Case Report: HAVCR2 mutation-associated Hemophagocytic lymphohistiocytosis

Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH

Study on the substitutability of nighttime light data for SDG indicators: a case study of Yunnan Province

Introdution: One crucial method to attain Sustainable Development Goals (SDGs) involves timely adjustment of development policies, promoting the realization of SDGs through a time-series assessment of the degree of accomplishment. In practical applications, data acquisition is a significant constraint in evaluating the SDGs, not only in China but across the globe. Hence, expanding data channels and exploring the feasibility of various data sources for sustainable development assessment are effective strategies to tackle the challenge of data acquisition.Methods: In light of this issue, this study selected Nighttime Light Data, a remote sensing data source closely linked to human social activities, as an alternative data source. Using Yunnan Province as an example, 16 localized indicators of social, economic, and environmental types were chosen. These indicators were then subjected to a correlation analysis with the Total Nighttime Light Index (TNLI). The relationships between different types of indicators and TNLI were analyzed at both temporal and spatial scales, thus identifying the indicators for which TNLI could serve as a suitable substitute measure.Results: The study indicates that when the SDG indicators are classified into economic, social and environmental categories, the total value of nighttime light presents a significant correlation and substitutability with economic indicators; significantly correlated with some social indicators, it can reveal the weak links in the development of underdeveloped areas; it is not significantly correlated with environmental indicators, while a trend correlation exists, which can provide some reference values.Discussion: This study has demonstrated the feasibility of using Nighttime Light Data for sustainable development assessment. It provides a novel evaluation method for countries that, despite a lack of resources for conducting sustainable development assessments, have a greater need for such assessments due to their lower economic development. Furthermore, a multitude of assessment methods can be developed based on Nighttime Light Data

Global prioritization of endemic zoonotic diseases for conducting surveillance in domestic animals to protect public health

Zoonotic diseases (zoonoses) originating from domestic animals pose a significant risk to people's health and livelihoods, in addition to jeopardizing animal health and production. Effective surveillance of endemic zoonoses at the animal level is crucial to assessing the disease burden and risk, and providing early warning to prevent epidemics in animals and spillover to humans. Here we aimed to prioritize and characterize zoonoses for which surveillance in domestic animals is important to prevent human infections at a global scale. A multi-criteria qualitative approach was used, where disease-specific information was obtained across literature of the leading international health organizations. Thirty-two zoonoses were prioritized, all of which have multi-regional spread, cause unexceptional human infections and have domestic animal hosts as important sources or sentinels of zoonotic infections. Most diseases involve multiple animal hosts and/or modes of zoonotic transmission, where a lack of specific clinical signs in animals further complicates surveillance. We discuss the challenges of animal health surveillance in endemic and resource-limited settings, as well as potential avenues for improvement such as the multi-disease, multi-sectoral and digital surveillance approaches. Our study will support global capacity-building efforts to strengthen the surveillance and control of endemic zoonoses at their animal sources

United against rabies forum:The one health concept at work

Human deaths from rabies are preventable and can be eliminated by applying a systematic One Health approach. However, this ancient disease still threatens the lives of millions of people in up to 150 countries and kills an estimated 59, 000 people every year. Rabies today is largely a disease of poverty, almost always linked to dog bites, with most deaths occurring in neglected communities in Africa and Asia. The disease places an immense economic burden on its victims, a cost that far outweighs the investment needed to control it. A global framework for rabies elimination in humans is set out in Zero by 30: The Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. Despite the existence of proven control strategies and agreement on the path to eliminating human rabies deaths, mortality numbers from rabies remain high, and COVID-19 has set back efforts even further. But COVID-19 has also highlighted the value of a One Health approach to zoonotic disease and pandemic prevention. Rabies control programs offer a practical route to building One Health capacities that can also address other zoonotic threats, including those with pandemic potential. The United Against Rabies Forum aims to accelerate progress on rabies elimination while applying a One Health approach. The Forum promotes cross-sector collaboration among stakeholders and supports countries in their rabies elimination efforts. Increased political engagement and resource mobilization, both internationally and nationally, will be needed to achieve global rabies goals and can also make One Health implementation a reality

Production and characterization of a recombinant single-chain antibody against Hantaan virus envelop glycoprotein

Hantaan virus (HTNV) is the type of Hantavirus causing hemorrhagic fever with renal syndrome, for which no specific therapeutics are available so far. Cell type-specific internalizing antibodies can be used to deliver therapeutics intracellularly to target cell and thus, have potential application in anti-HTNV infection. To achieve intracellular delivery of therapeutics, it is necessary to obtain antibodies that demonstrate sufficient cell type-specific binding, internalizing, and desired cellular trafficking. Here, we describe the prokaryotic expression, affinity purification, and functional testing of a single-chain Fv antibody fragment (scFv) against HTNV envelop glycoprotein (GP), an HTNV-specific antigen normally located on the membranes of HTNV-infected cells. This HTNV GP-targeting antibody, scFv3G1, was produced in the cytoplasm of Escherichia coli cells as a soluble protein and was purified by immobilized metal affinity chromatography. The purified scFv possessed a high specific antigen-binding activity to HTNV GP and HTNV-infected Vero E6 cells and could be internalized into HTNV-infected cells probably through the clathrin-dependent endocytosis pathways similar to that observed with transferrin. Our results showed that the E. coli-produced scFv had potential applications in targeted and intracellular delivery of therapeutics against HTNV infections

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(−5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity

Novel loci and pathways significantly associated with longevity

Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10⁻⁵). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Nature Publishing Group. The published article can be found at: http://www.nature.com/articles/srep2124

Students’ Perceptions of a Learning Support Initiative for b-MOOCs

Blended learning based on MOOCs (b-MOOC) has become a new and wide-spread approach to combining internet technologies with face-to-face instruction in higher education. In the implementation of b-MOOCs, learning support or scaffolding proves to be essential and determines to some extent the success of blended learning, while available literature shows lack of re-search on it. Aiming at exploring a feasible learning support approach for b-MOOCs in practice, this study constructed a support framework with four key elements of resources (R), interaction (I), strategy (S) and evaluation (E) support, briefed as RISE, and implemented it in the Business English course in a Chinese university. A survey and semi-structured interview were conducted to make clear its effects, the perceptions and expectations of students. It shows that the RISE support initiative got wide recognition and resulted in various improvements, promoting learning autonomy, improving learning strategy, increasing interaction and time devoted. As to suggestions, more targeted and higher degree of support is expected by learners and they show preference for face-to-face instruction and suggestion is raised that the proportion of face-to-face section should be no less than the online part. The results of this study may offer practical reference in b-MOOC design about how to support learning process of students and what components and methods are effective