The Frailty Index and colon cancer: a 2-sample Mendelian-randomization study.

Background: Frailty is closely related to cancer. Previous research has shown that cancer patients are prone to frailty, and frailty increases the risk of adverse outcomes in cancer patients. However, it is unclear whether frailty increases the risk of cancer. This 2-sample Mendelian-randomization (MR) study sought to analyze the relationship between frailty and the risk of colon cancer. Methods: The database was extracted from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) in 2021. The genome-wide association study (GWAS) data related to colon cancer was obtained from the GWAS website (http://gwas.mrcieu.ac.uk/datasets), involving 462,933 individuals' gene information. Single-nucleotide polymorphisms (SNPs) were defined as the instrumental variables (IVs). The SNPs closely associated with the Frailty Index at a genome-wide significance level were selected. To further screen the IVs, we selected the confounding factors using the PhenoScanner (http://www.phenoscanner.medschl.cam.ac.uk/phenoscanner). To estimate the causal effect of the Frailty Index on colon cancer, the MR-Egger regression, weighted median (WM1), inverse-variance weighted (IVW), and weight mode (WM2) methods were applied to calculate the SNP-frailty index and the SNP-cancer estimates. Cochran's Q statistic was used to estimate heterogeneity. The two-sample Mendelian randomization (TSMR) analysis was performed using the "TwoSampleMR" and "plyr" packages. All the statistical tests were 2-tailed, and a P value <0.05 was considered statistically significant. Results: We selected 8 SNPs as the IVs. The results of the IVW analysis [odds ratio (OR) =0.995, 95% confidence interval (CI): 0.990-1.001, P=0.052] showed that the genetic changes in the Frailty Index were not statistically associated with the risk of colon cancer, and no significant heterogeneity between these 8 genes was observed (Q =7.382, P=0.184). The MR-Egger (OR =0.987, 95% CI: 0.945-1.031, P=0.581), WM1 (OR =0.995, 95% CI: 0.990-1.001, P=0.118), WM2 (OR =0.996, 95% CI: 0.988-1.004, P=0.356), and SM (OR =0.996, 95% CI: 0.987-1.005, P=0.449) results were also consistent with each other. The sensitivity analysis based on the leave-one-out method showed that the individual SNPs did not affect the robustness of the results. Conclusions: Frailty might have no effect on the risk of colon cancer.

A new method for estimating ore grade based on sample length weighting.

Estimation of ore grade is very important for the value evaluation of ore deposits, and it directly affects the development of mineral resources. To improve the accuracy of the inverse distance weighting (IDW) method in ore grade estimation and reduce the smoothing effect of the IDW method in grade estimation, the weight calculation method involved in the IDW method was improved. The length parameter of the ore sample was used to calculate the weight of the IDW method. The length of the ore samples was used as a new factor of the weighting calculation. A new method of IDW integrated with sample length weighting (IDWW) was proposed. The grade estimation of Li, Al, and Fe in porcelain clay ore was used as a case study. A comparative protocol for grade estimation via the IDWW method was designed and implemented. The number of samples involved in the estimation, sample combination, sample grade distribution, and other factors affecting the grade estimation were considered in the experimental scheme. The grade estimation results of the IDWW and the IDW methods were used for comparative analysis of grades of the original and combined samples. The estimated results of the IDWW method were also compared with those of the IDW method. The deviation analysis of the estimated grade mainly included the minimum, maximum, mean, and coefficient of variation of the ore grade. The estimation effect of IDWW method was verified. The minimum deviations of the estimated grade of Li, Al, and Fe were between 9.129% and 59.554%. The maximum deviations were between 4.210 and 22.375%. The mean deviations were between - 1.068 and 7.187%. The deviations in the coefficient of variation were between 3.076 and 36.186%. The deviations in the maximum, minimum, mean, and coefficients of variation of the IDWW were consistent with those of the IDW, demonstrating the accuracy and stability of the IDWW method. The more the samples involved in the estimation, the greater the estimation deviations of IDW and IDWW methods. The estimated deviations of Li, Al, and Fe were affected by the shape of the grade distribution, when the same estimation parameters were used. The grade distribution pattern of the samples significantly influenced the grade estimation results. The IDWW method offers significant theoretical advantages and addresses the adverse effects of uneven sample lengths on the estimates. The IDWW method can effectively reduce the smoothing effect and improves the utilization efficiency of the original samples.

Relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders / 中国学校卫生

Objective@#To investigate the potential relationship between sensory characteristics and gray matter volumes in children with autism spectrum disorders (ASD), to provide a basis for the diagnosis and treatment of children with ASD.@*Methods@#A total of 40 ASD children who were treated or recovered in Xi an medical institutions and 16 typically developing (TD) children who were from several kindergatens in Xi an were invited for participation. Sensory characteristics were evaluated by the sensory processing and self regulation checklist, 3D structural brain images were obtained with TIWI, and gray matter volumes were analyzed by voxel based morphometry. Sensory characteristics and gray matter volumes were compared between groups and the relationship between sensory characteristics and different gray matter volumes were analyzed.@*Results@#The scores of auditory, visual, tactile, sensory processing ability and sensory under responsivity in the ASD group were lower than those in the TD group ( Z/t =-2.63, -2.57 , -3.11, -2.19, -3.83, P <0.05). Gray matter volumes in nine brain regions increased in the ASD group compared to the TD group, including the left and right posterior inferior lobe, right parahippocamal gyrus, left insula, left media frontal gyrus, left superion occipital gyrus, right superion occipital gyrus, right superion parietal lobe, and right posterion central gyrus ( t =3.53, 3.69 , 3.37, 3.86, 3.61, 3.37, 4.04, 3.38, 3.16, P <0.01). In the ASD group, the scores of visual, vestibular, proprioceptive, sensory processing ability, sensory seeking behavior and sensory over responsivity were negatively correlated with gray matter volumes of left superior occipital gyrus ( r =-0.36, -0.40, -0.39, -0.36, -0.40, -0.36), and the scores of visual, vestibular, and sensory over responsivity were negatively correlated with gray matter volumes of the right superior parietal lobule ( r =-0.36, -0.50, -0.42)( P <0.05).@*Conclusion@#The presence of paresthesia in children with ASD is associated with gray matter volumes of the left superior occipital gyrus and right superior parietal lobule.

Burden and trends of brain and central nervous system cancer from 1990 to 2019 at the global, regional, and country levels.

BACKGROUND: Regularly updated epidemiological data on the burden of brain and central nervous system (CNS) cancers are important in the prioritization of research and the allocation of resources. This study aimed to investigate incidence, mortality, disability, and trends in brain and CNS cancers between 1990 and 2019. METHODS: Epidemiological data, including the cancer incidence, mortality, disability-adjusted life years(DALYs), age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized DALY rate (per 100,000 population) stratified by region, country, sex, and age group were retrieved and extracted using the Global Health Data Exchange (GHDx) query tool. RESULTS: In 2019, there were 347,992(262,084-388,896) global cases of brain and CNS cancers, which showed a significant increase (94.35%) from the period between 1990 to 2019. The global ASIR in 2019 was 4.34 (3.27-4.86) per 100, 000 population, which showed an increasing trend for the years 1990-2019 (13.82% [-27.27-32.83]). In 2019, there were 246,253 (185,642-270,930) global deaths caused by brain and CNS cancers, which showed a significant increase (76.36%) during the study period. The global ASMR in 2019 was 3.05(2.29-3.36) per 100, 000 population, which did not change significantly over the study period (-1.19% [-36.79-13.86]). In 2019, there were 8,659,871 DALYs, which was a 109.04% increase compared with 1990. Similarly, during 1990-2019, the age-standardized DALY rate decreased by 10.39%. Additionally, 76.60% of the incident cases, 72.98% of the deaths, and 65.16% of the DALYs due to brain and CNS cancers occurred in the high-income and upper-middle-income regions. CONCLUSIONS: In conclusion, brain and CNS cancers remain a major public health burden, particularly in high-income regions. The global incidence, deaths, and DALYs of brain and CNS cancers were shown to have increased significantly from 1990 to 2019. The global ASIR kept rising steadily, while the ASMR and age-standardized DALY rate declined over the past three decades.

MiR-218 Targeted Regulation of Robol Expression Regulates Proliferation, Invasion and Migration of Glioma Cells.

In recent years, more and more researches has focused on "molecular targeted therapy" for basic genes and regulatory cells, but the effect is not ideal. Therefore, the discovery of new molecular targets with diagnostic and therapeutic significance can not only lay a solid foundation for molecular diagnosis and classification of lesions but also contribute to targeted therapy of glioma. This study aimed to discover the molecular mechanism of mir-218 targeting the regulation of robol expression on proliferation, invasion and migration of glioma cells and to provide a theoretical and experimental basis for finding therapeutic targets of glioma. The purpose of this study was to investigate the effect of mir-218 on gliomas by using the method of control experiment. The results showed that the number of gliomas under the action of mir-218 decreased from about 150 to about 80, and the number would tend to a fixed value range over time. In the experiment, the data decreased from about 150 to nearly 20, and compared with the control group, the control of glioma cell proliferation was very excellent.

Visible-Light-Promoted Desulfurative Alkylation of Alkyl Thianthrenium Salts with Activated Olefins.

Reactions involving an alkyl radical generated from a primary alcohol by photochemistry are rare and challenging. Herein, we present a photocatalyst- and metal-free approach that enables the generation of an alkyl radical from the corresponding alcohol and the subsequent C(sp3)-C(sp3) bond formation with activated olefin, via an alkyl thianthrenium salt/Hantzsch ester electron donor-acceptor complex. This protocol for the conversion of a C-OH bond to a C-C bond is highly functionality tolerant and can successfully be used in late-stage functionalization of pharmaceuticals.

Recombinant osteopontin provides protection for cerebral infarction by inhibiting the NLRP3 inflammasome in microglia.

Neuroinflammation is one of the most important secondary pathological events after cerebral infarction. Activation of NLRP3 inflammasome is a pivotal form of neuroinflammation. Osteopontin (OPN) is expressed during the subacute phase after cerebral infarction and has an important chemotactic effect on microglia. The aim of this study was to reveal the effect of recombinant OPN on brain injury after cerebral infarction and the regulation of NLRP3 inflammasome. We used the middle cerebral artery occlusion (MCAO) method-established focal cerebral ischemia model and LPS-induced inflammation model on neonate rat primary microglia. The effects of OPN on cerebral ischemic injury, neural function, microglia inflammation and NLRP3 inflammasome function were studied by immunofluorescence, staining, enzyme-linked immunosorbent assay and Western blot assay. We established MCAO cerebral ischemia and reperfusion injury model, and found that recombinant OPN reduced the volume of cerebral infarction and alleviated the ischemic injury degree of cerebral tissues, neurons, and neurological function. We found that OPN was also involved in the negative regulation of inflammasome and microglia activity in cerebral ischemic injury, and that OPN inhibited the activation of NLRP3 inflammasome and the function of microglia in a LPS-induced inflammatory model. Our findings show that recombinant OPN can reduce the ischemic infarct size and alleviate the cerebral ischemic injury of rats, which may be related to its efficient involvement in the inhibitory regulation of inflammasome and microglia inflammatory activation.

LncRNA SNHG6 functions as a ceRNA to regulate neuronal cell apoptosis by modulating miR-181c-5p/BIM signalling in ischaemic stroke.

Long non-coding RNAs (lncRNAs) play important roles in the pathogenesis of brain and neurodegenerative disorders. As far as we know, the functions and potential mechanisms of small nucleolar RNA host gene 6 (SNHG6) in ischaemic stroke have not been explored. This study aimed to examine the functional role of SNHG6 in the ischaemic stroke. Middle cerebral artery occlusion (MCAO) in mice and the oxygen glucose deprivation (OGD)-induced injury in neuronal cells were applied to mimic ischaemic stroke. TTC staining, quantitative real-time PCR, cell apoptosis assay, caspase-3 activity assay, Western blot, RNA immunoprecipitation and luciferase reporter assay were performed to evaluate the function and possible mechanisms of SNHG6 in the pathogenesis of ischaemic stroke. The results show that SNHG6 expression was significantly increased both OGD-induced neuronal cells and MCAO model mice. In vitro results showed that inhibition of SNHG6 increased cell viability, inhibited cell apoptosis and caspase-3 activity in OGD-induced neuronal cells. Consistently, knockdown of SNHG6 reduced brain infarct size and improved neurological scores in the MCAO mice. Mechanistic study further revealed that SNHG6 functioned as a competing endogenous RNA (ceRNA) for miR-181c-5p, which in turn repressed its downstream target of Bcl-2 interacting mediator of cell death (BIM) and inhibiting cell apoptosis. This study revealed a novel function of SNHG6 in the modulating neuronal apoptosis in the ischaemic stroke model, and the role of SNHG6 in the regulating of neuronal apoptosis was at least partly via targeting miR-181c-5p/BIM signalling pathway.

Knockdown of STIM1 improves neuronal survival after traumatic neuronal injury through regulating mGluR1-dependent Ca(2+) signaling in mouse cortical neurons.

Activation of glutamate receptors and followed increase of intracellular calcium concentration is a key pathological mechanism involved in secondary neuronal injury after traumatic brain injury (TBI). Stromal interaction molecule (STIM) proteins are considered to be important players in regulating neuronal Ca(2+) homeostasis under normal aging and pathological conditions. Here, we investigated the role of STIM1 in regulating metabotropic glutamate receptor 1 (mGluR1)-related Ca(2+) signaling and neuronal survival by using an in vitro traumatic neuronal injury (TNI) model. The expression of STIM1 was significantly increased at both mRNA and protein levels after TNI. Down-regulation of STIM1 by specific small interfere RNA significantly preserved neuronal viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell death after traumatic injury. Moreover, knockdown of STIM1 significantly alleviated the mGluR1-related increase of cytoplasmic Ca(2+) levels after TNI. By analyzing Ca(2+) imaging in Ca(2+)-free conditions, we demonstrated that the mGluR1-dependent inositol trisphosphate receptor and/or ryanodine receptor-mediated Ca(2+) release from the endoplasmic reticulum after TNI is strongly attenuated in the absence of STIM1. Together, our results demonstrate that in the mammalian nervous system, STIM1 is a key regulator of mGluR1-dependent Ca(2+) signaling and knockdown of STIM1 might be an effective intervention target in TBI.

[Strain in GaN epi-layer grown by hydride vapor phase epitaxy].

In the present paper, strain in GaN epitaxial layer grown by hydride vapor phase epitaxy (HVPE) was investigated by means of high-resolution X-ray diffraction (HRXRD), Raman spectra and photoluminescence (PL) measurements. Both the biaxial in-plane and out-of-plane strains (of the order of -10(-4) and 10(-4), respectively) and the hydrostatic strain component (of the order of -10(-5)) were extracted from HRXRD measurements. These values agreed well with the ones computed from the blue-shift of E2 Raman mode and the near-band-edge PL peak. The results showed that strains in GaN layer were superposed by the biaxial strain and hydrostatic strain.