FTO-mediated m6A modification of serum amyloid A2 mRNA promotes podocyte injury and inflammation by activating the NF-κB signaling pathway.

Diabetic kidney disease (DKD) is one of the severe complications of diabetes mellitus, yet there is no effective treatment. Exploring the development of DKD is essential to treatment. Podocyte injury and inflammation are closely related to the development of DKD. However, the mechanism of podocyte injury and progression in DKD remains largely unclear. Here, we observed that FTO expression was significantly upregulated in high glucose-induced podocytes and that overexpression of FTO promoted podocyte injury and inflammation. By performing RNA-seq and MeRIP-seq with control podocytes and high glucose-induced podocytes with or without FTO knockdown, we revealed that serum amyloid A2 (SAA2) is a target of FTO-mediated m6A modification. Knockdown of FTO markedly increased SAA2 mRNA m6A modification and decreased SAA2 mRNA expression. Mechanistically, we demonstrated that SAA2 might participate in podocyte injury and inflammation through activation of the NF-κB signaling pathway. Furthermore, by generating podocyte-specific adeno-associated virus 9 (AAV9) to knockdown SAA2 in mice, we discovered that the depletion of SAA2 significantly restored podocyte injury and inflammation. Together, our results suggested that upregulation of SAA2 promoted podocyte injury through m6A-dependent regulation, thus suggesting that SAA2 may be a therapeutic target for diabetic kidney disease.

Joint association of cardiovascular health and frailty with all-cause and cause-specific mortality: a prospective study.

BACKGROUND: Poor cardiovascular health (CVH) and physical frailty were reported to increase mortality risk, but their joint effects have not been fully elucidated. OBJECTIVES: We aimed to explore the separate and joint effects of CVH and frailty on mortality based on two perspectives of Life's Essential 8 (LE8) and Framingham Risk Score (FRS). METHODS: 21 062 participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were involved in this study. CVH was evaluated by the LE8 and FRS, and categorized into low, moderate and high CVH groups. Cox proportional hazard models were applied to estimate the separate and joint associations of CVH and frailty index (FI) with all-cause, cardiovascular disease (CVD) and cancer mortality. RESULTS: Over a median follow-up period of 87 months (95% CI: 86.0-88.0), 2036 deaths occurred. The separate linear dose-response relationships between CVH, frailty and mortality were observed (nonlinear P > .05). The combination of low CVH/frailty was negatively associated with all-cause mortality [hazard ratio (HR) and 95%CI: low LE8*FI, 5.30 (3.74, 7.52); high FRS*FI, 4.34 (3.20, 5.88)], CVD mortality [low LE8*FI, 6.57 (3.54, 12.22); high FRS*FI, 7.29 (3.92, 13.55)] and cancer mortality [low LE8*FI, 1.99 (1.14, 3.25); high FRS*FI, 2.32 (1.30, 4.15)], with high CVH/fit group as reference. Further stratified analyses showed that the combined burden of mortality from frailty and low CVH was greater among the young and females. CONCLUSIONS: Low CVH and frailty were independently and jointly correlated with greater risk of all-cause, CVD and cancer deaths, especially among the young and females.

Acute kidney injury in patients treated with immune checkpoint inhibitors: a single-center retrospective study.

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICI-AKI) is the most common renal complication and has attracted increasing amounts of attention. However, studies on this topic in Chinese cancer patients are very limited. Therefore, we conducted a retrospective study on the incidence, risk factors, clinical features and renal recovery of ICI-AKI in all patients with malignancies treated with ICIs in Shandong Provincial Hospital Affiliated to Shandong First Medical University. METHODS: In this single-center retrospective cohort study, the data of 904 patients who received immune checkpoint inhibitors (ICIs) treatment were retrospectively analyzed. Multivariable logistic regression was used to identify the predictors of ICI-AKI. RESULTS: A total of 46 of 904 patients receiving ICIs developed ICI-AKI, and the incidence of ICI-AKI was 5.1%. Patients developed ICI-AKI at a median of 9 weeks (IQR 3-23) after ICIs initiation. A lower baseline estimated glomerular filtration rate (eGFR) and use of antibiotics were associated with a higher risk of ICI-AKI. Renal recovery occurred in 17 patients (46%) at a median of 4 weeks (IQR 2-8) after ICI-AKI, including 16 (43%) with complete recovery and 1 (3%) with partial recovery. Of the 14 rechallenged patients, only one developed recurrent ICI-AKI. CONCLUSIONS: Patients with ICI-AKI were more likely to have impaired renal function at baseline and after treatment with antibiotics. Approximately half of the patients achieved renal recovery.

Reproductive factors and cardiovascular health in post-menopausal women: a special focus on natural menopause.

Female-specific reproductive factors might contribute to increased risk of cardiovascular disease, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the relationships between reproductive factors and the LE8 score among post-menopause women in the United States. We enrolled 3223 post-menopause women from National Health and Nutrition Examination Survey (NHANES). CVH groups based on LE8 score were low (0-49), moderate (50-79), and high good CVH levels (80-100). Multivariate ordinal logistic regressions were applied to estimate the associations between reproductive factors and the LE8 score. In multivariate model, early menarche (OR: 0.69, 95 percent CI: 0.51-0.93) and early menopause (OR: 0.57, 95 percent CI: 0.43-0.77) were associated with LE8 score compared with normal menarche and menopause; Meanwhile, ages at menarche and menopause were positively correlated with LE8 score. The number of pregnancies and full-term pregnancies were negatively associated with LE8 (OR for per pregnancy increase and 95 percent CI, 0.93 (0.88, 0.98), 0.93 (0.87, 0.99), separately). Overall, natural menopausal women with early age at menarche and menopause, and a higher number of pregnancies may have a high risk of lower CVH, and need to focus on their CVH.

Age-dependent interaction between Life's Essential 8 and chronic kidney disease: A national cross-sectional analysis.

OBJECTIVE: Chronic kidney disease (CKD), an age-related condition, is closely associated with cardiovascular disease. We aimed to examine the age-dependent interaction between Life's Essential 8 (LE8), the updated measurement of cardiovascular health (CVH), and CKD in the United States. METHODS: The cross-sectional study involved 25,529 participants from National Health and Nutrition Examination Survey in 2007-2018. Multivariate logistic regressions were used to estimate the age-dependent interaction between LE8 and CKD, and restricted cubic spline regressions were used to analyze the dose-response relationships between LE8 and CKD among adults and all age subgroups. RESULTS: Overall, 2934 (9.3%), 17,278 (66.2%), and 5317 (24.5%) participants had low, moderate, and high CVH, separately. After adjusting for the potential covariates, LE8 was negatively associated with CKD [odds ratio (OR) for per 1 standard deviation (SD) increase and 95%CI, 0.71 (0.67, 0.75)], with a nonlinear dose-response relationship (P for nonlinearity = 0.001). The inversed association was stronger among participants aged 65 and older (0.65 (0.59, 0.71)) compared to youngers [20-39 years, 0.63 (0.59, 0.58), 40-64 years, 0.63 (0.59, 0.58)] (P for interaction = 0.002). CONCLUSIONS: CVH, as measured by the LE8 score, was negatively associated with the presence of CKD in non-linear fashions, more pronounced in participants aged 65 and older compared to younger age groups.

Content-Seam-Preserving Multi-Alignment Network for Visual-Sensor-Based Image Stitching.

As an important representation of scenes in virtual reality and augmented reality, image stitching aims to generate a panoramic image with a natural field-of-view by stitching multiple images together, which are captured by different visual sensors. Existing deep-learning-based methods for image stitching only conduct a single deep homography to perform image alignment, which may produce inevitable alignment distortions. To address this issue, we propose a content-seam-preserving multi-alignment network (CSPM-Net) for visual-sensor-based image stitching, which could preserve the image content consistency and avoid seam distortions simultaneously. Firstly, a content-preserving deep homography estimation was designed to pre-align the input image pairs and reduce the content inconsistency. Secondly, an edge-assisted mesh warping was conducted to further align the image pairs, where the edge information is introduced to eliminate seam artifacts. Finally, in order to predict the final stitched image accurately, a content consistency loss was designed to preserve the geometric structure of overlapping regions between image pairs, and a seam smoothness loss is proposed to eliminate the edge distortions of image boundaries. Experimental results demonstrated that the proposed image-stitching method can provide favorable stitching results for visual-sensor-based images and outperform other state-of-the-art methods.

Plant cultivar determined bacterial community and potential risk of antibiotic resistance gene spread in the phyllosphere.

The global increased antibiotic resistance level in pathogenic microbes has posed a significant threat to human health. Fresh vegetables have been recognized to be an important vehicle of antibiotic resistance genes (ARGs) from environments to human beings. Phyllosphere ARGs have been indicated to be changed with plant species, yet the influence of plant cultivar on the phyllospheric resistome is still unclear. Here, we detected the ARGs and bacterial communities in the phyllosphere of two cultivars of cilantros and their corresponding soils using high-throughput quantitative PCR technique and bacterial 16S rRNA gene-based high-throughput sequencing, respectively. We further identified the potential bacterial pathogens and analyzed the effects of plant cultivar on ARGs, mobile genetic elements (MGEs), microbiome and potential bacterial pathogens. The results showed that the cultivars did not affect the ARG abundance and composition, but significantly shaped the abundance of MGEs and the composition structure of bacteria in the phyllosphere. The relative abundance of potential bacterial pathogens was significantly higher in the phyllosphere than that in soils. Mantel test showed that the ARG patterns were significantly correlated to the patterns of potential bacterial pathogens. Our results suggested that the horizontal gene transfer of ARGs in the phyllosphere might be different between the two cultivars of cilantro and highlighted the higher risk of phyllospheric microorganisms compared with those in soils. These findings extend our knowledge on the vegetable microbiomes, ARGs, and potential pathogens, suggesting more agricultural and hygiene protocols are needed to control the risk of foodborne ARGs.

Underestimation about the Contribution of Nitrate Reducers to Iron Cycling Indicated by Enterobacter Strain.

Nitrate-reducing iron(II) oxidation (NRFO) has been intensively reported in various bacteria. Iron(II) oxidation is found to be involved in both enzymatic and chemical reactions in nitrate-reducing Fe(II)-oxidizing microorganisms (NRFOMs). However, little is known about the relative contribution of biotic and abiotic reactions to iron(II) oxidation for the common nitrate reducers during the NRFO process. In this study, the typical nitrate reducers, four Enterobacter strains E. hormaechei, E. tabaci, E. mori and E. asburiae, were utilized as the model microorganisms. The comparison of the kinetics of nitrate, iron(II) and nitrite and N2O production in setups with and without iron(II) indicates a mixture of enzymatic and abiotic oxidation of iron(II) in all four Enterobacter strains. It was estimated that 22-29% of total oxidized iron(II) was coupled to microbial nitrate reduction by E. hormaechei, E. tabaci, E. mori, and E. asburiae. Enterobacter strains displayed an metabolic inactivity with heavy iron(III) encrustation on the cell surface in the NRFOmedium during days of incubation. Moreover, both respiratory and periplasmic nitrate-reducing genes are encoded by genomes of Enterobacter strains, suggesting that cell encrustation may occur with periplasmic iron(III) oxide precipitation as well as the surface iron(II) mineral coating for nitrate reducers. Overall, this study clarified the potential role of nitrate reducers in the biochemical cycling of iron under anoxic conditions, in turn, re-shaping their activity during denitrification because of cell encrustation with iron(III) minerals.

The effect of gap junction-mediated transfer of miR-200b on osteogenesis and angiogenesis in a co-culture of MSCs and HUVECs.

For successful engineering of pre-vascularized bone tissue in vitro, understanding the interactions between vasculogenic cells and bone-forming cells is a prerequisite. Mounting evidence indicates that microRNAs can serve as intercellular signals that allow cell-cell communication. Here, the role of the transfer of the microRNA miR-200b between vasculogenic and osteogenic cells was explored in a co-culture system. Rat bone-marrow derived mesenchymal stem cells (BMSCs) formed functional gap junctions composed of connexin 43 (Cx43, also known as GJA1) with human umbilical vein endothelial cells (HUVECs), through which miR-200b could transfer from BMSCs to HUVECs to regulate osteogenesis and angiogenesis. As a negative regulator, the decrease in miR-200b level in BMSCs derepressed the expression of VEGF-A, leading to increased osteogenic differentiation. Once inside HUVECs, miR-200b reduced the angiogenic potential of HUVECs through downregulation of ZEB2, ETS1, KDR and GATA2 Additionally, TGF-ß was found to trigger the transfer of miR-200b to HUVECs. Upon adding the TGF-ß inhibitor SB431542 or TGF-ß-neutralizing antibody, the formation of capillary-like structures in co-culture could be partially rescued. These findings may be fundamental to the development of a cell-based bone regeneration strategy.

Inhibiting expression of Cxcl9 promotes angiogenesis in MSCs-HUVECs co-culture.

The insufficient vascularization is a major challenge in bone tissue engineering, leading to partial necrosis of the implant. Pre-vascularization is a promising way via in vitro cells co-culture strategies using osteogenic cells and vasculogenic cells, and the cross-talk of cells is essential. In the present study, the effect of rat bone-marrow derived mesenchymal stem cells (BMSCs) on angiogenic capability of human umbilical vein endothelial cells (HUVECs) in growth medium (GM) and osteogenic induction medium (OIM) was investigated. It was demonstrated that cells co-cultured in OIM showed high efficiency in osteogenesis but failed to form capillary-like structure while the results of co-culture in GM were the opposite. By comparing the angiogenic capacity of co-cultures under GM and OIM, chemokine (C-X-C motif) ligand 9 (Cxcl9), secreted by BMSCs in OIM, was identified to be an angiostatic factor to counter-regulate vascular endothelial growth factor (VEGF) and prevent its binding to HUVECs, which abrogated angiogenesis of MSCs-ECs co-culture. Moreover, Cxcl9 was proved to suppress the osteogenic differentiation of BMSCs monoculture. The molecular mechanism of Cxcl9 activation in BMSCs involved mTOR/STAT1 signaling pathway. Therefore, blocking this signaling pathway via rapamycin addition resulted in the inhibition of Cxcl9 and improvement of osteogenic differentiation and angiogenic capacity of co-culture in OIM. These results reveal that Cxcl9 is a negative modulator of angiogenesis and osteogenesis, and its inhibition could promote pre-vascularization of bone tissue engineering.

Regulation of osteogenesis of human amniotic mesenchymal stem cells by sodium butyrate.

Human amniotic membrane-derived mesenchymal stem cells (hAMSCs) draw great interests for regenerative medicine due to convenient availability and low immunogenicity. However, suboptimal culture conditions limit their application. In recent years, small molecules have proven powerful in regulating stem cell fates and can be applied to stimulate their function. In the present study, the impacts of sodium butyrate (NaBu), a histone deacetylase inhibitor (HDACi), on hAMSCs were investigated. It was shown that NaBu at a low concentration inhibited cell proliferation by arresting cell cycle at G0/G1 rather than inducing apoptosis. When NaBu was supplemented at a concentration of <1.0 mM for 3 days during osteogenic induction, significantly more mineralized nodules were generated and the expression of osteogenesis-related genes (ALP, Runx2, Opn, and Ocn) and proteins (Col1a1, OPN, OCN, Runx2, and TAZ) were both significantly enhanced. However, a higher concentration (1.0 mM) and longer exposure time (14 days) of NaBu showed no such effects, which may be partially attributed to both the increased expression of histone deacetylase 8 (HDAC8) and reduced level of H3K9-Ace, thus leading to the transcriptional inhibition during osteogenesis. Further, it was indicated that ERK might be involved in the stimulatory effects of NaBu. These findings may be helpful to develop an efficient culture process for hAMSCs towards bone regeneration.

Identification of a diverse synthetic abietane diterpenoid library for anticancer activity.

A diverse natural-product-like synthetic abietane diterpenoid library contains about 56 compounds were obtained, and evaluated for their potential in vitro cytotoxic or antitumor activity against A549, PC-3 and SKOV-3 tumor cell lines by SRB assay. Treatment of A549 cells with the most potent compound ketone 19 showed induction of apoptosis, as revealed by JC-1 mitochondrial membrane potential staining, TUNNEL assay, western blotting analysis and flow cytometry assay.

Organoborane catalyzed regioselective 1,4-hydroboration of pyridines.

A bulky organoborane Ar(F)2BMe (Ar(F) = 2,4,6-tris(trifluoromethyl)phenyl, 1) has been synthesized. In C6D6 solution this organoborane and pyridine form a frustrated Lewis pair. Under mild conditions, 1 can efficiently catalyze 1,4-hydroboration of a series of pyridines. This reaction is highly chemo- and regioselective. The reaction intermediate, a boronium complex [Py2Bpin][Ar(F)2B(H)Me] (3), was characterized in solution by NMR spectroscopy, which was also confirmed by DFT calculation.

Levels of arsenic pollution in daily foodstuffs and soils and its associated human health risk in a town in Jiangsu Province, China.

The development of industries in rural areas can aggravate the arsenic (As) contamination of the local environment, which may pose unacceptable health risks to the local residents. This paper estimated the health risk posed by inorganic As (iAs) to residents via ingestion of soil, skin contact with soil and consumption of foodstuffs in a typical rural- industrial developed town in southern Jiangsu, China. The average concentrations of total As in soil, rice, fish, shrimp and crab, pork and eggs, vegetables and fruits were detected to be 10.367, 0.104 mg/kg dw (dry weight), 0.050, 0.415, 0.011, 0.013 and 0.017 mg/kg fw (fresh weight), respectively. All of these values are below the maximum allowable concentration in food and soil in China. The deterministic estimation results showed that the hazard quotient (HQ) and excess lifetime cancer risk (R) were 1.28 (0.78-2.31) and 2.38 × 10(-4) (2.71 × 10(-5)-5.09 × 10(-4)) for all age groups, respectively. Males in the age range of 2-29 years and females in the age range of 2-13 years and 18-29 years exhibited non-carcinogenic risk (HQ>1). Carcinogenic risk exceeded the acceptable level of 1 × 10(-)(5) for both genders at all ages. Furthermore, this risk rose with age. The probabilistic estimation results showed that about 28% of residents had non-carcinogenic risk due to over ingestion of iAs. The R value of 90% of residents was greater than 10(-)(5). The sensitivity analysis indicated that the cancer slope factor (SF), the ingestion rates of rice and the iAs concentration in rice were the most relevant variables affecting the assessment outcome. Based on these results, it is recommended that residents reduce their consumption of rice, though it should be noted that the assessment outcome has uncertainty due to estimating iAs from foodstuffs and not considering the bioaccessibility of iAs in foodstuffs. Nevertheless, measures like reducing industrial As emissions, forbidding the use of pesticides, fertilizers and sludge which contain As and optimizing water management in rice paddy fields should be taken to mitigate the risks.

A DNA/Upconversion Nanoparticle Complex Enables Controlled Co-Delivery of CRISPR-Cas9 and Photodynamic Agents for Synergistic Cancer Therapy.

Photodynamic therapy (PDT) depends on the light-irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue-penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co-delivery of CRISPR-Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single-stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G-quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2-related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G-quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H2O2 to O2, overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O2 to 1O2. The integration of gene editing and PDT allows substantial accumulation of 1O2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model.

Association between inflammatory biomarkers and mortality in individuals with type 2 diabetes: NHANES 2005-2018.

PURPOSE: This study aimed to examine independent association between inflammatory biomarkers and all-cause mortality as well as cardio-cerebrovascular disease (CCD) mortality among U.S. adults with diabetes. METHODS: A cohort of 6412 U.S. adults aged 20 or older was followed from the start until December 31, 2019. Statistical models such as Cox proportional hazards model (Cox) and Kaplan-Meier (K-M) survival curves were employed to investigate the associations between the inflammatory biomarkers and all-cause mortality and CCD mortality. RESULTS: After adjusting for confounding factors, the highest quartile of inflammatory biomarkers (NLR HR = 1.99; 95 % CI:1.54-2.57, MLR HR = 1.93; 95 % CI:1.46-2.54, SII HR = 1.49; 95 % CI:1.18-1.87, SIRI HR = 2.32; 95 % CI:1.81-2.96, nLPR HR = 2.05; 95 % CI:1.61-2.60, dNLR HR = 1.94; 95 % CI:1.51-2.49, AISI HR = 1.73; 95 % CI:1.4 1-2.12)) were positively associated with all-cause mortality compared to those in the lowest quartile. K-M survival curves indicated that participants with an inflammatory biomarker above a certain threshold had a higher risk of both all-cause mortality and CCD mortality (Log rank P < 0.05). CONCLUSION: Some biomarkers such as NLR, MLR, SII, AISI, SIRI, and dNLR, are significantly associated with all-cause mortality and CCD mortality among U.S. adults with diabetes. The risk of both outcomes increased when the biomarkers surpassed a specific threshold.

Mitochondrial metabolic reprogramming in diabetic kidney disease.

Diabetic kidney disease, known as a glomerular disease, arises from a metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play a key role in substance metabolism via oxidative phosphorylation to generate ATP. Cells undergo metabolic reprogramming as a compensatory mechanism to fulfill energy needs for survival and growth, attracting scholarly attention in recent years. Studies indicate that mitochondrial metabolic reprogramming significantly influences the pathophysiological progression of DKD. Alterations in kidney metabolism lead to abnormal expression of signaling molecules and activation of pathways, inducing oxidative stress-related cellular damage, inflammatory responses, apoptosis, and autophagy irregularities, culminating in renal fibrosis and insufficiency. This review delves into the impact of mitochondrial metabolic reprogramming on DKD pathogenesis, emphasizing the regulation of metabolic regulators and downstream signaling pathways. Therapeutic interventions targeting renal metabolic reprogramming can potentially delay DKD progression. The findings underscore the importance of focusing on metabolic reprogramming to develop safer and more effective therapeutic approaches.

Association of macronutrient consumption quality, food source and timing with depression among US adults: A cross-sectional study.

BACKGROUND: Growing evidence suggests that meal timing may influence dietary choices and mental health. Thus, this study examined the association between macronutrient consumption quality, food source, meal timing, and depression prevalence in Americans. METHODS: 23,313 National Health and Nutrition Survey participants from 2007 to 2016 were included in this cross-sectional study. Macronutrient intake was calculated for all day, dinner, and breakfast and subtypes into 4 classes. Based on the Patient Health Questionnaire, depression was defined as a 9-item score ≥ 10 on the PHQ-9. The correlation between macronutrients and depression prevalence was estimated with multivariable logistic regression models and isocaloric substitution effects. RESULTS: Low-quality carbohydrates (OR = 1.54, 95 % CI: 1.11, 2.12) were positively linked to depression compared with the lowest quartile, after adjusting for age and other covariates. In contrast, total high-quality carbohydrate (OR = 0.52, 95 % CI: 0.40, 0.66), total animal protein (OR = 0.60, 95 % CI: 0.45, 0.80), and total vegetable protein (OR = 0.61, 95 % CI: 0.43, 0.85) were negatively associated with depression was negatively associated. Replacing low-quality carbohydrates with high-quality carbohydrates throughout the day reduced the risk of depression by approximately 15 %. LIMITATIONS: Cross-sectional data. CONCLUSION: All in all, diet plays a crucial role in the prevention and treatment of depression. Especially in terms of macronutrient intake, high-quality, moderate intake can reduce the risk of depression. However, different subtypes of macronutrient consumption may have different effects on depression, so it becomes crucial to carefully consider the selection and combination of macronutrients.

Metabolic risks remain a serious threat to cardiovascular disease: findings from the Global Burden of Disease Study 2019.

Metabolic factors are major and controllable risk factors for cardiovascular diseases (CVD), and few studies have described this burden. We aim to assess it from 1990 to 2019 and predict the trends through 2034. Global Burden of Disease (GBD) provides data on sex, age, and socio-demographic index (SDI) levels. Numbers, age-standardized death rates (ASDR) and estimated annual percentage change (EAPC) were used. Future trends were estimated by NORDPRED model. The deaths cases of metabolic-related CVD increased from 8.61 million (95% UI: 7.91-9.29) to 13.71 million (95% UI: 12.24-14.94) globally. The ASDR continued to decline globally (EAPC = -1.36). The burden was heavier in male and middle-aged people and elderly people. CVD-related ASDR caused by high systolic blood pressure (SBP) had a downward trend globally (EAPC = -1.45), while trends of high body mass index (BMI) (EAPC = 1.29, 1.97, 0.92) and fasting plasma glucose (FPG) (EAPC = 0.95, 1.08, 0.46) were increasing in the middle, low-middle, and low SDI regions, respectively. Compared to 2015-2019, cumulative deaths will increase by 27.85% from 2030 to 2034, while ASDR will decrease 10.47%. The metabolic-related CVD burden remained high globally and deaths will continue to rise in the future. Men, middle-aged and elderly people were focus of concern. High SBP was globally well-managed over the past 30 years, but the CVD burden due to high BMI and FPG remained high. Exceptional initiatives are needed to regarding interventions targeting high BMI and FPG in middle and lower SDI regions.

Expression, purification, and enzymatic characterization of Bombyx mori nucleopolyhedrovirus DNA polymerase.

Bombyx mori nucleopolyhedrovirus (BmNPV) is a major viral agent that causes deadly grasserie disease in silkworms. BmNPV DNA polymerase (Bm-DNAPOL), encoded by the ORF53 gene, plays a central role in viral DNA replication. In this work, a His-tagged Bm-DNAPOL fusion protein, constructed using a novel MultiBac expression system, was overexpressed in Sf-9 insect cells, purified to near homogeneity on Ni-NTA agarose beads and further purified by ion-exchange chromatography. About 0.4 mg of enzyme was obtained from about 1 × 10(9) infected Sf-9 cells in suspension culture. Characterization of the highly purified enzyme indicated that Bm-DNAPOL is a monomer with an apparent molecular mass of approximately 110,000 Da. It possessed a specific activity of 15,126.3 U/mg under optimal in vitro reaction conditions and behaved in the manner of a proliferating cell nuclear antigen (PCNA)-independent DNA polymerase on both poly(dA)/oligo(dT) primer/template and singly premiered M13 DNA. BmNPV viral replication may be independent of replication factor C and a PCNA complex, while single-stranded DNA binding protein might play an important role in BmNPV DNA replication. These findings will be significant in studies on BmNPV-based disease in silkworms and for using silkworms as a bioreactor for the production of biomolecules of commercial importance.