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Abstract Background Mosquitoes are efficient vectors of medically significant flaviviruses and serve as hosts for insect-specific flaviviruses (ISFs). Aedes flavivirus (AEFV) is a classical ISF. Given the increasing discovery of ISFs, it is urgent to evaluate the potential risk of ISFs to human health as well as their impact on the transmission of pathogenic flaviviruses. Methods We isolated a strain of AEFV from wild Aedes albopictus populations in Hainan Province, China, using iodixanol density-gradient ultracentrifugation. The infection of the AEFV Hainan strain in Aedes, Culex, and four mammalian cell lines was investigated using fluorescence in situ hybridization (FISH) assays, and relative and absolute quantitative polymerase chain reaction (qPCR). Whether AEFV alters the vector competence of Ae. albopictus for pathogenic arboviruses and the underlying immune mechanisms were explored. Results The AEFV Hainan strain showed close genetic similarity to strains from Yunnan province of China, Thailand, and Peru. This strain was capable of infecting Ae. albopictus and Ae. aegypti but not Culex quinquefasciatus. Cell entry was the critical barrier for AEFV infection in Cx. quinquefasciatus cells. The infection risk of the AEFV Hainan strain in four mammalian cells (BHK-21, Vero, 293 T, and HeLa) was quite low due to the failure of cell entry or extremely limited replication. Prior infection of AEFV was detrimental to the replication of Zika virus and dengue virus serotype 2 in Ae. albopictus through activation of the Janus kinase/signal transducer and activator of transcription, Toll, or RNA interference pathway. Conclusions Our work excludes the risk of the AEFV Hainan strain to human health and highlights its potential as an immune inducer to sabotage Aedes mosquito ability for viral transmission. Graphical Abstract

Abstract Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging tick-borne disease with a high mortality rate. Haemaphysalis longicornis is the primary reservoir and vector of SFTSV. Here, we found that targeting subolesin (SUB), an anti-tick vaccine candidate, affects the infection and transmission of SFTSV in H. longicornis. RNAi-mediated knockdown of SUB repressed SFTSV infection in the salivary glands but not in the gut of H. longicornis, which may be associated with the modulation of protein processing in endoplasmic reticulum revealed by transcriptomic analysis. Knockdown of SUB decreased the survival and engorgement rates of ticks and impaired the horizontal and co-feeding transmission of SFTSV. Furthermore, active immunization with recombinant SUB inhibited the co-feeding transmission of SFTSV, although it had no significant effect on the blood-feeding behavior of infected ticks. Collectively, these results provide a potential target for controlling SFTS and other tick-borne viral diseases.

Abstract The main vectors of Zika virus (ZIKV) and dengue virus (DENV) are Aedes aegypti and Ae. albopictus, with Ae. aegypti being more competent. However, the underlying mechanisms remain unclear. Here, we find Ae. albopictus shows comparable vector competence to ZIKV/DENV with Ae. aegypti by blood-feeding after antibiotic treatment or intrathoracic injection. This suggests that midgut microbiota can influence vector competence. Enterobacter hormaechei_B17 (Eh_B17) is isolated from field-collected Ae. albopictus and conferred resistance to ZIKV/DENV infection in Ae. aegypti after gut-transplantation. Sphingosine, a metabolite secreted by Eh_B17, effectively suppresses ZIKV infection in both Ae. aegypti and cell cultures by blocking viral entry during the fusion step, with an IC50 of approximately 10 μM. A field survey reveals that Eh_B17 preferentially colonizes Ae. albopictus compared to Ae. aegypti. And field Ae. albopictus positive for Eh_B17 are more resistant to ZIKV infection. These findings underscore the potential of gut symbiotic bacteria, such as Eh_B17, to modulate the arbovirus vector competence of Aedes mosquitoes. As a natural antiviral agent, Eh_B17 holds promise as a potential candidate for blocking ZIKV/DENV transmission.

Diabetes disease caused by hyperglycemia has many complications, including cardiovascular disease, kidney disease and visual impairment. Effective and stable platform of enzyme-free glucose detection is significant important for the monitoring of diabetes disease. In this work, uniform single MXene layers were fabricated with large scale through HCl/LiF etching and tapered gold nanostructures (AuTNs) was electrodeposited on the MXene layers. The AuTNs with three-dimensional conical apex on the MXene layers can effectively increase the specific surface ratio and active sites. The composite materials of AuTNs and MXene layers assembled on the glassy carbon electrode (GCE) can significantly increase the electrochemical performance during glucose detection. The modified electrode of AuTNs/MXene/GCE shows good linearity from 0.1 nM to 10.0 mM, low limit of detection (LOD) of 1.43 nM and fast response time of 1.0 s, exhibiting high sensitivity, good stability and high selectivity for glucose during electrochemical detection. The high performance of the modified electrode provides promising potential application in enzyme-free sensor for the electrochemical detection of glucose.

Burkholderia semiarida was previously identified solely as a plant pathogen within the Burkholderia cepacia complex. We present a case in China involving recurrent pneumonia attributed to B. semiarida infection. Of note, the infection manifested in an immunocompetent patient with no associated primary diseases and endured for >3 years.

Abstract Background Ticks serve as vectors for a diverse array of pathogens, including viruses responsible for both human and livestock diseases. Symbiotic bacteria hold significant potential for controlling tick-borne disease. However, the alteration of tick gut bacterial community in response to pathogen infection has not been analyzed for any tick-borne viruses. Here, the impact of severe fever with thrombocytopenia syndrome virus (SFTSV) infection on bacterial diversity in the gut of Haemaphysalis longicornis is investigated. Methods Unfed tick females were artificially infected with SFTSV. The gut samples were collected and the genomic DNA was extracted. We then investigated alterations in gut bacterial composition in response to SFTSV infection through 16S rRNA gene sequencing. Results The study found that a reduction in the number of operational taxonomic units (OTUs) in the tick gut following SFTSV infection. However, there were no significant changes in alpha diversity indices upon infection. Four genera, including Corynebacterium, Arthrobacter, Sphingomonas, and Escherichia, were identified as biomarkers for the tick gut without SFTSV infection. Notably, the predicted correlation network indicated that the biomarkers Sphingomonas and Escherichia exhibited positive correlations within the same subcommunity, which was altered upon viral infection. Conclusions These findings revealed that the change in tick gut bacterial composition upon SFTSV infection and could facilitate the discovery new target for tick-borne viral disease control. Graphical Abstract

The deep-sea ecosystem, a less-contaminated reservoir of antibiotic resistance genes (ARGs), has evolved antibiotic resistance for microbes to survive and utilize scarce resources. Research on the diversity and distribution of these genes in deep-sea environments is limited. Our metagenomics study employed short-read-based (SRB) and assembled-contig-based (ACB) methods to identify ARGs in deep-sea waters and sediments and assess their potential pathogenicity. SRB prediction was found to be more effective for studying the abundance and diversity of these genes, while combining both methods better illustrated the relationship of ARGs with the hosts. Deep-sea waters (DSW) and trenches had the highest diversity of ARGs, including β-lactams, multidrug resistance genes, and rifamycins. Mobile genetic elements, such as IncQ and RP4 plasmids, were also identified. The ratio of nonsynonymous to synonymous substitutions (pN/pS) values of these genes suggest different evolutionary strategies in response to deep-sea conditions and possible human impacts. These resistome profiles provide valuable insights into their natural origins as well as the ecological and evolutionary implications of antibiotic resistance in deep-sea ecosystems. The exploration of the global distribution of ARGs in diverse deep-sea environments is a novel approach that will assist in understanding their potential reservoirs and evolutionary mechanisms. Therefore, employing a comprehensive approach to studying ARGs is particularly necessary. Unique microbial life in deep-sea ecosystems, especially in deep-sea cold seeps sediments (DSCSS), deep-sea waters (DSW), and trench waters (TW), could be a valuable source of new antibiotics and resistance discovery.

Abstract Background Remdesivir is considered to be a specific drug for treating coronavirus disease 2019. This systematic review aims to evaluate the clinical efficacy and risk of remdesivir alone and in combination with other drugs. Research design and methods The PubMed, Embase, SCIE, Cochrane Library, and American Clinical trial Center databases were searched up to 1 April 2022 to identify. Randomized controlled trials (RCTs) and observational studies comparing the efficacy of remdesivir monotherapy and combination therapy with that of control drugs. Results Ten RCTs and 32 observational studies were included in the analysis. Regarding the primary outcome, remdesivir use reduced mortality in patients with severe COVID-19 (RR = 0.57, 95% CI (0.48,0.68)) and shortened the time to clinical improvement (MD = -2.51, 95% CI (-2.75, -2.28)). Regarding other clinical outcomes, remdesivir use was associated with improved clinical status (RR = 1.08, 95%CI (1.01, 1.17)). Regarding safety outcomes, remdesivir use did not cause liver or kidney damage (RR = 0.87, 95%CI (0.68, 1.11)) (RR = 0.88, 95%CI (0.70,1.10)). Compared with remdesivir alone, remdesivir combined with other drugs (e.g., steroids, favipiravir, and convalescent plasma) had no effect on mortality. Conclusion The use of remdesivir can help to reduce the mortality of patients with severe COVID-19 and shorten the time to clinical improvement. There was no benefit of remdesivir combination therapy for other clinical outcomes. Trial registration PROSPERO registration number: CRD42022322859.

Abstract Background The pathogenic viruses transmitted by mosquitoes cause a variety of animal and human diseases and public health concerns. Virome surveillance is important for the discovery, and control of mosquito-borne pathogenic viruses, as well as early warning systems. Virome composition in mosquitoes is affected by mosquito species, food source, and geographic region. However, the complex associations of virome composition remain largely unknown. Results Here, we profiled the high-depth RNA viromes of 15 species of field-caught adult mosquitoes, especially from Culex, Aedes, Anopheles, and Armigeres in Hainan Island from 2018 to 2020. We detected 57 known and 39 novel viruses belonging to 15 families. We established the associations of the RNA viruses with mosquito species and their foods, indicating the importance of feeding acquisition of RNA viruses in determining virome composition. A large fraction of RNA viruses were persistent in the same mosquito species across the 3 years and different locations, showing the species-specific stability of viromes in Hainan Island. In contrast, the virome compositions of single mosquito species in different geographic regions worldwide are visibly distinct. This is consistent with the differences in food sources of mosquitoes distributed broadly across continents. Conclusions Thus, species-specific viromes in a relatively small area are limited by viral interspecific competition and food sources, whereas the viromes of mosquito species in large geographic regions may be governed by ecological interactions between mosquitoes and local environmental factors. Video Abstract

ABSTRACT Melioidosis is a severe and often fatal infectious disease caused by Burkholderia pseudomallei, which poses significant challenges due to its high mortality rate and frequent misdiagnosis. To effectively treat infected patients, especially in epidemic regions like Hainan with a high resistance rate to ceftazidime (CAZ), early diagnosis and resistance testing are critical. Here, we designed a strategy that combines RNase-HII-dependent PCR with lateral flow strip assay (LFSA) for simultaneous detection of B. pseudomallei and its CAZ resistance mutation. In this strategy, we utilized rhPCR technology to design specific primers with a C3-spacer modification. These primers target a 115-base pair region within the ORF2 of the B. pseudomallei type III secretion system gene cluster, as well as the P174L mutation in the penA gene, which is a major mutation associated with CAZ resistance in Hainan. The primers contain complementary RNA bases that can be hydrolyzed only in the presence of thermostable RNase-HII enzymes, facilitating subsequent PCR reactions. Additionally, we introduced two pairs of universal probes carrying fluorescein isothiocyanate (FITC) and biotin, as well as digoxin and biotin. The sequences of these universal probes align with specific regions of the primers, resulting in target products labeled with different tags. The resulting amplification products are then subjected to LFSA, where the presence of specific markers is visually interpreted based on color development. These markers flow to test line 1 (T1) and are captured by a fixed anti-FITC antibody, generating a red line that indicates the presence of B. pseudomallei. Similarly, the occurrence of a red line on test line 2 (T2), which is fixed with anti-digoxin antibodies, indicates the presence of the P174L mutation in B. pseudomallei. This protocol serves as an excellent tool for the rapid diagnosis of melioidosis and provides a basis for selecting appropriate antibiotic medication. It has the potential to revolutionize the diagnosis of melioidosis, particularly in resource-limited settings. Furthermore, this technique holds promise as a versatile tool for disease diagnosis in general. IMPORTANCE This study focused on the development of a reaction system using rhPCR to amplify a specific gene, ORF2, of B. pseudomallei and to identify the P174L mutation associated with increased drug resistance to ceftazidime (CAZ). The system incorporated universal primer probes and a simple temperature cycle reaction. The amplified products were then analyzed using lateral flow strip assay (LFSA) for strain identification and mutation interpretation. The developed system provides a reliable basis for diagnosing melioidosis and selecting appropriate drugs. Its potential impact is particularly significant in resource-limited settings where access to advanced diagnostic techniques is limited. This platform stands out for its simplicity, convenience, sensitivity, specificity, and portability. It shows promise as a point-of-care testing method for detecting single nucleotide polymorphism in genes associated with other diseases. By leveraging the advantages of this platform, researchers and healthcare professionals can potentially expand its use beyond melioidosis and apply it to the rapid detection of genetic variations in other disease-related genes.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tickborne bandavirus mainly transmitted by Haemaphysalis longicornis ticks in East Asia, mostly in rural areas. As of April 2022, the amplifying host involved in the natural transmission of SFTSV remained unidentified. Our epidemiologic field survey conducted in endemic areas in China showed that hedgehogs were widely distributed, had heavy tick infestations, and had high SFTSV seroprevalence and RNA prevalence. After experimental infection of Erinaceus amurensis and Atelerix albiventris hedgehogs with SFTSV, we detected robust but transitory viremias that lasted for 9–11 days. We completed the SFTSV transmission cycle between hedgehogs and nymph and adult H. longicornis ticks under laboratory conditions with 100% efficiency. Furthermore, naive H. longicornis ticks could be infected by SFTSV-positive ticks co-feeding on naive hedgehogs; we confirmed transstadial transmission of SFTSV. Our study suggests that the hedgehogs are a notable wildlife amplifying host of SFTSV in China.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei (Bp), a gram-negative bacillus. Sepsis is the most prevalent type of melioidosis. Due to factors such as lack of precision and slow presentation of bacterial culture tests, the misdiagnosis rate could exceed 100 per cent. Therefore, more reliable, and adaptable diagnostic methods are urgently needed. Weighted gene co-expression network analysis (WGCNA) was employed to screen the featured modules specially expressed in sepsis patients caused by Bp. Two representative co-expression modules were selected to perform gene ontology(GO) and KEGG analysis using ClusterProfiler package based on R language. We found that antigen processing and presentation of exogenous peptide antigen via MHC class I pathway, cytosol to ER transport and cell killing related pathways enriched in darkmagenta module which significantly correlated with the sepsis caused by Bp. Eventually, a diagnostic 6-mRNA signature consisting of ASPHD2, LAP3, SEPT4, FAM26F, WARS and LGALS3BP was identified, which could discern the sepsis caused by Bp compared with other organisms. This will provide a new insight in screening markers for early detection of sepsis caused by Bp, and the interaction between pathogens and hosts. This should shed light on the early detection of Bp-caused infectious diseases.

Abstract Background Burkholderia pseudomallei is a tropical pathogen that causes melioidosis. Its intrinsic drug-resistance is a leading cause of treatment failure, and the few available antibiotics require prolonged use to be effective. This study aimed to assess the clinical potential of B. pseudomallei phages isolated from Hainan, China. Methods Burkholderia pseudomallei strain (HNBP001) was used as the isolation host, and phages were recovered from domestic environmental sources, which were submitted to the host range determination, lytic property assays, and stability tests. The best candidate was examined via the transmission electron microscope for classification. With its genome sequenced and analyzed, its protective efficacy against B. pseudomallei infection in A549 cells and Caenorhabditis elegans was evaluated, in which cell viability and survival rates were compared using the one-way ANOVA method and the log-rank test. Results A phage able to lyse 24/25 clinical isolates was recovered. It was classified in the Podoviridae family and was found to be amenable to propagation. Under the optimal multiplicity of infection (MOI) of 0.1, an eclipse period of around 20 min and a high titer (1012 PFU/ml) produced within 1 h were demonstrated. This phage was found stabile at a wide range of temperatures (24, 37, 40, 50, and 60 °C) and pH values (3–12). After being designated as vB_BpP_HN01, it was fully sequenced, and the 71,398 bp linear genome, containing 93 open reading frames and a tRNA-Asn, displayed a low sequence similarity with known viruses. Additionally, protective effects of applications of vB_BpP_HN01 (MOI = 0.1 and MOI = 1) alone or in combination with antibiotics were found to improve viability of infected cells (70.6 ± 6.8%, 85.8 ± 5.7%, 91.9 ± 1.8%, and 96.8 ± 1.8%, respectively). A significantly reduced mortality (10%) and a decreased pathogen load were demonstrated in infected C. elegans following the addition of this phage. Conclusions As the first B. pseudomallei phage was isolated in Hainan, China, phage vB_BpP_HN01 was characterized by promising lytic property, stability, and efficiency of bacterial elimination during the in vitro/vivo experiments. Therefore, we can conclude that it is a potential alternative agent for combating melioidosis. Graphical Abstract

Abstract Burkholderia pseudomallei is a Gram-negative intracellular bacterium that causes melioidosis, a life-threatening disease. The interaction of B. pseudomallei with its host is complicated, and cellular response to B. pseudomallei infection is still largely unknown. In this study, we aimed to determine host-cell responses to B. pseudomallei at the proteomics level. We performed proteomic profiling of B. pseudomallei HNBP001-infected mouse macrophage RAW264.7 cells to characterize the cellular response dynamics during infection. Western blot analysis was utilized for the validation of changes in protein expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the clusterProfiler R package. Compared with the negative control (NC) group, 811 common proteins varied over time, with a cut-off level of two fold change and an adjusted P-value less than 0.05. The bioinformatics analysis revealed that the proteins significantly changed in the B. pseudomallei HNBP001 infection group (Bp group) were enriched in glycometabolism pathways, including glycolysis, fructose and mannose metabolism, pentose phosphate pathway, galactose metabolism, and carbon metabolism. Western blot analysis verified three selected proteins involved in glycometabolism pathways, namely PGM1, PKM, and PGK1 were increase over time post the infection. Furthermore, in vitro functional analysis revealed an increased glucose uptake and decreased ATP production and O-GlcNAcylation in the Bp group compared with control group, suggesting that B. pseudomallei HNBP001 infection induces changes in glycometabolism in RAW264.7 cells. These results indicate that glycometabolism pathways change in RAW264.7 cells post B. pseudomallei HNBP001 infection, providing important insights into the intimate interaction between B. pseudomallei and macrophages.

Since the pandemic started, the coronavirus disease 2019 (COVID-19) has spread worldwide. In patients with COVID-19, the gut microbiome (GM) has been supposed to be closely related to the progress of the disease. The gut microbiota composition and human genetic variation are also connected in COVID-19 patients, assuming a triangular relationship between the genome, GM, and COVID-19. Here, we reviewed the recent developments in the study of the relationship between gut microbiota and COVID-19. The keywords “COVID-19,” “microbiome,” and “genome” were used to search the literature in the PubMed database. We first found that the composition of the GM in COVID-19 patients varies according to the severity of the illness. Most obviously, Candida albicans abnormally increased while the probiotic Bifidobacterium decreased in severe cases of COVID-19. Interestingly, clinical studies have consistently emphasized that the family Lachnospiraceae plays a critical role in patients with COVID-19. Additionally, we have demonstrated the impact of microbiome-related genes on COVID-19. Specially, we focused on angiotensin-converting enzyme 2’s dual functions in SARS-CoV-2 infection and gut microbiota alternation. In summary, these studies showed that the diversity of GMs is closely connected to COVID-19. A triangular relationship exists between COVID-19, the human genome, and the gut flora, suggesting that human genetic variations may offer a chance for a precise diagnosis of COVID-19, and the important relationships between genetic makeup and microbiome regulation may affect the therapy of COVID-19.

Abstract Background The emergence of antimicrobial resistance against Mycobacterium tuberculosis (M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019. Results A total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%). Conclusions Our data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Objective: To identify the mosquito species collected in the field of 8 cities/counties of Hainan province, China and to analyze the characteristics of genetic differentiation of the predominant mosquito species. The types, contents and composition characteristics of the midgut microbiota of various mosquito species were explored to provide evidence for the control and prevention of mosquito-borne diseases in Hainan province. Methods: Adult mosquitoes were collected in the field using light traps, human lure or cattle lure methods. Morphology and DNA-barcoding technology (COI gene) were applied to identify the mosquito species. The V3-V4 hypervariable region of microbes 16S rRNA was used for high-throughput sequencing of the midgut microbiota, and SPSS 21.0 and R v3.1.1 software were employed to perform statistical analysis of the sequencing results and the Beta diversity analysis. Results: Aedes (Ae.) albopictus, Armigeres (Ar.) subalbatus and Culex (Cx.) pipiens pallpens were the three predominant species of the mosquito samples. Ae. albopictus was closely related to MK736660 (India) and JQ235749 (Yunnan), while MT541282 (DF, Dongfang) was a relatively independent population. The composition and structure of bacterial communities significantly varied among most of the samples (P

An accumulating body of research indicates that long-noncoding RNAs (lncRNAs) regulate the target genes and act as competitive endogenous RNAs (ceRNAs) playing an indispensable role in lung adenocarcinoma (LUAD). LUAD is frequently accompanied by the feature of chromosomal instability (CIN); however, CIN-related ceRNAs have not been investigated yet. We systematically analyzed and integrated CIN-related dysregulated ceRNAs characteristics in LUAD samples for the first time. In TCGA LUAD cohort, CIN in tumor samples was significantly higher than that in those of adjacent, and patients with high CIN risk tended to have worse clinical outcomes. We constructed a double-weighted CIN-related dysregulated ceRNA network, in which edge weight and node weight represented the disorder extent of ceRNA and the correlation of RNA expression level and prognosis, respectively. After module mining and analysis, a potential prognostic biomarker composed of 12 RNAs (8 mRNAs and 4 lncRNAs) named CIN-related dysregulated ceRNAs (CRDC) was obtained. The CRDC risk score had a positive relation with clinical stage and CIN, and patients with high CRDC risk scores exhibited poor prognosis. Moreover, CRDC tended to be an independent risk factor with high robustness to overcome the effect of multicollinearity among other explanatory variables for disease-specific survival (DSS) in TCGA and two GEO cohorts. The result of functional analysis indicated that CRDC was involved in multiple cancer progresses, especially immune-related pathways. The patients with lower CRDC risk had higher B cell, T cell CD4+, T cell CD8+, neutrophil, macrophage, and myeloid dendritic cell infiltration than the patients with higher CRDC risk. Meanwhile, patients with lower CRDC risk could get more benefits from immunological therapy. The results suggested that the CRDC could be a potential prognostic biomarker and an immunotherapy predictor for lung adenocarcinoma.

Introduction Hepatocellular carcinoma (HCC) ranks fourth in global cancer mortality, accounting for 8.2% of all cancer deaths. Early detection of HCC has a significant impact on clinical outcomes. The aim of this study was to identify blood-based biomarkers which are HCC-specific.Methods Comprehensive gene expression raw data of purified RNA of peripheral blood mononuclear cells (PBMC) was downloaded from GEO and was then analyzed. Differentially expressed genes (DEGs) in HCC were screened and the method of weighted gene co-expression network analysis was applied to identify candidate blood-based biomarkers associated with HCC.Results Three modules closely related to HCC were screened using WGCNA. Nuclear localization signal (NLS)-bearing protein import into nucleus biological process was the most significant enriched physiological process identified by MCODE, and 3 genes (DICER1, GMPS and NCOR1) were selected as biomarkers.Conclusion In our study, three novel blood-based HCC-specific diagnostic biomarkers for human hepatocellular carcinoma were identified. These findings may contribute to the non-invasive detection of early HCC patients.

The liver is an amazing organ due to its powerful regenerative capacity. Although many studies on liver regeneration have been documented, the detailed mechanisms remain unclear. Two-third partial hepatectomy (PH) in rodents plays a crucial role in the study of liver regeneration. In this study, the time series data of gene expression during liver regeneration in mouse were analyzed using the gene set numbered GSE6998 in GEO. A variety of bioinformatics methods, including masigPro, Weighted Gene Co-expression Network Analysis (WGCNA), spatial analysis of functional enrichment (SAFE) and ingenuity canonical pathway analysis (IPA) were used to identify and compare the significantly changed pathways, potential upstream regulators and key genes during liver regeneration. Our study showed that liver regeneration in the mouse is a coordinated process, which cell-cycle-related progress are at the centre of the interaction network involved in liver regeneration. Several candidate upstream regulators including PPARA, NFE2L2, MAD1 and CNR1 and some key genes such as Cdk1, Plk1, Cdc20, Aurka, Racgap1, Cenpa, Rrm1, Rrm2 were identified. In conclusion, these findings could contribute to revealing the molecular mechanism of liver regeneration after PH, which could provide new ideas and treatment methods for regenerative medicine, oncological drug development and oncological treatment.

There was an outbreak of Dengue fever on September 5, 2019, in Hainan Province, which has not been endemic for 28 years. We aim to describe the clinical and epidemiological features of the 2019 outbreak in Hainan Province and identify the cause. All type 1 Dengue fever cases that occurred in this outbreak of Hainan exhibited mild clinical symptoms. The epidemiological investigations indicate that the outbreak might originate from workers in the Xiuying area, Haikou City, form a concentrated outbreak, and then spread out. Bayesian phylogenies results and epidemiological data were used to infer a likely series of events for the dengue virus’s potential spread and trace the possible sources. The strains’ sequences were close to a sequence from the nearby Guangdong province, supporting the hypothesis that the dengue virus was imported from Guangdong province and then spread across Hainan province. Furthermore, it is interesting that two other strains didn’t group with this cluster, suggesting that additional introduction pathways might exist. The study indicated that the dengue fever epidemic presented two important modes in Hainan. Firstly, epidemics prevalence was caused by imported cases, and then endogenous epidemics broke out in the natural epidemic focus.

The midgut microbial community composition, structure, and function of field-collected mosquitoes may provide a way to exploit microbial function for mosquito-borne disease control. However, it is unclear how adult mosquitoes acquire their microbiome, how the microbiome affects life history traits and how the microbiome influences community structure. We analyzed the composition of 501 midgut bacterial communities from field-collected adult female mosquitoes, including Aedes albopictus, Aedes galloisi, Culex pallidothorax, Culex pipiens, Culex gelidus, and Armigeres subalbatus, across eight habitats using the HiSeq 4000 system and the V3−V4 hyper-variable region of 16S rRNA gene. After quality filtering and rarefaction, a total of 1421 operational taxonomic units, belonging to 29 phyla, 44 families, and 43 genera were identified. Proteobacteria (75.67%) were the most common phylum, followed by Firmicutes (10.38%), Bacteroidetes (6.87%), Thermi (4.60%), and Actinobacteria (1.58%). The genera Rickettsiaceae (33.00%), Enterobacteriaceae (20.27%), Enterococcaceae (7.49%), Aeromonadaceae (7.00%), Thermaceae (4.52%), and Moraxellaceae (4.31%) were dominant in the samples analyzed and accounted for 76.59% of the total genera. We characterized the midgut bacterial communities of six mosquito species in Hainan province, China. The gut bacterial communities were different in composition and abundance, among locations, for all mosquito species. There were significant differences in the gut microbial composition between some species and substantial variation in the gut microbiota between individuals of the same mosquito species. There was a marked variation in different mosquito gut microbiota within the same location. These results might be useful in the identification of microbial communities that could be exploited for disease control.

Hainan is a tropical island in southern China with abundant mosquito species, putting Hainan at risk of mosquito-borne virus disease outbreaks. The population genetic diversity of most mosquito species on Hainan Island remains elusive. In this study, we report the diversity of mosquito species and the genetic diversity of the predominant species on Hainan. Field populations of adults or larvae were collected from 12 regions of Hainan Island in 2018 and 2019. A fragment of the mitochondrial cytochrome c oxidase subunit I (coxI) gene was sequenced from 1,228 mosquito samples and used for species identification and genetic diversity analysis. Twenty-three known mosquito species from the genera Aedes, Armigeres, Culex, Mansonia, and Anopheles and nine unconfirmed mosquito species were identified. Aedes albopictus, Armigeres subalbatus, and Culex pipiens quinquefasciatus were the most prevalent mosquito species on Hainan. The regions north of Danzhou, Tunchang, and Qionghai exhibited high mosquito diversity (26 species). The order of the total haplotype diversity and nucleotide diversity of the populations from high to low was as follows: Culex tritaeniorhynchus, Ar. subalbatus, Culex pallidothorax, Culex gelidus, Ae. albopictus, and C. p. quinquefasciatus. Tajima’s D and Fu’s Fs tests showed that Ae. albopictus, C. p. quinquefasciatus, C. tritaeniorhynchus, and C. gelidus had experienced population expansion, while the Ar. subalbatus and C. pallidothorax populations were in genetic equilibrium. Significant genetic differentiation existed in the overall populations of Ae. albopictus, Ar. subalbatus, C. p. quinquefasciatus, and C. pallidothorax. The Ae. albopictus populations on Hainan were characterized by frequent gene exchange with populations from Guangdong and four other tropical countries, raising the risk of viral disease outbreaks in these regions. Two subgroups were reported in the Ar. subalbatus populations for the first time. Our findings may have important implications for vector control on Hainan Island.

Abstract Background: Suppurative parotitis caused by Burkholderia pseudomallei has been rarely found outside endemic areas. Case presentation: Herein, we report the recovery of Burkholderia pseudomallei from the pus of a suppurative parotitis observed in a 12-year-old boy who lived in Hainan province, China. Specimens of necrotic tissue were collected and sections were stained with hematoxylin and eosin. Pus sample was also collected for bacteriological examination. The suppurative inflammation was observed in the necrotic tissue section and Burkholderia pseudomallei were detected in the sample. Conclusion: In this adolescent, Burkholderia pseudomallei infection was present in the parotid, which consists of the first report of this bacterium in a parotitis case acquired in China.

Melioidosis is a severe tropical infectious disease caused by the soil-dwelling bacterium Burkholderia pseudomallei, predominantly endemic to Southeast Asia and northern Australia. Between the 1970s and the 1990s, the presence of B. pseudomallei causing melioidosis in humans and other animals was demonstrated in four coastal provinces in southern China: Hainan, Guangdong, Guangxi, and Fujian, although indigenous cases were rare and the disease failed to raise concern amongst local and national health authorities. In recent years, there has been a rise in the number of melioidosis cases witnessed in the region, particularly in Hainan. Meanwhile, although China has established and maintained an effective communicable disease surveillance system, it has not yet been utilized for melioidosis. Thus, the overall incidence, social burden and epidemiological features of the disease in China remain unclear. In this context, we present a comprehensive overview of both historical and current information on melioidosis in Southern China, highlighting the re-emergence of the disease in Hainan. Surveillance and management strategies for melioidosis should be promoted in mainland China, and more research should be conducted to provide further insights into the present situation.

Rhipicephalus sanguineus, a repulsive obligate blood feeder, is a three-host tick inflicting tremendous damage. Blood-sucking initiates tick-pathogen-host interactions along with alterations in the expression levels of numerous bioactive ingredients. Key molecules regulating blood meals were identified using the transcriptomic approach. A total number of 744 transcripts showed statistically significantly differential expression including 309 significantly upregulated transcripts and 435 significantly downregulated transcripts in semiengorged female ticks compared to unfed ticks, all collected in 2021. The top 10 differentially upregulated transcripts with explicit functional annotations included turripeptide OL55-like protein, valine tRNA ligase-like protein and ice-structuring glycoprotein-like protein. The top 10 differentially down-regulated transcripts were uncharacterized proteins. Gene Ontology (GO) enrichment analysis revealed four associated terms in the cellular component category and 16 in the molecular function category among the top 20 terms. Differentially expressed genes (DEGs) were enriched in GO terms ID 0000323 (lytic vacuole) and ID 0005773 (vacuole). The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included metabolism, cellular processes, organismal systems and human diseases. The DEGs were enriched in the KEGG term ID: ko-04142 (lysosome pathway) associated with intracellular digestion in the tick midgut epithelium. Molecular markers annotated via comparative transcriptomic profiling were expected to be candidate markers for the purpose of tick control. [ABSTRACT FROM AUTHOR]

Abstract Emerging evidence illustrates that osteoclasts (OCs) play diverse roles beyond bone resorption, contributing significantly to bone formation and regeneration. Despite this, OCs remain mysterious cells, with aspects of their lifespan—from origin, fusion, alterations in cellular characteristics, to functions—remaining incompletely understood. Recent studies have identified that embryonic osteoclastogenesis is primarily driven by osteoclast precursors (OCPs) derived from erythromyeloid progenitors (EMPs). These precursor cells subsequently fuse into OCs essential for normal bone development and repair. Postnatally, hematopoietic stem cells (HSCs) become the primary source of OCs, gradually replacing EMP-derived OCs and assuming functional roles in adulthood. The absence of OCs during bone development results in bone structure malformation, including abnormal bone marrow cavity formation and shorter long bones. Additionally, OCs are reported to have intimate interactions with blood vessels, influencing bone formation and repair through angiogenesis regulation. Upon biomaterial implantation, activation of the innate immune system ensues immediately. OCs, originating from macrophages, closely interact with the immune system. Furthermore, evidence from material-induced bone formation events suggests that OCs are pivotal in these de novo bone formation processes. Nevertheless, achieving a pure OC culture remains challenging, and interpreting OC functions in vivo faces difficulties due to the presence of other multinucleated cells around bone-forming biomaterials. We here describe the fusion characteristics of OCPs and summarize reliable markers and morphological changes in OCs during their fusion process, providing guidance for researchers in identifying OCs both in vitro and in vivo. This review focuses on OC formation, characterization, and the roles of OCs beyond resorption in various bone pathophysiological processes. Finally, therapeutic strategies targeting OCs are discussed.

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. Case presentation We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. Conclusions The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.