ZWC complex-mediated SPT5 phosphorylation suppresses divergent antisense RNA transcription at active gene promoters.

The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82 and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.

H2B ubiquitylation enhances H3K4 methylation activities of human KMT2 family complexes.

In mammalian cells, distinct H3K4 methylation states are created by deposition of methyl groups by multiple complexes of histone lysine methyltransferase 2 (KMT2) family proteins. For comprehensive analyses that directly compare the catalytic properties of all six human KMT2 complexes, we employed a biochemically defined system reconstituted with recombinant KMT2 core complexes (KMT2CoreCs) containing minimal components required for nucleosomal H3K4 methylation activity. We found that each KMT2CoreC generates distinct states and different levels of H3K4 methylation, and except for MLL3 all are stimulated by H2Bub. Notably, SET1BCoreC exhibited the strongest H3K4 methylation activity and, to our surprise, did not require H2B ubiquitylation (H2Bub); in contrast, H2Bub was required for the H3K4me2/3 activity of the paralog SET1ACoreC. We also found that WDR5, RbBP5, ASH2L and DPY30 are required for efficient H3K4 methyltransferase activities of all KMT2CoreCs except MLL3, which could produce H3K4me1 in the absence of WDR5. Importantly, deletion of the PHD2 domain of CFP1 led to complete loss of the H3K4me2/3 activities of SET1A/BCoreCs in the presence of H2Bub, indicating a critical role for this domain in the H2Bub-stimulated H3K4 methylation. Collectively, our results suggest that each KMT2 complex methylates H3K4 through distinct mechanisms in which individual subunits differentially participate.

Sex differences in perceived discomfort during seated static posture holding.

This study investigated how sex modifies postural discomfort perception during a sagittally-symmetric, seated static posture holding (SPH) task. Ten male and 10 female participants performed SPH and conducted subjective discomfort ratings in a total of 108 task conditions. A regression analysis found that the impacts of the body joint reactive moments on perceived discomfort were larger for the female group than the male whereas that of the shoulder joint angle was more pronounced for the male than the female. Also, some of the 108 task conditions were found to be more uncomfortable for the male group, while some others, for the female. The observed sex impacts are thought to be due to the sex differences in physical work capacities (muscular strength and joint flexibility). The results suggest that new posture analysis tools allowing sex-specific analyses are needed as they would improve the accuracy and precision of ergonomics posture analyses. Practitioner summary: This study empirically investigated how sex modifies postural discomfort perception during a seated posture holding (SPH) task. Sex was found to modify the impacts of joint reactive moments and the shoulder joint angle. The study results seem to reflect the sex differences in muscular strength and joint flexibility.

The association between cold hypersensitivity in the hands and feet and chronic disease: results of a multicentre study.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is a common symptom in Korea and patients with CHHF complain of coldness in the hands and feet in an environment that is not considered cold by unaffected people. In traditional East Asian medicine, CHHF is believed to be accompanied by various diseases and symptoms, and is considered a symptom that needs active treatment. CHHF is used for pattern identification in the cold pattern, yang deficiency, and constitution. This study aimed to examine the differences in frequencies of chronic diseases with respect to the presence of CHHF. METHODS: Disease history, CHHF, body measurements, and blood test survey data from 6149 patients collected by 25 medical institutes in Korea were obtained from the Korean Medicine Data Center. The participants were divided into CHHF (n = 1909) and non-CHHF groups (n = 3017) according to the CHHF survey. The differences in frequencies of 18 diseases were analysed using chi-square tests, and the odds ratios (ORs) for each disease according to CHHF status were examined via logistic regression with adjustment for age, sex, and body mass index (BMI). RESULTS: Based on chi-square test results, the CHHF group showed a higher frequency of the following diseases: anaemia, hypotension, chronic gastritis, reflux oesophagitis, chronic rhinitis, dysmenorrhoea, and gastroduodenal ulcer. Diseases found in lower frequencies were as follows: hypertension, diabetes mellitus, impaired fasting glucose, dyslipidaemia, stroke, fatty liver, and angina pectoris. In addition, from the logistic regression with adjustment for age, sex, and BMI, the CHHF group showed a lower OR in diabetes mellitus and dyslipidaemia than the non-CHHF group, but a higher OR in degenerative arthritis, chronic gastritis, gastroduodenal ulcer, reflux oesophagitis, and chronic rhinitis. CONCLUSIONS: This study showed that CHHF is associated with chronic disease. Further large-scale prospective studies are needed to validate these associations.

Association of serum 25-hydroxyvitamin D and serum total cholesterol with depressive symptoms in Korean adults: the Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012).

OBJECTIVE: To examine the hypothesis that the association between vitamin D deficiency and depressive symptoms is dependent upon total cholesterol level in a representative national sample of the South Korean population. DESIGN: This was a population-based cross-sectional study. SETTING: The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2012). SUBJECTS: We included 7198 adults aged 20-88 years. RESULTS: The incidence of depressive symptoms in individuals with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml) was 1·54-fold (95 % CI 1·20, 1·98) greater than in individuals without vitamin D deficiency (serum 25-hydroxyvitamin D ≥20 ng/ml). The relationship was stronger in individuals with normal-to-borderline serum total cholesterol (serum total cholesterol<240 mg/dl; OR=1·60; 95 % CI 1·23, 2·08) and non-significant in individuals with high serum total cholesterol (OR=0·97; 95 % CI 0·52, 1·81) after adjustment for confounding variables (age, sex, BMI, alcohol consumption, smoking status, regular exercise, income level, education level, marital status, changes in body weight, perceived body shape, season of examination date and cholesterol profiles). CONCLUSIONS: The association between vitamin D deficiency and depressive symptoms was weakened by high serum total cholesterol status. These findings suggest that both vitamin D and total cholesterol are important targets for the prevention and treatment of depression.

Interrelationships among common symptoms in the elderly and their effects on health-related quality of life: a cross-sectional study in rural Korea.

BACKGROUND: Because the world population is aging, it has become increasingly important to focus on and meet the healthcare needs of elderly individuals. This study aims to evaluate the relationships among common symptoms experienced by the elderly, including fatigue, pain, sleep disturbance, indigestion, and depression/anger/anxiety, and to assess how these symptoms affect health-related quality of life (HRQoL) in the elderly population after adjusting for sociodemographic characteristics and diagnosed diseases. METHODS: In a cross-sectional study conducted in 2014 in a rural area of Korea, we extracted data on 1328 elderly individuals aged 60 years or older. Their HRQoL was assessed using the EuroQol Five-Dimension (EQ-5D) questionnaire. The pairwise associations between each symptom and the influence of the symptoms on HRQoL were measured using logistic regression and multiple regression analysis. RESULTS: Each symptom was positively correlated with the other symptoms. The strongest association was observed between fatigue and pain (adjusted odds ratio = 8.127), and the weakest correlation was observed between sleep and indigestion (adjusted odds ratio = 2.521). Of the individuals experiencing symptoms other than sleep disturbance, those who reported comorbid symptoms tended to report higher symptom severity and a higher prevalence of symptoms persisting for ≥ 3 days compared with individuals who reported only one symptom. The number of symptoms was significantly correlated with the EQ-5D index (Spearman correlation coefficient = -0.370, p < 0.01) and the EQ Visual Analog Scale (EQ VAS) scores (Spearman correlation coefficient = -0.226, p < 0.01). Fatigue, pain, and sleep disturbance showed negative effects on all dimensions of EQ-5D. In multiple regression analysis, fatigue (ß = -0.073, p < 0.01), pain (ß = -0.140, p < 0.01), sleep disturbance (ß = -0.061, p < 0.05), and depression/anger/anxiety (ß = -0.065, p < 0.05) showed significant independent effects on the EQ-5D index when we adjusted for socioeconomic characteristics and diagnosed diseases. CONCLUSIONS: Fatigue, pain, sleep disturbance, and depression/anger/anxiety were correlated with one another, and they presented significant independent effects on the HRQoL of elderly individuals. Thus, multidisciplinary healthcare programs are required to address these common symptoms.

Sasang constitution may act as a risk factor for prehypertension.

BACKGROUND: Prehypertension (pre-HTN), similar to hypertension, has been associated with an elevated risk of cardiovascular disease. The aim of this study was to determine whether the Sasang constitution (SC) types could also be independent risk factors for pre-HTN. METHODS: A total of 2,806 eligible subjects, older than 20 years old from 25 medical clinics, participated. Clinical data, including the blood pressure, age, height, weight, and data from blood tests, were collected. One-way ANOVA with Scheffé's post-hoc analysis and the chi-square test were used, according to the SC and sex. Logistic regression was used to generate the odds ratios (ORs) and 95% confidence interval (CI) for pre-HTN. RESULTS: The pre-HTN prevalence rates of the Soeumin type, Soyangin type and Tae-eumin type were 59.4%, 60.1% and 74.9%, respectively, in men (p < 0.001) and 41.7%, 44.4% and 58.3% in women (p < 0.001). The Soyangin type was not more associated with increased ORs than the Soeumin type in any of the subjects with pre-HTN. Even after adjusting for sex, BMI, FBG, TC, TGs, HDL, and LDL, the Tae-eumin type in men was associated with increased ORs of pre-HTN compared with the Soeumin type (OR 1.57, 95% CI 1.03-2.39), but the Tae-eumin type in women was not associated with pre-HTN. CONCLUSIONS: This study suggested that the Tae-eumin type combined with sex might be significantly and independently associated with pre-HTN, especially high pre-HTN.

The prevalence of general and abdominal obesity according to sasang constitution in Korea.

BACKGROUND: Obesity is an important risk factor for cardiovascular and metabolic diseases and could affect mortality rates. Body mass index (BMI) and waist circumference (WC) have been used to classify obesity, and waist-to-hip ratio (WHR) has recently emerged as a discriminator of cardiovascular disease. Sasang constitution (SC) is a kind of well-known traditional Korean medicine: Tae-eumin (TE), Soeumin (SE), Taeyangin (TY) and Soyangin (SY) carrying a different level of susceptibility to chronic diseases. We aimed to examine the prevalence in general and abdominal obesity (AO) using BMI, WC and WHR according to SC in the Korean population. METHODS: A total of 3,348 subjects were recruited from 24 Korean medicine clinics. Obesity was divided into three categories: general obesity by BMI, abdominal obesity by waist circumference (WC AO) and abdominal obesity by waist-to-hip ratio (WHR AO). A Chi-square test was performed to compare prevalence, and logistic regression was conducted to generate odds ratios (ORs) according to SC (p < .05). RESULTS: The prevalence of general obesity was significantly higher in males than in females. The highest prevalence of general obesity, WC AO and WHR AO were all observed in the TE type, and the SY and SE types were followed in order, for both males and females respectively.The TE type was highly associated with increased risk of general obesity (OR = 20.2, 95% CI: 12.4-32.9 in males and OR = 14.3, 95% CI: 10.1-20.2 in females), of WC AO (OR = 10.7, 95% CI: 7.2-15.9 in males and OR = 7.5, 95% CI: 5.8-9.6 in females), and of WHR AO (OR = 4.6, 95% CI: 3.3-6.4 in males and OR = 3.8, 95% CI: 2.9-4.9 in females) compared with the SE type. In addition, after controlling for age, social status and eating habits, the ORs were similar to the crude model according to gender and SC. CONCLUSIONS: This study shows that the prevalence of obesity varies according to SC in the Korean population. In particular, the TE type was highly associated with increased ORs for general obesity, WC AO and WHR AO in both genders.

p300 KAT regulates SOX10 stability and function in human melanoma.

SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth, while SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10's role in melanoma proliferation, while preventing a concomitant increase in tumor cell invasion. Here, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on Chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor, A-485, downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXLhigh/MITFlow melanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion, and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.

p300 KAT regulates SOX10 stability and function in human melanoma.

SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth, while SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10's role in melanoma proliferation, while preventing a concomitant increase in tumor cell invasion. Here, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on Chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor, A-485, downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXLhigh/MITFlow melanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion, and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.

The CoREST repressor complex mediates phenotype switching and therapy resistance in melanoma.

Virtually all patients with BRAF-mutant melanoma develop resistance to MAPK inhibitors largely through nonmutational events. Although the epigenetic landscape is shown to be altered in therapy-resistant melanomas and other cancers, a specific targetable epigenetic mechanism has not been validated. Here, we evaluated the corepressor for element 1-silencing transcription factor (CoREST) epigenetic repressor complex and the recently developed bivalent inhibitor corin within the context of melanoma phenotype plasticity and therapeutic resistance. We found that CoREST was a critical mediator of the major distinct melanoma phenotypes and that corin treatment of melanoma cells led to phenotype reprogramming. Global assessment of transcript and chromatin changes conferred by corin revealed specific effects on histone marks connected to epithelial-mesenchymal transition-associated (EMT-associated) transcription factors and the dual-specificity phosphatases (DUSPs). Remarkably, treatment of BRAF inhibitor-resistant (BRAFi-R) melanomas with corin promoted resensitization to BRAFi therapy. DUSP1 was consistently downregulated in BRAFi-R melanomas, which was reversed by corin treatment and associated with inhibition of p38 MAPK activity and resensitization to BRAFi therapies. Moreover, this activity was recapitulated by the p38 MAPK inhibitor BIRB 796. These findings identify the CoREST repressor complex as a central mediator of melanoma phenotype plasticity and resistance to targeted therapy and suggest that CoREST inhibitors may prove beneficial for patients with BRAFi-resistant melanoma.

Could the Sasang constitution itself be a risk factor of abdominal obesity?

BACKGROUND: Abdominal obesity (AO) is a medical condition in which excess body fat accumulates in the abdomen. It may cause adverse effects on health and result in reduced life expectancy or increased health problems. While various genetic approaches have explained the risks of AO in Western society, the Sasang constitution (SC) has been identified as a risk factor in Korean medicine. Different SC types are associated with different fat distribution, body shapes and susceptibility to diseases. We evaluated whether the SC type could be a risk for AO in a cross-sectional study among Koreans. METHODS: In total, 2,528 subjects aged over 30 years were recruited from 23 medical clinics. We collected waist circumference (WC), weight, height, and some clinical information for AO from the subjects. A Chi-square test and a one-way ANOVA were performed according to SC type (p < .05), while multiple logistic regression was used to produce odds ratios (ORs). RESULTS: The rates of AO in Tae-eumin (TE), Soeumin (SE), and Soyangin (SY) types were 63.7%, 14.7%, and 32.8% in males and 84.8%, 41.7%, and 52.8% in females, respectively. The TE type was associated with increased AO prevalence compared with the SE and SY types in males (OR 1.79; 95% CI 1.02-3.15, p = 0.044 and OR 1.74; 95% CI 1.18-2.58, p = 0.006, respectively) and females (OR 1.51; 95% CI 1.03-2.23, p = 0.037 and OR 1.88; 95% CI 1.32-2.68, p < 0.001, respectively) after adjusting for age, BMI, hypertension, diabetes mellitus, hypertriglyceridemia, and low HDL cholesterol. CONCLUSIONS: This study suggested that SC, particularly the TE type, might be significantly and independently associated with AO and could be considered a risk factor in predicting AO.

Conductive N, S doped Copolymers as Stable Metal-Free Electrocatalysts for Water Splitting.

Noble metals (Pt) and metal oxides (IrC and RuO2) are heavily utilized as benchmark electrocatalysts for alkaline water splitting; however, these materials possess several drawbacks including high cost, poor selectivity and stability, and high environmental impact. To address these issues, we synthesized a novel metal-free conducting polypyrrole-polythiophene (Ppy-Ptp) copolymer and a separate Ppy electrode material for water-splitting applications. The Ppy-Ptp and Ppy electrocatalysts exhibited remarkable activity in the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. The optimal Ppy-Ptp (1:3) formulation, when deposited on a conductive nickel foam (NF) substrate, exhibited an exceptional OER performance with a low overpotential of approximately 250 mV at 20 mAcm-2, thereby outperforming the benchmark IrC/NF electrocatalyst (290 mV, 20 mAcm-2). Additionally, a similarly prepared Ppy/NF electrocatalyst exhibited an extraordinary HER performance with an overpotential of approximately 72 mV at 10 mA cm-2. Furthermore, an alkaline anion-exchange membrane (AEM) electrolyzer incorporating Ppy-Ptp (1:3) and Ppy as the anode and cathode materials, respectively, displayed operating potentials of 1.55, 1.70, and 1.78 V at 10, 50, and 100 mA cm-2, which are lower than those observed in previously reported electrolyzers. This electrolyzer also exhibited considerable operational endurance over 50 h at 50 mA cm-2, over which a negligible decay of 0.02 V was observed. The novel polymer-based metal-free catalysts presented herein therefore exhibit considerable potential as alternative electrocatalytic materials for sustainable industrial-scale H2 synthesis.

Efficient functional delivery of siRNA using mesoporous silica nanoparticles with ultralarge pores.

Among various nanoparticles, mesoporous silica nanoparticles (MSNs) have attracted extensive attention for developing efficient drug-delivery systems, mostly due to their high porosity and biocompatibility. However, due to the small pore size, generally below 5 nm in diameter, potential drugs that are loaded into the pore have been limited to small molecules. Herein, a small interfering RNA (siRNA) delivery strategy based on MSNs possessing pores with an average diameter of 23 nm is presented. The siRNA is regarded as a powerful gene therapeutic agent for treatment of a wide range of diseases by enabling post-transcriptional gene silencing, so-called RNA interference. Highly efficient, sequence-specific, and technically very simple target gene knockdown is demonstrated using MSNs with ultralarge pores of size 23 nm in vitro and in vivo without notable cytotoxicity.

A new method of diagnosing constitutional types based on vocal and facial features for personalized medicine.

The aim of the present study is to develop an accurate constitution diagnostic method based solely on the individual's physical characteristics, irrespective of psychologic traits, characteristics of clinical medicine, and genetic factors. In this paper, we suggest a novel method for diagnosing constitutional types using only speech and face characteristics. Based on 514 subjects, the area under the receiver operating characteristics curve (AUC) values of classification models in age and gender groups ranged from 0.64 to 0.89. We identified significant features showing statistical differences among three constitutional types by performing statistical analysis. Also, we selected a compact and discriminative feature subset for constitution diagnosis in each age and gender group. Our method may support the direction of improved diagnosis prediction and will serve to develop a personal and automatic constitution diagnosis software for improvement of the effectiveness of prescribed medications and development of personalized medicine.

Predicting sasang constitution using body-shape information.

Objectives. Body measurement plays a pivotal role not only in the diagnosis of disease but also in the classification of typology. Sasang constitutional medicine, which is one of the forms of Traditional Korean Medicine, is considered to be strongly associated with body shape. We attempted to determine whether a Sasang constitutional analytic tool based on body shape information (SCAT-B) could predict Sasang constitution (SC). Methods. After surveying 23 Oriental medical clinics, 2,677 subjects were recruited and body shape information was collected. The SCAT-Bs for males and females were developed using multinomial logistic regression. Stepwise forward-variable selection was applied using the score statistic and Wald's test. Results. The predictive rates of the SCAT-B for Tae-eumin (TE), Soeumin (SE), and Soyangin (SY) types in males and females were 80.2%, 56.9%, and 37.7% (males) and 69.3%, 38.9%, and 50.0% (females) in the training set and were 74%, 70.1%, and 35% (males), and 67.4%, 66.3%, and 53.7% (females) in the test set, respectively. Higher constitutional probability scores showed a trend for association with higher predictability. Conclusions. This study shows that the Sasang constitutional analytic tool, which is based on body shape information, may be relatively highly predictive of TE type but may be less predictive when used for SY type.

Evaluation of thermal sensitivity is of potential clinical utility for the predictive, preventive, and personalized approach advancing metabolic syndrome management.

A possible association between metabolic disorders and ambient temperature has been suggested, and cold exposure as a way of increasing energy expenditure has gained considerable interest for preventative/therapeutic measures toward metabolic disorders. Although thermal sensitivity, which has recently been studied in regard to its utility as a risk assessment/patient stratification for various diseases, might influence physiological responses to ambient temperature on an individual basis, more studies are needed. We aimed to investigate the association between self-identified thermal intolerance/sensation and metabolic syndrome (MetS) to verify the working hypothesis that individuals with altered thermal sensitivity may have a predisposition to MetS. We fitted generalized additive models for thermal intolerance/sensation using body mass index (BMI) and waist-hip ratio in women, and identified those with higher/lower thermal intolerance/sensation than those predicted by the models. Higher heat intolerance, higher heat sensation, and lower cold intolerance were associated with a higher prevalence of MetS. The risk of having MetS was increased in those who had two or three associated conditions compared with those with none of these conditions. In an analysis for MetS components, significant associations of thermal sensitivity were present with high glucose, triglyceride, and blood pressure levels. Overall, higher heat intolerance/sensation and lower cold intolerance were associated with increased prevalence of MetS even at a similar level of obesity. Our study indicates that evaluation of thermal sensitivity may help identify individuals at high risk for MetS, and lead to more advanced patient stratification and personalized treatment strategies for MetS, including cold-induced thermogenesis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00273-6.

Individual Differences in the Association of Lifestyle with Cardiometabolic Risk in Middle-Aged Koreans Based on Traditional Korean Medicine.

Cardiometabolic (CM) risk differs in morbidity and disease progression depending on lifestyle and individual characteristics. This cross-sectional study aimed to analyze the association between CM risk and lifestyle and examine whether this association varies based on Sasang constitution (SC), a Korean medicine classification. Data were analyzed from 1996 individuals participating in the Korean Medicine Daejeon Citizen Cohort study. Individuals with CM risk had two to five CM risk factors. Lifestyle factors included physical activity, sleep duration, and eating index. SC types were Taeeum-in (TE) and non-TE. We estimated the odds ratio (OR) and 95% confidence interval for CM risk based on SC and lifestyle factors. Among the participants, 33.9% had a CM risk, and the TE and non-TE groups were 26.2% and 7.7%, respectively. In the TE group, CM risk was associated with low physical activity (OR, 1.63) and moderate eating index (OR, 1.41). In the non-TE group, CM risk was associated with ≥8 h of sleep (OR, 1.87) and marginally associated with ≤6 h of sleep. In the TE group alone, CM risk was significantly associated with lifestyle patterns that combined the three lifestyle factors and was approximately two-fold higher in patterns involving less physical activity. The effects of lifestyle on CM risk differed across SC types. To decrease the burden of cardiovascular diseases in middle-aged adults, we recommend an individualized management strategy of healthy lifestyle interventions for cardiovascular risks.

Social Sustainability of a Firm: Orientation, Practices, and Performances.

This paper investigates how firms' social sustainability practices can influence their social performance and, ultimately, financial performance. We include two corporate social sustainability practices: employee-oriented (employee well-being and equity) and socially driven (corporate social involvement) practices. Three leading social theories (social identity theory, social exchange theory, and resource-based view) are applied in explaining how firms' social practices influence intermediate and bottom-line performance outcomes. Empirical results of 212 US manufacturing firms reveal that (1) the social orientation of the firm promotes firms' social performances (employee-oriented and community-oriented outcomes) directly; (2) social orientation also indirectly promotes employee-oriented outcomes via employee well-being and equity practices, and so does community-oriented outcome via corporate social involvement practices; and (3) the firms' social performances can enhance financial performance. The theoretical and managerial implications derived from these empirical results are discussed as well.

Downregulation of SETD5 Suppresses the Tumorigenicity of Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is an aggressive and incurable cancer. Although understanding of the molecular pathogenesis of HCC has greatly advanced, therapeutic options for the disease remain limited. In this study, we demonstrated that SETD5 expression is positively associated with poor prognosis of HCC and that SETD5 depletion decreased HCC cell proliferation and invasion while inducing cell death. Transcriptome analysis revealed that SETD5 loss downregulated the interferon-mediated inflammatory response in HCC cells. In addition, SETD5 depletion downregulated the expression of a critical glycolysis gene, PKM (pyruvate kinase M1/2), and decreased glycolysis activity in HCC cells. Finally, SETD5 knockdown inhibited tumor growth in xenograft mouse models. These results collectively suggest that SETD5 is involved in the tumorigenic features of HCC cells and that targeting SETD5 may suppress HCC progression.