The Free Triiodothyronine, Gamma-Glutamyl Transpeptidase and Spontaneous Bacterial Peritonitis Index: A Novel Model for Predicting 1-Year Mortality in Patients with HBV-Related Hepatic Encephalopathy.

Background and Aims: Hepatic encephalopathy (HE) is characterized by neuropsychiatric manifestations in patients with decompensated cirrhosis (DC) and/or liver failure. This study aimed to investigate the predictive value of thyroid hormone in patients with HE. Methods: Patients with DC and HE were enrolled, and multivariate logistic analysis was conducted to analyze the risk factors for 1-year mortality. Results: Among the 81 patients with HBV-related DC and HE, 9 (11.1%) died within 3 months, and 15 (18.5%) died within the first year. More patients with FT3 < 3.5pmol/L had ascites (33.3% vs 8.9%, P<0.01) and higher model for end-stage liver disease (MELD) (Z=3.669, P<0.01). Additionally, free triiodothyronine (FT3) levels were lower in the non-survivor group (P<0.01). FT3 exhibited a negative correlation with international normalized ratio and MELD (both P<0.05). Multivariate analysis revealed that FT3, gamma-glutamyl transpeptidase (GGT), and spontaneous bacterial peritonitis (SBP) were independent risk factors for 1-year mortality of HE. A new model incorporating FT3, GTT, and SBP demonstrated superiority to MELD based on the AUROC (0.9 and 0.752, P=0.04). Conclusion: Low FT3, but not thyroid-stimulating hormone and free tetraiodothyronine, was identified as an independent risk factor for 1-year mortality in patients with DC and HE. The newly proposed prognostic model, which includes FT3, GTT, and SBP, holds significant predictive value.

Needle retaining after electroacupuncture combined with cognitive training for post-stroke cognitive impairment: a multi-center randomized controlled trial. / ç”µé’ˆåŽç•™é’ˆè”åˆè®¤çŸ¥è®­ç»ƒæ²»ç–—è„‘å’ä¸­åŽè®¤çŸ¥åŠŸèƒ½éšœç¢ï¼šå¤šä¸­å¿ƒéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the efficacy of needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training in the treatment of post-stroke cognitive impairment (PSCI). METHODS: A total of 206 patients with PSCI were randomized into a needle retaining group (103 cases, 9 cases dropped out) and an electroacupuncture group (103 cases, 6 cases dropped out). In addition to the conventional basic medical treatment and the rehabilitation treatment, in the needle retaining group, electroacupuncture at Shenting (GV 24) and Baihui (GV 20) was applied, with continuous wave of 50 Hz in the first 15 min and with disperse-dense wave of 2 Hz/50 Hz in the last 15 min, the needles were continuously retained for 1 h after electroacupuncture, during which cognitive training was adopted; in the electroacupuncture group, cognitive training was performed after the same electric stimulation exerted for 30 min, without additional needles retaining. The treatment was given once a day, 5 times a week for totally 8 weeks in the two groups. Before and after 8-week treatment, the TCM syndrome score was observed; before and after 4,8-week treatment, the scores of mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and ability of daily living were observed in the two groups. The clinical efficacy of the two groups was evaluated after 8-week treatment. RESULTS: After 8-week treatment, the TCM syndrome scores were increased compared with those before treatment in both groups (P<0.05); the TCM syndrome score in the needle retaining group was higher than that in the electroacupuncture group (P<0.05).After 4,8-week treatment, the scores of MMSE, MoCA and ability of daily living were increased compared with those before treatment in both groups (P<0.05); MMSE, MoCA scores after 4,8-week treatment and ability of daily living score after 8-week treatment in the needle retaining group were higher than those in the electroacupuncture group (P<0.05). The total effective rate was 90.4% (85/94) in the needle retaining group, which was superior to 82.5% (80/97) in the electroacupuncture group (P<0.05). CONCLUSIONS: Both needle retaining after electroacupuncture combined with cognitive training and electroacupuncture combined with cognitive training can effectively treat PSCI, improve the clinical symptom, cognitive function and ability of daily living in PSCI patients. Needle retaining after electroacupuncture combined with cognitive training has a better therapeutic effect.

Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.

Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.

Organocatalytic intramolecular (4 + 2) annulation of enals with ynamides: atroposelective synthesis of axially chiral 7-aryl indolines.

Catalytic enantioselective transformation of alkynes has become a powerful tool for the synthesis of axially chiral molecules. Most of these atroposelective reactions of alkynes rely on transition-metal catalysis, and the organocatalytic approaches are largely limited to special alkynes which act as the precursors of Michael acceptors. Herein, we disclose an organocatalytic atroposelective intramolecular (4 + 2) annulation of enals with ynamides. This method allows the efficient and highly atom-economical preparation of various axially chiral 7-aryl indolines in generally moderate to good yields with good to excellent enantioselectivities. Computational studies were carried out to elucidate the origins of regioselectivity and enantioselectivity. Furthermore, a chiral phosphine ligand derived from the synthesized axially chiral 7-aryl indoline was proven to be potentially applicable to asymmetric catalysis.

Global, regional, and national burdens of myocarditis, 1990-2019: systematic analysis from GBD 2019 : GBD for myocarditis.

OBJECTIVES: Myocarditis, a health-threatening heart disease, is attracting increasing attention. This systematic study was conducted to study the prevalence of disease through the trends of incidence, mortality, disability-adjusted life years (DALYs) over the last 30 years, which would be helpful for the policymakers to better the choices for reasonable decisions. METHODS: The global, regional, and national burdens of myocarditis from 1990-2019 were analyzed by using the 2019 Global Burden of Disease (GBD) database. This study on myocarditis produced new findings according to age, sex, and Social-Demographic Index (SDI) by investigating DALYs, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and corresponding estimated annual percentage change (EAPC). RESULTS: The number of myocarditis incidence increased by 62.19%, from 780,410 cases in 1990 to 1,265,770 cases in 2019. The ASIR decreased by 4.42% (95%CI, from -0.26% to -0.21%) over the past 30 years. The number of deaths from myocarditis increased by 65.40% from 19,618 in 1990 to 324,490 in 2019, but the ASDR was relatively stable over the investigated period. ASDR increased in low-middle SDI regions (EAPC=0.48; 95%CI, 0.24 to 0.72) and decreased in low SDI regions (EAPC=-0.97; 95%CI, from -1.05 to -0.89). The age-standardized DALY rate decreased by 1.19% (95%CI, from -1.33% to -1.04%) per year. CONCLUSIONS: Globally, the ASIR and DALY for myocarditis decreased and the ASDR was stable over the past 30 years. The risk of incidences and death cases increased with age. Measures should be taken to control the risk of myocarditis in high-burden regions. Medical supplies should be improved in the high-middle SDI regions and middle SDI regions to reduce the deaths from myocarditis in these regions.

Clinical outcomes of recommended active pharmacotherapy agents from NICE guideline for post-traumatic stress disorder: Network meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA). METHODS: Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022. RESULTS: Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score. CONCLUSION: The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.

Solubilization of luteolin in PVP40 solid dispersion improves inflammation-induced insulin resistance in mice.

Our previous studies have confirmed that luteolin (LU) has a good therapeutic effect on obesity and its complications. However, due to its poor water solubility, the bioavailability is low with limited clinical application. Therefore, the water-soluble solid dispersions (SD) of luteolin were prepared with polyvinylpyrrolidone (PVP) (K10, K40 & K90) by solvent evaporation. The polyvinylpyrrolidone K40 (PVP40) was selected as the ideal carrier to formulate polyvinylpyrrolidone K40-luteolin solid dispersion (PVP40-LU SD), thereby the solubility of luteolin increased about 250 times compared to the pure luteolin, without changing its physical stability and activity. The crystallinity of luteolin was reduced after the formation of solid dispersion, and no strong drug-polymer interactions were observed. This prepared water-soluble luteolin inhibits the polarization of inflammatory macrophages by decreasing the expression of pro-inflammatory cytokine genes interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in vitro. Moreover, it can improve glucose tolerance and insulin sensitivity quickly after intraperitoneal injection in mice.

Mapping the potential for offshore aquaculture of salmonids in the Yellow Sea.

Mariculture has been one of the fastest-growing global food production sectors over the past three decades. With the congestion of space and deterioration of the environment in coastal regions, offshore aquaculture has gained increasing attention. Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss) are two important aquaculture species and contribute to 6.1% of world aquaculture production of finfish. In the present study, we established species distribution models (SDMs) to identify the potential areas for offshore aquaculture of these two cold-water fish species considering the mesoscale spatio-temporal thermal heterogeneity of the Yellow Sea. The values of the area under the curve (AUC) and the true skill statistic (TSS) showed good model performance. The suitability index (SI), which was used in this study to quantitatively assess potential offshore aquaculture sites, was highly dynamic at the surface water layer. However, high SI values occurred throughout the year at deeper water layers. The potential aquaculture areas for S. salar and O. mykiss in the Yellow Sea were estimated as 52,270 ± 3275 (95% confidence interval, CI) and 146,831 ± 15,023 km2, respectively. Our results highlighted the use of SDMs in identifying potential aquaculture areas based on environmental variables. Considering the thermal heterogeneity of the environment, this study suggested that offshore aquaculture for Atlantic salmon and rainbow trout was feasible in the Yellow Sea by adopting new technologies (e.g., sinking cages into deep water) to avoid damage from high temperatures in summer. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00141-2.

Asymmetric dearomatization catalysed by chiral Brønsted acids via activation of ynamides.

Chiral Brønsted acid-catalysed asymmetric synthesis has received tremendous interest over the past decades, and numerous efficient synthetic methods have been developed based on this approach. However, the use of chiral Brønsted acids in these reactions is mostly limited to the activation of imine and carbonyl moieties, and the direct activation of carbon-carbon triple bonds has so far not been invoked. Here we show that chiral Brønsted acids enable the catalytic asymmetric dearomatization reactions of naphthol-, phenol- and pyrrole-ynamides by the direct activation of alkynes. This method leads to the practical and atom-economic construction of various valuable spirocyclic enones and 2H-pyrroles that bear a chiral quaternary carbon stereocentre in generally good-to-excellent yields with excellent chemo-, regio- and enantioselectivities. The activation mode of chiral Brønsted acid catalysis revealed in this study is expected to be of broad utility in catalytic asymmetric reactions that involve ynamides and the related heteroatom-substituted alkynes.

Whole-genome resequencing of Japanese whiting ( Sillago japonica) provide insights into local adaptations.

The genetic adaptations of various organisms to heterogeneous environments in the northwestern Pacific remain poorly understood. Heterogeneous genomic divergence among populations may reflect environmental selection. Advancing our understanding of the mechanisms by which organisms adapt to different temperatures in response to climate change and predicting the adaptive potential and ecological consequences of anthropogenic global warming are critical. We sequenced the whole genomes of Japanese whiting ( Sillago japonica) specimens collected from different latitudinal locations along the coastal waters of China and Japan to detect possible thermal adaptations. Using population genomics, a total of 5.48 million single nucleotide polymorphisms (SNPs) from five populations revealed a complete genetic break between the Chinese and Japanese groups, which was attributed to both geographic distance and local adaptation. The shared natural selection genes between two isolated populations (i.e., Zhoushan and Ise Bay/Tokyo Bay) indicated possible parallel evolution at the genetic level induced by temperature. These genes also indicated that the process of temperature selection on isolated populations is repeatable. Moreover, we observed natural candidate genes related to membrane fluidity, possibly underlying adaptation to cold environmental stress. These findings advance our understanding of the genetic mechanisms underlying the rapid adaptations of fish species. Species distribution projection models suggested that the Chinese and Japanese groups may have different responses to future climate change, with the former expanding and the latter contracting. The findings of this study enhance our understanding of genetic differentiation and adaptation to changing environments.

The complete plastome of Andreaea rupestris Hedw. (Andreaeaceae, Bryophyta).

Andreaea rupestris Hedw., one of the lantern mosses, is the lectotype of the genus Andreaea Hedw. (Andreaeaceae). Here we present its complete plastome. The plastome of A. rupestris is successfully assembled from raw reads sequenced by HiSeq X ten system. Its total length is 135,214 bp consisting of four regions: large single copy (LSC) region (92,780 bp), small single copy (SSC) region (21,102 bp), and two inverted repeat regions (IRs; 10,666 bp per each). It contains 134 genes (88 coding genes, 8 rRNAs, and 38 tRNAs). The overall GC content is 30.3% and in the LSC, SSC, and IR regions are 27.5%, 26.5%, and 46.2%, respectively. The present data will be an important sequence resource for further studies on the important early diverging lineage of mosses.

Hsa_circ_0001696 modulates cell proliferation and migration in colorectal cancer.

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA molecules that are extensively expressed in a variety of species. Recently, increasing evidence suggests that circRNAs have vital functions indifferent types of human cancer, such as gastric cancer, papillary thyroid cancer and lung cancer. However, the roles of circRNAs in the development of colorectal cancer (CRC) remain unclear. The present study aimed to determine the molecular mechanism underlying hsa_circ_0001696 on the proliferation and migration of CRC cells. Reverse transcription-quantitative PCR analysis was performed to detect hsa_circ_0001696 expression in 18 paired CRC tissues and matched adjacent normal tissues. RNA interference was also performed to decrease hsa_circ_0001696 expression, and its biological effects were further assessed via flow cytometry, wound healing, colony formation and western blot assays. The results demonstrated that hsa_circ_0001696 expression was significantly lower in CRC tissues compared with adjacent normal tissues. Furthermore, hsa_circ_0001696 knockdown promoted cell proliferation and migration, and the number of cell colonies significantly increased. In addition, western blot analysis demonstrated that the protein expression levels of cyclin-dependent kinase 4 (CDK4), cyclin D, cyclin E and matrix metalloproteinase 9 (MMP9) increased. Taken together, the results of the present study demonstrated that hsa_circ_0001696 expression was downregulated in CRC tissues, and inhibition of hsa_circ_0001696 promoted cell proliferation and migration by regulating the levels of CDK4, cyclin D, cyclin E and MMP9.

Effectiveness, Acceptability and Safety of Pharmaceutical Management for Combat-Related PTSD in Adults Based on Systematic Review of Twenty-Two Randomized Controlled Trials.

Objective: This study assessed the efficacy, acceptability, and safety of pharmaceutical management for combat-related post-traumatic stress disorder (PTSD) to provide a clinical decision-making basis for clinicians. Method: A comprehensive search was conducted using Ovid MEDLINE, Ovid EMBASE, Cochrane Library, Scopus, ScienceDirect, and Web of Science for randomized controlled trails (RCTs), which reported pharmaceutical management and placobo for adults with combat-related PTSD, that were published until April 21, 2021. The effectiveness, acceptability, and adverse events (AEs), were designed as interested outcomes. The change in total symptoms of combat-related PTSD according to the clinician rating scale was defined as primary outcome, and the others were defined as secondary outcomes. Results: Twenty-two RCTs with 1,221 patients were involved. Compared with placebo, overall active comparators had statistical differences for all outcomes, including the change in total symptoms of combat-related PTSD [SMD = -0.36, 95%CI (-0.62,-0.09)], depression [SMD = -0.28, 95%CI (-0.45,-0.10)], anxiety [SMD = -0.44, 95%CI (-0.64,-0.23)], re-experience [SMD = -0.33, 95%CI (-0.52,-0.13)], avoidance [SMD = -0.24, 95%CI (-0.43,-0.05)], and hyper-arousal [SMD = -0.26, 95%CI (-0.48,-0.03)]. Compared with the placebo, in terms of acceptability, overall active comparators did not significantly decrease all-cause discontinuance rates [RR = 0.97, 95%CI (0.78,1.20)], and the significance decreased due to AEs [RR = 2.42, 95%CI (1.41,4.13)]. Nevertheless, overall there was no statistically significant difference for overall AEs, including somnolence, sedation, dizziness, paresthesia, anxiety, blurred vision, generalized anxiety disorder, and sleep disturbance. All funnel plots were symmetrical and no publication bias was found. Conclusion: Active drugs, especially amitriptyline, imipramine, and quetiapine, had a positive effect on the improvement of combat-related PTSD symptoms. Despite there being no significant increase in the AEs of the active drugs, the fact that the discontinuation rates of these drugs, including risperidone, imipramine, and topiramate, were increased deserves attention. Furthermore, as active drugs were effective across ethnic groups and battlefields, active drug regimens were revealed to be more appropriate for treating people with symptoms of extreme severe PTSD (≥80) or PTSD that is at least 8 weeks old. In addition, current evidence was from adults under 60 years of age and male combat-related PTSD. Whether this evidence can be extended to other populations of combat-related PTSD needs to be confirmed by subsequent high-quality, large-sample studies.

Rhodium-Catalyzed Tandem Reaction of Isocyanides with Azides and Oxygen Nucleophiles: Synthesis of Isoureas.

A novel rhodium-catalyzed tandem reaction of isocyanides with azides and various oxygen nucleophiles has been developed. The reaction provides a simple and highly efficient one-pot synthesis of various N-sulfonyl/acylisoureas with broad substrate scope in an atom-economical manner from readily available starting materials in a highly stereoselective manner.

Genetic polymorphisms of exon 1 of MBL2 contribute to tuberculosis risk especially in Asian populations: an updated meta-analysis of 26 studies.

BACKGROUND: Evidence suggests that genetic variations of exon 1 of mannose-binding lectin 2 (MBL2) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between MBL2 exon 1 polymorphisms (rs1800450, rs1800451, and rs5030737) and TB risk, but yielded inconclusive results. METHOD: We conducted this meta-analysis of 26 eligible case-control studies that included 7952 cases and 9328 controls to identify the strength of association. Odds ratio (OR) and 95% CI were used to evaluate the strength of association. Statistical analyses were performed by using STATA 12.1. RESULTS: We found a statistically significant correlation between MBL2 exon 1 polymorphisms and increased TB risk among three models: allele model (O vs A: OR =1.18, 95% CI: 1.01-1.38, Pheterogeneity<0.0001, I2=85.8%), homozygote comparison (OO vs AA: OR =1.49, 95%CI: 1.02-2.18, Pheterogeneity<0.0001, I2=79.1%), dominant model (AO/OO vs AA: OR =1.20, 95% CI: 1.01-1.43, Pheterogeneity<0.0001, I2=83.5%), especially in studies based on Asian populations among five models: allele model (O vs A: OR =1.29, 95% CI: 1.11-1.51, Pheterogeneity<0.0001, I2=66.0%), homozygote comparison (OO vs AA: OR =1.67, 95% CI: 1.09-2.55, Pheterogeneity=0.008, I2=54.2%), heterozygote comparison (AO vs AA: OR =1.26, 95% CI: 1.05-1.50, Pheterogeneity=0.001, I2=62.9%), dominant model (AO/OO vs. AA: OR =1.31, 95% CI: 1.10-1.56, Pheterogeneity=0.001, I2=64.2%), and recessive model (OO vs AO/AA: OR =1.50, 95% CI: 1.01-2.22, Pheterogeneity=0.023, I2=48.0%). Meta-regression results revealed that source of controls (p=0.009), but not ethnicity (p=0.687), genotyping method (p=0.231), and sample size (p=0.451) contributed to the source of heterogeneity. CONCLUSION: This meta-analysis suggests that MBL2 exon 1 polymorphisms may contribute to TB risk, especially in Asian populations.

Zinc-catalyzed reaction of isoxazoles with thioynol ethers involving an unprecedented 1,2-sulfur migration.

A novel zinc-catalyzed reaction of isoxazoles with thioynol ethers involving an unprecedented 1,2-sulfur migration has been developed, which represents the first example of a non-noble metal-catalyzed reaction between isoxazoles and alkynes. This method allows the facile and atom-economical synthesis of a range of valuable ß-keto enamides. Moreover, the computational study provides further evidence for the feasibility of the proposed reaction mechanism.

[Research on pharmacometabolomics].

Pharmacometabolomics is a new and rapidly growing field in life science, which use metabolomics for studying drug effects and variation in drug response. Recently, it has been widely used in individualized medicine research. The research process of pharmacometabolomic can be divided into three parts: metabolomic study of baseline samples, drug response analysis after drug administration and statistical analysis. By combining the baseline information on metabotype of an individual with the drug response phenotype after drug exposure, pharmacometabolomic method can be used to predict the efficacy and toxicity of drugs, which providing the theoretical basis for individualized medical treatment. In this paper, we give an overview of present studies in the application of pharmacometabolomics for predicting the individualized drug response. Besides, we also summarized the specific research processes and pharmacometabolomic methods.

Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

HLA-B*07, HLA-DRB1*07, HLA-DRB1*12, and HLA-C*03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 high-resolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B*07, DRB1*07, DRB1*12, and C*03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B*07 and DRB1*07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novel biological connection between HLA alleles and obesity.

Facile synthesis of α-alkoxyl amides via scandium-catalyzed oxidative reaction between ynamides and alcohols.

A novel and efficient scandium-catalyzed oxidative reaction between ynamides and alcohols for the facile synthesis of various α-alkoxyl amides is reported in this paper. The reaction avoids the need for the use of α-diazo carbonyls which are unstable and may cause some safety concerns. Instead, by using alkynes as the starting materials, this protocol features readily available substrates, compatibility with a broad range of functional groups, simple procedure, mild reaction conditions, and high chemoselectivity.