Synthesis Strategies, Preparation Methods, and Applications of Chiral Metal-Organic Frameworks.

Chiral metal-organic framework (CMOFs) is a kind of material with great application value in recent years. Formed by the coordination of metal ions or metal clusters with organic ligands. It is widely used in chemistry, biology, medicine and materials science because of its ordered and adjustable pores, multi-dimensional network structure, large specific surface area and excellent adsorption properties. In this paper, the synthesis strategies and preparation methods of chiral metal-organic frameworks are reviewed. In addition, the applications of chiral metal-organic framework materials in enantiomer recognition and separation, circularly polarized luminescence and asymmetric catalysis are systematically summarized. Finally, the challenges and prospects of the development of chiral metal-organic frame materials are analyzed in detail.

Janus ACSP Nanoparticle for Synergistic Chemodynamic Therapy and Radiosensitization.

Protective autophagy and DNA damage repair lead to tumor radio-resistance. Some hypoxic tumors exhibit a low radiation energy absorption coefficient in radiation therapy. High doses of X-rays may lead to side effects in the surrounding normal tissues. In order to overcome the radio-resistance and improve the efficacy of radiotherapy based on the characteristics of the tumor microenvironment, the development of radiosensitizers has attracted much attention. In this study, a Janus ACSP nanoparticle (NP) was developed for chemodynamic therapy and radiosensitization. The reactive oxygen species generated by the Fenton-like reaction regulated the distribution of cell cycles from a radioresistant phase to a radio-sensitive phase. The high-Z element, Au, enhanced the production of hydroxyl radicals (•OH) under X-ray radiation, promoting DNA damage and cell apoptosis. The NP delayed DNA damage repair by interfering with certain proteins involved in the DNA repair signaling pathway. In vivo experiments demonstrated that the combination of the copper-ion-based Fenton-like reaction and low-dose X-ray radiation enhanced the effectiveness of radiotherapy, providing a novel approach for synergistic chemodynamic and radiosensitization therapy. This study provides valuable insights and strategies for the development and application of NPs in cancer treatment.

The mediating effect of 24-h time-use behaviors on the relationship between depression and mortality: A compositional mediation analysis for survival outcomes.

BACKGROUND: A compositional mediation model of survival outcomes was established to explore whether 24-h time-use behaviors mediate the relationship between depression and mortality. METHODS: 4137 adults from the National Health and Nutrition Examination Survey (NHANES 2005-2006) were followed up to 2019. Cox proportional hazards regression model was used to estimate the total effect of depression on mortality. Compositional data analysis was used to examine the relationship between 24-h time-use compositions and mortality. Furthermore, we constructed a compositional mediation model for survival outcomes to investigate the mediating effect of 24-h time-use behaviors on depression and mortality. RESULTS: Compared with participants without depression, depressive patients had a significantly higher risk of overall mortality (HR = 1.49, 95 % CI: 1.25,1.79), cardiovascular disease -specific mortality (HR =1.89, 95 % CI: (1.37,2.63)) and mortality from causes other than cardiovascular disease or cancer (HR = 1.62, 95 % CI: (1.25,2.08)). Physical activity, especially moderate-to-vigorous physical activity, significantly mediated the relationship between depression and all-cause and CVD-specific mortality. LIMITATIONS: Despite being a cohort study, the exposure and mediatiors were measured at the baseline. Further research is necessary to require a temporal order between the exposure and mediating variables. CONCLUSIONS: Our findings indicate that 24-h time-use behaviors link depression to mortality. In particular, increasing the time spent on physical activity can reduce the risk of death in patients with depression. This finding provides potential interventions for reducing the risk of death in patients with depression.

HMGB1-mediated transcriptional activation of circadian gene TIMELESS contributes to endometrial cancer progression through Wnt-ß-catenin pathway.

TIMELESS (TIM) is a circadian gene which is implicated in the regulation of daily rhythm, DNA replication and repair, and cancer initiation and progression. Nevertheless, the role of TIM in endometrial cancer (EC) development is largely unknown. Bioinformatics analysis showed that TIM was aberrantly up-regulated in EC tissues and positively correlated with clinical or histological grade of EC. Functional studies showed that TIM knockdown reduced EC cell viability and restrained EC cell migration in vitro, as well as blocked xenograft tumor growth in vivo. Mechanistically, HMGB1 transcriptionally up-regulated TIM expression in EC cells. In addition, TIM could activate the transcription of the canonical Wnt ligand WNT8B, and TIM depletion could reduce the malignant potential of EC cells largely by targeting and down-regulating WNT8B. As a conclusion, HMGB1/TIM/WNT8B signal cascade was identified in this study for the first time. HMGB1 exerted its oncogenic role by activating the transcription of TIM, leading to the activation of Wnt signaling and EC progression.

Preclinical Evaluation and a Pilot Clinical Positron Emission Tomography Imaging Study of [68Ga]Ga-FAPI-FUSCC-II.

Fibroblast activation protein (FAP), a type II integral membrane serine protease, is a promising target for tumor diagnosis and therapy. OncoFAP has been recently discovered for PET imaging procedures for various solid malignancies. In this study, we presented the development of manual radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging. A novel series of [68Ga/177Lu]Ga/Lu-FAPI-FUSCC-I/II were produced with high radiochemical yields. [68Ga]Ga-FAPI-FUSCC-I/II and [177Lu]Lu-FAPI-FUSCC-I/II were stable in phosphate-buffered saline, fetal bovine serum, and human serum for at least 3 h. In vitro cellular uptake and blocking experiments implied that they had specificity to FAP. Additionally, the low nanomolar IC50 values of FAPI-FUSCC-II indicated that it had a high target affinity to FAP. The in vivo biodistribution and blocking study in mice bearing HT-1080-FAP tumors showed that both exhibited specific tumor uptake. [68Ga]Ga-FAPI-FUSCC-II showed a higher tumor uptake and a higher tumor/nontarget ratio than [68Ga]Ga-FAPI-FUSCC-I and [68Ga]Ga-FAPI-04. The results of ex vivo biodistribution were in accordance with the biodistribution results. Clinical [68Ga]Ga-FAPI-FUSCC-II-PET/CT imaging further demonstrated its favorable biodistribution and kinetics with elevated and reliable uptake by primary tumors (maximum standardized uptake value (SUVmax), 12.17 ± 6.67) and distant metastases (SUVmax, 9.24 ± 4.28). In summary, [68Ga]Ga-FAPI-FUSCC-II displayed increased tumor uptake and retention compared to [68Ga]Ga-FAPI-04, giving it potential as a promising tracer for the diagnostic imaging of malignant tumors with positive FAP expression.

DIA-based quantitative proteomic analysis of porcine endometrium in the peri-implantation phase.

The 12th day of gestation is a critical period for embryo loss and the beginning of imminent implantation in sows. Data independent acquisition (DIA) technology is one of the high-throughput, high-resolution and reproducible proteomics technologies for large-scale digital qualitative and quantitative research. The aim of this study was to identify and characterize the protein abundance landscape of Yorkshire pig endometrium on the 12th day of pregnancy (P12) and estrous cycle (C12) using DIA proteomics. A total of 1251 differentially abundant proteins (DAPs) were identified, of which 882 were up-regulated and 369 were down-regulated at P12. Functional enrichment analysis showed that the identified proteins were related to metabolism, biosynthesis and signaling pathways. Three proteins were selected for Western blot (WB) validation and the results were consistent with the DIA data. Further combined with transcriptome data, fibrinogen like 2 (FGL2) and S100 calcium binding protein A8 (S100A8) were verified to be highly abundant in the P12 endometrial epithelium. In summary, there were significantly different abundance of proteome profiles in C12 and P12 endometrium, suggesting that DAPs are associated with changes in endometrial receptivity, which laid the foundation for further research on related regulatory mechanisms. SIGNIFICANCE: The 12th day of gestation is an important point in the peri-implantation period of pigs, when the endometrium presents a receptive state under the stimulation of estrogen. DIA proteomics technology is an emerging protein identification technology in recent years, which can obtain protein information through comprehensive and unbiased scanning. In this study, DIA technology was used to characterize endometrial proteins in pigs during the peri-implantation period. The results showed that higher protein abundance was detected using the DIA technique, and some of these DAPs may be involved in regulating embryo implantation. This study will help to better reveal the related proteins involved in embryo implantation, and lay a foundation for further research on the mechanism of endometrial regulation of embryo implantation. SIGNIFICANCE OF THE STUDY: The 12th day of gestation is an important point in the peri-implantation period of pigs, when the endometrium presents a receptive state under the stimulation of estrogen. DIA proteomics technology is an emerging protein identification technology in recent years, which can obtain protein information through comprehensive and unbiased scanning. In this study, DIA technology was used to characterize endometrial proteins in pigs during the peri-implantation period. The results showed that higher protein abundance was detected using the DIA technique, and some of these DAPs may be involved in regulating embryo implantation. This study will help to better reveal the related proteins involved in embryo implantation, and lay a foundation for further research on the mechanism of endometrial regulation of embryo implantation.

Effect of Anesthesia During Pregnancy, Delivery, and Childhood on Autism Spectrum Disorder: A Systematic Review and Meta-analysis.

To investigate the association between exposure to anesthesia during three periods of pregnancy, delivery, and childhood and autism spectrum disorder (ASD). PubMed, Scopus, Web of Science, Embase, Google Scholar, PsycArticles, and PsycINFO were searched from the date of database inception to 1 December 2022. Studies reported the association between exposure to anesthesia during pregnancy, delivery, and childhood and ASD were included. Extracted variables included hazard ratio (HR), relative risk or odds ratio, standard error, and 95% confidence interval (CI). Effect estimates were pooled using random-effects meta-analysis. In total, 16 studies including 8,156,608 individuals were included in the meta-analysis. Labor epidural anesthesia during delivery was associated with ASD in the general population (adjusted HR = 1.16, 95% CI, 1.06-1.28) but not in the sibling population (adjusted HR = 1.06, 95% CI, 0.98-1.15). Other anesthesia during delivery was not associated with ASD (general population: adjusted HR = 1.08, 95% CI, 0.99-1.17; sibling population: adjusted HR = 1.20, 95% CI, 0.81-1.79). Three studies suggested that exposure to anesthesia during pregnancy was associated with ASD in offspring (adjusted HR = 2.15, 95% CI, 1.32-3.48). There was no significant association between exposure to general anesthesia during childhood and ASD (adjusted HR = 1.02, 95% CI, 0.60-1.72). This meta-analysis did not confirm the association between exposure to anesthesia during labour and ASD. Previous observational studies used the neurotoxicity of anesthesia to biologically explain significant associations, but in fact different controls for confounding factors led to differences in associations. The evidence for pregnancy and childhood was limited given the small number of studies in these periods.

Development of genome-wide association studies on childhood obesity and its indicators: A scoping review and enrichment analysis.

BACKGROUND: The progress of genome-wide association studies (GWAS) in childhood obesity and its indicators is challenging and there are differences in genetic studies in children and adults. OBJECTIVE: To illustrate the history of the development of GWAS in childhood obesity and its indicators and summarize the GWAS loci. METHODS: PubMed, Web of Science, Embase and GWAS Catalog databases were systematically searched from 1 January 2005 to 19 October 2022 for literature related to GWAS of childhood BMI, body fatness and obesity. The nearest genes were used as positional genes to perform gene set analyses including the enrichment of pathways, tissues and diseases. RESULTS: Twenty articles published between 2007 and 2021 were included in this scoping review, which identified 116 SNPs reaching genome-wide significance with childhood BMI (n = 50), body fatness (n = 31) and obesity (n = 35). The study populations were European in 16 studies, non-European in three studies (1 East Asian; 1 American; 1 Mexican) and trans-ancestry in one study. Several enriched pathways, tissues and diseases were identified through enrichment analysis of genes associated with childhood obesity and its indicators. CONCLUSIONS: The innovations in tools and methods enable GWAS to better explore the genetic characteristics of obesity in children and adolescents. However, the number of GWAS in American, Asian and African populations is limited compared to the European population.

Social determinants of health and gender differences in depression among adults: A cohort study.

The role of social determinants of health (SDoH) in gender differences in depression remains unclear among Chinese adults. We aimed to explore the association between SDoH and depression and investigate their role in explaining gender differences in depression. This prospective longitudinal cohort study used four wave surveys (2012, 2016, 2018, and 2020) of the China Family Panel Study (CFPS). Fourteen SDoH variables were assessed, and depression was measured using the 8-item short version of the Center for Epidemiologic Studies Depression Scale. The Cox proportional hazards regression and multiple mediation analysis were performed to estimate the effect sizes. The longitudinal sample included 18,874 participants aged 18-92 years (51.4 % males and 48.6 % females). Women had higher risk of depression than men. Unfavorable SDoH were associated with higher risk of depression. After including multiple SDoH in mediation analysis, multiple SDoH mediated 15.7 % of the total effect of gender on depression. In sum, SDoH significantly influenced depression, and specific factors explained gender differences in depression. Supporting women in education, employment, and community involvement could help reduce gender differences in depression.

Interaction and assembly of the DNA replication core proteins of Kaposi's sarcoma-associated herpesvirus.

IMPORTANCE: Eukaryotic DNA replication is a highly regulated process that requires multiple replication enzymes assembled onto DNA replication origins. Due to the complexity of the cell's DNA replication machinery, most of what we know about cellular DNA replication has come from the study of viral systems. Herein, we focus our study on the assembly of the Kaposi's sarcoma-associated herpesvirus core replication complex and propose a pairwise protein-protein interaction network of six highly conserved viral core replication proteins. A detailed understanding of the interaction and assembly of the viral core replication proteins may provide opportunities to develop new strategies against viral propagation.

Chiral Carbon Dots and Chiral Carbon Dots with Circularly Polarized Luminescence: Synthesis, Mechanistic Investigation and Applications.

Chiral carbon dots (CCDs) can be widely used in various fields such as chiral recognition, chiral catalysis and biomedicine because of their unique optical properties, low toxicity and good biocompatibility. In addition, CCDs with circularly polarized luminescence (CPL) can be synthesized, thus broadening the prospects of CCDs applications. Since the research on CCDs is still in its infancy, this paper reviews the chiral origin, formation mechanism, chiral evolution, synthesis and emerging applications of CCDs, with a special focus on CCDs with CPL activity. It is hoped that it will provide some reference to solve the current problems faced by CCDs. Finally, the opportunities and challenges of the current research on CCDs are described, and their future development trends have also been prospected.

Gut microbiota contribution to selenium deficiency-induced gut-liver inflammation.

There is limited knowledge about the factors that drive gut-liver axis changes after selenium (Se) deficiency-induced gut or liver injuries. Thus, we tested Se deficiency in mice to determine its effects on intestinal bacterial balance and whether it induced liver injury. Serum Se concentration, lipopolysaccharide (LPS) level, and liver injury biomarkers were tested using a biochemical method, while pathological changes in the liver and jejunum were observed via hematoxylin and eosin stain, and a fluorescence spectrophotometer was used to evaluate intestinal permeability. Tight junction (TJ)-related and toll-like receptor (TLR) signaling-related pathway genes and proteins were tested using quantitative polymerase chain reaction, western blotting, immunohistochemistry, and 16S ribosomal ribonucleic acid gene-targeted sequencing of jejunum microorganisms. Se deficiency significantly decreased glutathione peroxidase activity and disrupted the intestinal flora, with the most significant effect being a decrease in Lactobacillus reuteri. The expression of TJ-related genes and proteins decreased significantly with increased treatment time, whereas supplementation with Se, fecal microbiota transplantation, or L. reuteri reversed these decreases. Signs of liver injury and LPS content were significantly increased after intestinal flora imbalance or jejunum injury, and the levels of TLR signaling-related genes were significantly increased. The results indicated that Se deficiency disrupted the microbiota balance, decreased the expression of intestinal TJ factors, and increased intestinal permeability. By contrast, LPS increased due to a bacterial imbalance, which may induce inflammatory liver injury via the TLR4 signaling pathway.

Association between maternal postpartum depression and children's physical growth in early childhood: a birth cohort study.

Background: Untreated maternal postpartum depression (PPD) has consequences for children's physical growth, but no published study has evaluated changes in this effect over time. Here we therefore aimed to evaluate the dynamic effects of PPD on the physical growth of children in a prospective birth cohort. Methods: Between 2015 and 2019, 960 mother-child pairs in Changsha, China were followed up when the child was aged 1-48 months. Data were obtained through household surveys. The mothers' depressive symptoms were measured using the Edinburgh Postpartum Depression Scale (EPDS) at 1 month postpartum. Linear mixed models were used to examine the changes in the association of PPD and EPDS scores with physical growth in six different age groups of children between 1 and 48 months. Results: A total of 604 mother-child pairs completed the follow-up, and 3.3% of mothers reported PPD. No associations were found between PPD and weight or height growth at any age. While EPDS scores were associated with weight gain (ß = -0.014, 95% CI (-0.025, -0.002), P = 0.024) and height growth (ß = -0.044, 95% CI (-0.084, -0.004), P = 0.030) rates at 1-3 months, no associations were found in older children. Limitations: The number of mothers who reported PPD was relatively small, and the measurement of PPD was not continuously taken. Conclusions: After adjustments for confounders, no dynamic association was found between PPD and children's weight and height growth. EPDS scores, in contrast, did negatively affect children's weight and height growth at age 1-3 months, but this effect was not long-lasting.

PET imaging of PARP expression using 68Ga-labelled inhibitors.

PURPOSE: Imaging the PARP expression using 18F probes has been approved in clinical trials. Nevertheless, hepatobiliary clearance of both 18F probes hindered their application in monitoring abdominal lesions. Our novel 68Ga-labelled probes aim for fewer abdominal signals while ensuring PARP targeting by optimizing the pharmacokinetic properties of radioactive probes. METHODS: Three radioactive probes targeted PARP were designed, synthesized, and evaluated based on the PARP inhibitor Olaparib. These 68Ga-labelled radiotracers were assessed in vitro and in vivo. RESULTS: Precursors that did not lose binding affinity for PARP were designed, synthesized, and then labelled with 68Ga in high radiochemical purity (> 97%). The 68Ga-labelled radiotracers were stable. Due to the increased expression of PARP-1 in SK-OV-3 cells, the uptake of the three radiotracers by SK-OV-3 cells was significantly greater than that by A549 cells. PET/CT imaging of the SK-OV-3 models indicated that the tumor uptake of 68Ga-DOTA-Olaparib (0.5 h: 2.83 ± 0.55%ID/g; 1 h: 2.37 ± 0.64%ID/g) was significantly higher than that of the other 68Ga-labelled radiotracers. There was a significant difference in the T/M (tumor-to-muscle) ratios between the unblocked and blocked groups as calculated from the PET/CT images (4.07 ± 1.01 vs. 1.79 ± 0.45, P = 0.0238 < 0.05). Tumor autoradiography revealed high accumulation in tumor tissues, further confirming the above data. PARP-1 expression in the tumor was confirmed by immunochemistry. CONCLUSION: As the first 68Ga-labelled PARP inhibitor, 68Ga-DOTA-Olaparib displayed high stability and quick PARP imaging in a tumor model. This compound is thus a promising imaging agent that can be used in a personalized PARP inhibitor treatment regimen.

Effects of gestational ambient extreme temperature exposures on the risk of preterm birth in China: A sibling-matched study based on a multi-center prospective cohort.

BACKGROUND: Previous epidemiological findings on extreme temperature and preterm birth (PTB) were heterogeneous, especially for extreme cold exposure. Measured and unmeasured individual-level factors such as genetic factors or lifecourse exposures may constitute important contributors but have not been addressed. OBJECTIVES: We aimed to examine the association of gestational heat and cold exposure with PTB using a novel sibling-matched study. METHODS: Based on a multi-center population-based birth cohort across 16 counties in China, we included 10,826 sibling pairs born from March 2013 to December 2018. Conditional logistic and Cox Proportional Hazard regression models were used to estimate the effects of heat and cold exposure on PTB in each trimester, one and four weeks before delivery and the entire pregnancy. We also tested the heterogeneity in the association of temperature with PTB between siblings. FINDINGS: Exposure to heat during the third trimester and the entire pregnancy increased the risk of PTB. For heat (> 90th) defined with mean temperature, the odds ratios were 2.32 (1.63, 3.30) and 3.19 (2.22, 4.58), respectively. Cold exposure (< 10th) during the first, the third, and the entire pregnancy was associated with a higher PTB risk, with ORs (95%CIs) of 2.04 (1.43, 2.90), 3.13 (2.14, 4.58), and 4.26 (2.94, 6.19), respectively. We found slightly stronger associations of heat exposure during the entire pregnancy with the firstborn PTB, and stronger associations of cold exposure during one week and four weeks before delivery with secondborn PTB. CONCLUSIONS: Using a sibling-matched study, we took into account some mother-level unobserved confounding. Our research strengthens the evidence that gestational exposure to heat and cold increases the risk of PTB. Our findings may have important implications for improving the health of newborns in the context of climate change.

Enantioseparation Membranes: Research Status, Challenges, and Trends.

The purity of enantiomers plays a critical role in human health and safety. Enantioseparation is an effective way and necessary process to obtain pure chiral compounds. Enantiomer membrane separation is a new chiral resolution technique, which has the potential for industrialization. This paper mainly summarizes the research status of enantioseparation membranes including membrane materials, preparation methods, factors affecting membrane properties, and separation mechanisms. In addition, the key problems and challenges to be solved in the research of enantioseparation membranes are analyzed. Last but not least, the future development trend of the chiral membrane is expected.

Enhanced antitumor immune responses via a new agent [131I]-labeled dual-target immunosuppressant.

Radionuclides theranostic are ideal "partners" for bispecific antibodies to explore the immune response of patients and synergistic treatment. A bispecific single-domain antibody-Fc fusion protein, KN046, exhibits a good treatment effect by binding to programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). An ionizing-radiation stimulus mediated by a low-dose of [131I] may be used for immunopotentiation. In this study, we established [131I]-labeled KN046 as a novel radioimmunotherapy agent to treat malignant melanoma and explored the mechanism. METHODS: After intravenous injection of [131I]-KN046, SPECT/CT imaging was applied to identify candidate targets for KN046 immunotherapy. [18F]-FDG and [68 Ga]-NOTA-GZP (granzyme B-specific PET imaging agent) micro-PET/CT imaging was used to assess the immune response in vivo after [131I]-KN046 treatment. The synergistic treatment effect of [131I]-KN046 was evaluated by exploring the [131I]-based radionuclide-induced release of tumor immunogenicity-related antigens as well as the histology and survival of tumor-bearing mice after treatment. RESULTS: The constructed [131I]-KN046 exhibited high affinity and specificity for PD-L1/CTLA-4 immune targets and had excellent in vivo intratumoral retention capability so as to achieve good antitumor efficacy. More importantly, the combination of low-dose [131I] and KN046-enhanced immunosensitivity increased the immunotherapy response rates significantly. Exposure of tumor cells to [131I]-KN046 led to upregulated expression of MHC-I and Fas surface molecules and significant increases in the degree of T-cell activation and counts of tumor-infiltrating immunocytes. CONCLUSION: Use of low-dose [131I] combined with a dual-target immunosuppressant could be exploited to identify the subset of treatment responders but also exhibited great potential for enhancing antitumor immune responses.

Biomechanical analysis of a novel bone cement bridging screw system for the treatment of Kummell disease: a finite element analysis.

When bone cement is used to strengthen the vertebrae in patients with Kummell disease (KD), loosening and displacement of cement are common complications that can cause poor results. We developed a bone cement bridging screw system to avoid this complication. This three-dimensional finite element study aims to analyze the biomechanical properties of the novel bridging screw system and compare it to single vertebroplasty and vertebroplasty combined with pediculoplasty. After the effective establishment of a KD three-dimensional finite element model, the stability of the bone cement in the five treatment methods was analyzed and compared on four aspects. According to the calculation results of the maximum von Mises stress of bone cement and the relative displacement ratio of bone cement, it was determined that the stability of the bone cement was significantly improved when combined with the bridging screw system or pediculoplasty. In addition, according to the calculation results of the maximum von Mises stress of the inferior endplate of T12 and the displacement load ratio of the bone cement, we further found that after using the bridging screw system, the bone cement in the vertebral body has the best stability, and the risk of bone cement loosening or displacement is the lowest. In conclusion, for treating KD with bone cement augmentation, the bone cement bridging screw system combined with vertebroplasty has better stability and safety than ordinary single vertebroplasty and vertebroplasty combined with pediculoplasty. This treatment approach has the most robust ability to avoid loosening and displacement of bone cement.

The role of lipid traits in mediating the effect of body mass index on serum urate.

Objective: To explore whether total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride (TG) are mediators in the pathway of body mass index (BMI) on serum urate and determine the proportion of the mediation effect. Methods: This study used observational and two-sample Mendelian randomization (MR) analyses to explore the mediation effects of TC, HDL, LDL, and TG in the pathway of BMI on serum urate. We determined the size and the extent to which these lipids mediate any effect of BMI on serum urate. Results: Observational analysis results showed that HDL and TG can partially explain the association of BMI on serum urate, and the proportion of mediation effect was 10.2% and 8.9%, respectively. MR results demonstrated that TG has a causal effect on serum urate (ß = 0.22, 95% CI: 0.15, 0.29; p = 2.28×10-10.) and its proportion of mediation effect was 14.1%. TC, HDL, and LDL are not the mediators in the pathway of BMI on serum urate in MR estimates. Conclusion: To a certain extent, TG mediates the effect of BMI on serum urate, and the risk of gout may be reduced by controlling both BMI and TG.

Secular trends in the mortality of gastrointestinal cancers across China, Japan, the US, and India: An age-period-cohort, Joinpoint analyses, and Holt forecasts.

Background: Colon cancer, esophageal cancer, and stomach cancer are the common causes of morbidity and mortality in China, Japan, the US., and India. The current study aims to assess and compare secular trends of the mortality of gastrointestinal cancers during the period, 1990-2017 in age-specific, time period, and birth cohort effects. Method: We used the Joinpoint model to collect age-standardized mortality rates (ASMRs) for four countries. We designed an age-period-cohort (APC) analysis to estimate the independent effects on the mortality of three types of cancers. Result: The Joinpoint model shows that in addition to the death rate of esophageal cancer in Japan, the ASMR of esophageal cancer and stomach cancer in other countries declined rapidly. The APC analysis presented a similar pattern of age effect between four countries for colon cancer and stomach cancer, which increased from 20 to 89 age groups. Differently, the period effect rapidly increased for esophageal cancer and stomach cancer in the US, and the period effect in China presented a declining volatility, showing its highest value in 2007. In future, highest mortality trends are likely to occur in China. Conclusion: Therefore, the obvious increase in colon cancer recommended that earlier tactics must be performed to reduce mortality from specific causes from 2018 to 2027.