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Since 2013, a dengue epidemic has broken out in Yunnan, China and neighboring countries. However, after the COVID-19 pandemic in 2019, the number of dengue cases decreased significantly. In this retrospective study, epidemiological and genetic diversity characterizations of dengue viruses (DENV) isolated in Yunnan between 2017 and 2018 were performed. The results showed that the dengue outbreak in Yunnan from 2017 to 2018 was mainly caused by DENV1 (genotype I and genotype V) and DENV2 (Asia I, Asia II, and Cosmopolitan). Furthermore, correlation analysis indicated a significant positive correlation between the number of imported and local cases (correlation coefficient = 0.936). Multiple sequence alignment and phylogenetic divergence analysis revealed that the local isolates are closely related to the isolates from Myanmar and Laos. Interestingly, recombination analysis found that the DENV1 and DENV2 isolates in this study had widespread intra-serotype recombination. Taken together, the results of the epidemiological investigation imply that the dengue outbreak in Yunnan was primarily due to imported cases. This study provides a new reference for further investigations on the prevalence and molecular epidemiology of DENV in Yunnan, China.

Mosquitoes are capable of carrying complex pathogens, and their feeding habits on the mammalian blood can easily mediate the spread of viruses. Surveillance of mosquito-based arbovirus enables the early prevention and control of mosquito-borne arboviral diseases. The climate and geography of Yunnan Province in China are ideal for mosquitoes. Yunnan shares borders with several other countries; therefore, there exists a high risk of international transmission of mosquito-mediated infectious diseases. Previous studies have focused more on the Sino–Laos and Sino–Myanmar borders. Therefore, we focused on the neighborhoods of Malipo and Funing counties in Wenshan Prefecture, Yunnan Province, China, which are located along the Sino–Vietnam border, to investigate the species of mosquitoes and mosquito-borne viruses in the residential areas of this region. This study collected 10,800 mosquitoes from 29 species of 8 genera and grouped to isolate mosquito-borne viruses. In total, 62 isolates were isolated and classified into 11 viral categories. We demonstrated a new distribution of mosquito-borne viruses among mosquitoes in border areas, including Tembusu and Getah viruses, which can cause animal outbreaks. In addition, Dak Nong and Sarawak viruses originating from Vietnam and Malaysia, respectively, were identified for the first time in China, highlighting the complexity of mosquito-borne viruses in the Sino–Vietnam border region. The awareness of the importance of viral surveillance and prevention measures in border areas should be further encouraged to prevent future outbreaks of potentially infectious diseases.

Additional file 6: Table S4. Mean intra- and interspecific K2P distances of the ITS2 sequence (a) and COII sequence (b) in 12 Anopheles species. The numbers of intraspecific distances are shown in boldface for clarity. Numbers underlined indicate the highest intraspecific distance and the lowest interspecific distance. Abbreviations: n, no. of sequences; na, not applicable; arg., An. argyropus; nig., An. nigerrimus; nit., An. nitidus; ped., An. peditaeniatus; sin., An. sinensis; niv., An. nivipes; tes., An. tessellatus; dir., An. dirus; mac., An. maculatus; phi., An. philippinensis; koc., An. kochi; vag., An. vagus.

Additional file 9: Figure S5. Phylogenetic tree based on 18 ITS2 sequences (a) and 15 COII sequences (b) of Anopheles tessellatus from GenBank and our original data. Bootstrap values (1000 replicates) of maximum likelihood analyses are shown above/below the main lineages. Lineage designation is indicated on the right. Bars represent 2.0 substitutions per site based on ITS2 and 0.6 substitutions per site based on COII.

Additional file 5: Figure S2. Phylogenetic tree based on 1264 COII sequences (507 haplotypes) from GenBank and our original data. Bootstrap values (1000 replicates) of maximum likelihood analyses are shown above/below the main lineages. Lineage designation is indicated on the right. Bars represent 5.0 substitutions per site based on COII.

Additional file 8: Figure S4. ITS2 and COII sequence divergence. Each dot represents a species, with interspecific distance on the y-axis and intraspecific distance on the x-axis. The minimum interspecific (intergroup) divergence is plotted against the maximum intraspecific divergence. Red and green dots indicate the ITS2 and COII sequence divergence of 12 species including An. argyropus, An. nigerrimus, An. nitidus, An. peditaeniatus, An. sinensis, An. nivipes, An. tessellatus, An. dirus, An. maculatus, An. philippinensis, An. kochi and An. vagus.

Additional file 3: Figure S2. Neighbor-joining phylogenetic tree of the Hyrcanus group based on ITS2 (a) and COII sequences (b) from GenBank and our original data. Bootstrap values (1000 replicates) of neighbor-joining analyses are shown above/below the main lineages. Lineage designation is indicated on the right. Bars represent 20.00 substitutions per site based on ITS2 and 5.0 substitutions per site based on COII. Anopheles lindesayi and An. claviger were used as the outgroup taxa.

Additional file 4: Figure S3. Maximum Likelihood phylogenetic tree of the Hyrcanus group based on ITS2 (a) and COII sequences (b) from GenBank and our original data. Bootstrap values (1000 replicates) of maximum-likelihood analyses are shown above/below the main lineages. Lineage designation is indicated on the right. Bars represent 20.00 substitutions per site based on ITS2 and 7.0 substitutions per site based on COII. Anopheles lindesayi and An. claviger were used as the outgroup taxa.

Additional file 4. Supplementary Tables.

Additional file 6: Figure S5. The mismatch distribution graphs in Anopheles sinensis based on ITS2 (a) and COII (b). The X- and Y-axis show the number of pairwise differences and the frequency of the pairwise comparisons, respectively. The observed frequencies are represented by a dotted line. The frequency expected under the hypothesis of constant population model is depicted by a solid line.

Additional file 5: Figure S4. The mismatch distribution graphs in the Hyrcanus group based on ITS2 (a) and COII (b). The X- and Y-axis show the number of pairwise differences and the frequency of the pairwise comparisons, respectively. The observed frequencies are represented by a dotted line. The frequency expected under the hypothesis of constant population model is depicted by a solid line.arg. An. argyropus, bel. An. belenrae, cra. An. crawfordi, eng. An. engarensis, hyr. An. hyrcanus, hyr. spIR An. hyrcanus spIR, kle. An. kleini, kwe. An. kweiyangensis, les. An. lesteri, lia. An. liangshanensis, nig. An. nigerrimus, nit. An. nitidus, par. An. paraliae, ped. An. peditaeniatus, pse. An. pseudopictus, pul. An. pullus, pur. An. pursati, siner. An. sineroides, sin. An. sinensis

Additional file 1: Figure S1. Map of the three sampling sites in Laos: Pathoomphone County (Champasak Province, Laos-Cambodia border), Pak lay County (Xaignabouli Province, Laos-Thailand border) and Yot Ou County (Phongsaly Province, Laos–China border). The shapefile map of Lao PDR was downloaded and prepared by using Pixelmap Generator-Beta on line (amCharts, Vilnius, Lithuania) ( https://pixelmap.amcharts.com/ ), which is copyright free.

Additional file 2. Supplementary Figure 2.

Vertical transmission of the Zika virus (ZIKV) causes severe fetal defects, but the exact pathogenic mechanism is unclear. We identified up to a 10,480-fold higher expression of viral attachment factors AXL, GAS6, and PROS1 and a 3880-fold increase in ZIKV infectiousness/propagation in human term decidual stromal cells versus trophoblasts. Moreover, levels of viral attachment factors and ZIKV are significantly increased, whereas expression of innate immune response genes are significantly decreased, in human first trimester versus term decidual cells. ZIKV-infected decidual cell supernatants increased cytotrophoblasts infection up to 252-fold compared with directly infected cytotrophoblasts. Tizoxanide treatment efficiently inhibited Zika infection in both maternal and fetal cells. We conclude that ZIKV permissiveness, as well as innate immune responsiveness of human decidual cells, are gestational age dependent, and decidual cells augment ZIKV infection of primary human cytotrophoblast cultures, which are otherwise ZIKV resistant. Human decidual cells may act as reservoirs for trimester-dependent placental transmission of ZIKV, accounting for the higher Zika infection susceptibility and more severe fetal sequelae observed in early versus late pregnancy. Moreover, tizoxanide is a promising agent in preventing perinatal Zika transmission as well as other RNA viruses such as coronavirus.

Decomposition-based evolutionary algorithms are promising for handling many objective optimization problems with more than three objectives in the past decade. In the proposed algorithm, we develop a new dominance relation based on - efficiency order dominance (MOEA/D-\( \upvarepsilon{\text{EOD}} \)) in each sub-problem to realize the selection and update of the individuals. Besides, a dynamic adaptive weight vector generation method is proposed, which is able to dynamically adjust the weight vector setting according to the current distribution of the non-dominated solution set. The proposed algorithm has been tested extensively on six widely used benchmark problems, and an extensive comparison indicates that the proposed algorithm offers competitive advantages in convergence and diversity.

To reliably monitor the deformation of a single landslide is often a difficulty for DInSAR with mid-resolution SAR data. The high resolution SAR systems bring opportunities for the task. Among the landslides in Three Gorges area, Shuping landslide is typical and some previous works using DInSAR have been done during the last years. In this paper, 9 TerraSAR-X spotlight images are used to map the surface displacement of Shuping landslide. Conventional and coherent pixels based DInSAR are both applied. The deformation field of the landslide is mapped and 2 deformtion cones are identified. Meanwhile, this paper gives out the average deformation velocities of the coherent pixels during the period from January to March 2012. It is confirmed that DInSAR can become a valuable tool in studying and monitoring single landslides with high resolution SAR images. In the future, the DInSAR measurements along the line of sight direction should be converted to real slide direction of the landslide and analyzed joint with multi-source data.

It could be concluded that all multi-objective evolutionary algorithms draw their strength from two aspects: convergence and diversity. In order to achieve these goals, This paper proposes a hybrid methods that combines GA with simplex search method for multi-objective optimization using preference order ranking. Preference order ranking is used as fitness assignment methodology to accelerate the performance of convergence, especially when the number of objectives is very large. The proposed algorithm also uses three subsets to evolve simultaneous and each subset is divided on the basis of different criterion. In every generation, We carry out simplex-based local search in the first two subsets to achieve faster convergence and better diversity, and the individuals in third subset execute ordinary genetic operator to avoid premature convergence. The proposed algorithm has been compared with other MOEAs in high dimensional problems. The experimental results indicate that our algorithm produces better convergence and diversity performance.

Monitoring and governing the regional land subsidence along the highway and other linear projects has become an important basic work for the normal construction and operation in these regions. In this paper, by using the method of multi-track PS-InSAR integration, the land subsidence velocity varying with time along the JingHu highway (Beijing-Hebei) was studied with adjacent orbits ENVISAT ASAR data from 2008 to 2010. At the same time, the map of subsidence velocity along the highway was successfully extracted as well as the subsidence profile map. And 9 subsidence centers were verified along the highway according to these maps, which were consistent with the previous study. The results showed that the method not only unified the coordinate system of adjacent tracks, but also made cross-track, multi-image, large-scale PS-InSAR monitoring possible. Therefore, PS-InSAR monitoring results could provide a scientific reference for the subsidence control of highway and other linear projects, and protect the safe operation of the linear projects.

The problem of community structure detection in complex networks has been intensively investigated in recent years. Many algorithms were proposed based on optimization modularity. To overcome the solution limitation drawbacks of modularity function, as a new measure, modularity density for measuring the community structure was introduced. In this paper, we propose a genetic algorithm for detecting community structure in complex networks based on optimization modularity density. Experiments on synthetic and real life networks show the high capability of the method to successfully detect the network structure, particularly for the cases where the community structure is obscure.

Esophageal cancer is one of the most common cancers, and the 5-year survival rate is less than 10% due to lack of effective therapeutic agents. This study was to evaluate antitumor activity of Ec-LDP-Hr-AE, a recently developed bispecific enediyne-energized fusion protein, on esophageal carcinoma, targeting both EGFR (epidermal growth factor receptor) and HER2 (human epidermal growth factor receptor 2), because both EGFR and HER2 have been shown overexpression in over 30% of esophageal cancers. The fusion protein Ec-LDP-Hr-AE was encoded by a gene that was genetically constructed by fusing the oligopeptides ligand Ec (22 amino acids of EGF COOH-terminal) and Hr (VH CDR3 region of anti-HER2 C6.5 antibody) with lidamycin (LDM, an enediyne antibiotic with potent cytotoxicity) via two (G4S)3-linker. The encoded 18.4 kDa fusion protein was expressed in Escherichia coli and characterized its binding affinity with esophageal squamous cell carcinoma (ESCC) cells by flow-cytometry-based immunofluorescence assay. The results showed that Ec-LDP-Hr-AE protein bound to ESCC cells EC9706 and KYSE150 with high affinity (the Kd values were 5.283μmol/L and 3.562μmol/L, respectively). The potency of Ec-LDP-Hr-AE was determined on four human ESCC cell lines with differential expression of EGFR and HER2 using MTT assay. The bispecific Ec-LDP-Hr-AE showed potent cytotoxicity to EC1, EC109, EC9706 and KYSE150 cells with IC50 values in the picomolar level. Moreover, the bispecific Ec-LDP-Hr-AE was more potent than the monospecific counterparts (Ec-LDP-AE and LDP-Hr-AE) and LDM. Cell cycle distribution assay revealed that Ec-LDP-Hr-AE caused G2-M arrest in EC9706 and KYSE150 cells, in which the G2-M phase cells reached the peak with 0.1nmol/L of Ec-LDP-Hr-AE treatment. Ec-LDP-Hr-AE also induced cancer cell apoptosis in EC9706 and KYSE150 cells and the induction of apoptosis was in a dosage-dependent manner. The apoptotic index in the EC9706 cells exposed to 0.1, 0.5, or 1 nmol/L of Ec-LDP-Hr-AE were 15.0 ± 0.3%, 38.1 ± 0.6%, and 50.0 ± 0.4%, respectively. Western blotting showed that Ec-LDP-Hr-AE promoted caspase-3 and caspase-7 activities as well as PARP cleavage, indicating that Ec-LDP-Hr-AE-induced apoptosis was associated with mitochondria-caspase cascade. Moreover, Ec-LDP-Hr-AE inhibited KYSE150 cancer cell proliferation via decreasing phosphorylation of EGFR and HER2, and further exerted inhibition of the activation of their downstream signaling molecules (e.g. AKT and ERK). In summary, the bispecific energized fusion protein Ec-LDP-Hr-AE exhibited potent cytotoxicity to ESCC cells in vitro, leading to cell cycle arrest and apoptosis via targeting EGFR and HER2. These results suggest that Ec-LDP-Hr-AE could be a promising candidate for esophageal cancer targeting therapy. Citation Format: Guo Xiaofang, Xiaofei Zhu, Yue Shang, Shenghua Zhang, Yongsu Zhen, Wancai Yang. A bispecific enediyne-energized fusion protein Ec-LDP-Hr-AE enhances anti-cancer efficacy on esophageal cancer cells by targeting EGFR and HER2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5478. doi:10.1158/1538-7445.AM2013-5478

e15606 Background: Immune checkpoint inhibitors (anti-PD-1 antibodies) have been testified good response in DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancers (CRC), while DNA mismatch repair-proficient/microsatellite stable(pMMR/MSS) CRCs, accounting for 85% of all CRCs, display poor response. Effective combined therapies for pMMR/MSS are needed for patients with local advanced colorectal cancers. Methods: In this pilot study, we administered 6 preoperative doses of anti-PD-1 antibody Sintilimab and Oxaliplatin and 5-FU/CF (mFOLFOX6) combined with Bevacizumab (only 5 doses in order not to delay surgery) in patients with cT4NxM0 colon or upper rectal cancers. Sintilimab (at a fixed dose of 200mg) was administered intravenously every 2 weeks, with surgery planned approximately 12 weeks after the first dose. The primary end point was pathological complete response(pCR). We also evaluated the major pathological response, radiological and pathological regression, safety, tumor mutation burden and tumor microenvironment (TME) molecules. Results: As of data cutoff (Dec 31,2021), median follow-up was 4.5 months (IQR 1.5-9.4). All patients underwent R0 surgical resection without treatment-related surgical delays. Of the 18 tumors that were removed, 18 were completely resected. A pCR occurred in 10 of 18 resected tumors (56%) and a major pathological response (MPR, ≤10% residual viable tumor) in 14/18(78%). At data cutoff, 18 were alive and 17 were free of recurrence. Treatment-related adverse events of grade 3 or higher occurred in 10% of the patients. Among the pCR tumors, two were found to harbored POLE mutation. The degree of pathological regression was deeper than radiological tumor shrinkage. The expression of CD3+ or/and CD3+/CD4+ stroma around tumor in pretreated tissue was significantly lower when comparing pCR and non-pCR (both p= 0.024). Conclusions: Neoadjuvant Sintilimab combined with Bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery and lead to a striking 56% and 78% complete and major pathological response. Stroma down-regulation of CD3 or CD3/CD4 expression was related to pCR.