Phylogenomics and the rise of the angiosperms.

Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods1,2. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome3,4. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins5-7. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes8. This 15-fold increase in genus-level sampling relative to comparable nuclear studies9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

fhl2b mediates extraocular muscle protection in zebrafish models of muscular dystrophies and its ectopic expression ameliorates affected body muscles.

In muscular dystrophies, muscle fibers loose integrity and die, causing significant suffering and premature death. Strikingly, the extraocular muscles (EOMs) are spared, functioning well despite the disease progression. Although EOMs have been shown to differ from body musculature, the mechanisms underlying this inherent resistance to muscle dystrophies remain unknown. Here, we demonstrate important differences in gene expression as a response to muscle dystrophies between the EOMs and trunk muscles in zebrafish via transcriptomic profiling. We show that the LIM-protein Fhl2 is increased in response to the knockout of desmin, plectin and obscurin, cytoskeletal proteins whose knockout causes different muscle dystrophies, and contributes to disease protection of the EOMs. Moreover, we show that ectopic expression of fhl2b can partially rescue the muscle phenotype in the zebrafish Duchenne muscular dystrophy model sapje, significantly improving their survival. Therefore, Fhl2 is a protective agent and a candidate target gene for therapy of muscular dystrophies.

The relative and combined ability of stress hyperglycemia ratio and N-terminal pro-B-type natriuretic peptide to predict all-cause mortality in diabetic patients with multivessel coronary artery disease.

BACKGROUND: Stress hyperglycemia ratio (SHR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased mortality risk in diabetic patients with coronary artery disease (CAD). However, the role of these biomarkers in patients with diabetes and multivessel disease (MVD) remains unknown. The present study aimed to assess the relative and combined abilities of these biomarkers to predict all-cause mortality in patients with diabetes and MVD. METHODS: This study included 1148 diabetic patients with MVD who underwent coronary angiography at Tianjin Chest Hospital between January 2016 and December 2016. The patients were divided into four groups according to their SHR (SHR-L and SHR-H) and NT-proBNP (NT-proBNP-L and NT-proBNP-H) levels. The primary outcome was all-cause mortality. Multivariate Cox regression analyses were performed to evaluate the association of SHR and NT-proBNP levels with all-cause mortality. RESULTS: During a mean 4.2 year follow-up, 138 patients died. Multivariate analysis showed that SHR and NT-proBNP were strong independent predictors of all-cause mortality in diabetic patients with MVD (SHR: HR hazard ratio [2.171; 95%CI 1.566-3.008; P < 0.001; NT-proBNP: HR: 1.005; 95%CI 1.001-1.009; P = 0.009). Compared to patients in the first (SHR-L and NT-proBNP-L) group, patients in the fourth (SHR-H and NT-proBNP-H) group had the highest mortality risk (HR: 12.244; 95%CI 5.828-25.721; P < 0.001). The areas under the curve were 0.615(SHR) and 0.699(NT-proBNP) for all-cause mortality. Adding either marker to the original models significantly improved the C-statistic and integrated discrimination improvement values (all P < 0.05). Moreover, combining SHR and NT-proBNP levels into the original model provided maximal prognostic information. CONCLUSIONS: SHR and NT-proBNP independently and jointly predicted all-cause mortality in diabetic patients with MVD, suggesting that strategies to improve risk stratification in these patients should incorporate SHR and NT-porBNP into risk algorithms.

Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance.

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Pan-cancer analysis of NUP155 and validation of its role in breast cancer cell proliferation, migration, and apoptosis.

NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

EPC1/2 regulate hematopoietic stem and progenitor cell proliferation by modulating H3 acetylation and DLST.

Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1/2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells. This study demonstrates the functions of EPC1/2 in regulating histone H3 acetylation, and in regulating DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation and cooperating with transcription factors serum response factor and FOXR2 together, and in the subsequent HSPC emergence and proliferation. Our results demonstrate the essential roles of EPC1/2 in regulating H3 acetylation, and DLST as a linkage between EPC1 and EPC2 with mitochondria metabolism, in HSPC emergence and proliferation.

Data-driven hypothesis generation among inexperienced clinical researchers: A comparison of secondary data analyses with visualization (VIADS) and other tools.

Objectives: To compare how clinical researchers generate data-driven hypotheses with a visual interactive analytic tool (VIADS, a visual interactive analysis tool for filtering and summarizing large datasets coded with hierarchical terminologies) or other tools. Methods: We recruited clinical researchers and separated them into "experienced" and "inexperienced" groups. Participants were randomly assigned to a VIADS or control group within the groups. Each participant conducted a remote 2-hour study session for hypothesis generation with the same study facilitator on the same datasets by following a think-aloud protocol. Screen activities and audio were recorded, transcribed, coded, and analyzed. Hypotheses were evaluated by seven experts on their validity, significance, and feasibility. We conducted multilevel random effect modeling for statistical tests. Results: Eighteen participants generated 227 hypotheses, of which 147 (65%) were valid. The VIADS and control groups generated a similar number of hypotheses. The VIADS group took a significantly shorter time to generate one hypothesis (e.g., among inexperienced clinical researchers, 258 s versus 379 s, p = 0.046, power = 0.437, ICC = 0.15). The VIADS group received significantly lower ratings than the control group on feasibility and the combination rating of validity, significance, and feasibility. Conclusion: The role of VIADS in hypothesis generation seems inconclusive. The VIADS group took a significantly shorter time to generate each hypothesis. However, the combined validity, significance, and feasibility ratings of their hypotheses were significantly lower. Further characterization of hypotheses, including specifics on how they might be improved, could guide future tool development.

Survey and clinical considerations of gender identity in lower primary school children.

BACKGROUND: Gender consciousness directly affects the development of gender identity, which is a continuous and lifelong process. Meanwhile, hospitalization is a part of many children's lives and has an impact on their gender development. AIM: To investigate the current situation of gender identity in lower primary school children by conducting a survey of 202 hospitalized children in the lower grades and to provide a theoretical basis and foundation for the cultivation of gender identity and medical treatment of children based on the results. This study aims to inspire clinical medical staff to scientifically and reasonably arrange hospital wards for lower primary school children and pay attention to gender protection during the medical treatment process and to help children shape a unified and clear gender identity, which will enable them to better integrate into society and promote their personality development. METHODS: The gender consciousness scale for elementary and middle school students was used for the survey. RESULTS: Gender identity was already present in lower primary school children. The children's gender roles and gender equality consciousness were strong, exceeding the critical value, but their gender characteristics, gender identity, and gender ideal consciousness were weak. Children aged 6 had the weakest gender identity, and girls had significantly stronger gender identity than boys. CONCLUSION: Gender identity is already present in lower primary school children, providing a basis and inspiration for the cultivation of gender identity and medical treatment of lower primary school children. Clinical medical staff should be aware of and understand these results and should scientifically and reasonably arrange hospital wards for lower primary school children.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Obscurin Maintains Myofiber Identity in Extraocular Muscles.

Purpose: The cytoskeleton of the extraocular muscles (EOMs) is significantly different from that of other muscles. We aimed to investigate the role of obscurin, a fundamental cytoskeletal protein, in the EOMs. Methods: The distribution of obscurin in human and zebrafish EOMs was compared using immunohistochemistry. The two obscurin genes in zebrafish, obscna and obscnb, were knocked out using CRISPR/Cas9, and the EOMs were investigated using immunohistochemistry, qPCR, and in situ hybridization. The optokinetic reflex (OKR) in five-day-old larvae and adult obscna-/-;obscnb-/- and sibling control zebrafish was analyzed. Swimming distance was recorded at the same age. Results: The obscurin distribution pattern was similar in human and zebrafish EOMs. The proportion of slow and fast myofibers was reduced in obscna-/-;obscnb-/- zebrafish EOMs but not in trunk muscle, whereas the number of myofibers containing cardiac myosin myh7 was significantly increased in EOMs of obscurin double mutants. Loss of obscurin resulted in less OKRs in zebrafish larvae but not in adult zebrafish. Conclusions: Obscurin expression is conserved in normal human and zebrafish EOMs. Loss of obscurin induces a myofiber type shift in the EOMs, with upregulation of cardiac myosin heavy chain, myh7, showing an adaptation strategy in EOMs. Our model will facilitate further studies in conditions related to obscurin.

Deficiency of copper responsive gene stmn4 induces retinal developmental defects.

As part of the central nervous system (CNS), the retina senses light and also conducts and processes visual impulses. The damaged development of the retina not only causes visual damage, but also leads to epilepsy, dementia and other brain diseases. Recently, we have reported that copper (Cu) overload induces retinal developmental defects and down-regulates microtubule (MT) genes during zebrafish embryogenesis, but whether the down-regulation of microtubule genes mediates Cu stress induced retinal developmental defects is still unknown. In this study, we found that microtubule gene stmn4 exhibited obviously reduced expression in the retina of Cu overload embryos. Furthermore, stmn4 deficiency (stmn4-/-) resulted in retinal defects similar to those seen in Cu overload embryos, while overexpression of stmn4 effectively rescued retinal defects and cell apoptosis occurred in the Cu overload embryos and larvae. Meanwhile, stmn4 deficient embryos and larvae exhibited reduced mature retinal cells, the down-regulated expression of microtubules and cell cycle-related genes, and the mitotic cell cycle arrests of the retinal cells, which subsequently tended to apoptosis independent on p53. The results of this study demonstrate that Cu stress might lead to retinal developmental defects via down-regulating expression of microtubule gene stmn4, and stmn4 deficiency leads to impaired cell cycle and the accumulation of retinal progenitor cells (RPCs) and their subsequent apoptosis. The study provides a certain referee for copper overload in regulating the retinal development in fish.

Copper nanoparticles and silver nanoparticles impair lymphangiogenesis in zebrafish.

Lymphatic system distributes in almost all vertebrate tissues and organs, and plays important roles in the regulation of body fluid balance, lipid absorption and immune monitoring. Although CuNPs or AgNPs accumulation has been reported to be closely associated with delayed hatching and motor dysfunction in zebrafish embryos, their biological effects on lymphangiogenesis remain unknown. In this study, thoracic duct was observed to be partially absent in both CuNPs and AgNPs stressed zebrafish larvae. Specifically, CuNPs stress induced hypermethylation of E2F7/8 binding sites on CCBE1 promoters via their producing ROS, thereby leading to the reduction of binding enrichment of E2F7/8 on CCBE1 promoter and its subsequently reduced expression, then resulting in defective lymphatic vessel formation. Differently, AgNPs stress induced down-regulated CCBE1 expression via down-regulating mRNA and protein levels of E2F7/8 transcription factors, thereby resulting in defective lymphatic vessel formation. This study may be the first to demonstrate that CuNPs and AgNPs damaged lymphangiogenesis during zebrafish embryogenesis, mechanistically, CuNPs epigenetically regulated the expression of lymphangiogenesis regulator CCBE1 via hypermethylating its promoter binding sites of E2F7/8, while AgNPs via regulating E2F7/8 expression. Meanwhile, overexpression of ccbe1 mRNA effectively rescued the lymphangiogenesis defects in both AgNPs and CuNPs stressed larvae, while overexpression of e2f7/8 mRNA effectively rescued the lymphangiogenesis defects in AgNPs rather than CuNPs stressed larvae. The results in this study will shed some light on the safety assessment of nanomaterials applied in medicine and on the ecological security assessments of nanomaterials. Video Abstract.

Lonicera japonica protects Pelodiscus sinensis by inhibiting the biofilm formation of Aeromonas hydrophila.

Aquaculture has suffered significant financial losses as a result of the infection of zoonotic Aeromonas hydrophila, which has a high level of resistance to classic antibiotics. In this study, we isolated an A. hydrophila strain B3 from diseased soft-shelled turtle (Pelodiscus sinensis), which is one of the most commercially significant freshwater farmed reptiles in East Asia, and found that A. hydrophila was its dominant pathogen. To better understand the inhibition effect and action mechanism of Chinese herbs on A. hydrophila, we conducted Chinese herbs screening and found that Lonicera japonica had a significant antibacterial effect on A. hydrophila B3. Experimental therapeutics of L. japonica on soft-shelled turtle showed that the supplement of 1% L. japonica to diet could significantly upregulate the immunity-related gene expression of soft-shelled turtle and protect soft-shelled turtle against A. hydrophila infection. Histopathological section results validated the protective effect of L. japonica. As the major effective component of L. japonica, chlorogenic acid demonstrated significant inhibitory effect on the growth of A. hydrophila with MIC at 6.4 mg/mL. The in vitro assay suggested that chlorogenic acid could inhibit the hemolysin/protease production and biofilm formation of A. hydrophila and significantly decrease the expression of quorum sensing, biofilm formation, and hemolysin-related genes in A. hydrophila. Our results showed that the Chinese herb L. japonica would be a promising candidate for the treatment of A. hydrophila infections in aquaculture, and it not only improves the immune response of aquatic animals but also inhibits the virulence factor (such as biofilm formation) expression of A. hydrophila. KEY POINTS: • A. hydrophila was the dominant pathogen of the diseased soft-shelled turtle. • L. japonica can protect soft-shelled turtle against A. hydrophila infection. • Chlorogenic acid inhibits the growth and biofilm formation of A. hydrophila.

Copper overload induces apoptosis and impaired proliferation of T cell in zebrafish.

Copper is an essential biometal for cell development and function, however, unbalanced copper homeostasis in T cell development and the underlying mechanisms are largely unexplored. Here, we use a zebrafish model to investigate the effect of copper overload in T cell development. We show that copper stressed zebrafish larvae exhibit a significant reduction in T cells with increased cell apoptosis and impaired cell proliferation. T cell progenitors, hematopoietic stem and progenitor cells, also exhibit increased cell apoptosis. Copper overload induces production of ROS and the down-regulations of its resistance genes foxos, and ectopic expression of foxo3a, ROS scavenger GSH, could both effectively rescue the reduction of T cells in copper overload larvae. Moreover, foxm1-cytoskeleton axis, parallel to ROS-foxo axis, also mediates the copper overload induced T cell developmental defects. Meanwhile, ROS destroys expression of cytoskeleton rather than of foxm1 in the cells to induce cell apoptosis and the impaired proliferation. The functional integrity of copper transporters cox17 and atp7b are required for copper stress in inducing T cell apoptosis and proliferation impairment. Our findings demonstrate that the down-stream ROS-foxo/cytoskeleton and foxm1-cytoskeleton signaling pathways contribute jointly to copper overload induced T cell apoptosis and proliferation defects, which are depend on the integral function of Cox17 and Atp7b, and provide new insight into the copper homeostasis in T lymphocyte development.

How do clinical researchers generate data-driven scientific hypotheses? Cognitive events using think-aloud protocol.

Objectives: This study aims to identify the cognitive events related to information use (e.g., "Analyze data", "Seek connection") during hypothesis generation among clinical researchers. Specifically, we describe hypothesis generation using cognitive event counts and compare them between groups. Methods: The participants used the same datasets, followed the same scripts, used VIADS (a visual interactive analysis tool for filtering and summarizing large data sets coded with hierarchical terminologies) or other analytical tools (as control) to analyze the datasets, and came up with hypotheses while following the think-aloud protocol. Their screen activities and audio were recorded and then transcribed and coded for cognitive events. Results: The VIADS group exhibited the lowest mean number of cognitive events per hypothesis and the smallest standard deviation. The experienced clinical researchers had approximately 10% more valid hypotheses than the inexperienced group. The VIADS users among the inexperienced clinical researchers exhibit a similar trend as the experienced clinical researchers in terms of the number of cognitive events and their respective percentages out of all the cognitive events. The highest percentages of cognitive events in hypothesis generation were "Using analysis results" (30%) and "Seeking connections" (23%). Conclusion: VIADS helped inexperienced clinical researchers use fewer cognitive events to generate hypotheses than the control group. This suggests that VIADS may guide participants to be more structured during hypothesis generation compared with the control group. The results provide evidence to explain the shorter average time needed by the VIADS group in generating each hypothesis.

Enhancing Leaf Area Index Estimation for Maize with Tower-Based Multi-Angular Spectral Observations.

The leaf area index (LAI) played a crucial role in ecological, hydrological, and climate models. The normalized difference vegetation index (NDVI) has been a widely used tool for LAI estimation. However, the NDVI quickly saturates in dense vegetation and is susceptible to soil background interference in sparse vegetation. We proposed a multi-angular NDVI (MAVI) to enhance LAI estimation using tower-based multi-angular observations, aiming to minimize the interference of soil background and saturation effects. Our methodology involved collecting continuous tower-based multi-angular reflectance and the LAI over a three-year period in maize cropland. Then we proposed the MAVI based on an analysis of how canopy reflectance varies with solar zenith angle (SZA). Finally, we quantitatively evaluated the MAVI's performance in LAI retrieval by comparing it to eight other vegetation indices (VIs). Statistical tests revealed that the MAVI exhibited an improved curvilinear relationship with the LAI when the NDVI is corrected using multi-angular observations (R2 = 0.945, RMSE = 0.345, rRMSE = 0.147). Furthermore, the MAVI-based model effectively mitigated soil background effects in sparse vegetation (R2 = 0.934, RMSE = 0.155, rRMSE = 0.157). Our findings demonstrated the utility of tower-based multi-angular spectral observations in LAI retrieval, having the potential to provide continuous data for validating space-borne LAI products. This research significantly expanded the potential applications of multi-angular observations.

Baicalin Relieves Airway Inflammation in COPD by Inhibiting miR-125a.

To investigate the effects of Baicalin on the apoptosis of human bronchial epithelial cells (16HBE) induced by cigarette smoke extract (CSE) and the release of inflammatory factors, and to clarify its possible mechanism. CSE was used to treat 16HBE cells and construct COPD cell model. The activity of 16HBE cells was detected by CCK-8 and BrdU. Real-time fluorescence quantitative PCR (RT-QPCR) was used to detect the expression level of miR-125a in each group of 16HBE cells. At the same time, the levels of 16HBE inflammatory cytokines IL-1ß, IL-8, IL-6, and TNF-α were detected. The apoptosis rate of 16HBE cells in each group was detected by TUNEL. Compared with the control group, the proliferation of 16HBE cells in CSE group was decreased. Baicalin reversed the effect of 2% CSE on the proliferation of 16HBE cells. Baicalin also reversed the effect of 2% CSE on apoptosis and inflammatory factors in 16HBE cells. miR-125a is highly expressed in COPD, and Baicalin can inhibit the expression of miR-125a. Silencing miR-125a reduces apoptosis and inflammatory response of 16HBE cells in COPD. miR-125a reversed the effects of Baicalin on apoptosis and inflammation of 16HBE cells. Baicalin can reduce CSE-induced apoptosis of human bronchial epithelial cells and release of inflammatory factors, and its mechanism may be related to the inhibition of miR-125a.

Metagenomic analysis of individual mosquitos reveals the ecology of insect viruses.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Using a meta-transcriptomic approach, we analysed the virome of 2,438 individual mosquitos (79 species), spanning ~4000 km along latitudes and longitudes in China. From these data we identified 393 core viral species associated with mosquitos, including seven (putative) arbovirus species. We identified potential species and geographic hotspots of viral richness and arbovirus occurrence, and demonstrated that host phylogeny had a strong impact on the composition of individual mosquito viromes. Our data revealed a large number of viruses shared among mosquito species or genera, expanding our knowledge of host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, possibly facilitated by long-distance mosquito migrations. Together, our results greatly expand the known mosquito virome, linked the viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the ecology of viruses of insect vectors.