing the early history of aerobic metabolism and planet oxygenation.

The standard molecular clock describes a constant rate of molecular evolution and provides a powerful framework for evolutionary timescales. Here, we describe the existence and implications of a molecular clock of folds, a universal recurrence in the discovery of new structures in the world of proteins. Using a phylogenomic structural census in hundreds of proteomes, we build phylogenies and time lines of domains at fold and fold superfamily levels of structural complexity. These time lines correlate approximately linearly with geological timescales and were here used to date two crucial events in life history, planet oxygenation and organism diversification. We first dissected the structures and functions of enzymes in simulated metabolic networks. The placement of anaerobic and aerobic enzymes in the time line revealed that aerobic metabolism emerged about 2.9 billion years (giga-annum; Ga) ago and expanded during a period of about 400 My, reaching what is known as the Great Oxidation Event. During this period, enzymes recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably, the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within the span of oxygen rise, suggesting that oxygen also triggered diversification of life. The implications of a molecular clock of folds are many and important for the neutral theory of molecular evolution and for understanding the growth and diversity of the protein world. The clock also extends the standard concept that was specific to molecules and their timescales and turns it into a universal timescale-generating tool.

Chemical basis of metabolic network organization.

Although the metabolic networks of the three domains of life consist of different constituents and metabolic pathways, they exhibit the same scale-free organization. This phenomenon has been hypothetically explained by preferential attachment principle that the new-recruited metabolites attach preferentially to those that are already well connected. However, since metabolites are usually small molecules and metabolic processes are basically chemical reactions, we speculate that the metabolic network organization may have a chemical basis. In this paper, chemoinformatic analyses on metabolic networks of Kyoto Encyclopedia of Genes and Genomes (KEGG), Escherichia coli and Saccharomyces cerevisiae were performed. It was found that there exist qualitative and quantitative correlations between network topology and chemical properties of metabolites. The metabolites with larger degrees of connectivity (hubs) are of relatively stronger polarity. This suggests that metabolic networks are chemically organized to a certain extent, which was further elucidated in terms of high concentrations required by metabolic hubs to drive a variety of reactions. This finding not only provides a chemical explanation to the preferential attachment principle for metabolic network expansion, but also has important implications for metabolic network design and metabolite concentration prediction.