Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Virus-induced gene silencing (VIGS) in Chinese narcissus and its use in functional analysis of NtMYB3

Virus-induced gene silencing (VIGS) is a natural defense mechanism of plants, which can cause sequence-specific degradation of viral RNA and is often used for studying the functional genome. At present, the VIGS system mediated by Tobacco rattle virus (TRV) has been successfully established in many plant species. However, the VIGS system in Chinese narcissus had not been reported yet. In this paper, the first use of the TRV-VIGS system in Chinese narcissus is described in detail. By injecting pTRV2-GFP into narcissus leaves, we confirmed that TRV could infect narcissus and move in narcissus plants. After the inoculation of pTRV2-NtPDS by two methods, phenomena such as photo-bleaching appeared in narcissus leaves and qRT-PCR results proved that PDS gene of narcissus was successfully silenced. Besides, pTRV2-NtMYB3 was inoculated into basal plates of narcissus to study the function of NtMYB3; the results showed that NtMYB3 is an inhibitor of flavonoids biosynthesis, which can increase the content of proanthocyanidins in basal plates of narcissus by repressing the expression level of NtFLS. These results indicate that the TRV-VIGS system has been successfully established in Chinese narcissus and successfully applied to the functional study of NtMYB3

Fractional amplitude of low-frequency fluctuations and functional connectivity in comatose patients subjected to resting-state functional magnetic resonance imaging

Objective: The objective of the study is to investigate the changes of fractional amplitude of low-frequency fluctuations (fALFFs) and functional connectivity (FC) in the brain function of comatose patients with resting-state blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD-fMRI) and to discuss the underlying neurophysiological mechanism of disease. Materials and Methods: Resting-state BOLD-fMRI scans were conducted on 20 comatose patients and 20 age-matched and gender-matched controls. The differences of fALFF between two groups were analyzed with two-sample t-test; significant differences of connectivity between groups were acquired to calculate the FC of the precuneus with other brain regions. Results: Compared to the control group, the comatose patients exhibited a significant reduction in fALFF in various areas, including the right cingulate gyrus, left precuneus, right inferior parietal lobule, right superior parietal lobule, bilateral anterior/posterior central gyrus, middle frontal gyrus, right superior frontal gyrus, right superior temporal gyrus, and the bilateral cerebellar hemispheres (P < 0.05, Alphasim correction). Compared with controls, the brain region FC correlated with the precuneus reduced mainly located in the bilateral inferior parietal lobule, posterior central gyrus, lenticular nucleus, left anterior central gyrus, left medial frontal gyrus, left anterior lobe of the cerebellum, right insula, right transverse temporal gyri, and right thalamus. Regions whose FC increased include the left superior frontal gyrus, left side of the callosum, left superior parietal lobule, and both sides of the cingulate (P < 0.05, Alphasim correction). Conclusion: Measurements of fALFF and FC obtained by resting-state BOLD-fMRI could provide considerable information for the analysis and evaluation of the brain function of comatose patients from the perspective of local function and global functional network and provide the theoretical basis for the study of coma nerve physiological mechanism

Rapid monitoring the water extraction process of Radix Paeoniae Alba using near infrared spectroscopy

Near infrared (NIR) spectroscopy has been developed into one of the most important process analytical techniques (PAT) in a wide field of applications. The feasibility of NIR spectroscopy with partial least square regression (PLSR) to monitor the concentration of paeoniflorin, albiflorin, gallic acid, and benzoyl paeoniflorin during the water extraction process of Radix Paeoniae Alba was demonstrated and verified in this work. NIR spectra were collected in transmission mode and pretreated with smoothing and/or derivative, and then quantitative models were built up using PLSR. Interval partial least squares (iPLS) method was used for the selection of spectral variables. Determination coefficients (Rcal2 and Rpred2), root mean squares error of prediction (RMSEP), root mean squares error of calibration (RMSEC), and residual predictive deviation (RPD) were applied to verify the performance of the models, and the corresponding values were 0.9873 and 0.9855, 0.0487mg/mL, 0.0545mg/mL and 8.4 for paeoniflorin; 0.9879, 0.9888, 0.0303mg/mL, 0.0321mg/mL and 9.1 for albiflorin; 0.9696, 0.9644, 0.0140mg/mL, 0.0145mg/mL and 5.1 for gallic acid; 0.9794, 0.9781, 0.00169mg/mL, 0.00171mg/mL and 6.9 for benzoyl paeoniflorin, respectively. The results turned out that this approach was very efficient and environmentally friendly for the quantitative monitoring of the water extraction process of Radix Paeoniae Alba

An injectable gelatin/sericin hydrogel loaded with human umbilical cord mesenchymal stem cells for the treatment of uterine injury

Abstract Abnormal endometrial receptivity is a major cause of the failure of embryo transplantation, which may lead to infertility, adverse pregnancy, and neonatal outcomes. While hormonal treatment has dramatically improved the fertility outcomes in women with endometriosis, a substantial unmet need persists in the treatment. In this study, methacrylate gelatin (GelMA) and methacrylate sericin (SerMA) hydrogel with human umbilical cord mesenchymal stem cells (HUMSC) encapsulation was designed for facilitating endometrial regeneration and fertility restoration through in situ injection. The presented GelMA/10%SerMA hydrogel showed appropriate swelling ratio, good mechanical properties, and degradation stability. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell encapsulation ability of HUMSC. Further in vivo experiments demonstrated that GelMA/SerMA@HUMSC hydrogel could increase the thickness of endometrium and improve the endometrial interstitial fibrosis. Moreover, regenerated endometrial tissue was more receptive to transfer embryos. Summary, we believed that GelMA/SerMA@HUMSC hydrogel will hold tremendous promise to repair or regenerate damaged endometrium

Do testosterone and sex hormone-binding globulin affect cancer risk? A Mendelian randomization and bioinformatics study

AbstractUsing Mendelian Randomization (MR) and large-scale Genome-Wide Association Study (GWAS) data, this study aimed to investigate the potential causative relationship between testosterone and sex hormone-binding globulin (SHBG) levels and the onset of several cancers, including pathway enrichment analyses of single nucleotide polymorphisms (SNPs) associated with cancer allowed for a comprehensive bioinformatics approach, which offered a deeper biological understanding of these relationships. The results indicated that increased testosterone levels in women were associated with a higher risk of breast and cervical cancers but a lower risk of ovarian cancer. Conversely, increased testosterone was linked to lower stomach cancer risk for men, whereas high SHBG levels were related to decreased risks of breast and prostate cancers. The corresponding genes of the identified SNPs, as revealed by pathway enrichment analysis, were involved in significant metabolic and proliferative pathways. These findings emphasize the need for further research into the biological mechanisms behind these associations, paving the way for potential targeted interventions in preventing and treating these cancers