抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

Epithelial–mesenchymal transition (EMT) is a cellular programme that is known to be crucial for embryogenesis, wound healing and malignant progression. During EMT, cell–cell and cell–extracellular matrix interactions are remodelled, which leads to the detachment of epithelial cells from each other and the underlying basement membrane, and a new transcriptional programme is activated to promote the mesenchymal fate. In the context of neoplasias, EMT confers on cancer cells increased tumour-initiating and metastatic potential and a greater resistance to elimination by several therapeutic regimens. In this Review, we discuss recent findings on the mechanisms and roles of EMT in normal and neoplastic tissues, and the cell-intrinsic signals that sustain expression of this programme. We also highlight how EMT gives rise to a variety of intermediate cell states between the epithelial and the mesenchymal state, which could function as cancer stem cells. In addition, we describe the contributions of the tumour microenvironment in inducing EMT and the effects of EMT on the immunobiology of carcinomas. Epithelial–mesenchymal transition (EMT) is crucial for embryogenesis, wound healing and cancer development, and confers greater resistance to cancer therapies. This Review discusses the mechanisms of EMT and its roles in normal and neoplastic tissues, the contribution of cell-intrinsic signals and the microenvironment to inducing EMT, and its effects on the immunobiology of carcinomas.

New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer

Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.

Environment dominates over host genetics in shaping human gut microbiota

저작근 근전도에 관한 정상교합자와 ii급 부정교합자의 비교 연구

Background Poststroke depression and anxiety, independent predictor of poor functional outcomes, are common in the acute phase of stroke. Up to now, there is no fast-onset antidepressive and anxiolytic agents suitable for the management of acute stroke. ZL006-05, a dual-target analgesic we developed, dissociates nitric oxide synthase from postsynaptic density-95 while potentiates α2-containing γ-aminobutyric acid type A receptor. This study aims to determine whether ZL006-05 can be used as an antistroke agent with fast-onset antidepressant and anxiolytic effects. Methods Photothrombotic stroke and transient middle cerebral artery occlusion were induced in rats and mice. Infarct size was measured by TTC(2,3,5-Triphenyltetrazolium chloride) staining or Nissl staining. Neurological defects were assessed by four-point scale neurological score or modified Neurological Severity Scores. Grid-walking, cylinder and modified adhesive removal tasks were conducted to assess sensorimotor functions. Spatial learning was assessed using Morris water maze task. Depression and anxiety were induced by unpredictable chronic mild stress. Depressive behaviours were assessed by tail suspension, forced swim and sucrose preference tests. Anxiety behaviours were assessed by novelty-suppressed feeding and elevated plus maze tests. Pharmacokinetics, toxicokinetics and long-term toxicity studies were performed in rats. Results Administration of ZL006-05 in the acute phase of stroke attenuated transient and permanent ischaemic injury and ameliorated long-term functional impairments significantly, with a treatment window of 12 hours after ischemia, and reduced plasminogen activato-induced haemorrhagic transformation. ZL006-05 produced fast-onset antidepressant and anxiolytic effects with onset latency of 1 hour in the normal and CMS mice, had antidepressant and anxiolytic effects in stroke mice. ZL006-05 crossed the blood–brain barrier and distributed into the brain rapidly, and had a high safety profile in toxicokinetics and long-term toxicological studies. Conclusion ZL006-05 is a new neuroprotectant with fast-onset antidepressant and anxiolytic effects and has translational properties in terms of efficacy, safety and targeting of clinical issues.

/pdf/preclinical-evaluation-of-zl006-05-a-new-antistroke-drug-2g1iic0b.pdf

Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects

A visible-light-driven Mn-catalyzed C(sp3)-H amidation of diphenylmethane derivatives with dioxazolones was described. These reactions occur with an external photosensitizer-free process and feature satisfactory to good yields (up to 81%) under mild conditions. Mechanistic investigations revealed that the reaction proceeded via a Mn-acyl nitrene intermediate and that H-atom abstraction was the rate-determining step. Computational studies showed that the decarboxylation of dioxazolone depends on the conversion of ground sextet state dioxazolone-bounding Mn species to quartet spin state via visible-light irradiation.

Visible-Light-Promoted Mn-Catalyzed C(sp3)-H Amidation with Dioxazolones.

BACKGROUND
The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.


METHODS
The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.


RESULTS
A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54%-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.


CONCLUSION
The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence of the HELIOS stent for the evaluation of Interventional Cardiologists and Policymakers.


CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT03916432.

A novel biodegradable polymer-coated sirolimus-eluting stent: the 1-year results of the HELIOS registry.

In order to solve the current problems of the single effect of traditional sand control measures, the high cost of cleaning and maintenance, and the inability to provide long-term sustainable protection, this paper proposes a new type of sand barrier with the dual effect of sand conduction and sand blocking. Through field research of wind and sand disasters along the Hami-Lop Nor Railway, wind tunnel testing and numerical simulation of the new sand barrier, the wind velocity flow field, wind speed variation curve, wind protection effectiveness and sand barrier retention rate of the new sand barrier under different design parameters were studied. The results show that the sand barrier with 10H spacing (H is the height of the sand barrier) has the worst sand guiding and blocking effect. The sand barriers with 6H and 8H spacing have less difference in sand guiding and sand blocking effects. Both of them are better than the sand barrier with 10H spacing. The sand blocking effect of the new sand barrier was proportional to the angle (α). The sand guide effect was the opposite. When the angle is certain, the greater the wind speed and the better the sand guide effect. The results show that the new sand barrier is different from the traditional sand barrier in that it has both sand guiding and sand blocking functions, which provides a new method and scientific basis for sand damage control of Hami-Lop Nor Railway.

/pdf/optimization-study-on-the-design-parameters-of-sand-barriers-2ls5z7h6.pdf

Optimization Study on the Design Parameters of Sand Barriers along the Hami-Lop Nor Railway Line

Highly exposed surfaces of anatase TiO2 crystals are of interest due to their excellent photogenerated electron–hole pair separation effect and high photocatalytic activity. In this work, a Z-mechanism biosensor with reduced graphene oxide (rGO) and anatase TiO2 nanocrystals combined with PDA (TiO2/rGO/PDA) was successfully synthesized. rGO was combined with the co-exposed (001) and (101) facets of TiO2 nanocrystals to construct a Z-mechanism in which rGO acts as an electron transport medium and provides a channel for the transfer of electrons, resulting in TiO2 nanocrystals with high photoelectron–hole pair separation efficiency and strong redox ability. The coated PDA polymer not only could absorb visible light but also has good stability and biocompatibility, which helps to increase the adsorption of target enzyme molecules. The TiO2/rGO/PDA/GOx biosensor with the Z-mechanism displays the sensitivity of 13.82 μA mM−1 cm−2 in 0.1M PBS solution (pH = 7.4) with a linear range of 0–3 mM and the LOD of 0.034 µM. In general, the application of the Z-mechanism in biosensors would provide a new orientation for the design of biosensors.

Fei Li

Papers

Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects

Visible-Light-Promoted Mn-Catalyzed C(sp3)-H Amidation with Dioxazolones.

A novel biodegradable polymer-coated sirolimus-eluting stent: the 1-year results of the HELIOS registry.

Optimization Study on the Design Parameters of Sand Barriers along the Hami-Lop Nor Railway Line

Graphene-assisted titanium dioxide Z-mechanism photoelectrode as enzymatic glucose biosensor