Structural studies of WDR5 in complex with MBD3C WIN motif reveal a unique binding mode.

The nucleosome remodeling and deacetylase (NuRD) complex plays a pivotal role in chromatin regulation and transcriptional repression. In mice, methyl-CpG binding domain 3 isoform C (MBD3C) interacts specifically with the histone H3 binding protein WD repeat-containing protein 5 (WDR5) and forms the WDR5-MBD3C/Norde complex. Despite the functional significance of this interaction on embryonic stem cell gene regulation, the molecular mechanism underlying MBD3C recognition by WDR5 remains elusive. Here, we determined the crystal structure of WDR5 in complex with the peptide (residues 40-51) derived from the MBD3C protein at a resolution of 1.9 Å. Structural analysis revealed that MBD3C utilizes a unique binding mode to interact with WDR5, wherein MBD3C Arg43 and Phe47 are involved in recognizing the WDR5-interacting (WIN) site and Tyr191-related B site on the small surface of WDR5, respectively. Notably, the binding induces a ∼91° rotation of WDR5 Tyr191, generating the hydrophobic B site. Furthermore, mutation experiments combined with isothermal titration calorimetry (ITC) assays confirmed the importance of both Arg43 and Phe47 in mediating WDR5 binding affinity. By determining structures of various peptides bound to WDR5, we demonstrated that the WDR5 WIN site and B site can be concurrently recognized by WIN motif peptides containing ''Arg-Cies/Ser-Arg-Val-Phe'' consensus sequence. Overall, this study reveals the structural basis for the formation of the WDR5-MBD3C subcomplex and provides new insights into the recognition mode of WDR5 for the WIN motif. Moreover, these findings shed light on structural-based designs of WDR5-targeted anti-cancer small molecule inhibitors or peptide-mimic drugs.

Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe.

Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca2+ by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells.

Associations between antenatal corticosteroid exposure and neurodevelopment in infants.

BACKGROUND: It has been well recognized that antenatal administration of dexamethasone to pregnant women at risk of preterm delivery may markedly accelerate fetal maturation and reduce the risk of adverse perinatal outcomes in their preterm infants, particularly for births before 34 weeks of gestation. Since 2015, antenatal corticosteroid administration has been extended beyond 34 weeks of gestation by clinical guidelines, as it might have beneficial effects on fetal maturation and perinatal outcomes. However, concerns regarding the potential influence of antenatal corticosteroid treatment on offspring neurodevelopment have been raised. OBJECTIVE: This study aimed to investigate whether maternal antenatal corticosteroid administration was associated with neurodevelopment in infants at 1 year of age. STUDY DESIGN: In this prospective and longitudinal birth cohort study, women were followed up throughout gestation, and their infants underwent a Bayley Scales of Infant and Toddler Development, Third Edition, screening test at 1 year of age between December 2018 and September 2020. Finally, 1609 pregnant women and 1759 infants were included in the current study. Using a generalized linear mixed model, we examined the association between antenatal corticosteroid exposure and infant neurodevelopment in cognitive, receptive communication, expressive communication, fine motor, and gross motor functions. RESULTS: Of the 1759 infants eligible for this study, 1453 (82.6%) were singletons. A total of 710 infants were exposed to antenatal corticosteroids, among whom 415 were dexamethasone exposed and 483 were prednisone exposed. Dexamethasone was prescribed most often in late pregnancy, whereas prednisone was often used before 8 weeks of gestation among women who conceived through assisted reproductive technology. Compared with those who had no exposure, antenatal corticosteroid exposure was associated with an increased risk of infants being noncompetent in the cognitive development domain after adjusting for conventional risk factors (adjusted risk ratio, 1.53; 95% confidence interval, 1.08-2.18; P=.017). For medication-specific exposure, those exposed vs not exposed to antenatal dexamethasone were 1.62-fold (95% confidence interval, 1.10-2.38; P=.014) more likely to be noncompetent in the cognitive development domain at 1 year. The association did not vary markedly between preterm and term infants, singletons and twins, or assisted reproductive technology-conceived and spontaneously conceived infants (all P>.05 for heterogeneity). In contrast, a null association was observed for the risk of being noncompetent in any domain of neurodevelopment with antenatal prednisone exposure at early pregnancy. CONCLUSION: Here, antenatal corticosteroid, particularly dexamethasone exposure, was markedly associated with an increased risk of infants being noncompetent in the cognitive development domain at 1 year of age. These findings may provide new information when weighing the benefits and potential risks of maternal antenatal corticosteroid administration.

The rates and medical necessity of cesarean delivery in China, 2012-2019: an inspiration from Jiangsu.

BACKGROUND: The World Health Organization (WHO) in 2015 stated that every effort should be made to provide cesarean delivery (CD) for women in need. In China, the two-child policy largely prompts the number of advanced age childbirth, which raises the possibility of an increasing number of women who need a c-section. The aim of this study was to assess the trends in the overall and medical indication-classified CD rates in the era of the two-child policy in Jiangsu, China. METHODS: A retrospective cross-sectional study of 291,448 women who delivered in 11 hospitals in Jiangsu province between 2012 and 2019 was conducted. Medical cesarean indication for each woman was ascertained by manually reviewing the medical records. The 291,448 women were divided into two subgroups according to the presence of the indications: the indicated group (7.80%) and the non-indicated group (92.20%). We then fitted joinpoint regression and log-binomial regression models to estimate trends in the CD rates across the study period. RESULTS: The overall CD rate was observed with a declining trend from 52.51% in 2012-2015 to 49.76% in 2016-2019 (adjusted RR, 0.92; 95% CI, 0.91-0.93; P < 0.001), along with an annual percentage change (APC) to be - 1.0 (95% CI, - 2.1 to 0.0) across the period. The participants were then divided into two subgroups according to the presence of medical CD indications: the indicated group (7.80%) and the non-indicated group (92.20%).We found the declining trend was most pronounced in the non-indicated group, with the CD rates decreased from 50.02% in 2012-2015 to 46.27% in 2016-2019 (adjusted RR, 0.90; 95% CI, 0.89-0.90; P < 0.001). By contrast, we observed a steady trend in the CD rate of the indicated group, which maintained from 87.47% in 2012-2015 to 86.57% in 2016-2019 (P = 0.448). In the indicated group, a higher risk of adverse pregnancy outcomes was revealed for those women who delivered vaginally as compared with those who received c-section. We further investigated that women with following specific indications had a higher proportion of vaginal delivery, i.e., pregnancy complications, fetal macrosomia, and pregnancy complicated with tumor (34.70%, 10.84%, and 16.34%, respectively). Women with the above 3 indications were observed with a higher risk of adverse pregnancy outcomes if delivered vaginally. The incidence rates of the medical indications among the general population increased considerably over the 8-year period (P < 0.001). CONCLUSIONS: Although the overall CD rate apparently decreased in the recent years, along with the decline of the unnecessary CD rate, a considerable proportion of indicated women were not provided with CD service in Jiangsu, China. Instead of targeting the overall CD rate, we need to take actions to reduce unnecessary CD rate and provide adequate c-section service for women with indications, particularly for those with underlying diseases and suspected fetal macrosomia.

Hepatitis B virus infection and the risk of cancer among the Chinese population.

The relationship between hepatitis B virus (HBV) and nonhepatocellular cancers remains inconclusive. This large case-control study aimed to assess the associations between HBV infection status and multiple cancers. Cases (n = 50 392) and controls (n = 11 361) were consecutively recruited from 2008 to 2016 at the First Affiliated Hospital of Nanjing Medical University. Multivariable adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression by adjusting age and gender. A meta-analysis based on published studies was also performed to verify the associations. Of these, 12.1% of cases and 5.5% of controls were hepatitis B surface antigen (HBsAg) seropositive. We observed significant associations between HBsAg seropositivity and esophagus cancer (aOR [95% CI] = 1.32 [1.13-1.54]), stomach cancer (1.46 [1.30-1.65]), hepatocellular carcinoma (HCC; 39.11 [35.08-43.59]), intrahepatic and extrahepatic bile duct carcinoma (ICC and ECC; 3.83 [2.58-5.67] and 1.72 [1.28-2.31]), pancreatic cancer (PaC; 1.37 [1.13-1.65]), non-Hodgkin lymphoma (NHL; 1.88 [1.61-2.20]) and leukemia (11.48 [4.05-32.56]). Additionally, compared to participants with HBsAg-/anti-HBs-/anti-HBc-, participants with HBsAg-/anti-HBs-/anti-HBc+, indicating past HBV-infected, had an increased risk of esophagus cancer (aOR [95% CI] = 1.46 [1.24-1.73]), stomach cancer (1.20 [1.04-1.39]), HCC (4.80 [3.95-5.84]) and leukemia (15.62 [2.05-119.17]). Then the overall meta-analysis also verified that HBsAg seropositivity was significantly associated with stomach cancer (OR [95% CI] = 1.23 [1.14-1.33]), ICC (4.05 [2.78-5.90]), ECC (1.73 [1.30-2.30]), PaC (1.26 [1.09-1.46]), NHL (1.95 [1.55-2.44]) and leukemia (1.54 [1.26-1.88]). In conclusion, both our case-control study and meta-analysis confirmed the significant association of HBsAg seropositivity with stomach cancer, ICC, ECC, PaC, NHL and leukemia. Of note, our findings also suggested that the risk of stomach cancer elevated for people whoever exposed to HBV.

PANDA: A comprehensive and flexible tool for quantitative proteomics data analysis.

SUMMARY: As the experiment techniques and strategies in quantitative proteomics are improving rapidly, the corresponding algorithms and tools for protein quantification with high accuracy and precision are continuously required to be proposed. Here, we present a comprehensive and flexible tool named PANDA for proteomics data quantification. PANDA, which supports both label-free and labeled quantifications, is compatible with existing peptide identification tools and pipelines with considerable flexibility. Compared with MaxQuant on several complex datasets, PANDA was proved to be more accurate and precise with less computation time. Additionally, PANDA is an easy-to-use desktop application tool with user-friendly interfaces. AVAILABILITY AND IMPLEMENTATION: PANDA is freely available for download at https://sourceforge.net/projects/panda-tools/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Research on Early Identification of Bipolar Disorder Based on Multi-layer Perceptron Neural Network].

Multi-layer perceptron (MLP) neural network belongs to multi-layer feedforward neural network, and has the ability and characteristics of high intelligence. It can realize the complex nonlinear mapping by its own learning through the network. Bipolar disorder is a serious mental illness with high recurrence rate, high self-harm rate and high suicide rate. Most of the onset of the bipolar disorder starts with depressive episode, which can be easily misdiagnosed as unipolar depression and lead to a delayed treatment so as to influence the prognosis. The early identifica- tion of bipolar disorder is of great importance for patients with bipolar disorder. Due to the fact that the process of early identification of bipolar disorder is nonlinear, we in this paper discuss the MLP neural network application in early identification of bipolar disorder. This study covered 250 cases, including 143 cases with recurrent depression and 107 cases with bipolar disorder, and clinical features were statistically analyzed between the two groups. A total of 42 variables with significant differences were screened as the input variables of the neural network. Part of the samples were randomly selected as the learning sample, and the other as the test sample. By choosing different neu- ral network structures, all results of the identification of bipolar disorder were relatively good, which showed that MLP neural network could be used in the early identification of bipolar disorder.

Microbial cell factory for butyl butyrate production: Knowledges and perspectives.

Butyl butyrate is a short-chain fatty acid ester (C8) with a fruity aroma. It has broad prospects in the fields of foods, cosmetics and biofuels. At present, butyl butyrate is produced by chemical synthesis in the industry, but it is highly dependent on petroleum-based products. The growing concerns regarding the future scarcity of fossil fuels have been strongly promoted the transition from traditional fossil fuels and products to renewable bioenergy and biochemicals. Therefore, it is necessary to develop a green biochemical technology to replace traditional petroleum-based materials. In recent years, microorganisms such as Escherichia coli and Clostridium have been engineered to serve as cell factories for the sustainable one-pot production of short-chain fatty acid esters, including butyl butyrate. This opinion highlights the recent development in the use of lipases and alcohol acyltransferases (AATs) for butyl butyrate production in microbial fermentation, as well as future perspectives.

Preparation of a novel polypyrrole/dolomite composite adsorbent for efficient removal of Cr(VI) from aqueous solution.

A novel adsorbent, deposited PPy on the DMI (PPy/DMI) composite, was successfully synthesized for Cr(VI) removal from aqueous solution. PPy/DMI composite was characterized by BET, SEM, TEM, XRD, and XPS. The SEM and TEM analyses revealed that DMI can greatly reduce the aggregation of PPy and significantly enhance its adsorption performance. The Cr(VI) removal was highly pH dependent. The high selectivity of PPy/DMI composite for Cr(VI) removal was found even in the presence of co-existing ions. The adsorption kinetic process followed the pseudo-second-order equation, demonstrating that the Cr(VI) adsorption behavior onto PPy/DMI is chemisorption. Furthermore, the intra-particle diffusion model implied that the adsorption was controlled by both liquid membrane diffusion and internal diffusion. The adsorption isotherm data fitted well with the Langmuir model with the maximum adsorption capacity (406.50 mg/g at 323 K) which was considerably higher than that of other PPy-based adsorbents. The Cr(VI) adsorption onto PPy/DMI composite was endothermic. The main mechanisms of Cr(VI) removal are involved in adsorption through electrostatic attractions, ion exchange, and in situ reduction. The results suggested that PPy/DMI composite could be a promising candidate for efficient Cr(VI) removal from aqueous solution.

[Research on tumor information grid framework].

In order to realize tumor disease information sharing and unified management, we utilized grid technology to make the data and software resources which distributed in various medical institutions for effective integration so that we could make the heterogeneous resources consistent and interoperable in both semantics and syntax aspects. This article describes the tumor grid framework, the type of the service being packaged in Web Service Description Language (WSDL) and extensible markup language schemas definition (XSD), the client use the serialized document to operate the distributed resources. The service objects could be built by Unified Modeling Language (UML) as middle ware to create application programming interface. All of the grid resources are registered in the index and released in the form of Web Services based on Web Services Resource Framework (WSRF). Using the system we can build a multi-center, large sample and networking tumor disease resource sharing framework to improve the level of development in medical scientific research institutions and the patient's quality of life.

Appropriate cold stimulation changes energy distribution to improve stress resistance in broilers.

Appropriate cold stimulation can improve stress resistance in broilers and alleviate the adverse impacts of a cold environment. To investigate the effects of intermittent mild cold stimulation (IMCS) on energy distribution in the livers of broilers, 96 healthy 1-d-old Ross-308 male broilers were randomly divided into the control group (CC) and the cold stimulation group (H5). The CC group was raised at a normal thermal temperature, i.e., 35 °C until 3 d, after which the temperature was dropped gradually by 0.5 °C/d until 20 °C at 33 d. This temperature was maintained until 49 d. The H5 group was raised at the same temperature as the CC group until 14 d (35 to 29.5 °C) and at 3 °C below the temperature of the CC group starting at 0930 hours for 5 h every other day from 15 to 35 d (26 to 17°C). The temperature was returned to 20 °C at 36 d and maintained until 49 d. At 50 d, all broilers were subjected to acute cold stress (ACS) at 10 °C for 6 and 12 h. We found that IMCS had positive effects on production performance. Using transcriptome sequencing of the broiler livers, 327 differentially expressed genes (DEG) were identified, and highly enriched in fatty acid biosynthesis, fatty acid degradation, and the pyruvate metabolism pathway. When compared to the CC group, the mRNA levels of ACAA1, ACAT2, ACSL1, CPT1A, LDHB, and PCK1 in the H5 group were increased at 22 d (P < 0.05). The LDHB mRNA level was upregulated in the H5 group at 29 d compared to the CC group (P < 0.05). After 21 d of IMCS (at 36 d), the mRNA expression levels of ACAT2 and PCK1 were found to be significantly increased in the H5 group compared to the CC group (P < 0.05). Seven days after the IMCS had ended (at 43 d), the mRNA levels of ACAA1, ACAT2, and LDHB in the H5 group were higher than in the CC group (P < 0.05). The mRNA levels of heat shock protein (HSP) 70, HSP90, and HSP110 in the H5 group were higher than in the CC group after 6 h of ACS (P < 0.05). The protein levels of HSP70 and HSP90 in the H5 group were downregulated after 12 h of ACS, compared to the CC group (P < 0.05). These results indicated that IMCS at 3 °C lower than the normal temperature could improve energy metabolism and stress resistance in the livers of broilers, alleviate the damage of short-term ACS on broilers, help broilers adapt to the low temperature, and maintain stable of energy metabolism in the body.

Cold stimulation has a great impact on broilers. Excessive cold stimulation can lead to damage, while intermittent mild cold stimulation (IMCS) can make broilers adapt to the cold environment. Low temperature will make the body produce lots of heat to maintain metabolic stability. The liver controls the energy metabolism, and the avian livers are the main organ regulating lipid metabolism. In this study, the broilers of different ages were subjected to cold stimulation training and then acute cold stress (ACS). We found that IMCS had positive effects on production performance. Through transcriptome sequencing, we found that the differentially expressed genes were highly enriched in the energy metabolism pathway, and the expression levels of the most key genes and heat shock proteins were upregulated. The stress resistance was also enhanced, which could alleviate the damage of short-term ACS to the body. The broilers gradually adapted to the low-temperature environment and finally established cold adaptation. The findings of this work will be helpful to the development of animal husbandry in cold regions and improve animal welfare.

Regulating the Lithium Ions' Local Coordination Environment through Designing a COF with Single Atomic Co Site to Achieve Dendrite-Free Lithium-Metal Batteries.

The detrimental growth of lithium dendrites and unstable solid electrolyte interphase (SEI) inhibit the practical application of lithium-metal batteries. Herein, atomically dispersed cobalt coordinate conjugated bipyridine-rich covalent organic framework (sp2 c-COF) is explored as an artificial SEI on the surface of the Li-metal anode to resolve these issues. The single Co atoms confined in the structure of COF enhance the number of active sites and promote electron transfer to the COF. The synergistic effects of the Co─N coordination and strong electron-withdrawing cyano-group can adsorb the electron from the donor (Co) at a maximum and create an electron-rich environment, hence further regulating the Li+ local coordination environment and achieving uniform Li-nucleation behavior. Furthermore, in situ technology and density functional theory calculations reveal the mechanism of the sp2 c-COF-Co inducing Li uniform deposition and promoting Li+ rapid migration. Based on these advantages, the sp2 c-COF-Co modified Li anode exhibits a low Li-nucleation barrier of 8 mV, and excellent cycling stability of 6000 h.

Comparison of Clinical Characteristics and Outcomes of MAFLD and NAFLD in Chinese Health Examination Populations.

Background and Aims: The recently proposed concept of metabolic dysfunction-associated fatty liver disease (MAFLD) has remained controversial. We aimed to describe the features and associated outcomes to examine the diagnostic ability of MAFLD for identifying high-risk individuals. Methods: In this retrospective cohort study, we enrolled 72,392 Chinese participants between 2014 and 2015. Participants were classified as MAFLD, nonalcoholic fatty liver disease (NAFLD), non-MAFLD-NAFLD, and a normal control group. The primary outcomes were liver-related and cardiovascular disease (CVD) events. Person-years of follow-up were calculated from enrolment to the diagnosis of the event, or the last date of data (June, 2020). Results: Of the 72,392 participants, 31.54% (22,835) and 28.33% (20,507) qualified the criteria for NAFLD or MAFLD, respectively. Compared with NAFLD, MAFLD patients were more likely to be male, overweight, and have higher biochemical indices including liver enzyme levels. Lean MAFLD diagnosed with ≥2 or ≥3 metabolic abnormalities presented similar clinical manifestations. During the median follow-up of 5.22 years, 919 incident cases of severe liver disease and 2,073 CVD cases were recorded. Compared with the normal control group, the NAFLD and MAFLD groups had a higher cumulative risk of liver failure and cardiac-cerebral vascular diseases. There were no significant differences in risk between the non-MAFLD-NAFLD and normal group. Diabetes-MAFLD group had the highest incidence of liver-related and cardiac-cerebral vascular diseases, lean MAFLD came second, and obese-MAFLD had the lowest incidence. Conclusions: This real-world study provided evidence for rationally assessing the benefit and practicability of the change in terminology from NAFLD to MAFLD. MAFLD may be better than NAFLD in identifying fatty liver with worse clinical features and risk profile.

Identification and Validation of Prognostic Biomarkers Specifically Expressed in Macrophage in IgA Nephropathy Patients Based on Integrated Bioinformatics Analyses.

Background: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and a frequent cause of end-stage renal disease. The inflammation cascade due to the infiltration and activation of immune cells in glomeruli plays an essential role in the progression of IgAN. In this study, we aimed to identify hub genes involved in immune infiltration and explore potential prognostic biomarkers and therapeutic targets in IgAN. Methods: We combined the single-cell and bulk transcriptome profiles of IgAN patients and controls with clinical data. Through single-cell analysis and weighted gene co-expression network analysis (WGCNA), Gene Ontology (GO) enrichment analysis, and differentially expressed gene (DEG) analysis in the bulk profile, we identified cell-type-specific potential hub genes in IgAN. Real hub genes were extracted via validation analysis and clinical significance analysis of the correlation between the expression levels of genes and the estimated glomerular filtration rate (eGFR) in the external dataset. Gene set enrichment analysis was performed to predict the probable roles of the real hub genes in IgAN. Results: A total of eleven cell clusters were classified via single-cell analysis, among which macrophages showed a variable proportion between the IgAN and normal control samples. We recognized six functional co-expression gene modules through WGCNA, among which the black module was deemed an IgAN-related and immune-involving module via GO enrichment analysis. DEG analysis identified 45 potential hub genes from genes enriched in GO terms. A total of twenty-three potential hub genes were specifically expressed in macrophages. Furthermore, we validated the differential expression of the 23 potential hub genes in the external dataset and identified nine genes with prognostic significance as real hub genes, viz., CSF1R, CYBB, FPR3, GPR65, HCLS1, IL10RA, PLA2G7, TYROBP, and VSIG4. The real hub gens are thought to contribute to immune cell regulation, immunoreaction, and regulation of oxidative stress, cell proliferation, and material metabolism. Conclusion: In this study, we demonstrated that macrophages infiltrated the glomeruli and contributed to the inflammatory response in IgAN. Based on integrated bioinformatics analyses of single-cell and bulk transcriptome data, we highlighted nine genes as novel prognostic biomarkers, which may enable the development of innovative prognostic and therapeutic strategies for IgAN.

Genome-Wide Identification, Characterization, and Expression Analysis of CHS Gene Family Members in Chrysanthemum nankingense.

The chalcone synthase (CHS) gene family catalyzes the first committed step in the biosynthesis of flavonoids and plays key roles in various biological processes in plants. However, systematic studies of the CHS gene family in chrysanthemum remain unknown to date. In this study, 16 CnCHS genes were identified by searching the complete genome sequence of Chrysanthemum nankingense. Most contained two exons and one intron with Chal-sti-synt_N and Chal-sti-synt_C domains. A phylogenetic tree of CnCHSs indicated divergence into three major groups, including I, II, and III. Analyses of the genes and promoters of these genes indicated that there are many cis-acting elements that respond to light, phytohormones, stress, and developmental stages. The CnCHS genes have extensive patterns of expression in various tissues and stages of flower development. Tandemly repeated and segmental repeat genes were expressed at higher levels in different tissues than most of the CnCHS genes that have been identified. CnCHS10 is expressed at higher levels in various flower organs than in vegetative tissues, particularly in disc floret petals and pistils. Our study provides valuable information for the systematic analysis of the CnCHS gene family, which also contributes to further research on flavonoid synthesis and petal colors of chrysanthemum.

Effect of Smoking on Lung Function Decline in a Retrospective Study of a Health Examination Population in Chinese Males.

Objective: China has established a goal of reducing adult smoking prevalence from 27.7% to 20% by 2030. Understanding the possible ongoing impairment in lung function in smokers, is critically important to encourage the populations to change their smoking behavior. Methods: A total of 14,273 males joined the health examination at Huadong Sanatorium from Jan 2012 to Dec 2019 were included. In cross-sectional analysis, we used multiple linear regression to evaluate the association between baseline lung function and smoking status. Then, 3,558 males who received ≥2 spirometry exams were analyzed in longitudinal study. Annual lung function decline was compared using mixed linear models adjusted for confounders. Results: In cross-sectional analysis, compared with never-smokers, decreases of -133.56 mL (95% CI: -167.27, -99.85) and -51.44 mL (-69.62, -33.26) in FEV1, -1.48% (-1.94, -1.02) and -1.29% (-1.53, -1.04) in FEV1/FVC were observed in former and current smokers. In longitudinal analysis, significant declines were observed in FEV1 [5.04 (2.30, 7.78) mL] and FEV1/FVC [0.09 (0.05, 0.13) %] in current smokers but not observed in former smokers after adjustment. Participants with long duration of smoking cessation had decelerate lung function than short duration. The annual decline rate of current smokers with high smoking intensity (≥30 cigarettes per day) was 13.80 and 14.17 times greater than that of never-smokers in FEV1 and FVC. Thus, early smoking cessation can slow down lung function decline trend for current smokers. Conclusions: The harms of current smoking on lung function emphasize the necessity of smoking cessation, especially for those with comorbidities.

Weight Change across Adulthood in Relation to Non-Alcoholic Fatty Liver Disease among Non-Obese Individuals.

BACKGROUND: To investigate the associations of weight change patterns across adulthood with the risk of non-alcoholic fatty liver disease (NAFLD). METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 cycle, we performed a retrospective cohort study with 2212 non-obese participants aged 36 years old over. Weight change patterns were categorized as "stable non-obese", "early adulthood weight gain", "middle and late adulthood weight gain" and "revert to non-obese" according to the body mass index (BMI) at age 25, 10 years prior and at baseline. Vibration-controlled transient elastography (VCTE) was performed to diagnose NAFLD. Modified Poisson regression was used to quantify the associations of weight change patterns with NAFLD. RESULTS: Compared with participants in the "stable non-obese" group, those who gained weight at early or middle and late adulthood had an increased risk of NAFLD, with an adjusted rate ratio (RR) of 2.19 (95% CI 1.64-2.91) and 1.92 (95% CI 1.40-2.62), respectively. The risk of NAFLD in "revert to the non-obese" group showed no significant difference with the stable non-obese group. If the association of weight change and NAFLD was causal, we estimated that 73.09% (95% CI 55.62-82.93%) of incident NAFLD would be prevented if the total population had a normal BMI across adulthood. CONCLUSIONS: Weight gain to obese at early or middle and late adulthood was associated with an evaluated risk of NAFLD. A large proportion would have been prevented with effective weight intervention.

The prevalence of nonalcoholic fatty liver disease in Chinese adults screened by vibration controlled transient elastography and its diagnostic discrepancy compared with ultrasound.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in China as assessed using vibration-controlled transient elastography (VCTE) and its consistency with ultrasound is still unknown. We aimed to conduct a head-to-head comparison of consecutive measurements of NAFLD with ultrasound or VCTE to evaluate the discrepancy in the prevalence and distribution of NAFLD screened by two non-invasive techniques. METHODS: We collected VCTE and ultrasound examination data from 4,388 participants who underwent health check-ups at the Health Promotion Center of Jiangsu Province Hospital between January 2017 and December 2019. The major outcome was the presence of hepatic steatosis, which was defined as a median controlled attenuation parameter (CAP) ≥ 248 dB/m by VCTE or the definition of steatosis by ultrasound. RESULTS: Among the 4,388 participants, 2,214 were diagnosed with NAFLD by VCTE (CAP ≥ 248 dB/m, 50.46%). Participants with severe steatosis (CAP ≥ 280 dB/m) were commonly male (77.94% vs. 50.38%, P < 0.001), were obese (45.09% vs. 1.79%, P < 0.001), had a worse metabolic profile, had elevated liver enzyme levels, and had advanced fibrosis. The prevalence of ultrasound-diagnosed NAFLD was 56.42%. After consistency analysis, VCTE and ultrasound showed moderate agreement regarding the diagnosis of NAFLD (κ = 0.475). We then compared the characteristics and clinical features of the four groups classified by the diagnosis results of the two techniques. NAFLD participants diagnosed by VCTE only were older, more obese, and had worse metabolic and biochemical profiles than NAFLD participants diagnosed by ultrasound only; in particular, the former had a higher proportion of abnormal alanine aminotransferase and aspartate aminotransferase levels and a higher proportion of advanced fibrosis than the latter. CONCLUSIONS: More than half of Chinese adults were affected by NAFLD according to VCTE. Screening based on VCTE is more likely to identify NAFLD patients with severe clinical features than ultrasound. Therefore, VCTE is a more practical non-invasive tool for the screening and follow-up of NAFLD in China.

Associations of systemic inflammation markers with identification of pulmonary nodule and incident lung cancer in Chinese population.

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), easily accessible systemic inflammation response parameters, were reported to associate with poor lung cancer prognosis. However, research on the effects of these markers on the risk of positive nodules (PNs) and lung cancer is limited. METHODS: Participants in this retrospective study were those who had their first computed tomography (CT) screening at Jiangsu Province Hospital's Health Promotion Center between January 1, 2017 and December 31, 2020. We identified PNs (≥6 mm in diameter) from free text of CT reports and lung cancer from medical records. Multivariate logistic analysis was used to assess the association between NLR, PLR, or SII and PNs or lung cancer. RESULTS: The detected rate of PNs was 9.60% among the 96,476 participants. Age, smoking and body mass index were possible influencing factors for PNs. We observed linear dose-effect relationship between NLR, PLR, or SII and PNs (pnon-linear  > 0.05). Compared with low quintile, participants with top quintiles of NLR, PLR or SII had an increased risk of PNs, with the adjusted ORs of 1.19 (1.11-1.28), 1.11 (1.04-1.19) or 1.11 (1.03-1.18), respectively. Meanwhile, NLR showed the U-shaped relationship with lung cancer, with adjusted ORs of 1.40 (1.08-1.81) comparing highest NLR quintile to the third quintile. The high PLR and SII showed significantly associated with lung cancer with adjusted ORs of 1.29 (0.99-1.68) and 1.35 (1.04-1.74) comparing to the lowest quintile. CONCLUSIONS: The high levels of systemic inflammation markers were associated with the risk of positive pulmonary nodules and lung cancer, which suggested systemic immune response may be an important pre-clinical feature for the early identification of diseases.

Healthy Lifestyle Is Associated with Reduced Mortality in Patients with Non-Alcoholic Fatty Liver Disease.

Background and Aims: It is unclear whether a healthy lifestyle impacts mortality in the presence of non-alcoholic fatty liver disease (NAFLD). The present study aimed to examine the joint association of several modifiable lifestyle factors with mortality risk for NAFLD patients. Methods: We collected lifestyle behavior data form the National Health and Nutrition Examination Survey (NHANES) III from 1988 to 1994 and follow-up data form NHANES III-linked mortality data through 2015. We estimated joint association between four healthy lifestyle factors (non-smoking, non-drinking, regular physical activity, a healthy diet) after NAFLD diagnosis and mortality using Cox proportional hazards regression models. Results: During a median of 22.83 years of follow-up, 2932 deaths occurred. The risk of all-cause mortality decreased significantly with the healthy lifestyle scores increasing (p < 0.001). NAFLD patients with a favorable lifestyle (3 or 4 healthy lifestyle factors) reduced 36% of all-cause mortality and 43% of cardiovascular disease (CVD) mortality compared with those with an unfavorable lifestyle (0 or 1 healthy lifestyle factor) (HR, 0.64 [95% CI, 0.50−0.81], 0.57 [95% CI, 0.37−0.88]). Compared with the non-NAFLD group, the number of NAFLD patients required to adhere to a favorable lifestyle to prevent one cardiovascular disease death in 20 years was fewer (77 vs. 125). Conclusions: For the NAFLD patients, adopting a healthy lifestyle could significantly reduce their risk of death.