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Abstract Background Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers. Methods This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored. Results Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy. Conclusions Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.

Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.Results Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6–8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI.Conclusions In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.

Abstract γ -aminobutyric acid (GABA) is closely related to the growth, development and stress resistance of plants. Combined with the previous study of GABA to promote the cotton against abiotic stresses, the characteristics and expression patterns of GABA branch gene family laid the foundation for further explaining its role in cotton stress mechanism. Members of GAD, GAB-T and SSADH (three gene families of GABA branch) were identified from the Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii genome. The GABA branch genes were 10 GAD genes, 4 GABA-T genes and 2 SSADH genes. The promoter sequences of genes mainly contains response-related elements such as light, hormone and environment.Phylogenetic analysis shows that GAD indicating that even in the same species, the homologous sequences in the family. The GABA-T gene of each cotton genus was in sum the family had gene loss in the process of dicotyledon evolution. SSADH families Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum and Gossypium raimondii were closely related to the dicot plants.GABA gene is involved in the regulation of salt stress and high temperature in Gossypium hirsutum.GABA attenuated part of the abiotic stress damage by increasing leaf protective enzyme activity and reducing reactive oxygen species production.This lays the foundation for a thorough analysis of the mechanism of GABA in cotton stress resistance.

The occurrence and spread of Verticillium dahliae (V. dahliae) in cotton depends on the combined effects of pathogens, host plants, and the environment, among which temperature is one of the most important environmental factors. Studying how temperature impacts the occurrence of V. dahliae in cotton and the mechanisms governing host defense responses is crucial for disease prevention and control. Understanding the dual effects of temperature on both pathogens and hosts can provide valuable insights for developing effective strategies to manage this destructive fungal infection in cotton. This study was based on the deciduous V. dahliae Vd-3. Through cultivation at different temperatures, Vd-3 formed the most microsclerotia and had the largest colony diameter at 25 °C. Endospore toxins were extracted, and 48 h was determined to be the best pathogenic time point for endotoxins to infect cotton leaves through a chlorophyll fluorescence imaging system and phenotypic evaluation. Transcriptome sequencing was performed on cotton leaves infected with Vd-3 endotoxins for 48 h at different culture temperatures. A total of 34,955 differentially expressed genes (DEGs) were identified between each temperature and CK (no pathogen inoculation), including 17,422 common DEGs. The results of the enrichment analysis revealed that all the DEGs were involved mainly in photosynthesis and sugar metabolism. Among the 34,955 DEGs, genes in the biosynthesis and signal transduction pathways of jasmonic acid (JA), salicylic acid (SA), and ethylene (ET) were identified, and their expression patterns were determined. A total of 5652 unique DEGs were clustered into six clusters using the k-means clustering algorithm, and the functions and main transcription factors (TFs) of each cluster were subsequently annotated. In addition, we constructed a gene regulatory network via weighted correlation network analysis (WGCNA) and identified twelve key genes related to cotton defense against V. dahliae at different temperatures, including four genes encoding transcription factors. These findings provide a theoretical foundation for investigating temperature regulation in V. dahliae infecting cotton and introduce novel genetic resources for enhancing resistance to this disease in cotton plants.

Background: There is limited research providing an overall understanding of bone mineral density (BMD) changes throughout different stages of life. This study aimed to investigate the pattern of BMD changes across childhood, adolescence, adulthood, and old age, as well as exploring the critical time of peak BMD (PBMD). Methods: Participants of three major ethnicities from National Health and Nutrition Examination Survey 1999 to 2018 were involved: 46,381 and 20,944 participants aged 8–85 years old were included in the Lumbar spine BMD (LSBMD) and femoral neck BMD (FNBMD) studies, respectively. BMD was measured using dual-energy X-ray absorptiometry. The generalized additive model was used to construct smoothed percentile curves. Results: Both males and females experienced a sharp increase in LSBMD during puberty, with females reaching their PBMD earlier than males. Females’ LSBMD remained higher than males’ before the age of approximately 50, except for Non-Hispanic Blacks. For males, LSBMD reached a plateau at around 30 years old after reaching the peak value. Females exhibited two peak points on the fitted curves, with the second PBMD occurring around 36–37 years old. Ethnic variations were observed, with Non-Hispanic Blacks displaying the highest BMD levels at all ages. Non-Hispanic Whites and Mexican Americans had lower BMD levels, with Mexican Americans generally exhibiting the lowest BMD. FNBMD reached its peak earlier than LSBMD, and males consistently had higher FNBMD than females. Conclusions: This nationally representative study contributes to the understanding of BMD changes across the lifespan, and might provide guidance for bone health interventions in different population groups.

BackgroundIntrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy with a steadily increasing incidence worldwide. ICC has insidious onset, rapid progression, and poor prognosis. More multidisciplinary clinical studies are needed to continuously explore safer and more efficient diagnosis and treatment modes for ICC.Methods and resultsA 66-year-old female patient with ICC rapidly developed systemic multiple metastases after surgery, and the first-line two-drug combination chemotherapy was not effective. Due to cyclin-dependent kinase inhibitor 2A mutation and programmed cell death-ligand 1-positive, a partial response and progression-free survival of 9.5 months were achieved after a second-line treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with immunotherapy. The patient developed thromboembolism 7 months after treatment and died due to disseminated intravascular coagulation.ConclusionThe combination of targeted and immune therapy has revealed a potentially effective regimen for the effective treatment of patients with ICC, which needs to be observed in larger clinical studies. The thromboembolism rates in real-world patients treated with CDK4/6 inhibitors are higher than those reported in clinical trials, and the application of prophylactic anticoagulation in this patient population may be questionable.

Abstract The canonical estimation of distribution algorithm (EDA) easily falls into a local optimum with an ill-shaped population distribution, which leads to weak convergence performance and less stability when solving global optimization problems. To overcome this defect, we explore a novel EDA variant with an ensemble of three distribution modification strategies, i.e., archive-based population updating (APU), multileader-based search diversification (MSD), and the triggered distribution shrinkage (TDS) strategy, named E3-EDA. The APU strategy utilizes historical population information to rebuild the search scope and avoid ill-shaped distributions. Moreover, it continuously updates the archive to avoid overfitting the distribution model. The MSD makes full use of the location differences among populations to evolve the sampling toward promising regions. TDS is triggered when the search stagnates, shrinking the distribution scope to achieve local exploitation. Additionally, the E3-EDA performance is evaluated using the CEC 2014 and CEC 2018 test suites on 10-dimensional, 30-dimensional, 50-dimensional and 100-dimensional problems. Moreover, several prominent EDA variants and other top methods from CEC competitions are comprehensively compared with the proposed method. The competitive performance of E3-EDA in solving complex problems is supported by the nonparametric test results.

Abstract Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. MTSS1 downregulation correlates with improved ICB efficacy in patients. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination at Lysine 263, leading to PD-L1 endocytic sorting and lysosomal degradation. In addition, EGFR-KRAS signaling in lung adenocarcinoma suppresses MTSS1 and upregulates PD-L1. More importantly, combining AIP4-targeting via the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in immunocompetent mice and humanized mice. Overall, our study discovers an MTSS1-AIP4 axis for PD-L1 monoubiquitination and reveals a potential combinatory therapy with antidepressants and ICB.

Objective To establish the donor bank for local region and distinguish the donors based on the past blood donation frequency and blood donation type, so as to improve the application efficiency of platelet bank. Methods 1) According to the donation type and frequency of blood donors, the blood donors who had joined China Marrow Donor Program(CMDP)in our center from 2011 to 2020 were screened and classified. They are classified as reserve donors, prospective donors, and active donors. The donors, who met the selection conditions of active donors, were enrolled from all apheresis donors in 2020 to expand the local platelet bank. 2) In 2020, 739 blood donors who met the conditions of active donors were screened(including donors who had entered CMDP), and their HLA-A/B loci were detected by HLA high-resolution genotyping, and HPA was detected by Q-PCR genotyping. 3) The compatible platelets provided by three types of donors in 2021 were calculated. Results 1) Taiyuan platelet bank, composed of donors with different previous donation experiences, had been constructed, including 739 active donors, 3840 prospective donors and 18 715 reserve donors. The composition ratio of ABO blood groups among three types of donors was found to be similar via chi square test; there were more male than female in three groups. 2) In 2021, the ratio of the average redonation by active donors in the platelet bank to the regular donation by the general donors was 14.4∶3.98. 3) Of the 142 compatible platelets, supplied to PTR patients in 2021, 83.8% of them came from the redonation of active donors after registration in the bank, and 9.9% and 6.3% from prospective donors and reserve donors, respectively. 4) In 2021, 28.1% of the stored pheresis platalets in our center had HLA typing data, and 54.2% of compatible platelets were retrieved from the inventory, which timely met the needs of clinical patients. Conclusion Integrating resources and distinguishing the activity degree of donors in platelet bank can reduce the cost of bank building and improve the application efficiency of the platelet bank.

Abstract The metabolic syndrome (MetS) has been well linked with coronary heart disease (CHD) in the general population, but studies have rarely explored their association among patients with stroke. We examine prevalence of MetS and its association with CHD in patients with first-ever ischemic stroke. This hospital-based study included 1851 patients with first-ever ischemic stroke (mean age 61.2 years, 36.5% women) who were hospitalized into two university hospitals in Shandong, China (January 2016–February 2017). Data were collected through interviews, physical examinations, and laboratory tests. MetS was defined following the National Cholesterol Education Program (NCEP) criteria, the International Diabetes Federation (IDF) criteria, and the Chinese Diabetes Society (CDS) criteria. CHD was defined following clinical criteria. Data were analyzed using binary logistic regression models. The overall prevalence of MetS was 33.4% by NECP criteria, 47.2% by IDF criteria, and 32.5% by CDS criteria, with the prevalence being decreased with age and higher in women than in men (p

Background: There is limited evidence on the effect of low birthweight on the use of cardiovascular medications and the role of health behaviors. This study aims to determine the independent effect of low birthweight and its combination with adult health behaviors on the number of dispensed cardiovascular medications. Methods: We included 15618 participants with information on birthweight and self-reported health behaviors. Dispensed cardiovascular medications were identified from the Prescribed Drug Register based on a three-digit level Anatomical Therapeutic Chemical classification code (C01 to C10 and B01) and categorized into 0, 1, and ≥2 different types of medications. We applied multinomial logistic regression models estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results: Participants with low birthweight had a higher estimated OR of using ≥2 types of cardiovascular medications (OR = 1.46, 95% CI = 1.06, 2.01). Further, an increased risk for using ≥2 types of cardiovascular medications was found in participants with poor health behaviors for normal (OR = 2.17, 95% CI = 1.80, 2.62) and high (OR = 1.84, 95% CI = 1.29, 2.62) birthweight. The strongest effect on using ≥2 types of cardiovascular medications was found for low birthweight and poor health behaviors (OR = 3.14, 95% CI = 1.80, 5.50). Conclusion: This cohort study provides evidence that low birthweight increases the risk of using more types of cardiovascular medications in adulthood. This study also suggests that ideal health behaviors reduce this risk.

Cotton mechanized harvesting is the development direction of cotton production. The rapid development of mechanized cotton harvesting in Xinjiang has significantly increased the efficiency of cotton harvesting and reduced the harvesting cost. However, in the rapid development of mechanized cotton harvesting, there are also the problems of net yield, recovery rate and poor harvesting quality, which lead to the poor quality competitiveness of mechanized cotton harvesting. In order to solve the problem of mechanized cotton loss, the key is to reduce the problem of cotton miscellaneous, and breed cotton varieties suitable for mechanized harvesting. The purpose of this study was to clarify the key trait correlation of defoliation through the establishment and association analysis of foliation and deciduous phenotype indicators in cotton. In this study, the phenotypic indexes of defoliation and deciduous traits were established through the comprehensive analysis of the defoliation rate of 273 cotton germplasm resources and other 11 related phenotypic traits in the field, in order to provide guidance for the breeding and production of cotton varieties collected by breeders. In addition to peeling rate, an analysis of the association between 11 agronomic parameters and peeling rate and hanging rate revealed that the number of effective branches, chlorophyll SPAD value, fruit branch angle, and hanging rate have substantial correlation in 3 years. Hence The hanging rate, fruit branch angle, effective branch number, and chlorophyll SPAD value can be used as the evaluation indicators of varieties for peeling ability trait index.

FCS-like zinc finger (FLZ) is a plant-specific gene family that plays an important regulatory role in plant growth and development and its response to stress. However, studies on the characteristics and functions of cotton FLZ family genes are still lacking. This study systematically identified members of the cotton FLZ gene family based on cotton genome data. The cotton FLZ family genes were systematically analyzed by bioinformatics, and their expression patterns in different tissues and under low-temperature stress were analyzed by transcriptome and qRT–PCR. The G. hirsutum genome contains 56 FLZ genes distributed on 20 chromosomes, and most of them are located in the nucleus. According to the number and evolution analysis of FLZ family genes, FLZ family genes can be divided into five subgroups in cotton. The G. hirsutum FLZ gene has a wide range of tissue expression types, among which the expression is generally higher in roots, stems, leaves, receptacles and calyx. Through promoter analysis, it was found that it contained the most cis-acting elements related to methyl jasmonate (MeJA) and abscisic acid (ABA). Combined with the promoter and qRT–PCR results, it was speculated that GhFLZ11, GhFLZ25, GhFLZ44 and GhFLZ55 were involved in the response of cotton to low-temperature stress. Taken together, our findings suggest an important role for the FLZ gene family in the cotton response to cold stress. This study provides an important theoretical basis for further research on the function of the FLZ gene family and the molecular mechanism of the cotton response to low temperature.

Abstract Giant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.

Disseminated tumor cells often become dormant before awakening for metastatic growth. Here, the authors report that the lncRNA, NR2F1-AS1, is upregulated in dormant mesenchymal-like breast cancer stem-like cells and promotes dissemination but inhibits proliferation, leading to metastatic dormancy.

Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit β (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL-20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete the IL-20RB ligand IL-19, and IL-19 stimulated IL-20RB–expressing tumor cells to activate downstream JAK1/STAT3 signaling, leading to enhanced proliferation of tumor cells in bone. Importantly, blocking IL-20RB with a neutralizing antibody significantly suppressed bone metastasis of lung cancer. Overall, our data revealed a direct protumor role of osteoclastic niche in bone metastasis and supported IL-20RB–targeting approaches for metastasis treatment.

The present study examined the prevalence and pattern of comorbidity among Chinese patients with first-ever acute ischemic stroke, and assessed the associations of specific comorbidity patterns with physical and cognitive functioning after stroke occurrence. A hospital-based cross-sectional study was conducted among 2,151 patients with first-ever ischemic stroke (age ≥40 years; 64.2% men) who were admitted to two university hospitals in Shandong, China between 2016 and 2017. Data on demographics, lifestyles, chronic health conditions, and use of medications were collected through in-person interviews, clinical examinations, and laboratory tests. Physical functioning was assessed by the Barthel index (BI) and the modified Rankin Scale (mRS) while cognitive functioning was assessed by the Montreal Cognitive Assessment test. The results showed that comorbidity was present in 90.9% of the stroke patients (women vs. men: 95.2 vs. 88.7%, P < 0.001). Exploratory factor analysis identified three patterns of comorbidity, i.e., patterns of degenerative-cardiopulmonary, heart-gastrointestinal-psychiatric, and metabolic-kidney diseases. The number of comorbidities was significantly associated with a higher likelihood of moderate-to-severe physical dependence [odds ratio (95% CI) = 1.15 (1.06–1.25) for BI and 1.12 (1.04–1.21) for mRS, all P < 0.01] and cognitive impairment [odds ratio (95% CI) = 1.11 (1.02–1.20), P = 0.017], after adjusting for multiple covariates. Almost all the three comorbidity patterns were associated with increased likelihoods of physical dependence (range for odds ratios: 1.26–1.33) and cognitive impairment (range for odds ratios: 1.25–1.34). No significant association was found between degenerative-cardiopulmonary pattern and mRS. These findings suggest that comorbidity is associated with poor physical and cognitive functioning during the acute phase of ischemic stroke. Routine assessments of comorbidity and cognitive and physical function among patients with acute ischemic stroke should be considered in stroke research and clinical practice.

(1) Background: Potentially inappropriate medications (PIMs) in older adults are associated with drug-related problems, adverse health consequences, repeated hospital admissions and a higher risk of mortality. In Saudi Arabia and some Arab countries, studies of PIMs among large cohorts of older adults are limited. This study aimed to determine the prevalence of PIMs, trends and associated factors among outpatient older adults in Saudi Arabia. (2) Methods: A cross-sectional study was carried out. Over three years (2017–2019), data on 23,417 people (≥65 years) were retrieved from outpatient clinics in a tertiary hospital in Riyadh, Saudi Arabia. PIMs were assessed using the 2019 Beers Criteria. Covariates included sex, age, nationality, number of dispensed medications, and number of diagnoses. A generalized estimating equation model was used to assess trends and factors associated with PIMs. (3) Results: The prevalence of PIMs was high and varied between 57.2% and 63.6% over the study years. Compared with 2017, the prevalence of PIMs increased significantly, with adjusted odds ratios (OR) (95% confidence interval (95% CI)) of 1.23 (1.18–1.29) and 1.15 (1.10–1.21) for 2018 and 2019, respectively. Factors associated with being prescribed PIMs included ≥5 dispensed medications (OR_adjusted = 23.91, 95% CI = 21.47–26.64) and ≥5 diagnoses (OR_adjusted = 3.20, 95% CI = 2.88–3.56). Compared with females, males had a lower risk of being prescribed PIMs (OR_adjusted = 0.90, 95% CI = 0.85–0.94); (4) Conclusions: PIMs were common with an increasing trend among older adults in Saudi Arabia. A higher number of dispensed medications, increased number of diagnoses and female sex were associated with being prescribed PIMs. Recommendations on how to optimize prescriptions and implement de-prescribing strategies are urgently needed.

Abstract Background As the population is ageing, the need for informal caregivers increases, and thus we need to know more about the effects on caregivers. This study aims to determine both cross-sectional and longitudinal associations between perceived limitation of informal caregiving and mental health of caregivers. Methods This population-based cohort study was based on the Swedish Psykisk hälsa, Arbete och RelaTioner (PART) study, and 9346 individuals aged 18–65 were included. Data were collected through questionnaires, interviews and Swedish registers. Informal care was defined as care given to a family member. Self-reported and diagnosed depression and anxiety were included as outcomes. Covariates included sex, age, social support and socio-economic position. Ordinal logistic regression and Cox regression were performed to determine the associations between caregiving and anxiety or depression. Results Self-reported depression and anxiety was only increased among those experiencing limitations (adjusted odds ratios [aOR] 2.00, 95% confidence intervals [CI] 1.63–2.47 for depression; aOR 2.07, 95% CI 1.57–2.74 for anxiety) compared to those not giving care, respectively. The adjusted hazard ratio (aHR) were increased for diagnosed depression (aHR 1.97, 95% CI 1.27–3.05) and for diagnosed anxiety (aHR 1.86, 95% CI 1.06–3.25) among those giving care and experiencing limitations, compared to those not giving care. No significant associations were found in caregivers without limitations. Conclusion Caregivers experiencing limitations showed a significant association with short- and long-term anxiety and depression. This study implies the importance of exploring the degree to which informal caregiving can be provided without adding burden to caregivers.

Background: Although some studies have shown the average side effects of cardiovascular medication, the short-term effect after newly initiated cardiovascular medications has not been studied in any detail. We aim to determine the effect of newly initiated cardiovascular medications resulting in unintentional poisoning and to identify those at high risk. Methods: A case-crossover design was used. From the Swedish National Patient Register, a total of 9,354 persons aged ≥ 50 and hospitalized with a first event of unintentional poisoning between July 2006 and September 2018 were identified. Through linkage to the Prescribed Drug Register, exposure to newly initiated cardiovascular medication during the case period (1–28 days prior to the onset date of unintentional poisoning) was compared with that in a corresponding control period (113–140 days prior to the onset date). Conditional logistic regression was used to determine the associations in total, for different time periods as well as by age, sex, underlying comorbidity, and use of other medications. Results: Newly initiated cardiovascular medications were associated with a higher risk of unintentional poisoning, especially during the first week after initiation (odds ratio [OR]=1.39), (95% confidence interval [CI]=1.08–1.79). The risk of unintentional poisoning was comparable across age groups, sex, underlying comorbidities, and medications with OR (95% CI) ranging from 1.15 (0.75–1.74) to 2.00 (1.15–3.47). Conclusion: This large population-based case-crossover study showed that newly initiated cardiovascular medication is associated with an increased risk of unintentional poisoning, particularly during the first week after initiation. The risk is comparable across age, sex, underlying comorbidity, and medications.

Abstract Background Cardiovascular health (CVH) metrics among Chinese older adults are poorly understood. We investigated sex disparities in CVH metrics and their management among rural-dwelling older adults in China. Methods This community-based study included 5026 participants (age ≥ 65 years; 57.2% women) in the baseline survey of a multimodal intervention study in rural China. In March–September 2018, data were collected through face-to-face interviews, clinical examinations, and laboratory tests. We defined six CVH metrics (three behavioral factors—smoking, body mass index, and physical activity; three biological factors—blood pressure, total cholesterol, and blood glucose) following the modified American Heart Association’s recommendations. We performed descriptive analysis separately for men and women. Results Of all participants, only 0.8% achieved ideal levels in all six CVH metrics. Men were more likely than women to have ideal levels in all CVH metrics but smoking. Women had higher prevalence of ideal global (9.7% vs. 7.8%) and behavioral (18.3% vs. 9.5%) CVH metrics (p

Abstract Background Prevention and control of cardiometabolic conditions and cardiovascular disease (CVD) in China may contribute to sustainable CVD reduction globally, given the fact that one-fifth of the worldwide population is in China. Knowing the distribution of behavioral risk factors (e.g., smoking and physical inactivity), especially at a national level in China, would be extremely relevant to the field of public health and CVD prevention. The objectives of this study were to investigate the nationwide prevalence of obesity, smoking, heavy drinking, and physical inactivity in Chinese adults, and further explore whether cardiometabolic conditions would modify the distribution of behavioral risk factors. Methods This population-based study is based on the China Health and Retirement Longitudinal Study (2011–2012), including 17,302 adults (≥45 years, mean age 59.67 years, female 51.66%) from 25 provinces in China. Data on demographics, lifestyle factors, health status and history of diseases were collected via structured interviews and laboratory tests. Smoking, heavy drinking, obesity, and physical inactivity were defined following standard guidelines. We performed descriptive analysis and logistic regressions in this study. Results The overall prevalence of heavy drinking, obesity, current smoking, and physical inactivity among middle-aged and older adults was 7.23% (95% confidence interval 6.53—7.29%), 11.53% (10.43—12.62%), 27.46% (26.30—28.62%), and 44.06% (41.19—46.92%), respectively. The prevalence varied between rural and urban areas as well as among geographic areas, with higher prevalence in the Northern and Northeastern regions. Heavy drinking and obesity were significantly associated with incident hypertension, diabetes, and high cholesterol; while current smoking was significantly associated with incident hypertension. Compared with healthy individuals, participants who self-reported a diagnosis of hypertension, high cholesterol, or diabetes were less likely to smoke currently and drink alcohol heavily, but more likely to be physically inactive and obese. Conclusions Among Chinese middle-aged and older adults, the prevalence of behavioral risk factors varies by geographic region. Further effort is required to improve physical activity and fitness for Chinese adults, especially those with cardiometabolic conditions.

Summary: Background: Secondhand smoke exposure can cause morbidity and premature mortality. However, the global prevalence of, and trends in, secondhand smoke exposure among adolescents are poorly documented. We aimed to assess the prevalence of, and trends in, secondhand smoke exposure among adolescents from 1999 to 2018. Methods: We did an analysis of the most recent data from the Global Youth Tobacco Survey (GYTS), a nationally representative, self-administered, school-based cross-sectional survey of tobacco use and related factors among adolescents aged 12–16 years worldwide. Data from 142 countries and territories that had done a GYTS between 2010 and 2018, comprising 711 366 participants, were used to assess the prevalence of secondhand smoke exposure. Data from 131 countries and territories that had done two or more surveys between 1999 and 2018, comprising 1 405 458 participants, were used to assess trends in secondhand smoke exposure. The frequency of secondhand smoke exposure at home, in public places, or in any place was defined as follows, based on students' responses: 1 or more days, 3 or more days, 5 or more days, or daily during the past 7 days. Findings: Based on the most recent surveys done in 142 countries between Jan 1, 2010, and Dec 31, 2018, the global prevalence of secondhand smoke exposure in any place was 62·9% (95% CI 61·7–64·1) on 1 or more days, 51·0% (49·8–52·1) on 3 or more days, 40·1% (38·9–41·2) on 5 or more days, and 32·5% (31·5–33·6) daily during the past 7 days. The prevalence of secondhand smoke exposure at home was 33·1% (95% CI 32·1–34·1) on 1 or more days, 20·1% (19·3–20·9) on 3 or more days, 14·9% (14·2–15·7) on 5 or more days, and 12·3% (11·7–13·0) daily during the past 7 days; and in public places the prevalence of secondhand smoke exposure was 57·6% (56·4–58·8) on 1 or more days, 43·4% (42·2–44·6) on 3 or more days, 30·3% (29·2–31·5) on 5 or more days, and 23·5% (22·5–24·5) daily during the past 7 days. Between Jan 1, 1999, and Dec 31, 2018, the prevalence of secondhand smoke exposure (on ≥1 day during the past 7 days) in any place decreased in 57 (43·5%) of 131 countries, increased in 27 (20·6%), and remained unchanged in 47 (35·9%). Although the prevalence of secondhand smoke exposure at home decreased in 86 (65·6%) countries, the prevalence in public places did not change in 46 (35·1%) countries and increased in 40 (30·5%). Interpretation: Secondhand smoke exposure among adolescents remains a serious public health challenge worldwide. Although the prevalence of secondhand smoke exposure at home decreased in most countries, the prevalence in public places increased or remained unchanged in most countries between 1999 and 2018. These findings emphasise the need to strengthen smoke-free policies, especially in public places. Funding: Youth Team of Humanistic and Social Science of Shandong University, Jinan, China. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

Background: Exercise can protect myocardial infarction (MI) and downregulate cardiac Homeodomain-Interacting Protein Kinase 2 (HIPK2). However, the role of HIPK2 in MI is unclear. Methods: HIPK2–/– mice and miR-222–/– rats, HIPK2 inhibitor (PKI1H) and adeno-associated virus serotype 9 (AAV9) carrying miR-222 were applied in the study. Animals were subjected to running, swimming, acute MI or post-MI remodeling. HIPK2 inhibition and P53 activator were used in neonatal rat cardiomyocytes (NRCMs) and human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to oxygen glucose deprivation/reperfusion (OGD/R). Serum miR-222 levels were analyzed in healthy people and MI patients that were survival or readmitted to the hospital and/or died. Findings: Cardiac HIPK2 protein levels were reduced by exercise while increased in MI. In vitro, HIPK2 suppression by lentiviral vectors or inhibitor prevented apoptosis induced by OGD/R in NRCMs and hESC-CMs. HIPK2 inhibitor-treated mice and HIPK2–/– mice reduced infarct size after acute MI, and preserved cardiac function in MI remodeling. Mechanistically, protective effect against apoptosis by HIPK2 suppression was reversed by P53 activators. Furthermore, increasing levels of miR-222, targeting HIPK2, protected post-MI cardiac dysfunction, whereas cardiac dysfunction post-MI was aggravated in miR-222–/– rats. Moreover, serum miR-222 levels were significantly reduced in MI patients, as well as in MI patients that were readmitted to the hospital and/or died compared to those not. Interpretation: Exercise-induced HIPK2 suppression attenuates cardiomyocytes apoptosis and protects MI by decreasing P-P53. Inhibition of HIPK2 represents a potential novel therapeutic intervention for MI. Funding: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to JJ Xiao), National Natural Science Foundation of China (82020108002, 81722008, and 81911540486 to JJ Xiao, 81400647 to MJ Xu, 81800265 to YJ Liang), Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JJ Xiao), the grant from Science and Technology Commission of Shanghai Municipality (18410722200 and 17010500100 to JJ Xiao), the “Dawn” Program of Shanghai Education Commission (19SG34 to JJ Xiao), Shanghai Sailing Program (21YF1413200 to QL Zhou). JS is supported by Horizon2020 ERC-2016-COG EVICARE (725229).

Heat shock transcription factors (HSFs) are involved in environmental stress response and plant development, such as heat stress and flowering development. According to the structural characteristics of the HSF gene family, HSF genes were classified into three major types (HSFA, HSFB, and HSFC) in plants. Using conserved domains of HSF genes, we identified 621 HSF genes among 13 cotton genomes, consisting of eight diploid and five tetraploid genomes. Phylogenetic analysis indicated that HSF genes among 13 cotton genomes were grouped into two different clusters: one cluster contained all HSF genes of HSFA and HSFC, and the other cluster contained all HSF genes of HSFB. Comparative analysis of HSF genes in Arabidopsis thaliana, Gossypium herbaceum (A1), Gossypium arboreum (A2), Gossypium raimondii (D5), and Gossypium hirsutum (AD1) genomes demonstrated that four HSF genes were inherited from a common ancestor, A0, of all existing cotton A genomes. Members of the HSF gene family in G. herbaceum (A1) genome indicated a significant loss compared with those in G. arboretum (A2) and G. hirsutum (AD1) A genomes. However, HSF genes in G. raimondii (D5) showed relative loss compared with those in G. hirsutum (AD1) D genome. Analysis of tandem duplication (TD) events of HSF genes revealed that protein-coding genes among different cotton genomes have experienced TD events, but only the two-gene tandem array was detected in Gossypium thurberi (D1) genome. The expression analysis of HSF genes in G. hirsutum (AD1) and Gossypium barbadense (AD2) genomes indicated that the expressed HSF genes were divided into two different groups, respectively, and the expressed HSF orthologous genes between the two genomes showed totally different expression patterns despite the implementation of the same abiotic stresses. This work will provide novel insights for the study of evolutionary history and expression characterization of HSF genes in different cotton genomes and a widespread application model for the study of HSF gene families in plants.

To overcome the premature convergence caused by the ill-distribution of solutions in the basic Gaussian estimation of distribution algorithm (GEDA), this paper explores a novel GEDA variant with random walk strategies, namely RW-GEDA. In RW-GEDA, the weighted maximum likelihood estimation method is used to estimate the Gaussian distribution. The new candidates are sampled using a shifted mean to enhance exploration performance. When the algorithm stagnates, two random walk strategies, namely, Gaussian random walk and Lévy walk, are activated to enrich the population diversity. Moreover, RW-GEDA is executed in an Eigen coordinate framework to promote the evolution towards the dominant region. The performance of RW-GEDA is evaluated by using the CEC 2014 test suite and compared with other top algorithms from different communities as well as promising GEDA extensions. The statistical results demonstrate the competitive performance of our proposed RW-GEDA in terms of efficiency and accuracy. In addition, RW-GEDA is applied to solve the optimal missile guidance handover problem. To fill the gap in solving this problem, a novel missile guidance advantage model is established, and the optimal missile guidance handover is determined by optimizing the control variables of unmanned combat aerial vehicles. The validity and practicability of the problem model as well as the accuracy and efficiency of RW-GEDA are demonstrated by the experimental results.

This paper considers the sequential fault diagnosis problem with unreliable tests which exist widely in practice. This problem involves real-time inference of the most likely set of failure sources, i.e., fault state, based on unreliable test outcomes. The purpose of this paper is to optimize test set and diagnostic strategy so as to cut down the test cost while isolating the fault accurately, and a method for optimal diagnosis strategy based on partially observable Markov decision process (POMDP) is presented. The components of the POMDP tailed to optimizing the diagnostic strategy are specified, and the solution to the POMDP-based model, namely the optimal strategy, is obtained to describe the optimal test sequence for fault diagnosis. The performance of the proposed method is evaluated with simulation experiments. All the results indicate that this method performs good in diagnostic efficiency and accuracy, even compared with the strategies of traditional methods.

By virtue of its large-covered spatial information and high-resolution spectral information, hyperspectral images make lots of mapping-based fine-grained remote sensing applications possible. However, due to the inconsistency of land-cover types between different images, most hyperspectral image classification methods keep their effectiveness by training on every image and saving all classification models and training samples, which limits the promotion of related remote sensing tasks. To deal with the aforementioned issues, this paper proposes a hyperspectral image classification method based on class-incremental learning to learn new land-cover types without forgetting the old ones, which enables the classification method to classify all land-cover types with one final model. Specially, when learning new classes, a knowledge distillation strategy is designed to recall the information of old classes by transferring knowledge to the newly trained network, and a linear correction layer is proposed to relax the heavy bias towards the new class by reapportioning information between different classes. Additionally, the proposed method introduces a channel attention mechanism to effectively utilize spatial–spectral information by a recalibration strategy. Experimental results on the three widely used hyperspectral images demonstrate that the proposed method can identify both new and old land-cover types with high accuracy, which proves the proposed method is more practical in large-coverage remote sensing tasks.

Abstract Background Evidence is scarce on the trend in prevalence of geriatric syndromes (GS). This study assesses how GS prevalence changes over time in Swedish older community-dwellers by socio-demography, and attempts to highlight factors that may contribute to explain the trend. Methods Data from Stockholm County Council Public Health Surveys in 2006, 2010 and 2014 were used. Old adults, aged 65–84 years, with measurements on GS items were identified. Thus, a total of 17,560 participants were selected in 2006 (n = 6295), 2010 (n = 6733) and 2014 (n = 4532). Data on socio-demographics, lifestyles and health status were collected through questionnaires. GS was defined as having at least one of the following: insomnia, urinary incontinence, severe hearing/vision problem, functional decline, fall and depressive disorder. Logistic regression was performed to assess the prevalence trend as well as the change in the associations of sociodemographic factors, health behaviors and chronic disease with GS. Results From 2006 to 2014, the prevalence of GS remained stable (P trend = 0.54). However, among old adults born outside Nordic countries, it increased significantly from 73.0% in 2006, 78.0% in 2010 to 83.0% in 2014 (P trend 0.05). Conclusions At population level, GS prevalence remained stable at a high level among Swedish old community-dwellers. There are noteworthy differences in GS trend between population groups, in particular to the detriment of older adults born outside Nordic countries.

Objective Compelling evidence suggests that childhood adversities are associated with an increased risk of hypertension in middle age and old age. The link between childhood adversities and blood pressure in youth is less clear. In this cohort study, we examined the association between death of a parent during childhood and blood pressure in early adulthood in men.Setting Sweden.Participants We studied 48 624 men born in 1949–1951 who participated in the compulsory military conscription in 1969/1970 in Sweden. Information on death of a parent during childhood was obtained from population-based registers. Information on covariates was obtained from the questionnaire and the clinical examination completed at conscription and from population-based registers.Outcome measures Blood pressure was measured at conscription according to standard procedures.Results The multivariable least square means of systolic and diastolic blood pressure did not differ between bereaved (128.25 (127.04–129.46) and 73.86 (72.89–74.84) mm Hg) and non-bereaved study participants (128.02 (126.86–129.18) and 73.99 (73.06–74.93) mm Hg). Results were similar when considering the cause of the parent’s death, the gender of the deceased parent or the child’s age at loss. Loss of a parent in childhood tended to be associated with an increased hypertension risk (OR and 95% CI: 1.10 (1 to 1.20)); the association was present only in case of natural deaths.Conclusion We found no strong support for the hypothesis that stress following the loss of a parent during childhood is associated with blood pressure or hypertension in youth in men.

BackgroundVery few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia.Methods and findingsThis cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)'s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p < 0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses.ConclusionsIn this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia.

Objective This study aimed to assess using Doppler ultrasound for analyzing stability of deep venous thrombosis (DVT) of the lower extremities. Methods Patients with DVT of the lower extremities who were treated from August 2017 to December 2019 were selected. The patients were divided into stable and unstable groups according to whether thrombus was collected in a filter. Related ultrasound and blood test results were analyzed and compared. Results A total of 126 patients with DVT of the lower extremities were included, of whom 74 were in the stable group and 52 were in the unstable group. There were significant differences in the prothrombin time (PT), and lipoprotein alpha, D-dimer, and triglyceride levels between the groups. D-dimer levels >2800 ug/L, smoking, history of venous thrombosis, PT >13.15 s, and body mass index >24.45 kg/m 2 were independent risk factors for stability of DVT of the lower extremities. The area under the curve with combined detection of DVT was significantly higher than that for body mass index, PT, and D-dimer alone. Conclusion Doppler ultrasound may be reliable for analyzing the stability of DVT of the lower extremities. Related strategies targeting risk factors are required for reducing DVT of the lower extremities.

BackgroundThe patterns of blood pressure trajectory (i.e., change over time) over life-course remain to be explored. In this study, we aim to determine the trajectories of systolic blood pressure (SBP) from adulthood to late life and to assess its impact on the risk of cardiovascular diseases (CVDs).MethodsBased on the China Health and Nutrition Survey, a total of 3566 participants aged 20-50 years at baseline (1989) with at least three SBP measurements during 1989-2011 were included. SBP was measured through physical examination, and socio-demographic factors, lifestyles, medications, and CVDs were based on self-reported questionnaire. Latent class growth modeling was performed to examine SBP trajectory. Odds ratio (OR) and 95% confidence interval (CI) from logistic regression was used to determine the association between SBP trajectory and CVDs.ResultsFive trajectory groups of SBP were identified: Class 1: rapid increase (n = 113, 3.2%); Class 2: slight increase (n = 1958, 54.9%); Class 3: stable (n = 614, 17.2%); Class 4: increase (n = 800, 22.4%); Class 5: fluctuant (n = 81, 2.3%). After adjustment of demographic factors, baseline SBP, and lifestyles, compared with the "slight increase" group, the OR (95% CI) of CVDs was 0.65 (0.32, 1.28) for "stable" group, 2.24 (1.40, 3.58) for "increase" group, 3.95 (1.81, 8.62) for "rapid increase" group, and 4.32 (1.76, 10.57) for "fluctuant" group. After stratified by use of antihypertensive drugs, the association was only significant for "rapid increase" group among those using antihypertensive drugs with OR (95% CI) of 2.81 (1.01, 7.77).ConclusionsHaving a rapidly increasing SBP over life-course is associated with a higher risk of CVDs. This implies the importance of monitoring lifetime change of blood pressure for the prevention of CVDs.

Soil salinization is the main abiotic stress factor affecting agricultural production worldwide, and salt stress has a significant impact on plant growth and development. Cotton is one of the most salt-tolerant crops. Therefore, the selection and utilization of salt-tolerant germplasm resources and the excavation of salt resistance genes play important roles in improving cotton production in saline–alkali soils. In this study, we analysed the population structure and genetic diversity of a total 149 cotton plant materials including 137 elite Gossypium hirsutum cultivar accessions collected from China and 12 elite Gossypium hirsutum cultivar accessions collected from around the world. Illumina Cotton SNP 70 K was used to obtain genome-wide single-nucleotide polymorphism (SNP) data for 149 elite Gossypium hirsutum cultivar accessions, and 18,430 highly consistent SNP loci were obtained by filtering. It was assessed by using PCA principal component analysis so that the 149 elite Gossypium hirsutum cultivar accessions could be divided into two subgroups, including subgroup 1 with 78 materials and subgroup 2 with 71 materials. Using the obtained SNP and other marker genotype test results, under salt stress, the salt tolerance traits 3d Germination potential, 3d Radicle length drop rate, 7d Germination rate, 7d Radicle length drop rate, 7d Germination weight, 3d Radicle length, 7d Radicle length, Relative Germination potential, Relative Germination rate, 7d Radicle weight drop rate, Salt tolerance index 3d Germination potential index, 3d Radicle length index, 7d Radicle length index, 7d Radicle weight index and 7d Germination rate index were evaluated by GWAS (genome-wide association analysis). A total of 27 SNP markers closely related to the salt tolerance traits and 15 SNP markers closely related to the salt tolerance index were detected. At the SNP locus associated with phenotyping, Gh_D01G0943, Gh_D01G0945, Gh_A01G0906, Gh_A01G0908, Gh_D08G1308 and Gh_D08G1309 related to plant salt tolerance were detected, and they were found to be involved in intracellular transport, sucrose synthesis, osmotic pressure balance, transmembrane transport, N-glycosylation, auxin response and cell amplification. This study provides a theoretical basis for the selection and breeding of salt-tolerant upland cotton varieties.

Extreme high temperatures are threatening cotton production around the world due to the intensification of global warming. To cope with high-temperature stress, heat-tolerant cotton cultivars have been bred, but the heat-tolerant mechanism remains unclear. This study selected heat-tolerant (‘Xinluzao36′) and heat-sensitive (‘Che61-72′) cultivars of cotton treated with high-temperature stress as plant materials and performed comparative nanopore sequencing transcriptome analysis to reveal the potential heat-tolerant mechanism of cotton. Results showed that 120,605 nonredundant sequences were generated from the raw reads, and 78,601 genes were annotated. Differentially expressed gene (DEG) analysis showed that a total of 19,600 DEGs were screened; the DEGs involved in the ribosome, heat shock proteins, auxin and ethylene signaling transduction, and photosynthesis pathways may be attributed to the heat tolerance of the heat-tolerant cotton cultivar. This study also predicted a total of 5118 long non-coding RNAs (lncRNAs)and 24,462 corresponding target genes. Analysis of the target genes revealed that the expression of some ribosomal, heat shock, auxin and ethylene signaling transduction-related and photosynthetic proteins may be regulated by lncRNAs and further participate in the heat tolerance of cotton. This study deepens our understandings of the heat tolerance of cotton.

Abstract Background Whether the suggested inverse association between total cholesterol and mortality in old age varies according to cause of death and use of cholesterol medications remains to be elucidated. The aim of this study was to assess the associations of total cholesterol with cardiovascular and non-cardiovascular mortality in old age, and to explore whether their associations vary by use of cholesterol-lowering medications. Methods The study participants included 3090 older adults (age ≥ 60 years, 63.7% women) from a population-based cohort study, i.e., the Swedish National study on Aging and Care in Kungsholmen, Stockholm. At baseline (2001–2004), data on demographic factors, lifestyles, cardiovascular risk factors, use of medications, global cognitive function, mobility limitation, and apolipoprotein E genotype were collected through interviews, clinical examinations, laboratory tests as well as from the Swedish national patient register. Vital statistics data (e.g., date and causes of death) till December 31, 2011 for all participants were derived from Swedish cause of death register. Data were analyzed using Cox proportional hazards model for all-cause mortality and Fine-Gray competing risks regression model for cause-specific mortality controlling for multiple potential confounders. Results During 23,196 person-years of follow-up (median per person, 7.5 years), 1059 (34.3%) participants died. Compared to normal total cholesterol (

Abstract Background The residents’ knowledge, attitudes and practices related to ambient air pollution and health will help to improve the understanding of environmental protection and make environmental health policies more targeted and effective. This study aimed at knowing the attitudes and behaviors towards ambient air pollution and health. Methods A cross-sectional survey was conducted in Ningbo, China in January 2015. Personal information and questions pertaining to the knowledge, attitudes and practices towards ambient air pollution and health were collected through questionnaire investigations. Descriptive statistics, chi-square tests and multiple unconditional logistic regression analysis were used. Results The questionnaire was completed by 1604 respondents (59.41 % women). The awareness rate was 64.59 % and varied significantly with age, levels of education, and occupation (all p

Background: Clinical practice guidelines recommended that hypertension in children and adolescents should be defined based on elevated blood pressure (BP) on at least three separate occasions. Therefore, in the present study, we aimed to estimate the prevalence of hypertension based on three separate visits among Chinese children and adolescents and to examine its relationship with obesity.Methods: A school-based cross-sectional survey was performed in children and adolescents in Jinan, China between September 2012 and September 2014. A total of 7,832 children and adolescents aged 6–17 years were included. Anthropometric data and BP were measured by trained examiners. Elevated BP was defined as BP ≥ 95th percentile for age and sex based on the Chinese reference data. Participants with elevated BP at the first visit underwent a second visit 2 weeks later, and a third visit was conducted if BP was still high at the second visit. Hypertension was defined as having an elevated BP at all three visits. Obesity was defined in three ways by using body mass index, waist circumference, and waist-to-height ratio.Results: The prevalence of elevated BP decreased substantially across three separate visits, with the prevalence of 17.2, 8.6, and 4.9%, respectively. Obesity was an independent risk factor for elevated BP during each visit. Based on the body mass index, obesity was associated with higher risk of elevated BP, with the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of 8.6 (6.8–11.0), 12.5 (9.1–17.3), and 14.0 (8.9–22.2), respectively, at the first, second and third visit. The ORs of elevated BP were similar in association with obesity defined by waist circumference or waist-to-height ratio.Conclusions: The prevalence of hypertension based on three visits was ~5% in Chinese children and adolescents. There was a dose-response relationship between obesity and elevated BP across three visits.

BackgroundExamining body mass index (BMI) change over life course is crucial for cardiovascular health promotion and prevention. So far, there is very few evidence on the long-term change of BMI from childhood to late life. This study aimed to examine the life-course trajectory patterns of BMI and then to link the trajectory patterns to cardiovascular risk factors in adulthood.MethodsBased on longitudinal data from the China Health and Nutrition Survey, 5276 participants (aged 6-60) at baseline (in 1989) with up to 7 measurements of BMI during 1989-2009 were selected in this study. Cardiovascular risk factors including high blood pressure, high blood glucose and high blood lipids were assessed in 2411 participants in 2009. Latent growth curve modelling was used to analyse the BMI trajectories, and logistic regression was used to examine the associations between trajectory patterns and cardiovascular risk factors.ResultsFour trajectories patterns of BMI over life course (age 6-80) were identified: Normal-Stable (22.4% of the total participants), Low normal-Normal-Stable (44.1%), Low normal-Normal-Overweight (27.2%), and Overweight-Obese (4.3%). Compared to those with Normal-Stable pattern, those with Low normal-Normal-Stable pattern, Low normal-Normal-Overweight pattern and Overweight-Obese pattern had higher risk of high blood pressure (odds ratio range = 1.6-6.6), high blood glucose (1.7-9.1), dyslipidemia (2.6-5.9) and having at least two of the three cardiovascular risk factors (3.9-30.9).ConclusionsHaving a stable BMI within normal range over life course is associated with the lowest cardiovascular risk, whereas remaining overweight and obese over life course is associated with the highest cardiovascular risk.

Background: Tobacco use is an important risk factor for non-communicable diseases worldwide. However, the global extent and prevalence of tobacco use in adolescents is poorly described. Using previously collected survey data, we aimed to assess tobacco use and second-hand smoke exposure in young adolescents aged 12–15 years in 68 low-income and middle-income countries. Methods: We used data from the Global School-based Student Health Survey (2006–13) and the China Global Tobacco Youth Survey (2013), which are school-based surveys of young adolescents aged 12–15 years that assess health behaviours using a standardised, anonymous, self-reported questionnaire. We calculated the prevalence of current tobacco use and exposure to second-hand smoke in young adolescents from 68 low-income and middle-income countries that collected these data in the surveys. We used a multilevel model to estimate the association between parental tobacco use, second-hand smoke, and adolescent tobacco use, adjusting for sex, age, school, school class, country's purchasing power parity, smoking initiation age, national prevalence of tobacco use among adults, year the WHO FCTC was ratified for each country, proxy of socioeconomic status, and survey year. Findings: The mean prevalence of current tobacco use was 13·6%, ranging from 2·8% in Tajikistan to 44·7% in Samoa. In most countries, the prevalence of tobacco use was higher for boys than girls, and higher for adolescents aged 14–15 years than for those aged 12–13 years. The overall prevalence of second-hand smoke exposure was 55·9%, ranging from 16·4% in Tajikistan to 85·4% in Indonesia. Parental tobacco use (as reported by the young adolescents), especially maternal use, was associated with tobacco use in young adolescents (odds ratio 2·06, 95% CI 1·93–2·19, for maternal and 1·29, 1·23–1·35 for paternal use). Second-hand smoke exposure was also a risk factor for young adolescents' tobacco use (2·56, 2·43–2·69). However, the prevalence of tobacco use was not associated with a country's purchasing power parity. Interpretation: Tobacco use and second-hand smoke exposure were frequent among young adolescents aged 12–15 years in low-income and middle-income countries. Parental tobacco use and second-hand smoke exposure were strongly associated with young adolescents' tobacco use. The data emphasise the need to strengthen tobacco control interventions and programmes in young adolescents from low-income and middle-income countries. Funding: This work was partly supported by the Young Scholars Program of Shandong University (2015WLJH51), the Shandong Provincial Natural Science Foundation (ZR2012HQ033), and the National Natural Science Foundation (81302496).

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Isoxazoline and isoxazole derivatives represent an important class of five-membered heterocycles, which play a pivotal role in drug discovery. In our previous study, we developed a series of isoxazole derivatives with an efficient method. In this study, we evaluated their effects on tumor cell growth. HCT116 cells were treated with isoxazole derivatives; an cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 (half maximal inhibitory concentration) of each derivative. Compound SHU00238, which was obtained by the copper nitrate-mediated [2+2+1] cycloaddition reaction of olefinic azlactone with naphthalene-1,4-dione, has a lower IC50; we analyzed its inhibitory activity in further assays. Cell apoptosis was estimated by flow cytometry analysis in vitro. SHU00238 injection was used to treat tumor-bearing mice. We found that SHU00238 suppressed cell viability and promoted cell apoptosis in vitro. SHU00238 treatment significantly inhibited colonic tumor growth in vivo. Furthermore, we compared the miRNAs expression changes in HCT116 cells before and after SHU00238 treatment. MiRNA profiling revealed that SHU00238 treatment affected cell fate by regulating a set of miRNAs. In conclusion, SHU00238 impedes CRC tumor cell proliferation and promotes cell apoptosis by miRNAs regulation.

BackgroundCardiometabolic risk factors and related cardiovascular diseases represent major threats to healthy aging.ObjectiveWe aimed to estimate distribution, pharmacological treatment, and control of main cardiometabolic risk factors among older people.MethodsThis population-based study included 3363 participants (age≥60 years, 64.9% women) in the Swedish National study on Aging and Care in Kungsholmen, in central Stockholm, Sweden (2001-2004). Data on demographics, cardiometabolic risk factors (hypertension, obesity, diabetes, and high cholesterol), and medication use were collected through face-to-face interviews, clinical examinations, laboratory tests, and the inpatient register. Cardiometabolic risk factors were defined following the most commonly used criteria. Prevalence was standardized using local census data.ResultsThe age- and sex-standardized prevalence of diabetes, obesity, high cholesterol, and hypertension was 9.5%, 12.8%, 49.7%, and 74.9%, respectively. The prevalence of hypertension and diabetes increased with age, whereas the prevalence of obesity and high cholesterol decreased with age. Forty-nine percent of older adults had two or more cardiometabolic risk factors; 9.8% had three or more. Overall, 55.5% of people with hypertension, 50.3% with diabetes, and 25.0% with high cholesterol received pharmacological treatment. Of those treated pharmacologically, 49.4%, 38.1%, and 85.5% reached therapeutic goals for hypertension (blood pressureConclusionsHypertension, high cholesterol, and clustering of cardiometabolic risk factors were common among older people in Stockholm, but pharmacological treatment and control of these major factors can be improved. Appropriate management of cardiometabolic profiles among older people may help improve cardiovascular health and achieve healthy aging.

The burden of chronic diseases in China is substantial now. Data on patterns of chronic diseases and multimorbidity among older adults, especially among those living in rural areas, are sparse.We aim to investigate the prevalence and patterns of chronic disease pairs and multimorbidity in elderly people living in rural China.This population-based study included 1480 adults aged 60 years and over (mean age 68.5 years, 59.4% women) living in a rural community. Data were derived from the Confucius Hometown Aging Project in Shandong, China (June 2010-July 2011). Chronic diseases were diagnosed through face-to-face interviews, clinical examinations, and laboratory tests. Patterns of chronic disease pairs and multimorbidity were explored using logistic regression and exploratory factor analyses.The prevalence of individual chronic diseases ranged from 3.0% for tumor to 76.4% for hypertension, and each disease was often accompanied with three or more other chronic diseases. The observed prevalence of pairs of chronic conditions exceeded the expected prevalence for several conditions, such as cardiovascular diseases and metabolic disorders, as well as pulmonary diseases and degenerative disorders. Chronic multimorbidity (≥2 chronic diseases) affected more than 90% of subjects, and two patterns of chronic multimorbidity were identified: cardiopulmonary-mental-degenerative disorder pattern (overall prevalence, 58.2%), and cerebrovascular-metabolic disorder pattern (62.6%). Prevalence of the cardiopulmonary-mental-degenerative disorder pattern increased with age, and was higher in men than women; whereas prevalence of the cerebrovascular-metabolic disorder pattern was higher in women than in men but did not vary by age.Chronic multimorbidity was highly prevalent among older Chinese adults living in rural areas, and there were specific patterns of the co-occurrence of chronic diseases. Effort is needed to identify possible preventative strategies based on the potential clustering of chronic diseases.

OBJECTIVES: Epidemiological data concerning atherosclerotic disease among older people in rural China are sparse. We seek to determine prevalence and cardiovascular risk factor profiles for peripheral artery disease (PAD) and carotid atherosclerosis (CAS) among Chinese older people living in a rural community. METHODS: This cross-sectional study included 1499 participants (age ≥60 years, 59.0% women) of the Confucius Hometown Aging Project in Shandong, China. From June 2010-July 2011, data were collected through interviews, clinical examinations, and laboratory tests. PAD was defined as an ankle-brachial index ≤0.9. Carotid intima-media thickness (cIMT) and carotid artery stenosis were assessed by ultrasonography. We defined moderate stenosis as carotid stenosis ≥50%, and severe stenosis as carotid stenosis ≥70%. cIMT≥1.81 mm was considered as an increased cIMT (a measure of CAS). Data were analyzed with multiple logistic models. RESULTS: The prevalence was 5.7% for PAD, 8.9% for moderate stenosis, 1.8% for severe stenosis, and 11.2% for increased cIMT. After controlling for multiple potential confounders, diabetes, an increased low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, and hypertension were significantly or marginally associated with PAD. Ever smoking, hypertension, and an increased LDL-C/HDL-C ratio were significantly associated with an increased likelihood of increased cIMT. An increasing number of those cardiovascular risk factors were significantly associated with an increasing odds ratio of PAD and increased cIMT, respectively (p for linear trend

Upland cotton (Gossypium hirsutum) is the most important plant producing natural fibers for the textile industry. In this study, we first investigated the phenotypic variation of seven agronomic traits of 273 diverse cotton accessions in the years 2017 and 2018, which were from 18 geographical regions. We found large variations among the traits in different geographical regions and only half of the traits in either years 2017 or 2018 followed a normal distribution. We then genotyped the collection with 81,612 high quality SNPs. Phylogenetic tree and population structure revealed a diverse genetic structure of the core collection, and geographical diversification was an important factor, but account for part of the variances of genetic diversification. We then performed genome-wide association study for the seven traits in the years 2017 and 2018, and the average values of each trait in the two years, respectively. We identified a total of 19 significant marker-trait associations and found that Pollen Ole e 1 allergen/ extension could be the candidate gene associated with the fall-off cotton bolls from the last three branches. In addition, large variations were observed for the heritability of traits in the years 2017 and 2018. These results provide new potential candidate genes for further functional validation, which could be useful for genetic improvement and breeding of new cotton cultivars with better agronomic performances. [ABSTRACT FROM AUTHOR]