A unified global genotyping framework of dengue virus serotype-1 for a stratified coordinated surveillance strategy of dengue epidemics

Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.

Hymecromone:a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression

Currently,there is no effective drugs for treating clinically COVID-19 except dexamethasone.We previously revealed that human identical sequences of SARS-CoV-2 promote the COVID-19 progression by upregulating hyaluronic acid(HA).As the inhibitor of HA synthesis,hymecromone is an approved prescription drug used for treating biliary spasm.Here,we aimed to investigate the relation between HA and COVID-19,and evaluate the therapeutic effects of hymecromone on COVID-19.Firstly,HA was closely relevant to clinical parameters,including lymphocytes(n=158;r=−0.50;P<0.0001),C-reactive protein(n=156;r=0.55;P<0.0001),D-dimer(n=154;r=0.38;P<0.0001),and fibrinogen(n=152;r=0.37;P<0.0001),as well as the mass(n=78;r=0.43;P<0.0001)and volume(n=78;r=0.41;P=0.0002)of ground-glass opacity,the mass(n=78;r=0.48;P<0.0001)and volume(n=78;r=0.47;P<0.0001)of consolidation in patient with low level of hyaluronan(HA<48.43 ng/mL).Furthermore,hyaluronan could directly cause mouse pulmonary lesions.Besides,hymecromone remarkably reduced HA via downregulating HAS2/HAS3 expression.Moreover,89%patients with hymecromone treatment had pulmonary lesion absorption while only 42%patients in control group had pulmonary lesion absorption(P<0.0001).In addition,lymphocytes recovered more quickly in hymecromone-treated patients(n=8)than control group(n=5)(P<0.05).These findings suggest that hymecromone is a promising drug for COVID-19 and deserves our further efforts to determine its effect in a larger cohort.

Mutually exclusive epigenetic modification on SIX6 with hypermethylation for precancerous stage and metastasis emergence tracing

Dear Editor,Aberrant DNA methylation gets involved in cancer initiation,progression,and recurrence,which in turn makes it an ideal cancer biomarker.Various methylation markers or their panels have been developed in diverse cancer types.However,the model-constructing based marker mining strategy and incompatibility of application have greatly impeded their ways to clinic.Thus,single methylation marker applicable to all/most cancer types and multiple clinical scenarios is desperately needed.The hope came from the unexpected observation that HIST1H4F was universally hypermethylated in all 17 cancer types;thus,we raised the concept of“Universal Cancer Only Marker(UCOM)”and established a paradigm for discovery and clinical application of UCOM.1 Recently,a novel UCOM,hypermethylated PCDHGB7,was identified and found to advance cervical cancer(CC)screening to the precancerous stage.2 During the screening of UCOM,we discerned a bunch of cancer cell-differentially methylated regions.1 Among them,sine oculis(SIX)homeobox family of transcription factors,which were found to function as tumorigenesis regulator by promoting epithelial-to-mesenchymal transition and metastasis recently in addition to their traditional roles in tissue formation and organogenesis,3 sparked our special attention.Herein,we interrogate whether SIX6 methylation could serve as a novel UCOM and its potential applications.

Identification and validation of predictive factors for progression to severe COVID-19 pneumonia by proteomics

Dear Editor,Recent study showed that around 80%of coronavirus disease-19(COVID-19)patients are moderate cases who will recover with or without conventional treatment,while the remaining 20%developed severe disease requiring intensive care.1 Early and accurate screening of new COVID-19 patients to identify those who will develop severe disease will facilitate decision-making on appropriate treatment regimens and reasonable allocation of limited healthcare resources.Therefore,novel predictive factors for disease progress from moderate to severe are urgently needed.

Epidemiological and Clinical Features of Patients with Scrub Typhus—Guangzhou City,Guangdong Province,China,2012–2018

Summary What is already known about this topic?Scrub typhus(ST)causes public health challenges in the“tsutsugamushi triangle”in the Asia-Pacific area greater than 13 million square kilometers,affecting an estimated one million people each year.What is added by this report?A retrospective study based on 4,501 hospitalized patients with ST in Guangzhou City,China,described the epidemiological and clinical characteristics,laboratory findings of ST.