Genome sequences of the first Autographiviridae phages infecting marine Roseobacter.

The ubiquitous and abundant marine phages play critical roles in shaping the composition and function of bacterial communities, impacting biogeochemical cycling in marine ecosystems. Autographiviridae is among the most abundant and ubiquitous phage families in the ocean. However, studies on the diversity and ecology of Autographiviridae phages in marine environments are restricted to isolates that infect SAR11 bacteria and cyanobacteria. In this study, ten new roseophages that infect marine Roseobacter strains were isolated from coastal waters. These new roseophages have a genome size ranging from 38 917 to 42 634 bp and G+C content of 44.6-50 %. Comparative genomics showed that they are similar to known Autographiviridae phages regarding gene content and architecture, thus representing the first Autographiviridae roseophages. Phylogenomic analysis based on concatenated conserved genes showed that the ten roseophages form three distinct subgroups within the Autographiviridae, and sequence analysis revealed that they belong to eight new genera. Finally, viromic read-mapping showed that these new Autographiviridae phages are widely distributed in global oceans, mostly inhabiting polar and estuarine locations. This study has expanded the current understanding of the genomic diversity, evolution and ecology of Autographiviridae phages and roseophages. We suggest that Autographiviridae phages play important roles in the mortality and community structure of roseobacters, and have broad ecological applications.

Improvements on Gaussian mixture model and its application in identifying aerosol types in two major cities in the Yangtze River Delta, China.

Accurately identifying the authentic local aerosol types is one of the fundamental tasks in studying aerosol radiative effects and model assessment. In this paper, improvements were made to the traditional Gaussian Mixture Model, leading to the following results: 1) This study introduces several improvements to the traditional Gaussian Mixture Model (GMM), referred to as M-GMMs. These improvements include the incorporation of multivariate kurtosis coefficients, Mahalanobis distance instead of Euclidean distance, and weights of variables. The M-GMMs overcome the issues related to dimensional units and correlations among multiple parameters, thereby enhancing the estimation of the covariance matrix. 2) The proposed M-GMMs model was evaluated for its clustering performance using machine-generated data with known classifications and real iris flower data. The results demonstrated that the classification performance of M-GMMs was superior to other models. Furthermore, compared to the slightly less effective K-means algorithm (which requires manual definition of the number of aerosol types), the M-GMMs model was able to automatically iterate and produce consistent classification results based on similar characteristics. 3) There is still a significant disparity between the characteristics of real stations and typical aerosols. Directly evaluating local aerosols using the characteristics of typical aerosols results in substantial errors. However, the M-GMMs model can effectively reflect the authentic aerosol characteristics at the local level. 4) The M-GMMs model was utilized to perform cluster analysis on the Xuzhou and Nanjing stations of AERONET. This analysis yielded quantitative proportions, temporal distribution characteristics, and spectral distribution features of aerosol types in the two regions. The improved M-GMMs model presented in this paper enables more accurate and continuous characterization of aerosol type variations. Its findings hold significant theoretical and practical value in reassessing aerosol radiative effects.

Dimeric eremophilane-type sesquiterpenoids from the peeled stems of Syringa pinnatifolia.

A continued phytochemical investigation guided by 1H NMR and LC-MS data on the ethanol extract from the peeled stems of Syringa pinnatifolia Hemsl. led to the isolation of 16 undescribed dimeric eremophilane sesquiterpenoids, namely syringenes R-Z (1-9) and A1-G1 (10-16). These structures were elucidated by extensive analysis of spectroscopic data, including HRESIMS, NMR, quantum-mechanics-based computational analysis of NMR chemical shifts, and single-crystal X-ray diffraction analyses, and a concise rule for determination of relative configuration of angular methyl was proposed. The results of the cardioprotective assay demonstrated that 3 exhibits a protective effect against hypoxia-induced injuries in H9c2 cells. This effect was observed at a concentration of 10 µM, with a protective rate of 28.43 ± 11.80%.

Identification of key genes and immune infiltration in osteoarthritis through analysis of zinc metabolism-related genes.

BACKGROUND: Osteoarthritis (OA) represents a prominent etiology of considerable pain and disability, and conventional imaging methods lack sensitivity in diagnosing certain types of OA. Therefore, there is a need to identify highly sensitive and efficient biomarkers for OA diagnosis. Zinc ions feature in the pathogenesis of OA. This work aimed to investugate the role of zinc metabolism-related genes (ZMRGs) in OA and the diagnostic characteristics of key genes. METHODS: We obtained datasets GSE169077 and GSE55235 from the Gene Expression Omnibus (GEO) and obtained ZMRGs from MSigDB. Differential expression analysis was conducted on the GSE169077 dataset using the limma R package to identify differentially expressed genes (DEGs), and the intersection of DEGs and ZMRGs yielded zinc metabolism differential expression-related genes (ZMRGs-DEGs). The clusterProfiler R package was employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of ZMRGs-DEGs. Potential small molecule drugs were predicted using the CMap database, and immune cell infiltration and function in OA individuals were analyzed using the ssGSEA method. Protein-protein interaction (PPI) networks were constructed to detect Hub genes among ZMRGs-DEGs. Hub gene expression levels were analyzed in the GSE169077 and GSE55235 datasets, and their diagnostic characteristics were assessed using receiver operating characteristic (ROC) curves. The gene-miRNA interaction network of Hub genes was explored using the gene-miRNA interaction network website. RESULTS: We identified 842 DEGs in the GSE169077 dataset, and their intersection with ZMRGs resulted in 46 ZMRGs-DEGs. ZMRGs-DEGs were primarily enriched in functions such as collagen catabolic processes, extracellular matrix organization, metallopeptidase activity, and pathways like the IL-17 signaling pathway, Nitrogen metabolism, and Relaxin signaling pathway. Ten potential small-molecule drugs were predicted using the CMap database. OA patients exhibited distinct immune cell abundance and function compared to healthy individuals. We identified 4 Hub genes (MMP2, MMP3, MMP9, MMP13) through the PPI network, which were highly expressed in OA and demonstrated good diagnostic performance. Furthermore, two closely related miRNAs for each of the 4 Hub genes were identified. CONCLUSION: 4 Hub genes were identified as potential diagnostic biomarkers and therapeutic targets for OA.

Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2ß1.

Thrombosis represents the leading cause of death and disability upon major adverse cardiovascular events (MACEs). Numerous pathological conditions such as COVID-19 and metabolic disorders can lead to a heightened thrombotic risk; however, the underlying mechanisms remain poorly understood. Our study illustrates that 2-methylbutyrylcarnitine (2MBC), a branched-chain acylcarnitine, is accumulated in patients with COVID-19 and in patients with MACEs. 2MBC enhances platelet hyperreactivity and thrombus formation in mice. Mechanistically, 2MBC binds to integrin α2ß1 in platelets, potentiating cytosolic phospholipase A2 (cPLA2) activation and platelet hyperresponsiveness. Genetic depletion or pharmacological inhibition of integrin α2ß1 largely reverses the pro-thrombotic effects of 2MBC. Notably, 2MBC can be generated in a gut-microbiota-dependent manner, whereas the accumulation of plasma 2MBC and its thrombosis-aggravating effect are largely ameliorated following antibiotic-induced microbial depletion. Our study implicates 2MBC as a metabolite that links gut microbiota dysbiosis to elevated thrombotic risk, providing mechanistic insight and a potential therapeutic strategy for thrombosis.

Relationship Between Ultra-Processed and Minimally Processed Food Intake and Cardiovascular Health Among US Women of Reproductive Age.

Objectives: Ultra-processed food (UPF) intake is associated with worse cardiovascular health (CVH), but associations between unprocessed/minimally processed foods (MPFs) and CVH are limited, especially among women of reproductive age (WRA). Materials and Methods: For 5,773 WRA (20-44 years) in National Health and Nutrition Examination Survey (NHANES) 2007-2018, we identified UPFs and MPFs using the Nova classification and based on 24-hour dietary recalls. We calculated usual percentages of calories from UPFs and MPFs using the National Cancer Institute's usual intake method. Seven CVH metrics were scored, and CVH levels were grouped by tertile. We used multivariable linear and multinomial logistic regression to assess associations between UPFs and MPFs and CVH. Results: The average usual percentage of calories from UPFs and MPFs was 57.2% and 29.3%, respectively. There was a graded, positive association between higher UPF intake and higher odds of poor CVH: adjusted odds ratios (aORs) for the lowest versus highest CVH were 1.74 (95% confidence interval: 1.51-2.01), 2.67 (2.07-3.44) and 4.66 (3.13-6.97), respectively, comparing quartile 2 (Q2)-Q4 to the lowest quartile (Q1) of UPF intake. Higher MPF intake was associated with lower odds of poor CVH: aORs for the lowest CVH were 0.61 (0.54-0.69), 0.39 (0.31-0.50), and 0.21 (0.14-0.31). Patterns of association remained consistent across subgroups and in sensitivity analyses. Conclusions: Higher UPF intake was associated with worse CVH, while higher MPF intake was associated with better CVH among WRA in the United States. Our analyses highlight an opportunity for WRA to improve nutrition and their CVH.

Depressive Symptoms and Mortality Among US Adults.

Importance: Depression is a common mental health disorder in the US. Depressive symptoms have been associated with increased cardiovascular disease incidence and mortality, but studies have largely focused on narrow population subgroups. Objective: To examine the association between depressive symptoms and mortality in a large, diverse, nationally representative sample of US adults, and to examine how lifestyle factors mediate this association. Design, Setting, and Participants: This was a prospective cohort study of a nationally representative sample of US adults using National Health and Nutrition Examination Survey 2005 to 2018 data linked with the National Death Index through 2019 for adults aged 20 years and older. Data were analyzed between March 1 and May 26, 2023. Main Outcomes and Measures: All-cause, cardiovascular disease, and ischemic heart disease mortality. Depressive symptoms were defined by Patient Health Questionnaire-9 scores and were categorized as none or minimal, mild, and moderate to severe. Secondarily, we assessed degree of mediation by lifestyle factors. Results: A total of 23 694 participants were included (unweighted n = 11 862 male [weighted 49.8%]; mean [SE] age, 44.7 [0.24] years). Prevalences of mild and moderate to severe depression were 14.9% and 7.2%, respectively. For all-cause mortality, hazard ratios were 1.35 (95% CI, 1.07-1.72) for mild depressive symptoms vs none and 1.62 (95% CI, 1.24-2.12) for moderate to severe depressive symptoms vs none. The corresponding hazard ratios were 1.49 (95% CI, 1.11-2.00) and 1.79 (95% CI, 1.22-2.62) for cardiovascular disease mortality and 0.96 (95% CI, 0.58-1.60) and 2.21 (95% CI, 1.24-3.91) for ischemic heart disease mortality. The associations were largely consistent across subgroups. Approximately 11.0% to 16.1% of the associations between depression and mortality could be explained by lifestyle factors. Feeling tired or having little energy, poor appetite or overeating, and having little interest in doing things were independently associated with all-cause and cardiovascular disease mortality but not with ischemic heart disease mortality. Conclusions and Relevance: In this prospective cohort study of a nationally representative sample of US adults, there was a graded positive association between depressive symptoms and mortality. Public health efforts to improve awareness and treatment of depression and associated risk factors could support a comprehensive, nationwide strategy to reduce the burden of depression.

SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1ß-stimulated chondrocytes via PINK1/BECN1 pathway.

Recently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1ß treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1ß treatment promoted inflammatory factor secretion in chondrocytes, promoted cell apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1ß effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1ß-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1ß-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1ß induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression.

Luminescence properties and energy-transfer behavior of Y2-x-yBixEuyMgTiO6 phosphors.

In recent years, double perovskite has become a research hotspot of luminescent matrix materials due to its flexible structure, easy doping and good thermal stability. By using a high temperature solid-state technique, Bi3+ and Eu3+ co-doped Y2-x-yBixEuyMgTiO6 (0 ≤ x ≤ 0.1, 0 ≤ y ≤ 0.5) phosphors were made. X-ray diffraction (XRD) analysis shows that the crystal structure of all samples is monoclinic system, P21/n; Bi3+ and Eu3+ can be doped into the position of Y3+ in the substitution system of Y2MgTiO6. Both photoluminescence spectroscopy (PL) and X-ray excitation luminescence spectroscopy (XEL) were used to investigate the link between Bi3+ and Eu3+ doping concentrations and luminescence intensity. PL shows that: When 375 nm is used as the excitation wavelength, by varying the doping concentration of Eu3+ in the Y1.995-yBi0.005EuyMgTiO6 phosphor, it is possible to create the color-tunable emission from blue to red; The introduction of an appropriate amount of Bi3+ will increase the typical Eu3+ emission; The way that the system's Bi3+ and Eu3+ exchange energy can be observed by combining the fluorescence decay curve and photoluminescence. Fitting by concentration quenching model shows that the resonant dipole-dipole transition is the mechanism of energy transfer between Bi3+→Eu3+; X-rays may successfully stimulate the phosphor, and the spectral distribution of XEL and PL is basically the same; The introduction of an appropriate amount of Bi3+ is also beneficial to improving the sensitivity of XEL; Changes in temperature affect the sample's emission intensity; In addition, the samples remain stable for an extended period while being continuously exposed to X-rays at various environmental temperatures. The a forementioned findings suggest that the phosphor has potential use value in the lighting industry, X-ray imaging and temperature sensor.

Genomic diversity and biogeographic distributions of a novel lineage of bacteriophages that infect marine OM43 bacteria.

The marine methylotrophic OM43 clade is considered an important bacterial group in coastal microbial communities. OM43 bacteria, which are closely related to phytoplankton blooms, have small cell sizes and streamlined genomes. Bacteriophages profoundly shape the evolutionary trajectories, population dynamics, and physiology of microbes. The prevalence and diversity of several phages that infect OM43 bacteria have been reported. In this study, we isolated and sequenced two novel OM43 phages, MEP401 and MEP402. These phages share 90% of their open reading frames (ORFs) and are distinct from other known phage isolates. Furthermore, a total of 99 metagenomic viral genomes (MVGs) closely related to MEP401 and MEP402 were identified. Phylogenomic analyses suggest that MEP401, MEP402, and these identified MVGs belong to a novel subfamily in the family Zobellviridae and that they can be separated into two groups. Group I MVGs show conserved whole-genome synteny with MEP401, while group II MVGs possess the MEP401-type DNA replication module and a distinct type of morphogenesis and packaging module, suggesting that genomic recombination occurred between phages. Most members in these two groups were predicted to infect OM43 bacteria. Metagenomic read-mapping analysis revealed that the phages in these two groups are globally ubiquitous and display distinct biogeographic distributions, with some phages being predominant in cold regions, some exclusively detected in estuarine stations, and others displaying wider distributions. This study expands our knowledge of the diversity and ecology of a novel phage lineage that infects OM43 bacteria by describing their genomic diversity and global distribution patterns. IMPORTANCE OM43 phages that infect marine OM43 bacteria are important for host mortality, community structure, and physiological functions. In this study, two OM43 phages were isolated and characterized. Metagenomic viral genome (MVG) retrieval using these two OM43 phages as baits led to the identification of two phage groups of a new subfamily in the family Zobellviridae. We found that group I MVGs share similar genomic content and arrangement with MEP401 and MEP402, whereas group II MVGs only possess the MEP401-type DNA replication module. Metagenomic mapping analysis suggests that members in these two groups are globally ubiquitous with distinct distribution patterns. This study provides important insights into the genomic diversity and biogeography of the OM43 phages in the global ocean.

Genomic analysis and characterization of phages infecting the marine Roseobacter CHAB-I-5 lineage reveal a globally distributed and abundant phage genus.

Marine phages play an important role in marine biogeochemical cycles by regulating the death, physiological metabolism, and evolutionary trajectory of bacteria. The Roseobacter group is an abundant and important heterotrophic bacterial group in the ocean, and plays an important role in carbon, nitrogen, sulfur and phosphorus cycling. The CHAB-I-5 lineage is one of the most dominant Roseobacter lineages, but remains largely uncultured. Phages infecting CHAB-I-5 bacteria have not yet been investigated due to the lack of culturable CHAB-I-5 strains. In this study, we isolated and sequenced two new phages (CRP-901 and CRP-902) infecting the CHAB-I-5 strain FZCC0083. We applied metagenomic data mining, comparative genomics, phylogenetic analysis, and metagenomic read-mapping to investigate the diversity, evolution, taxonomy, and biogeography of the phage group represented by the two phages. The two phages are highly similar, with an average nucleotide identity of 89.17%, and sharing 77% of their open reading frames. We identified several genes involved in DNA replication and metabolism, virion structure, DNA packing, and host lysis from their genomes. Metagenomic mining identified 24 metagenomic viral genomes closely related to CRP-901 and CRP-902. Genomic comparison and phylogenetic analysis demonstrated that these phages are distinct from other known viruses, representing a novel genus-level phage group (CRP-901-type). The CRP-901-type phages do not contain DNA primase and DNA polymerase genes, but possess a novel bifunctional DNA primase-polymerase gene with both primase and polymerase activities. Read-mapping analysis showed that the CRP-901-type phages are widespread across the world's oceans and are most abundant in estuarine and polar waters. Their abundance is generally higher than other known roseophages and even higher than most pelagiphages in the polar region. In summary, this study has greatly expanded our understanding of the genetic diversity, evolution, and distribution of roseophages. Our analysis suggests that the CRP-901-type phage is an important and novel marine phage group that plays important roles in the physiology and ecology of roseobacters.

Distinguishing artificial spin ice states using magnetoresistance effect for neuromorphic computing.

Artificial spin ice (ASI) consisting patterned array of nano-magnets with frustrated dipolar interactions offers an excellent platform to study frustrated physics using direct imaging methods. Moreover, ASI often hosts a large number of nearly degenerated and non-volatile spin states that can be used for multi-bit data storage and neuromorphic computing. The realization of the device potential of ASI, however, critically relies on the capability of transport characterization of ASI, which has not been demonstrated so far. Using a tri-axial ASI system as the model system, we demonstrate that transport measurements can be used to distinguish the different spin states of the ASI system. Specifically, by fabricating a tri-layer structure consisting a permalloy base layer, a Cu spacer layer and the tri-axial ASI layer, we clearly resolve different spin states in the tri-axial ASI system using lateral transport measurements. We have further demonstrated that the tri-axial ASI system has all necessary required properties for reservoir computing, including rich spin configurations to store input signals, nonlinear response to input signals, and fading memory effect. The successful transport characterization of ASI opens up the prospect for novel device applications of ASI in multi-bit data storage and neuromorphic computing.

Multivariate analysis of prognostic factors in patients with lung cancer.

Objective: Lung cancer is the leading cause of cancer-related mortality in China. The purpose of this study was to determine the effect of non-therapeutic and therapeutic factors of patients with lung cancer on survival rate. Methods: In this retrospective study, a total of 458 patients diagnosed as lung cancer at the Department of Thoracic Surgery, the Fourth Affiliated Hospital of Hebei Medical University from September 2008 to October 2013 were enrolled. The COX proportional hazards model was used to analyze the possible factors affecting the survival of patients. Model variables included age, sex, family history, smoking, tumor location, pathological type, stage, chemotherapy, radiotherapy, operation, and targeted therapy. Results: The median survival time (MST) was 32.0 months (95% CI: 29.0-34.0 months), while the 1-, 3-, and 5-year survival rates were 70.74%, 36.90%, and 30.13%, respectively. The univariate analysis showed that stage, chemotherapy, radiotherapy, and operation significantly affected the median survival time of patients. Multivariate cox regression analysis suggested that sex (female vs male, 2.096, 95% CI: 1.606-2.736), stage (stage I vs IV, 0.111, 95% CI: 0.039-0.314; stage II vs IV, 0.218, 95%CI: 0.089-0.535), chemotherapy (no vs yes, 0.469, 95% CI: 0.297-0.742), and operation (no vs yes, 2.667, 95% CI: 1.174-6.055) were independently associated with the survival of patients with lung cancer. Conclusion: Our study showed that male, early stage, operation were protective factors for the survival of patients, while female, advanced stage, chemotherapy were risk factors for the survival of patients. Larger studies are required to address the usefulness of these prognostic factors in defining the management of patients with lung cancer.

Chronic atrophic gastritis in different ages in South China: a 10-year retrospective analysis.

OBJECTIVES: To explore the prevalence, characteristics, age distribution and etiology changes of chronic atrophic gastritis (CAG) in South China. METHODS: This study included all patients who underwent endoscopy examinations from 2011 to 2020 in our hospital. Patients were divided into groups 1 (2011-2015) and 2 (2016-2020). The prevalence, characteristics, age distribution and etiology changes of CAG were compared between groups. RESULTS: Overall CAG prevalence was 20.92% (24,084/115,110) from 2011 to 2020; prevalence significantly differed between groups (18.78%, 8468/45,087, in group 1 and 22.30%, 15,616/70,023, in group 2). Patients with CAG had significantly younger age (under 45) and more corpus atrophy and more autoimmune atrophic gastritis (AAG) in group 2 than in group 1. AAG prevalence in group 2 was 30.11% (4702/15,616) significantly higher than 13.57% (1149/8468) in group 1. 82 patients with AAG later exhibited gastric cancer without obvious clinical features over the decade. CONCLUSIONS: CAG is increasing and seems starting earlier among people during the study period. We need to focus on diagnosis and treatment of corpus related atrophy and AAG, especially for the young. Laboratory examination, endoscopic biopsy and surveillance are important for CAG.

The Ethanol Extract of Syringa oblata Heartwood, a Mongolian Folk Medicine Containing Major Lignans, Exerts Analgesic and Sedative Effects on Mice.

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.

Tubiechong patching promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The external use of traditional Chinese medicine (TCM) to treat fractures has a long history of clinical application and theoretical basis, and is also one of the characteristic treatment methods of TCM with significant efficacy and many advantages. Among the commonly used external Chinese medicines, Tubiechong is noteworthy. AIM OF THE STUDY: To elucidate whether local patching of Tubiechong can promote fracture healing and explore its mechanism of action. MATERIALS AND METHODS: A rat tibia fracture model was constructed by the modified Einhorn modeling method. X-ray films were taken to evaluate the progress of fracture healing. Serum bone alkaline phosphatase (BALP), osteocalcin (BGP) and the C-terminal content of collagen type I (CTX-I) were analyzed by ELISA. CD31 immunohistochemistry was used to evaluate angiogenesis in the tibia segment. The effects of Tubiechong decoction (TD) on HUVEC proliferation, migration and invasion were detected by MTT assay, wound healing assay and Transwell migration assay, respectively. RNA-seq was performed to identify differentially expressed genes (DEGs). Enrichment of functions and signaling pathway analysis were performed based on the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to study gene expression levels. Western blotting (WB) was used to detect the expression of relevant regulatory proteins. RESULTS: The healing time of rat tibia fractures in the three TD dose groups was shortened. The serum levels of BALP, BGP and CTX- I in the TD-treated group were higher than those in the NC group. The X-ray results showed that on the 7th day after surgery, the fracture healing degree of the high-dose TD group was significantly better than that of the NC group, and the fracture healing degrees of each TD treatment group were significantly higher than those of the NC group on the 14th, 17th, and 21st days after the operation. The CD31 immunohistochemistry results showed that the number of blood vessels and the vascular area in the TD treatment group were higher than those in the NC group. In vitro, TD promoted the proliferation, wound healing and migration of HUVECs. GO analysis of transcriptome sequencing results showed that TD significantly altered the expression of genes related to cell growth, metabolism, and motility. According to KEGG annotations, VEGFA was upregulated. Eight DEGs were enriched in the VEGFA-VEGFR2 signaling pathway, of which six were upregulated. KEGG signaling pathway analysis showed that the most abundant DEGs were in mitogen-activated protein kinase (MAPK) signaling pathway. qRT-PCR showed that VEGFA gene expression in HUVECs was 7.8 times that of the control group after 1 mg/mL TD treatment for 24 h, and WB experiments showed that its protein expression was 3 times that of the control group. WB results showed that the phosphorylated ERK gene was highly expressed, while the expression levels of phosphorylated P38 and phosphorylated JNK protein remained unchanged. CONCLUSION: Tubechong patching therapy promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway.

Sodium, added sugar and saturated fat intake in relation to mortality and CVD events in adults: Canadian National Nutrition Survey linked with vital statistics and health administrative databases.

This study aimed to determine whether higher intakes of Na, added sugars and saturated fat are prospectively associated with all-cause mortality and CVD incidence and mortality in a diverse population. The nationally representative Canadian Community Health Survey-Nutrition 2004 was linked with the Canadian Vital Statistics - Death Database and the Discharge Abstract Database (2004-2011). Outcomes were all-cause mortality and CVD incidence and mortality. There were 1722 mortality cases within 115 566 person-years of follow-up (median (interquartile range) of 7·48 (7·22-7·70) years). There was no statistically significant association between Na density or energy from saturated fat and all-cause mortality or CVD events for all models investigated. The association of usual percentage of energy from added sugars and all-cause mortality was significant in the base model with participants consuming 11·47 % of energy from added sugars having 1·34 (95 % CI 1·01, 1·77) times higher risk of all-cause mortality compared with those consuming 4·17 % of energy from added sugars. Overall, our results did not find statistically significant associations between the three nutrients and risk of all-cause mortality or CVD events at the population level in Canada. Large-scale linked national nutrition datasets may not have the discrimination to identify prospective impacts of nutrients on health measures.

Trends in EMS-attended out-of-hospital cardiac arrest survival, United States 2015-2019.

AIM: Everyday, nearly 1000 U.S. adults experience out-of-hospital cardiac arrest (OHCA). Survival to hospital discharge varies across many factors, including sociodemographics, location of arrest, and whether bystander intervention was provided. The current study examines recent trends in OHCA survival by location of arrest using a cohort of emergency medical service (EMS) agencies that contributed data to the Cardiac Arrest Registry to Enhance Survival. METHODS: The 2015 CARES cohort (N = 122,613) includes EMS agencies contributing data across five consecutive years, 2015-2019. We assessed trends in EMS-attended OHCA survival for the 2015 CARES cohort by location of arrest - public, residential, nursing home. Unadjusted and adjusted percentages were estimated using 3-level hierarchical logistic regression models among cases aged 18-65 years. RESULTS: Overall, survival from EMS-attended OHCA significantly increased from 12.5% in 2015 to 13.8% in 2019 (p = 0.001). Survival from bystander witnessed arrests also increased significantly from 17.8% in 2015 to 19.7% in 2019 (p = 0.004). The trend for survival increased overall and for bystander witnessed OHCAs occurring in public places and nursing homes. CONCLUSION: Increasing trends for EMS-attended OHCA survival were observed in the overall and bystander witnessed groups. No change in the trend for survival was observed among OHCAs in the groups most likely to have a desirable outcome - bystander witnessed, with a shockable rhythm, and receiving bystander intervention. Reporting and monitoring of OHCA may be an important first step in improving outcomes. Additional community interventions focused on bystander CPR and AED use may be warranted.

Associations between ultra- or minimally processed food intake and three adiposity indicators among US adults: NHANES 2011 to 2016.

OBJECTIVE: Ultraprocessed food (UPF) intake is associated with BMI, but effects on regional adipose depots or related to minimally processed food (MPF) intake are unknown. METHODS: Data included 12,297 adults in the National Health and Nutrition Examination Survey (NHANES), 2011 to 2016. This study analyzed associations between usual percentage of kilocalories from UPFs and MPFs and three adiposity indicators: supine sagittal abdominal diameter to height ratio (SADHtR, estimates visceral adiposity); waist circumference to height ratio (WHtR, estimates abdominal adiposity); and BMI, using linear and multinomial logistic regression. RESULTS: Standardized ß coefficients per 10% increase in UPF intake were 0.0926, 0.0846, and 0.0791 for SADHtR, WHtR, and BMI, respectively (all p < 0.001; p > 0.26 for pairwise differences). For MPF intake, the ß coefficients were -0.0901, -0.0806, and -0.0688 (all p < 0.001; p > 0.18 pairwise). Adjusted odds ratios (95% CI) for adiposity tertile 3 versus tertile 1 (comparing UPF intake quartiles 2, 3, and 4 to quartile 1) were 1.33 (1.22-1.45), 1.67 (1.43-1.95), and 2.24 (1.76-2.86), respectively, for SADHtR; 1.31 (1.19-1.44), 1.62 (1.37-1.91), and 2.13 (1.63-2.78), respectively, for WHtR; and 1.27 (1.16-1.39), 1.53 (1.31-1.79), and 1.96 (1.53-2.51), respectively, for BMI. MPF intake showed inverse associations with similar trends in association strength. CONCLUSIONS: Among US adults, abdominal and visceral adiposity indictors were positively associated with UPFs and inversely associated with MPFs.