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PURPOSE: The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain. METHODS: This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined. RESULTS: 46% PSC patients harbored KRAS mutation and 23% harbored EGFR mutation. Univariable analysis identified type and cTNM stage as significant predictor of PFS (type: HR 0.216; 95% CI 0.133-0.349; P < 0.001, cTNM stage: HR 0.483; 95% CI 0.269-0.846; P = 0.014) and OS (type: HR 0.269; 95% CI 0.156-0.465; P < 0.001, cTNM stage: HR 0.435; 95% CI 0.219-0.865; P = 0.018). Multivariable analysis confirmed sex, type and cTNM stage as independent predictors of PFS (sex: HR 2.026; 95%CI 1.027-3.996; P = 0.042; type: HR0.140; 95% CI 0.083-0.238; P < 0.001, cTNM stage: HR0.305; 95% CI 0.165-0.564; P < 0.001) and OS (type: HR0.231; 95% CI 0.132-0.404; P < 0.001, cTNM stage: HR 0.394; 95% CI 0.194-0.797; P = 0.010). Significant differences in PFS (P < 0.0001) and OS (P = 0.022) were observed between PSC and LUAD, and for PC compared with SCC (PFS: P = 0.00036, OS: P = 0.0053). Additionally, PSC patients treated with immunotherapy showed significantly better OS (P = 0.0019) compared with those treated without immunotherapy. CONCLUSIONS: PSC exhibits high KRAS and EGFR mutation rates, and spindle cell carcinoma has a worse prognosis. Immunotherapy shows potential as a treatment for advanced PSC.

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OBJECTIVES: Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. METHODS: The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. RESULTS: The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. CONCLUSION: miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.

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Abstract Objectives Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. Methods The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. Results The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. Conclusion miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.

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BACKGROUND: Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs. METHODS: The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein-protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining. RESULTS: In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05). CONCLUSION: The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.

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PURPOSE: The efficacy of immune checkpoint inhibitors such as programmed cell death ligand 1 (PD-L1) antibodies in non-small cell lung cancer (NSCLC) is limited, and combined use with other therapies is recommended. Dipeptidyl peptidase 4 (DPP4) inhibitors, a class of small molecule inhibitors, are highly effective for treating type 2 diabetes. Emerging evidence implicates DPP4 inhibitors as immunomodulators that modify aspects of innate and adaptive immunity. We evaluated the combination of a DPP4 inhibitor (anagliptin) and PD-L1 blockade in an NSCLC mouse model. METHODS: The effect of the combination of anti-PD-L1 and anagliptin was evaluated in subcutaneous mouse models of NSCLC. Tumor-infiltrating immune cells were analyzed by flow cytometry. Bone marrow-derived monocytes of C57BL/6 mice were isolated in vitro to examine the underlying mechanism of anagliptin on the differentiation and polarization of macrophage. RESULTS: Anagliptin dramatically improved the efficacy of PD-L1 antibody monotherapy by inhibiting macrophage formation and M2 polarization in the tumor microenvironment. Mechanistically, anagliptin suppressed the production of reactive oxygen species in bone marrow monocytes by inhibiting NOX1 and NOX2 expression induced by macrophage colony-stimulating factor, reduced late ERK signaling pathway activation, and inhibited monocyte-macrophage differentiation. However, the inhibitory effect was reactivated by lipopolysaccharide and interferon-gamma interacting with corresponding receptors during M1 macrophage polarization, but not M2. CONCLUSIONS: Anagliptin can enhance PD-L1 blockade efficacy in NSCLC by inhibiting macrophage differentiation and M2 macrophage polarization, and combination therapy may be a promising strategy for treating PD-L1 blockade therapy-resistant patients with NSCLC.

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Nanosized copper particles (nano Cu) have been incorporated into products in multiple industries, although studies have demonstrated that these particles are nephrotoxic. We investigated the cytotoxicity of nanosized copper particles on rat mesangial cells and measured rates of apoptosis, the expression of caspase-3, and generation of reactive oxygen species. We also measured autophagy through the acridine orange (AO) staining and expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62 to screen the underlying mechanism of toxicity. Nanosized copper particles inhibited mesangial cell viability, up-regulated the activity of caspase-3, and increased the rates of apoptosis and the generation of reactive oxygen species in a concentration-dependent manner. Exposure to nano Cu increased the formation of acidic vesicular organelles and the expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62, and treatment with an autophagy inhibitor reduced nephrotoxicity. This indicated that the autophagy pathway is involved in the toxicity induced by nanosized copper particles to mesangial cells. This finding can contribute to the development of safety guidelines for the evaluation of nanomaterials in the future.

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Nanosized copper particles (nano Cu) have been incorporated into products in multiple industries, although studies have demonstrated that these particles are nephrotoxic. We investigated the cytotoxicity of nanosized copper particles on rat mesangial cells and measured rates of apoptosis, the expression of caspase-3, and generation of reactive oxygen species. We also measured autophagy through the acridine orange (AO) staining and expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62 to screen the underlying mechanism of toxicity. Nanosized copper particles inhibited mesangial cell viability, up-regulated the activity of caspase-3, and increased the rates of apoptosis and the generation of reactive oxygen species in a concentration-dependent manner. Exposure to nano Cu increased the formation of acidic vesicular organelles and the expression of Beclin-1, microtubule-associated protein 1 light chain 3, and p62, and treatment with an autophagy inhibitor reduced nephrotoxicity. This indicated that the autophagy pathway is involved in the toxicity induced by nanosized copper particles to mesangial cells. This finding can contribute to the development of safety guidelines for the evaluation of nanomaterials in the future.

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Owing to the high mineralization and high treatment cost, Ordovician limestone water is often regarded as a mine wastewater. In order to make rational use of mine water with high mineralization and turn waste into treasure. In this work, the natural water quality of Ordovician mine water in the Weibei coalfield had been tested, and the suspended matter and trace elements of Ordovician mine water in the selected deep detained area had been further tested. As a contrast, the water quality of Ordovician mine water after heating and concentration had been tested. The mechanical and hydraulic parameters of concentrated mine water-loess and concentrated mine water-cement slurry had been tested and compared with conventional slurry. The results showed characteristics of deep detained Ordovician limestone mine water is high salinity, certain suspended matters, limited special material and high permanent hardness. However, compressive strength of loess samples increased, while the permeability reduced. The initial setting-time of the modified material was short, while it showed an increased compressive strength. In practical terms, the quantity of grouting produced in engineering applications can be reduced by 16%, whereas the discharge of high-mineralized mine water can be decreased by about 40,000 m3/a.

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OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

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OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

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OBJECT: To explore the treatment effect of the anterior medial neurovascular interval approach to coronal shear fractures of the distal humerus. METHODS: This prospective study included two female patients who were 30-64 years old, with a mean age of 47 years. Fractures were caused by falling from a bicycle. The time between the injury and operation was 1-2 days, with a mean time interval of 1.5 days. Two patients with coronal shear fracture of the distal humerus were treated with open reduction and internal fixation using anterior neurovascular interval approach. RESULTS: There were no intraoperative and postoperative neurological and vascular complications or infections, and the fracture was united. At 12 months after the surgery, the patient returned to work without pain, and with a normal range of motion for elbow and forearm rotation. The X-rays revealed excellent fracture union, no signs of heterotopic ossification, and no traumatic arthritis. According to Mayo's evaluation standards for elbow function, a score of 100 is excellent. CONCLUSIONS: The application of the anterior neurovascular interval approach of the elbow in the treatment of shear fracture of the articular surface of the distal humerus, particularly the trochlea of the humerus, can reduce the stripping of the soft tissue.

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SUMMARY OBJECT: To explore the treatment effect of the anterior medial neurovascular interval approach to coronal shear fractures of the distal humerus. METHODS: This prospective study included two female patients who were 30-64 years old, with a mean age of 47 years. Fractures were caused by falling from a bicycle. The time between the injury and operation was 1-2 days, with a mean time interval of 1.5 days. Two patients with coronal shear fracture of the distal humerus were treated with open reduction and internal fixation using anterior neurovascular interval approach. RESULTS: There were no intraoperative and postoperative neurological and vascular complications or infections, and the fracture was united. At 12 months after the surgery, the patient returned to work without pain, and with a normal range of motion for elbow and forearm rotation. The X-rays revealed excellent fracture union, no signs of heterotopic ossification, and no traumatic arthritis. According to Mayo's evaluation standards for elbow function, a score of 100 is excellent. CONCLUSIONS: The application of the anterior neurovascular interval approach of the elbow in the treatment of shear fracture of the articular surface of the distal humerus, particularly the trochlea of the humerus, can reduce the stripping of the soft tissue.

RESUMO OBJETIVO: Explorar o efeito do tratamento com uma abordagem anterior do intervalo neurovascular médio para fraturas de cisalhamento coronal da porção distal do úmero. METODOLOGIA: Este estudo prospectivo incluiu duas pacientes do sexo feminino de 30-64 anos de idade, com idade média de 47 anos. As fraturas foram causadas por quedas de bicicleta. O tempo entre a lesão e a operação foi de 1-2 dias, com um intervalo de tempo médio de 1,5 dias. Duas pacientes com cisalhamento coronal da porção distal do úmero foram tratadas com redução aberta e fixação interna utilizando a abordagem anterior do intervalo neurovascular. RESULTADOS: Não houve complicações neurológicas e vasculares intra e pós-operatórias, nem complicações ou infecções, e a fratura foi unida. Após 12 meses da cirurgia, as pacientes retornaram ao trabalho sem dor e com uma amplitude normal de movimento de rotação do antebraço e cotovelo. Os raios-X revelaram excelente união das fraturas, sem sinais de ossificação heterotópica e sem artrite traumática. De acordo com as diretrizes da clínica Mayo para avaliação da função do cotovelo, uma pontuação de 100 é considerada excelente. CONCLUSÃO: A aplicação da abordagem anterior do intervalo neurovascular do cotovelo no tratamento de uma fratura de cisalhamento da superfície articular da porção distal do úmero, especificamente da tróclea do úmero, pode reduzir o desgaste do tecido mole.

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This study aimed to investigate the roles of miRNA in the development of ovarian follicles in sows with high ovulation rate. The miRNA expression profiles in middle-size ovarian follicles between Meishan and Duroc sows were characterized by Affymetrix miRNA GeneChip. Seven differentially expressed miRNA were identified. KEGG pathways analyzed the predicted target genes of differentially expressed miRNA by using the DAVID website. The MAPK signaling pathway may affect the process of ovarian follicle development. Our study suggested that miR-21, miR-199a, miR-708, and miR-4334 might play a vital role in the development of ovarian follicles of sow.(AU)

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Rice is the most important food crop in the developing world. For rice production systems to address the challenges of increasing demand and climate change, potential and on-farm yield increases must be increased. Breeding is one of the main strategies toward such aim. Here, we hypothesize that climatic and atmospheric changes for the upland rice growing period in central Brazil are likely to alter environment groupings and drought stress patterns by 2050, leading to changing breeding targets during the 21st century. As a result of changes in drought stress frequency and intensity, we found reductions in productivity in the range of 200-600 kg/ha (up to 20%) and reductions in yield stability throughout virtually the entire upland rice growing area (except for the southeast). In the face of these changes, our crop simulation analysis suggests that the current strategy of the breeding program, which aims at achieving wide adaptation, should be adjusted. Based on the results for current and future climates, a weighted selection strategy for the three environmental groups that characterize the region is suggested. For the highly favorable environment (HFE, 36%-41% growing area, depending on RCP), selection should be done under both stress-free and terminal stress conditions; for the favorable environment (FE, 27%-40%), selection should aim at testing under reproductive and terminal stress, and for the least favorable environment (LFE, 23%-27%), selection should be conducted for response to reproductive stress only and for the joint occurrence of reproductive and terminal stress. Even though there are differences in timing, it is noteworthy that stress levels are similar across environments, with 40%-60% of crop water demand unsatisfied. Efficient crop improvement targeted toward adaptive traits for drought tolerance will enhance upland rice crop system resilience under climate change.

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Background: Zymomonas mobilis is a Gram-negative microaerophilic bacterium with excellent ethanol-producing capabilities. The RecET recombination system provides an efficient tool for direct targeting of genes in the bacterial chromosome by PCR fragments. Results: The plasmids pSUZM2a-RecET and pSUZM2a-RecE588T were first developed to co-express RecE or RecE588 and RecT for homologous recombination. Thereafter, the PCR fragments of the tetracycline resistance marker gene flanked by 60 bp of adhA (alcohol dehydrogenase I) or adhB (alcohol dehydrogenase II) homologous sequences were electroporated directly into ZM4 cells harboring pSUZM2a-RecET or pSUZM2a-RecE588T. Both adhA and adhB were replaced by the tetracycline resistance gene in ZM4, yielding two mutant strains, Z. mobilis ZM4 ΔadhA and Z. mobilis ZM4 ΔadhB. These two mutants showed varying extent of reduction in ethanol production, biomass generation, and glucose metabolism. Furthermore, enzyme activity of alcohol dehydrogenase II in Z. mobilis ZM4 ΔadhB exhibited a significant reduction compared to that of wild-type ZM4. Conclusion: This approach provided a simple and useful method for introducing mutations and heterologous genes in the Z. mobilis genome.

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Background: Pullulanase production in both wild-type strains and recombinantly engineered strains remains low. The Shine-Dalgarno (SD) sequence and stem-loop structure in the 5' or 3' untranslated region (UTR) are well-known determinants of mRNA stability. This study investigated the effect of mRNA stability on pullulanase heterologous expression. Results: We constructed four DNA fragments, pulA, SD-pulA, pulA-3t, and SD-pulA-3t, which were cloned into the expression vector pHT43 to generate four pullulanase expression plasmids. The DNA fragment pulA was the coding sequence (CDS) of pulA in Klebsiella variicola Z-13. SD-pulA was constructed by the addition of the 5' SD sequence at the 5' UTR of pulA. pulA-3t was constructed by the addition of a 3' stem-loop structure at the 3' UTR of pulA. SD-pulA-3t was constructed by the addition of the 5' SD sequence at the 5' UTR and a 3' stem-loop structure at the 3' UTR of pulA. The four vectors were transformed into Escherichia coli BL21(DE3). The pulA mRNA transcription of the transformant harboring pHT43-SD-pulA-3t was 338.6%, 34.9%, and 79.9% higher than that of the other three transformants, whereas the fermentation enzyme activities in culture broth and intracellularly were 107.0 and 584.1 times, 1.2 and 2.0 times, and 62.0 and 531.5 times the amount of the other three transformants (pulA, SD-pulA, and pulA-3 t), respectively. Conclusion: The addition of the 5' SD sequence at the 5' UTR and a 3' stem-loop structure at the 3' UTR of the pulA gene is an effective approach to increase pulA gene expression and fermentation enzyme activity.

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Background: Zymomonas mobilis, as a novel platform for bio-ethanol production, has been attracted more attention and it is very important to construct vectors for the efficient expression of foreign genes in this bacterium. Results: Three shuttle vectors ( pSUZM 1, pSUZM2 and pSUZM3 ) were first constructed with the origins of replication from the chromosome and two native plasmids (pZZM401 and pZZM402) of Z. mobilis ZM4, respectively. The three shuttle vectors were stable in Z. mobilis ZM4 and have 3,32 and 27 copies, respectively. The promoter Ppdc (a), from the pyruvate decarboxylase gene, was clonedinto the shuttle vectors, generatingthe expressionvectors pSUZM1(2, 3)a. The codon-optimized glucoamylase gene from Aspergillus awamori combined with the signal peptide sequence from the alkaline phosphatase gene of Z. mobilis was cloned into pSUZM1(2, 3)a, resulting in the plasmids pSUZM1a-GA, pSUZM2a-GA and pSUZM3a-GA, respectively. After transforming these plasmids into Z. mobilis ZM4, the host was endowed with glucoamylase activity for starch hydrolysis. Both pSUZM2a-GA and pSUZM3a-GA were more efficientatproducingglucoamylase thanpSUZM1a-GA. Conclusions: These results indicated that these expression vectors are useful tools for gene expression in Z. mobilis and this could provide a solid foundation for further studies of heterologous gene expression in Z. mobilis.

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Eight serum specimens collected from dengue patients in Guatemala and Honduras during the Central American epidemic of 2007 were analyzed. Virus identification and serotyping performed by a nested RT-PCR assay revealed two DENV-1 isolates from Guatemala, four DENV-2 isolates, two each from Guatemala and Honduras, and two DENV-4 isolates from Honduras. Viral genotyping determined by phylogenetic analysis of the complete envelope gene sequences demonstrated that the DENV-2 isolates from Guatemala and Honduras fell into the American/Asian Genotype III, and were most closely related to DENV-2/NI/BID-V2683-1999 isolated from a dengue case in Nicaragua in 1999; and the DENV-4 F07-076 isolate from Honduras belonged to genotype II, and was most closely related to DENV-4/US/BID-V1093/1998 isolated from Puerto Rico in 1998. Our results suggest that the 2007 dengue outbreaks in Guatemala and Honduras were most likely caused by the re-emergence of earlier, indigenous DENV strains rather than by newly introduced strains and there were at least three serotypes of DENV co-circulating during the 2007 Central American epidemics.