Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China

AimsThe body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China.MethodsIn total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004–2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD.ResultsThree distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged <50 years.ConclusionBRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China

Saturation evaluation of tight sandstone in the Dayi structure, West Sichuan Depression

Tight sandstone reservoirs are characterized by poor physical properties, strong heterogeneity, and complex pore structures, resulting in low reservoir saturation calculation accuracy, and the log interpretations do not match the gas test results. In response to the aforementioned problems, the tight sandstone reservoir of the third member of the Xujiahe Formation of the Dayi structure in the Western Sichuan Depression was investigated through a series of experiments on petrophysical properties, casting thin-section identification, rock resistivity, nuclear magnetic resonance, and high-pressure mercury intrusion. Then, after a systematic analysis of the influence of different factors, including physical properties, mineral composition, and pore structure, on the rock-electric parameters, the parameters of the Archie model were appropriately corrected. The results showed that, for tight sandstone reservoirs, the cementation exponent was mainly affected by the physical properties and clay content, and the saturation exponent was controlled by the proportion of relatively large pore components in the total pore system. Therefore, the non-linear least squares method was used to construct the variable cementation index model; the pseudo-capillary pressure curve was constructed, and a new parameter “the large-pore proportion,” which is used to optimize the saturation exponent, was proposed in combination with the fractal theory. Finally, an Archie model with variable parameters was used to process the actual logging data in the study area. The results show that this method can obtain more accurate gas saturation, providing a new idea and method for fine sandstone saturation logging evaluation

Metabolism of Bis(4-fluorobenzyl)trisulfide and Its Formation of Hemoglobin Adduct in Rat Erythrocytes

ABSTRACT Bis(4-fluorobenzyl)trisulfide (BFBTS) is a promising new antitumor agent under investigation. It was metabolized rapidly in vivo in rat, but the metabolic fate and primary site of metabolism have not been clarified. In this study, we investigated the role of blood in the metabolism of BFBTS and compared the BFBTS metabolic potencies in whole blood, plasma, and red blood cells (RBCs) in vitro. Three major metabolites of BFBTS [bis(4-fluorobenzyl) disulfide, para-fluorobenzyl-mercaptan, and para-fluorobenzoic acid] were detected in RBCs and whole blood. Significant metabolism of BFBTS was observed in RBCs that were identified as the primary site of BFBTS metabolism. Thiols, including endogenous thiols and hemoglobin, were proven to be the critical factor in BFBTS metabolism. S-Fluorobenzylmercaptocysteine Hb (hemoglobin) adducts were characterized in vitro at BFBTS concentration of 250 mM and higher, whereas such Hb adducts were not detected in RBCs from Sprague-Dawley rats receiving a single intravenous injection of BFBTS at a high dose of 50 mg/kg. Liquid chromatography-tandem mass spectrometry results revealed that adduction induced by BFBTS was prone to take place at Cys125 of globin b chains. Otherwise, glutathionylation of Hb was also observed that may be attributed to the oxidative effect of BFBTS. In summary, BFBTS was unstable when it met with thiols, and RBCs were the main site of BFBTS metabolism. Hb adducts induced by BFBTS could be detected in vitro at high concentration but not in vivo even at high dose

Based on systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for diabetes

PurposeDiabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic “druggable” genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.Material and methodWe used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.ResultOverall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM.ConclusionThis study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes

QTL Detection for Kernel Size and Weight in Bread Wheat (Triticum aestivum L.) Using a High-Density SNP and SSR-Based Linkage Map

High-density genetic linkage maps are essential for precise mapping quantitative trait loci (QTL) in wheat (Triticum aestivum L.). In this study, a high-density genetic linkage map consisted of 6312 SNP and SSR markers was developed to identify QTL controlling kernel size and weight, based on a recombinant inbred line (RIL) population derived from the cross of Shixin828 and Kenong2007. Seventy-eight putative QTL for kernel length (KL), kernel width (KW), kernel diameter ratio (KDR), and thousand kernel weight (TKW) were detected over eight environments by inclusive composite interval mapping (ICIM). Of these, six stable QTL were identified in more than four environments, including two for KL (qKL-2D and qKL-6B.2), one for KW (qKW-2D.1), one for KDR (qKDR-2D.1) and two for TKW (qTKW-5A and qTKW-5B.2). Unconditional and multivariable conditional QTL mapping for TKW with respect to TKW component (TKWC) revealed that kernel dimensions played an important role in regulating the kernel weight. Seven QTL-rich genetic regions including seventeen QTL were found on chromosomes 1A (2), 2D, 3A, 4B and 5B (2) exhibiting pleiotropic effects. In particular, clusters on chromosomes 2D and 5B possessing significant QTL for kernel-related traits were highlighted. Markers tightly linked to these QTL or clusters will eventually facilitate further studies for fine mapping, candidate gene discovery and marker-assisted selection (MAS) in wheat breeding

Seroprevalence of Neutralizing Antibodies to Human Adenovirus Type 4 and 7 in Healthy Populations From Southern China

Human adenoviruses type 4 (HAdV4) and 7 (HAdV7) are two major respiratory pathogens and sporadically cause outbreaks of acute respiratory diseases. The neutralizing antibody (nAb) response to these two adenoviruses in civilian populations, which is important for dissecting previous circulations and predicting potential outbreaks, remains largely unknown. In this study, we generated replication-competent HAdV4 and HAdV7 reporter viruses expressing secreted-alkaline-phosphatase (SEAP), and established neutralization assays to investigate the seroprevalence of pre-existing nAb in healthy volunteers from Hunan Province, southern China. The seropositivity rates are 58.4 and 63.8% for anti-HAdV4 nAb and anti-HAdV7 nAb, respectively. High nAb titers (> 1000) were frequently detected in HAdV4-seropositive individuals, whereas most HAdV7-seropositive volunteers had moderate nAb titers (201–1000). The seropositivity rates of anti-HAdV4 nAb and anti-HAdV7 nAb increase with age, with individuals younger than 20 exhibiting the lowest seropositivity rates. Both seropositivity rates and nAb titers are comparable between different sex groups. Notably, HAdV4-seropositive individuals tend to be HAdV7-seropositive and vice versa. Because HAdV4 antisera showed no neutralizing activity to HAdV7 whereas HAdV7 antisera cannot neutralize HAdV4, a subgroup of individuals might be susceptible to infection by HAdV4 and HAdV7 and thus generate nAb to both of them. These results revealed the continuous circulation of HAdV4 and HAdV7 and the lack of protective immunity in more than 35% of people, which emphasized the surveillance of these two HAdVs and the development of prophylactic vaccines

Threshold effect and sex characteristics of the relationship between chronic inflammation and BMI

Abstract Chronic inflammation is an important pathway for obesity to harm health, the aggravation of chronic inflammation occurs without clinical symptoms. BMI is closely related to chronic inflammation, and it is a predictive factor of chronic inflammation, but the following questions remain unanswered: Are the effects of chronic inflammation on different BMI intervals consistent? Are the effects of BMI on chronic inflammation consistent between male and female? This study aimed to explore the threshold effect, and sex characteristics of the relationship between chronic inflammation and BMI. Methods: People with normal weight, overweight, and obesity were selected as subjects for cross-sectional study. BMI, hs-CRP, adiponectin and irisin was tested. Multiple regression analysis and generalized additive models were used to examine the association between hs-CRP and BMI. Results: 119 adults were recruited (normal weight: n = 30, 28.1 ± 7.65 years, BMI: 22.04 ± 1.55; overweight: n = 29, 27.45 ± 7.47 years, BMI: 26.11 ± 1.22; and obesity: n = 60, 28.82 ± 6.05 years, BMI: 33.68 ± 3.57). After adjusting for age and sex, BMI was found to be positively associated with the chronic inflammatory marker hs-CRP (β = 0.45; P  24.6 (β = 0.54; P  0.05). The pro-inflammatory effect caused by BMI increase in female (β = 0.56; P  0.05). Conclusions: BMI has a threshold effect on chronic inflammation, BMI greater than 24.3 is positively correlated with hs-CRP. BMI in 18.5–24.3 is not correlated with hs-CRP. Furthermore, when the BMI greater than 33, hs-CRP is not positively correlated with BMI in male, whereas the pro-inflammatory effect of BMI increase becomes greater in female. Highlights: • BMI has a threshold effect on chronic inflammation. BMI in 18.5–24.3 is not correlated with chronic inflammation, and BMI greater than 24.3 is positively correlated with chronic inflammation. • The pro-inflammatory effect caused by BMI increase in female is higher than that in male. In particular, when the BMI is greater than 33, chronic inflammation is not positively correlated with BMI in male, whereas the pro-inflammatory effect of BMI increase becomes greater in female