Economic burden of dengue fever in China: A retrospective research study

BackgroundDengue fever has been a significant public health challenge in China. This will be particularly important in the context of global warming, frequent international travels, and urbanization with increasing city size and population movement. In order to design relevant prevention and control strategies and allocate health resources reasonably, this study evaluated the economic burden of dengue fever in China in 2019.MethodsThe economic burden of dengue fever patients was calculated from both family and the organisation perspectives. A survey was conducted among 1,027 dengue fever patients in Zhejiang, Chongqing, and Yunnan Provinces. Treatment expenses, lost working days, and insurance reimbursement expenses information were collected to estimate the total economic burden of dengue fever patients in 2019. The expenditures related to dengue fever prevention and control from government, Center for Disease Control and Prevention (CDC), communities and subdistrict offices of 30 counties (or districts) in Zhejiang Province and Chongqing City were also collected.ResultsThe direct, indirect and total economic burden for dengue fever patients in 2019 in the three Provinces were about 36,927,380.00 Chinese Yuan (CNY), 10,579,572.00 CNY and 46,805,064.00 CNY, respectively. The costs for prevention and control of dengue fever for the counties (or districts) without cases, counties (or districts) with imported cases, and counties (or districts) with local cases are 205,800.00 CNY, 731,180.00 CNY and 6,934,378.00 CNY, respectively. The total investment of dengue fever prevention and control in the 30 counties in China in 2019 was approximately 3,166,660,240.00 CNY.ConclusionThe economic burden of dengue fever patients is relatively high, and medical insurance coverage should be increased to lighten patients’ direct medical economic burden. At the same time, the results suggests that China should increase funding for primary health service institutions to prevent dengue fever transmission.     

Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer

A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC₅₀ value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC₅₀ value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.     

不同施肥处理对土壤水稳定性团聚体及有机碳分布的影响

以国家褐潮土16 a的长期肥料试验为平台(北京昌平),研究长期不同施肥对耕层土壤水稳定性团聚体及其有机碳的影响。主要研究结果:与耕种农田土壤相比,长期撂荒(CK0)可以提高水稳定性大团聚体的含量及其有机碳含量和储量。而农田耕作后,破坏了水稳性大团聚体,相应地增加水稳性微团聚体的含量。与长期不施肥种植作物(CK)相比,长期施氮磷钾肥(NPK)、氮磷钾配施有机肥(NPKM)和氮磷钾秸秆还田(NPKS)处理对水稳性团聚体数量分布和平均重量直径(MWD)有显著影响,其中对2mm和0.25 2mm水稳性大团聚体的促进作用最明显,说明施肥处理增加的新碳主要向0.25 2mm和2mm团聚体富集。在不同水平水稳性团聚体中,2mm和0.25 2mm两个级别的水稳性大团聚体有机碳的含量显著高于0.0530.25mm和0.053mm水稳性微团聚体。化肥与有机肥配施(NPKM)处理可提高水稳性大团聚体含量,改善土壤团聚体的结构。长期小麦-玉米→小麦-大豆复种轮作并施氮磷钾化肥的处理(NPKF)各级团聚体中有机碳的含量高于长期小麦-玉米轮作并施氮磷钾化肥的处理(NPK)。     

北京地区热力景观格局及典型城市景观的热环境效应

城市热环境是城市生态环境中的一个重要指标,将景观生态学理论融入到热环境研究中,尝试探讨北京地区热力景观格局及城市公园、道路景观的热环境效应。地表温度反演是分析热力景观格局及典型城市景观热环境效应的前提,论文以北京地区为例,首先利用两景ASTER影像数据采用TES算法定量反演地表温度。通过半变异函数分析地表温度空间异质性,确定最大采样尺度,然后在景观统计软件Fragstats中,计算不同粒度下的景观格局指数,分析热力景观格局及其尺度效应。通过景观斑块特征分析和缓冲区分析,探讨公园景观斑块、道路景观廊道特征的热环境效应。总体上公园景观对应的平均温度随着公园面积、边界长度的增加而减小,随着公园周长面积比增大而增大;随着距离公园渐远,地表温度升高,且升温趋势变缓。随着道路密度增加,道路平均温度显著升高,标准差显著降低,道路密度等级与道路平均温度的相关系数达到0.8021;随着距离道路中心线距离增加,缓冲区内的平均温度略有下降,但变化微弱。因此,应充分重视公园景观在缓解城市热环境方面的作用,合理布局城市道路。     

A protein–protein interaction map reveals that the Coxiella burnetii effector CirB inhibits host proteasome activity

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91–120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection.     

A Fluorescent Recombinase Aided Amplification Assay for Detection of Babesia microti

Babesia microti is one of the most common causative agents of babesiosis. A sensitive and rapid detection is necessary for screening potentially infected individuals. In this study, B. microti cytochrome c oxidase subunit I (cox1) was selected as the target gene, multiple primers were designed, and optimized by a recombinase-aided amplification (RAA) assay. The optimal primers and probe were labeled with fluorescein. The sensitivity of fluorescent RAA (fRAA) was evaluated using gradient diluents of the cox1 recombinant plasmid and genomic DNA extracted from whole blood of B. microti infected mice. The specificity of fRAA was assessed by other transfusion transmitted parasites. The analytical sensitivity of the fRAA assay was 10 copies of recombinant plasmid per reaction and 10 fg/μl B. microti genomic DNA. No cross-reaction with any other blood-transmitted parasites was observed. Our results demonstrated that the fRAA assay would be rapid, sensitive, and specific for the detection of B. microti.     

VEGF/VEGFR-Targeted Therapy and Immunotherapy in Non-small Cell Lung Cancer: Targeting the Tumor Microenvironment

Non-small cell lung cancer (NSCLC) is the leading cause of death by cancer worldwide. Despite developments in therapeutic approaches for the past few decades, the 5-year survival rate of patients with NSCLC remains low. NSCLC tumor is a complex, heterogeneous microenvironment, comprising blood vessels, cancer cells, immune cells, and stroma cells. Vascular endothelial growth factors (VEGFs) are a major mediator to induce tumor microvasculature and are associated with the progression, recurrence, and metastasis of NSCLC. Current treatment medicines targeting VEGF/VEGF receptor (VEGFR) pathway, including neutralizing antibodies to VEGF or VEGFR and receptor tyrosine kinase inhibitors, have shown good treatment efficacy in patients with NSCLC. VEGF is not only an important angiogenic factor but also an immunomodulator of tumor microenvironment (TME). VEGFs can suppress antigen presentation, stimulate activity of regulatory T (Treg) cells, and tumor-associated macrophages, which in turn promote an immune suppressive microenvironment in NSCLC. The present review focuses on the angiogenic and non-angiogenic functions of VEGF in NSCLC, especially the interaction between VEGF and the cellular components of the TME. Additionally, we discuss recent preclinical and clinical studies to explore VEGF/VEGFR-targeted compounds and immunotherapy as novel approaches targeting the TME for the treatment of NSCLC.     

一种多聚羟基烷酸产生菌的诱变育种

以野生型自养黄杆菌为出发菌株,经亚硝酸、紫外线、60Coγ射线诱变处理选得三株性状优良的突变株（Uγ－、Uγ－17、Uγ－20）。Uγ－1突变株的菌落形态为菊花形,白色。Uγ-17和Uγ－20突变株的菌落形态均为圆凸光滑型,微黄色。40h的摇瓶发酵结果表明,Uγ－1、Uγ－17、Uγ－20突变株的干细胞产量分别为8．1g／1、11．2g／1、10．5g／1,其产物对干细胞的得率系数（y_p/x）分别为0．74、0．75、0．79。与野生型菌株相比,这些突变株的干细胞产量yp/x分别增加     

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLA^Glu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLA^Glu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (IC^Glu) to BLA^Glu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MD^Glu) to BLA^Glu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund’s adjuvant (CFA) into their paws. Optical inhibition of the IC^Glu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MD^Glu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the IC^Glu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MD^Glu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete IC^Glu→BLA and MD^Glu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.