Causality between sarcopenia and diabetic nephropathy: a bidirectional Mendelian randomization study

Background and purposeObservational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study.MethodologyWe data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN from the genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a Reverse MR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis’s accuracy further.ResultsAccording to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right β = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left β = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different.ConclusionNotably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone

Experimental study on shear mechanical properties and damage evolution ofartificial structural plane under constant normal stiffness

To study the influence of asperity angle and normal stiffness on the shear mechanical properties of the structural plane, a direct shear test of the artificial structural plane with constant normal stiffness (CNS) was carried out using the self-developed coal rock shear seepage coupling test system. The results show that the shear stress presents a periodic oscillation attenuation trend when the asperity angles are 15° and 30°. At the end of shearing, the reduction in peak shear stress with the increase of normal stiffness is 1.78, 1.42, 1.36 and 1.27 MPa, respectively, which is gradually decreasing. While the asperity angle is 45°, the shear stress gradually tends to residual strength after reaching the peak shear stress, and there is a one-to-one correspondence between normal displacement evolution and shear stress. With the increase of the asperity angles, the shear stiffness increases gradually. With the increase of normal stiffness, the peak shear stress of structural planes with 15° and 45° asperity angles increases linearly, and when the asperity angle is 30°, it presents the characteristic of piecewise function, but the peak shear dilatancy angle gradually decreases. The failure mode of the structural plane is obtained by analyzing the mass loss before and after shearing, the proportion of debris particle size, and the evolution of three-dimensional morphology parameters. When the fluctuation angles are 15° and 45°, the failure modes are relatively single, namely wear failure and tooth cutting failure. When the fluctuation angle is 30°, the failure mode has a strong and complex dependence on the experimental conditions, mainly including tooth tip shear failure and full tooth cutting failure. By combining the three-dimensional spatial point cloud data of the structural plane with the normal displacement values at the corresponding shear displacement, a simulated cloud map of the structural plane gap width at a specific shear displacement is obtained, which analyzes the dynamic evolution process of the structural plane during the shear process and obtains its failure mechanism

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Experimental Study on Mechanical Properties and Stability Analysis of Structural Plane under Unloading Normal Stress

Excavation in rock induces the unloading of stress in excavation-disturbed zones and can cause the structural plane to reach shear failure due to the unloading of normal stress. Unloading normal stress tests of a regular sawtooth structural plane were conducted in this study to investigate the influence of the unloading velocities (v) and asperity angles (θ) on mechanical properties and the stability of the structural plane. The average value of normal displacement (Du1) and the shear displacement of unloading (Dsu) gradually increases with an increase in θ and Du1 accounts for 59.70%, 31.81%, and 18.60% of the height of a single asperity under different θ. However, Du2, Ds, and the unloading capacity (Δσn) gradually decreased. Moreover, Ds account for 24.52%, 11.61%, and 7.4% of the length of a single asperity, respectively. With an increase in θ and v, three-dimensional (3D) morphology parameters and normal deformation energy (Un) decreased gradually, indicating that the damage degree of the structural plane increases. The analysis of the evolution of the gap width of the structural plane at the initial point, unloading point, and instability point indicates that the greater the θ or the smaller the v, the lower would be the likelihood for the structural plane to be damaged. Concurrently, its instability is more sudden and the impact tendency is stronger

Experimental Study on Mechanical Properties and Stability Analysis of Structural Plane under Unloading Normal Stress

Excavation in rock induces the unloading of stress in excavation-disturbed zones and can cause the structural plane to reach shear failure due to the unloading of normal stress. Unloading normal stress tests of a regular sawtooth structural plane were conducted in this study to investigate the influence of the unloading velocities (v) and asperity angles (θ) on mechanical properties and the stability of the structural plane. The average value of normal displacement (Du1) and the shear displacement of unloading (Dsu) gradually increases with an increase in θ and Du1 accounts for 59.70%, 31.81%, and 18.60% of the height of a single asperity under different θ. However, Du2, Ds, and the unloading capacity (Δσn) gradually decreased. Moreover, Ds account for 24.52%, 11.61%, and 7.4% of the length of a single asperity, respectively. With an increase in θ and v, three-dimensional (3D) morphology parameters and normal deformation energy (Un) decreased gradually, indicating that the damage degree of the structural plane increases. The analysis of the evolution of the gap width of the structural plane at the initial point, unloading point, and instability point indicates that the greater the θ or the smaller the v, the lower would be the likelihood for the structural plane to be damaged. Concurrently, its instability is more sudden and the impact tendency is stronger

Experimental Investigation of Non-Linear Seepage Characteristics in Rock Discontinuities and Morphology of the Shear Section in the Shear Process

Considering the increasing frequency of geological disasters related to groundwater activities, it is important to study the relationship between geological dislocation and groundwater flow for the safety assessment of engineering rock mass stability. To elucidate the non-linear seepage characteristics at rock discontinuities during shearing, a custom-made device was used to conduct seepage tests at discontinuities that exhibit varying undulation angles and different shear displacements. The results show that as the shear displacement increases, the shear stress at a structural plane involving different undulation angles fluctuates with an increasing trend. Based on an identical shear displacement condition, the shear strengths of the structural planes increase as the undulation angle increases, and this enhances the shear expansion. Concerning an identical fluctuation angle and hydraulic gradient, the seepage flow at a structural plane increases as the shear displacement increases. By contrast, both the linear term coefficient a and non-linear term coefficient b in the Forchheimer fitting equation decrease as the shear displacement increases. In addition, the critical Reynolds number initially increases, followed by stabilisation as the shear displacement increases, and this number varies between 9.65 and 1758.52. The shear fracture morphology of the structural plane exhibits obvious anisotropy. During shearing, the roughness coefficient decreases in all but the vertical direction. The dominant seepage channel is perpendicular to the shear direction. The findings can provide a valuable reference for the stability research and analysis of rock slopes with structural planes

Identification and Characterization of a Novel Hepta-Segmented dsRNA Virus From the Phytopathogenic Fungus Colletotrichum fructicola

A novel hepta-segmented double-stranded RNA (dsRNA) virus was isolated and characterized from the strain FJ-4 of the phytopathogenic fungus Colletotrichum fructicola, and was named Colletotrichum fructicola chrysovirus 1 (CfCV1). The full-length cDNAs of dsRNA1–7 were 3620, 2801, 2687, 2437, 1750, 1536, and 1211 bp, respectively. The 5′- and 3′-untranslated regions of the seven dsRNAs share highly similar internal sequence and contain conserved sequence stretches, indicating that they have a common virus origin. The 5′-and 3′-UTRs of the seven dsRNAs were predicted to fold into stable stem-loop structures. CfCV1 contains spherical virions that are 35 nm in diameter consisting of seven segments. The largest dsRNA of CfCV1 encodes an RNA-dependent RNA polymerase (RdRp), and the second dsRNA encodes a viral capsid protein (CP). The dsRNA5 encodes a C2H2-type zinc finger protein containing an R-rich region and a G-rich region. The smallest dsRNA is a satellite-like RNA. The functions of the other proteins encoded by dsRNA3, dsRNA4, dsRNA6 are unknown. Phylogenetic analysis, based on RdRp and CP, indicated that CfCV1 is phylogenetically related to Botryosphaeria dothidea chrysovirus 1 (BdCV1), and Penicillium janczewskii chrysovirus 2 (PjCV2), a cluster of an independent cluster II group in the family Chrysoviridae. Importantly, all the seven segments of CfCV1 were transmitted successfully to other virus-free strains with an all-or-none fashion. CfCV1 exerts minor influence on the growth of C. fructicola but can confer hypovirulence to the fungal host. To our knowledge, this is the first report of a hepta-segmented tentative chrysovirus in C. fructicola

Hillock formation and suppression on c-plane homoepitaxial GaN Layers grown by metalorganic vapor phase epitaxy

Hillocks on c-plane homoepitaxial GaN epilayers were investigated. They were observed on epilayers grown on [1 (1) over bar 00] direction miscut free-standing GaN substrates with miscut angle not larger than 0.2 degrees and were absent when substrate miscut angle increased to 0.4 degrees. Atomic force microscopy (AFM) and cathodoluminescence measurements reveal a close correlation between hillocks and dislocation clusters, while hillocks are absent on layers grown on GaN substrate free of dislocation clusters. We believe that the hillocks originate from spiral growth around dislocation clusters. Larger strain induced by dislocation accumulation may be responsible for the hillock formation around dislocation clusters. (C) 2013 Elsevier B.V. All rights reserved

Dynamics of carbendazim-resistant frequency of pathogen associated with the epidemic of Fusarium head blight

Carbendazim resistance was detected using 4701 Fusarium graminearum species complex (FGSC) isolates collected from major wheat producing regions in China from 2018 to 2020. A total of 348 carbendazim-resistant isolates were identified. The majority of carbendazim-resistant isolates were detected in Jiangsu and Anhui Provinces. 227 and 88 isolates were obtained from each of Jiangsu and Anhui Provinces with the high resistance frequency of 41.12% and 20.56%. The predominant resistant isolates harboring point mutation F167Y (79.31%), followed by E198Q (16.38%) and F200Y (4.31%). Compared with F. graminearum, F. asiaticum isolates were more likely to produce carbendazim resistance. In this study, we firstly detected carbendazim-resistant isolates in Hebei, Shaanxi, Sichuan and Hunan Province. In Jiangsu, Anhui and Zhejiang, the frequency of carbendazim-resistant isolates maintained a high level resulting in stable carbendazim-resistant populations. We also found the dynamic of carbendazim-resistant frequency in most provinces showed similar trend of the epidemic of FHB. Our results facilitate the understanding of the current situation of carbendazim resistance of FHB pathogens, and will be helpful for fungicides selection in different wheat producing areas in China