Study on current status and climatic characteristics of wine regions in China

The aim of this paper is to improve the knowledge of the current status and climatic characteristics of Chinese wine regions. An investigation of Chinese winegrowing regions, which concerned the distribution, area and cultivars, was conducted using "questionnaires + expert consultation + available literature". On the basis of the results of the investigation, a map was drawn to depict the distribution of Chinese wine regions. Furthermore, observation records of weather stations located within winegrowing zones during 1982–2011 were employed to analyze the climatic characteristics of each region by using the climatic indices of frost-free season (FFS), dryness index (DI), and extremely low temperature (ELT). According to the findings of the investigation, wine grapes have been widely cultivated in 179 counties of China, with a total cultivation area of 163,200 ha. 'Cabernet Sauvignon' was the most widely cultivated variety. The analysis of the climatic characteristics revealed a regional difference within and between wine regions. Moreover, most wine regions were suitable for wine production in terms of the climatic indices, which in turn verified the applicability of the climate indices system

3D-printed integrative probeheads for magnetic resonance

射频探头前端作为核磁共振设备的核心部件之一，极大程度的决定着系统实验性能的优劣。探头前端通常由射频线圈、射频电路及样品检测管道等部分组成。现有的射频线圈制作技术主要是通过手工或机械手段按照所需的线圈形状进行绕制。但是，当线圈结构较为复杂、不规则，或体积尺寸较小时，常规绕制方法便难以满足结构设计和制造的精度需求，因此造成线圈性能的劣化，增大检测区域的射频场不均匀性，对核磁共振检测产生负面影响。本研究中，利用3D打印熔融沉积制造或光敏树脂选择性固化技术精确加工出一体化磁共振探头前端，使用常温液态金属填充线圈模型管路形成射频线圈，搭建出稳定的一体化磁共振射频探头。利用高精度3D打印和液态金属灌注技术制备出包含有射频线圈和定制化样品管道结构在内的一体化磁共振射频探头前端，克服了传统磁共振三维微型线圈成型困难、与样品腔匹配程度差等问题，提高了探头的信噪比，为定制化的磁共振检测提供了新思路。 该工作由厦门大学电子科学与技术学院陈忠教授、游学秋副研究员和孙惠军高级工程师共同指导完成，博士研究生谢君尧为论文第一作者。厦门大学电子科学与技术学院黄玉清高级工程师、王忻昌副教授、倪祖荣助理教授、硕士研究生张德超，化学化工学院杨朝勇教授、博士研究生李星锐，萨本栋微米纳米科学技术研究院陈宏教授为合作作者。【Abstract】Magnetic resonance (MR) technology has been widely employed in scientific research, clinical diagnosis and geological survey. However, the fabrication of MR radio frequency probeheads still face difficulties in integration, customization and miniaturization. Here, we utilized 3D printing and liquid metal filling techniques to fabricate integrative radio frequency probeheads for MR experiments. The 3D-printed probehead with micrometer precision generally consists of liquid metal coils, customized sample chambers and radio frequency circuit interfaces. We screened different 3D printing materials and optimized the liquid metals by incorporating metal microparticles. The 3D-printed probeheads are capable of performing both routine and nonconventional MR experiments, including in situ electrochemical analysis, in situ reaction monitoring with continues-flow paramagnetic particles and ions separation, and small-sample MR imaging. Due to the flexibility and accuracy of 3D printing techniques, we can accurately obtain complicated coil geometries at the micrometer scale, shortening the fabrication timescale and extending the application scenarios.The work is supported by the National Natural Science Foundation of China (Grants U1632274, 11761141010, U1805261, 11475142, 22073078, and 61801411), and China Postdoctoral Science Foundation (2017M622075).研究工作得到国家自然科学基金、中国博士后科学基金等项目支持

Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro

A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here we demonstrate that CRISPR-Cas13d offers a broad-spectrum antiviral (BSA) to inhibit many SARS-CoV-2 variants and diverse human coronavirus strains with >99% reduction of the viral titer. We show that Cas13d-mediated coronavirus inhibition is dependent on the crRNA cellular spatial colocalization with Cas13d and target viral RNA. Cas13d can significantly enhance the therapeutic effects of diverse small molecule drugs against coronaviruses for prophylaxis or treatment purposes, and the best combination reduced viral titer by over four orders of magnitude. Using lipid nanoparticle-mediated RNA delivery, we demonstrate that the Cas13d system can effectively treat infection from multiple variants of coronavirus, including Omicron SARS-CoV-2, in human primary airway epithelium air-liquid interface (ALI) cultures. Our study establishes CRISPR-Cas13 as a BSA which is highly complementary to existing vaccination and antiviral treatment strategies

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Genetic architecture of subcortical brain structures in 38,851 individuals

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development