A cross-talk between epithelium and endothelium mediates human alveolar–capillary injury during SARS-CoV-2 infection

COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection     

Semiparametric Regression in Size-Biased Sampling

Summary .  Size-biased sampling arises when a positive-valued outcome variable is sampled with selection probability proportional to its size. In this article, we propose a semiparametric linear regression model to analyze size-biased outcomes. In our proposed model, the regression parameters of covariates are of major interest, while the distribution of random errors is unspecified. Under the proposed model, we discover that regression parameters are invariant regardless of size-biased sampling. Following this invariance property, we develop a simple estimation procedure for inferences. Our proposed methods are evaluated in simulation studies and applied to two real data analyses.     

Tooth Eruption Results from Bone Remodelling Driven by Bite Forces Sensed by Soft Tissue Dental Follicles: A Finite Element Analysis

Intermittent tongue, lip and cheek forces influence precise tooth position, so we here examine the possibility that tissue remodelling driven by functional bite-force-induced jaw-strain accounts for tooth eruption. Notably, although a separate true ‘eruptive force’ is widely assumed, there is little direct evidence for such a force. We constructed a three dimensional finite element model from axial computerized tomography of an 8 year old child mandible containing 12 erupted and 8 unerupted teeth. Tissues modelled included: cortical bone, cancellous bone, soft tissue dental follicle, periodontal ligament, enamel, dentine, pulp and articular cartilage. Strain and hydrostatic stress during incisive and unilateral molar bite force were modelled, with force applied via medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain was maximal in the soft tissue follicle as opposed to surrounding bone, consistent with follicle as an effective mechanosensor. Initial numerical analysis of dental follicle soft tissue overlying crowns and beneath the roots of unerupted teeth was of volume and hydrostatic stress. To numerically evaluate biological significance of differing hydrostatic stress levels normalized for variable finite element volume, ‘biological response units’ in Nmm were defined and calculated by multiplication of hydrostatic stress and volume for each finite element. Graphical representations revealed similar overall responses for individual teeth regardless if incisive or right molar bite force was studied. There was general compression in the soft tissues over crowns of most unerupted teeth, and general tension in the soft tissues beneath roots. Not conforming to this pattern were the unerupted second molars, which do not erupt at this developmental stage. Data support a new hypothesis for tooth eruption, in which the follicular soft tissues detect bite-force-induced bone-strain, and direct bone remodelling at the inner surface of the surrounding bony crypt, with the effect of enabling tooth eruption into the mouth.     

山岳型乡村旅游地“三生”空间演变及优化——德庆金林水乡的案例实证

以德庆县金林水乡为例,采用参与式观察和空间统计法,选取2000、2008年和2018年3个时段分析旅游发展对山岳型乡村旅游地"三生"空间的影响,并探讨了金林水乡"三生"空间的发展瓶颈及优化路径。研究发现:(1)旅游开发前,金林水乡土地结构与用地功能单一且呈片状分布;村落呈现传统乡村风貌,基础设施不健全;空间形态变化稳定,扩张缓慢。(2)旅游开发后,土地利用类型多样化,出现新型复合用地;土地功能利用复杂化,以服务旅游业为主;村庄景观风貌现代化,生活空间更加宜居。(3)旅游开发前后对比可得,土地平面占地规模化,空间用地以居民点为核心,呈圈层状向外围扩张;生产-生活-生态空间相互转化,乡村聚落重构特征较为显著;村落景观风貌的变化较大,呈现城镇化趋势。(4)金林水乡"三生"空间演化与旅游发展存在的问题表现在生产用地效率不高,生活用地质量较低,生态空间不断萎缩,在旅游产业发展上表现为旅游产品单一且缺乏创新,旅游服务功能不完善等。为此从生活空间的提质、生产空间增效、生态空间保护、旅游产业创新以及土地利用五方面提出优化建议。     

Rapid improvement of rice eating and cooking quality through gene editing toward glutelin as target

Rice eating and cooking quality (ECQ) is a major concern of breeders and consumers, determining market competitiveness worldwide. Rice grain protein content (GPC) is negatively related to ECQ, making it possible to improve ECQ by manipulating GPC. However, GPC is genetically complex and sensitive to environmental conditions; therefore, little progress has been made in traditional breeding for ECQ. Here, we report that CRISPR/Cas9-mediated knockout of genes encoding the grain storage protein glutelin rapidly produced lines with downregulated GPC and improved ECQ. Our finding provides a new strategy for improving rice ECQ.