Targeting TRPV1 signaling: Galangin improves ethanol-induced gastric mucosal injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Galangin, a bioactive compound extracted from Alpinia officinarum Hance (Zingiberaceae), a plant with significant ethnopharmacological importance, has been used for thousands of years as a spice, condiment, and medicinal agent for various conditions, including gastrointestinal disorders. Although there is evidence suggesting its potential to improve gastric ulcers, the molecular mechanisms underlying its anti-ulcer properties are not fully understood. OBJECTIVE: of the Study: This study aimed to investigate the effects of galangin on ethanol-induced acute gastric mucosal injury (AGMI) in mice and elucidate its molecular mechanisms. MATERIALS AND METHODS: Sixty BALB/c mice were randomly assigned into two main groups: a normal control group (n = 10) and an ethanol-induced group (n = 50). After establishing the AGMI model in mice using a combination of 40% ethanol and anhydrous ethanol, the ethanol-induced group was further subdivided into five subgroups (n = 10): an omeprazole control group (20 mg/kg), an untreated ethanol group, and three treatment groups receiving high-dose (50 mg/kg) or low-dose (25 mg/kg) galangin or capsazepine (CPZ, 2 mg/kg). The protective effects of galangin were evaluated through mucosal injury indices, hematoxylin and eosin staining, and quantification of inflammatory markers (IL-1ß, IL-6, IL-8, and TNF-α). Oxidative stress levels and matrix metalloproteinase activity were measured using specific assay kits. Molecular docking was conducted to assess the binding affinity of galangin to key proteins within the transient receptor potential vanilloid 1 (TRPV1) pathway. Real-time fluorescence quantitative PCR (qPCR) was used to determine mRNA expression levels of TRPV1, calmodulin (CaM), substance P (SP), and CGRP in gastric tissues. Protein expression levels of TRPV1, nerve growth factor (NGF), tropomyosin receptor kinase A (TRKA), transforming growth factor beta (TGF-ß), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) were assessed through Western blot analysis. In cellular experiments, Culture of Human Gastric Epithelial Cells (GES-1) were treated with various concentrations of galangin after 7% ethanol induction. Cell proliferation, apoptosis, and migration were evaluated using Hoechst 33258 staining and transwell migration assays. TRPV1 protein expression was detected using immunofluorescence, and the expression levels of Bcl-2, BCL2-Associated X (BAX), and Caspase-3 were quantified by qPCR. Additionally, specific probe kits were used to measure intracellular calcium ions (Ca2+) and mitochondrial membrane potential. RESULTS: The findings indicate that galangin significantly improved mucosal pathology by reducing ulcer indices and inflammatory levels, while enhancing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) concentration. Galangin also reduced matrix metalloproteinase-2 (MMP-2), m metalloproteinase-9 (MMP-9) levels, promoting mucosal repair. At the cellular level, galangin decreased intracellular calcium ion concentration and mitigated the decline in mitochondrial membrane potential, enhance the restoration of mucosal cells, increased migration and proliferation, and reduced apoptosis. Molecularly, galangin demonstrated favorable binding to TRPV1, NGF, TRKA, TGF-ß, COX-2, and NF-κB, and reversed the elevated expression of these proteins. Additionally, galangin downregulated the mRNA expression of TRPV1, CaM, SP, CGRP, BAX, and Caspase-3 in gastric tissues/cells, while upregulating Bcl-2 mRNA expression. CONCLUSION: Galangin mitigates AGMI by inhibiting the overactivation of the TRPV1 pathway, thereby blocking aberrant signal transduction. This study suggests that galangin has therapeutic potential against ethanol-induced AGMI and may be a viable alternative for the treatment of alcohol-induced gastric mucosal injuries.

Money for operator: the impact of linked agricultural subsidy on incomes.

The reform of China's "three subsidies" has shifted the method of subsidization from payment based on the contracted area to payment based on the actual operational area. Within this context, studying the income-generating impact of the "three subsidies" holds significant practical relevance. Using data from the 2018 China Labor-force Dynamic Survey, this paper employs basic estimation, mediating effect, and moderating effect models to analyze the heterogeneity of agricultural subsidies' impact on rural household income, the mediating effect of agricultural mechanization, and the moderating effect of operation scale. Our findings indicate that agricultural subsidies, known as the "three subsidies", have increased total rural household income and agricultural income while decreasing wage income. However, they have shown no significant impact on business income. Notably, agricultural subsidies have significantly elevated the income of food-producing households, with agricultural mechanization partially mediating this effect. Operation scale positively moderates the impact of agricultural subsidies on rural household income and agricultural mechanization. Heterogeneity analysis indicates that agricultural subsidies have a more significant impact on rural household income among agricultural producers in the eastern region.

Classification of a Massive Number of Viral Genomes and Estimation of Time of Most Recent Common Ancestor (tMRCA) of SARS-CoV-2 Using Phylodynamic Analysis.

Estimating the time of most recent common ancestor (tMRCA) is important to trace the origin of pathogenic viruses. This analysis is based on the genetic diversity accumulated in a certain time period. There have been thousands of mutant sites occurring in the genomes of SARS-CoV-2 since the COVID-19 pandemic started; six highly linked mutation sites occurred early before the start of the pandemic and can be used to classify the genomes into three main haplotypes. Tracing the origin of those three haplotypes may help to understand the origin of SARS-CoV-2. In this article, we present a complete protocol for the classification of SARS-CoV-2 genomes and calculating tMRCA using Bayesian phylodynamic method. This protocol may also be used in the analysis of other viral genomes. Key features • Filtering and alignment of a massive number of viral genomes using custom scripts and ViralMSA. • Classification of genomes based on highly linked sites using custom scripts. • Phylodynamic analysis of viral genomes using Bayesian evolutionary analysis sampling trees (BEAST). • Visualization of posterior distribution of tMRCA using Tracer.v1.7.2. • Optimized for the SARS-CoV-2.

Design, Synthesis, and Anti-Hepatocellular Carcinoma Evaluation of Sesquiterpene Lactone Epimers Trilobolide-6-O-isobutyrate Analogs.

Hepatocellular carcinoma (HCC), one of the most common malignant cancers with a low 5-year survival rate, is the third leading cause of cancer-related deaths worldwide. The finding of novel agents and strategies for the treatment of HCC is an urgent need. Sesquiterpene lactones (SLs) have attracted extensive attention because of their potent antitumor activity. In this study, a new series of SL derivatives (3-18) were synthesized using epimers 1 and 2 as parent molecules, isolated from Sphagneticola trilobata, and evaluated for their anti-HCC activity. Furthermore, the structures of 4, 6, and 14 were confirmed by X-ray single-crystal diffraction analyses. The cytotoxic activities of 3-18 on two HCC cell lines, including HepG2 and Huh7, were evaluated using the CCK-8 assay. Among them, compound 10 exhibited the best activity against the HepG2 and Huh7 cell lines. Further studies showed that 10 induced cell apoptosis, arrested the cell cycle at the S phase, and induced the inhibition of cell proliferation and migration in HepG2 and Huh7. In addition, absorption, distribution, metabolism, and excretion (ADME) properties prediction showed that 10 may possess the properties to be a drug candidate. Thus, 10 may be a promising lead compound for the treatment of HCC.

Polyvinyl alcohol films incorporated with clove essential oil emulsions stabilized by soy protein isolate-derived amyloid fibrils: Fabrication, characterization, and its application for active packaging.

This study aimed to prepare a novel emulsion film with high stability, using soy protein-derived amyloid fibrils (SAFs) as an emulsifier incorporating clove essential oil (CEO) as the active component, and the polyvinyl alcohol (PVA) matrix to stabilize the system. The results demonstrated that SAFs can successfully stabilize CEO. Emulsion prepared by SAFS and CEO (SAC) exhibited a small droplet size and better dispersibility compared with SPI and CEO (SC) emulsion. According to FT-IR results, PVA addition increased the hydrogen bond interactions among emulsion film components, thus further reinforcing the protein matrix, increasing the tensile strength (TS) (41.18 MPa) and elongation at break (E) (121.62 %) of the films. The uniform appearance of SAC-PVA (SACP) emulsion films was confirmed by SEM images. Furthermore, SACP emulsion films show distinctive barrier properties, optical properties, and outstanding antioxidant properties. Finally, emulsion films exhibited excellent preservation of strawberries, resulting in an effective decline of the decay rate.

RNA-Seq-Based Transcriptomics and GC-MS Quantitative Analysis Reveal Antifungal Mechanisms of Essential Oil of Clausena lansium (Lour.) Skeels Seeds against Candida albicans.

Infections caused by Candida albicans (C. albicans) and increasing resistance to commonly used drugs lead to a variety of mucosal diseases and systemic infectious diseases. We previously confirmed that the essential oil of Clausena lansium (Lour.) Skeels seeds (CSEO) had antifungal activity against C. albicans, but the detailed mechanism between the chemical components and antifungal activity is unclear. In this study, a quantitative analysis of five volatile components of CSEO, including sabinene, α-phellandrene, ß-phellandrene, 4-terpineol, and ß-caryophyllene, was carried out using the gas chromatography-mass spectrometry (GC-MS) method. Both the broth dilution and kinetic growth methods proved that the antifungal activity of CSEO against fluconazole-resistant C. albicans was better than that of its main components (sabinene and 4-terpineol). To further investigate the inhibitory mechanism, the transcriptional responses of C. albicans to CSEO, sabinene, and 4-terpineol treatment were determined based on RNA-seq. The Venn diagram and clustering analysis pattern of differential expression genes showed the mechanism of CSEO and 4-terpineol's anti-C. albicans activity might be similar from the perspective of the genes. Functional enrichment analysis suggested that CSEO regulated adherence-, hyphae-, and biofilm-formation-related genes, which may be CSEO's active mechanism of inhibiting the growth of fluconazole-resistant C. albicans. Overall, we preliminarily revealed the molecular mechanism between the chemical components and the antifungal activity of CSEO against C. albicans. This study provides new insights to overcome the azole resistance of C. albicans and promote the development and application of C. lansium (Lour.) Skeels seeds.

Diversity and structure of the root-associated bacterial microbiomes of four mangrove tree species, revealed by high-throughput sequencing.

Background: Root-associated microbes of the mangrove trees play important roles in protecting and maintaining mangrove ecosystems. At present, most of our understanding of mangrove root-related microbial diversity is obtained from specific mangrove species in selected geographic regions. Relatively little is known about the composition of the bacterial microbiota existing in disparate mangrove species microenvironments, particularly the relationship among different mangrove species in tropical environments. Methods: We collected the root, rhizosphere soil, and non-rhizosphere soil of four mangrove trees (Acanthus ilicifolius, Bruguiera gymnorrhiza, Clerodendrum inerme, and Lumnitzera racemosa) and detected the 16S rRNA gene by a conventional PCR. We performed high throughput sequencing using Illumina Novaseq 6000 platform (2 × 250 paired ends) to investigate the bacterial communities related with the different mangrove species. Results: We analyzed the bacterial diversity and composition related to the diverse ecological niches of mangrove species. Our data confirmed distinct distribution patterns of bacterial communities in the three rhizocompartments of the four mangrove species. Microbiome composition varied with compartments and host mangrove species. The bacterial communities between the endosphere and the other two compartments were distinctly diverse independent of mangrove species. The large degree of overlap in critical community members of the same rhizocompartment across distinct mangrove species was found at the phylum level. Furthermore, this is the first report of Acidothermus found in mangrove environments. In conclusion, understanding the complicated host-microbe associations in different mangrove species could lay the foundation for the exploitation of the microbial resource and the production of secondary metabolites.

Cytotoxic Indole Diterpenoids from a Sphagneticola trilobata-Derived Fungus Aspergillus sp. PQJ-1.

Two new indole diterpene derivatives, 5S-hydroxy-ß-aflatrem (1) and 14R-hydroxy-ß-aflatrem (2), along with one known analogue, 14-(N,N-dimethl-L-valyloxy)paspalinine (3), were isolated from the fermentation broth of the fungus Aspergillus sp. PQJ-1 derived from Sphagneticola trilobata. The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. All the compounds (1-3) were evaluated for their cytotoxicity against A549, Hela, Hep G2, and MCF-7 cell lines. Compounds 1 and 2 exhibited selective inhibition against Hela cells. Further studies showed that 1 significantly induced apoptosis and suppressed migration and invasion in Hela cells. Moreover, 1 could up-regulate pro-apoptotic genes BAX and Caspase-3 and down-regulate anti-apoptotic genes Bcl-xL and XIXP.

The long non-coding RNA BBOX1 antisense RNA 1 is upregulated in polycystic ovary syndrome (PCOS) and suppresses the role of microRNA-19b in the proliferation of ovarian granulose cells : Short title: BBOX1 antisense RNA 1 in cell proliferation.

BACKGROUND: MicroRNA-19b (miR-19b) has been reported to be downregulated in polycystic ovary syndrome (PCOS), while its upstream regulators are unclear. We speculated that miR-19b could potentially form a binding relationship with BBOX1 antisense RNA 1 (BBOX1-AS1), a long non-coding RNA recognized for its critical role in ovarian cancer. Subsequently, we investigated into their interaction in PCOS. METHODS: The expression of miR-19b and BBOX1-AS1 in follicular fluid from both control women (n = 80) and women with PCOS (n = 80) was detected by RT-qPCR. Correlations were analyzed with Pearson' correlation coefficient. The binding of miR-19b to the wild-type (-wt) ad mutant (-mut) BBOX1-AS1 was determined by RNA-RNA pulldown assay. Their interactions were detected by overexpression assay. Bromodeoxyuridine (BrdU) assay was applied for proliferation analysis. RESULTS: BBOX1-AS1 was highly upregulated, while miR-19b was downregulated in PCOS. There was no close correlation across PCOS and the control samples. Consistently, they did not regulate the expression of each other in granulosa cells. However, BBOX1-AS1-wt, but not BBOX1-AS1-mut, could directly interact with miR-19b. BBOX1-AS1 suppressed the role of miR-19b in inhibiting granulosa cell proliferation. CONCLUSION: BBOX1-AS1 is highly upregulated in PCOS, and it may serve as an endogenous competing RNA for miR-19b to suppress its role in inhibiting granulosa cell proliferation. Our study suggested the role of BBOX1-AS1 as a potential target to treat PCOS.

DNA self-assembly nanoflower reverse P-glycoprotein mediated drug resistance in chronic myelogenous leukemia therapy.

Introduction: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder caused by the BCR-ABL chimeric tyrosine kinase. Vincristine (VCR) is widely used in leukemia therapy but is hindered by multidrug resistance (MDR). Methods: We prepared DNA nanoflower via self-assembly for the delivery of VCR and P-glycoprotein small interfering RNA (P-gp siRNA). Results and Discussion: The as-prepared nanoflower had a floriform shape with high loading efficiency of VCR (80%). Furthermore, the nanoflower could deliver VCR and P-gp siRNA into MDR CML cells and induce potent cytotoxicity both in vitro and in vivo, thus overcoming MDR of CML. Overall, this nanoflower is a promising tool for resistant CML therapy.

Genome characterization based on the Spike-614 and NS8-84 loci of SARS-CoV-2 reveals two major possible onsets of the COVID-19 pandemic.

The global COVID-19 pandemic has lasted for 3 years since its outbreak, however its origin is still unknown. Here, we analyzed the genotypes of 3.14 million SARS-CoV-2 genomes based on the amino acid 614 of the Spike (S) and the amino acid 84 of NS8 (nonstructural protein 8), and identified 16 linkage haplotypes. The GL haplotype (S_614G and NS8_84L) was the major haplotype driving the global pandemic and accounted for 99.2% of the sequenced genomes, while the DL haplotype (S_614D and NS8_84L) caused the pandemic in China in the spring of 2020 and accounted for approximately 60% of the genomes in China and 0.45% of the global genomes. The GS (S_614G and NS8_84S), DS (S_614D and NS8_84S), and NS (S_614N and NS8_84S) haplotypes accounted for 0.26%, 0.06%, and 0.0067% of the genomes, respectively. The main evolutionary trajectory of SARS-CoV-2 is DS→DL→GL, whereas the other haplotypes are minor byproducts in the evolution. Surprisingly, the newest haplotype GL had the oldest time of most recent common ancestor (tMRCA), which was May 1 2019 by mean, while the oldest haplotype DS had the newest tMRCA with a mean of October 17, indicating that the ancestral strains that gave birth to GL had been extinct and replaced by the more adapted newcomer at the place of its origin, just like the sequential rise and fall of the delta and omicron variants. However, the haplotype DL arrived and evolved into toxic strains and ignited a pandemic in China where the GL strains had not arrived in by the end of 2019. The GL strains had spread all over the world before they were discovered, and ignited the global pandemic, which had not been noticed until the virus was declared in China. However, the GL haplotype had little influence in China during the early phase of the pandemic due to its late arrival as well as the strict transmission controls in China. Therefore, we propose two major onsets of the COVID-19 pandemic, one was mainly driven by the haplotype DL in China, the other was driven by the haplotype GL globally.

Follicular Fluid-Derived Small Extracellular Vesicles Alleviate DHEA-Induced Granulosa Cell Apoptosis by Delivering LINC00092.

Polycystic ovary syndrome (PCOS) is a perplexing condition in females of reproductive age. Dysplasia of ovarian granulosa cell (GC) is implicated in PCOS. Follicular fluid (FF)-extracellular vesicles (Evs) are important in cell-cell communication during follicular development. The current study elaborated on the function and mechanism of FF-Evs in the viability and apoptosis of GC cells in PCOS development. Human GC cells KGN were treated with dehydroepiandrosterone (DHEA) to mimic a PCOS-like condition in vitro, which were further co-cultured with the FF-derived Evs (FF-Evs). The FF-Evs treatment significantly reduced DHEA-induced apoptosis of KGN cells while promoting cell viability and migration. The lncRNA microarray analysis showed that FF-Evs mainly deliver LINC00092 into the KGN cells. Knockdown of LINC00092 negated the protective effect of FF-Evs against DHEA-induced damage on KGN cells. Moreover, by performing bioinformatics analyses and biotin-labeled RNA pull-down assay, we found that LINC00092 could bind to the RNA binding protein LIN28B and inhibit its binding to pre-microRNA-18-5p, which allowed biogenesis of pre-miR-18-5p and increased the expression of miR-18b-5p, a miRNA with known alleviating role in PCOS by suppressing the PTEN mRNA. Collectively, the present work demonstrates that FF-Evs can alleviate DHEA-induced GC damage by delivering LINC00092.

LINC00092 derived from follicular fluid alleviated the symptoms of PCOS through inactivation of phosphatase and tensin homolog by recruiting KDM5A.

Mounting literatures suggest that follicular fluid-derived exosomes (FF-Evs) influence the progression of progression of polycystic ovary syndrome (PCOS). The present study was designed to dissect the underlying mechanisms by which FF-Evs affect the PCOS. A rat model of PCOS was established using Letrozole induction. After treatment with FF-Evs, rats were examined for alterations in hormones, blood glucose, and lipid levels in serum, oestrus cycle, pathology in the ovaries, and apoptosis of ovarian cells. The functional rescue assays were performed to analyze the impact of long non-coding RNA 00092 (LINC00092) on PCOS rats. The cis-regulatory elements involved in the regulation of phosphatase and tensin homolog (PTEN) expression were analyzed using bioinformatic analysis, followed by verification of the mechanism. FF-Evs treatment ameliorated Letrozole-induced enhancement of weight, insulin resistance, dyslipidemia, and LH/FSH ratio, reduction of luteal cells, granulosa cells, and healthy follicles, prolonged oestrus, oestrous cycle arrest, ovarian tissue fibrosis, and ovarian cell apoptosis in rats, which were counteracted by treatment with shRNA targeting LINC00092. Regarding the mechanism, FF-Evs augmented LINC00092 expression in rats. LINC00092 bound to lysine demethylase 5 A (KDM5A), and KDM5A facilitated the demethylation of H3K4me3 to restrain the transcriptional activity of PTEN. Taken together, FF-Evs delivered LINC00092 repressed the transcriptional activity of PTEN by binding to KDM5A to enhance demethylation of H3K4me3, thereby reducing apoptosis in ovarian cells and alleviating PCOS symptoms.

In-Depth Insight into the Ag/CNQDs/g-C3N4 Photocatalytic Degradation of Typical Antibiotics: Influence Factor, Mechanism and Toxicity Evaluation of Intermediates.

In this paper, the photocatalytic degradation efficiency of typical antibiotics (norfloxacin (NOR), sulfamethoxazole (SMX) and tetracycline hydrochloride (TCH)) by Ag/CNQDs/g-C3N4 under visible light irradiation was studied. Various strategies were applied to characterize the morphology, structure and photochemical properties of the Ag/CNQDs/g-C3N4 composites. The superior photocatalytic activity of Ag/CNQDs/g-C3N4 was attributed to the wide light response range and the enhancement of interfacial charge transfer. At the same time, the effect of the influence factors (pH, Humic acid (HA) and coexisting ions) on the antibiotics degradation were also investigated. Furthermore, the electron spin resonance (ESR) technology, free radical quenching experiments, LC/MS and DFT theoretical calculations were applied to predict and identify the active groups and intermediates during the photocatalytic degradation process. In addition, Ag/CNQDs/g-C3N4 exhibited the obvious antibacterial effect to Escherichia coli due to the addition of Ag NPs. This study develops a new way for the removal of emerging antibiotic pollution from wastewaters.

Genome analysis of SARS-CoV-2 haplotypes: separation and parallel evolution of the major haplotypes occurred considerably earlier than their emergence in China.

More than 3 years have passed since the outbreak of COVID-19 and yet, the origin of the causal virus SARS-CoV-2 remains unknown. We examined the evolutionary trajectory of SARS-CoV-2 by analyzing non-redundant genome sets classified based on six closely linked mutations. The results indicated that SARS-CoV-2 emerged in February 2019 or earlier and evolved into three main haplotypes (GL, DS, and DL) before May 2019, which then continued to evolve in parallel. The dominant haplotype GL had spread worldwide in the summer (May to July) of 2019 and then evolved into virulent strains in December 2019 that triggered the global pandemic, whereas haplotypes DL and DS arrived in China in October 2019 and caused the epidemic in China in December 2019. Therefore, haplotype GL neither originated in China nor from the viral strains that caused the epidemic in China. Accordingly, considering data solely from China would be inadequate to reveal the mysterious origin of SARS-CoV-2, emphasizing the necessity of global cooperation.

Observations of linear aggregation behavior in rotifers (Brachionus calyciflorus).

Linear aggregation is present in some animals, such as the coordinated movement of ants and the migration of caterpillars and spinylobsters, but none has been reported on rotifers. The rotifers were collected and clone cultured in the laboratory at 25 ± 1°C, under natural light (light intensity ~130 lx, L:D = 14:10). The culture medium(pH = 7.3) was formulated as described by Suga et al., and rotifers were fed on the micro algae Scenedesmus obliquus grown in HB-4 medium to the exponential growth stage. When density was high (150 individuals ml-1), the behavior of rotifers was observed using a stereo microscope (Motic ES-18TZLED). In this paper, linear aggregation in Brachionus calyciflorus was found for the first time, and experiments were carried out to verify the correlation between linear aggregation and culture density of B. calyciflorus. With the increase of density, the number of aggregations increase, the number of individuals in the aggregation increased, and the maintenance time of the aggregation was also increased. Therefore, we speculate that the formation of aggregates is related to density and may be a behavioral signal of density increase, which may transmit information between density increase and formation of dormant eggs.

Species Diversity and Antifungal Susceptibilities of Oral Yeasts from Patients with Head and Neck Cancer.

PURPOSE: To investigate the colonization and susceptibility to antifungal drugs of oral yeasts in head and neck cancer patients in Hainan, China. METHODS: Oral mucosa samples from 211 head and neck cancer patients were collected. Oral yeasts were isolated and identified to species by rDNA ITS sequencing. The susceptibilities of all yeasts to amphotericin B, fluconazole, fluorocytosine, itraconazole, and ketoconazole were determined. RESULTS: Yeasts were isolated from 124 of the 211 oral swabs. The 124 yeast isolates were classified into following 10 species, from the most frequent to the least frequent, Candida albicans (53.2%), Candida tropicalis (22.6%), Candida krusei (6.5%), Kodamaea ohmeri (5.6%), Candida parapsilosis (4.8%), Hanseniaspora opuntiae (2.4%), Candida metapsilosis (1.6%), Pichia terricola (1.6%), Pichia norvegensis (0.8%), and Trichosporon asahii (0.8%). The overall frequencies of resistance among the yeasts to amphotericin B, fluconazole, flucytosine, itraconazole, and ketoconazole were 4.8%, 8.1%, 16.1%, 9.7%, and 9.7%, respectively. One C. albicans strain and one C. tropicalis strain were tolerant/resistant to all five drugs. CONCLUSION: Given the high prevalence of oral yeast colonization in head and neck cancer patients and the observed resistance of certain yeast isolates to the five antifungal drugs, our results suggest that rapid identification and susceptibility testing should be implemented before antifungal treatment is applied among patients with head and neck cancer in Hainan.

Widespread multiple insecticide resistance in the major dengue vector Aedes albopictus in Hainan Province, China.

BACKGROUND: Aedes albopictus is a highly invasive mosquito and has become a potential vector of dengue, chikungunya and Zika viruses. Insecticide-based mosquito interventions are the main tools for vector-borne disease control. However, mosquito resistance to insecticides is a major threat to effective prevention and control. Five Ae. albopictus populations across Hainan Province, China were investigated for susceptibility to multiple insecticide and resistance mechanisms. RESULTS: Larval bioassays indicated that resistance to pyrethroids was common in all larval populations. Adult bioassays revealed all populations were either resistant or highly resistant to at least four of the six synthetic insecticides (deltamethrin, permethrin, cyfluthrin, propoxur, malathion, and DDT) tested. Pre-exposure of mosquitoes to the synergistic agent piperonyl butoxide (PBO) increased mosquito mortality by 2.4-43.3% in bioassays to DDT, malathion, and permethrin and rendered mosquito sensitive to deltamethrin, cyfluthrin, and propoxur. The frequency of knockdown resistance (kdr) mutations (F1534S and F1534C) ranged from 69.8% to 89.3% and from 38.1% to 87.0% in field-resistant and sensitive populations, respectively. F1534S mutation was significantly associated with pyrethroid resistance. No mutation was detected in the acetylcholinesterase (ace-1) gene in the two examined populations. CONCLUSION: This study provides evidence of widespread resistance to multiple insecticides in Ae. albopictus in Hainan Province, China. Both kdr mutations and metabolic detoxification were potential causes of insecticide resistance for Ae. albopictus. Our findings highlight the need for insecticide resistance management and mosquito control measures that do not entirely depend on synthetic insecticides. © 2020 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Spatial heterogeneity and temporal dynamics of mosquito population density and community structure in Hainan Island, China.

BACKGROUND: Mosquitoes are vectors of many tropical diseases. Understanding the ecology of local mosquito vectors, such as species composition, distributions, population dynamics, and species diversity is important for designing the optimal strategy to control the mosquito-borne diseases. METHODS: Entomological surveillance of adult mosquitoes was conducted in five sites representing different ecological settings across Hainan Island from January to December of 2018 using BG Sentinel (BGS) traps and Centers for Disease Prevention and Control (CDC) light traps. In each site, we selected three areas representing urban, suburban and rural settings. Eighteen trap-days were sampled in each setting at each site, and CDC light traps and BGS traps were setup simultaneously. Mosquito species composition, distribution, population dynamics, and species diversity were analyzed. Mosquito densities were compared between different study sites and between different settings. RESULTS: Nine species of mosquitoes belonging to four genera were identified. Culex quinquefasciatus (80.8%), Armigeres subalbatus (13.0%) and Anopheles sinensis (3.1%) were the top three species collected by CDC light traps; Cx. quinquefasciatus (91.9%), Ae. albopictus (5.1%), and Ar. subalbatus (2.8%) were the top three species collected by BGS traps. Predominant species varied among study sites. The population dynamics of Ae. albopictus, An. sinensis and Cx. quinquefasciatus showed clear seasonal variation regardless of study sites with a varied peak season for different species. Mosquito abundance of all species showed significant differences among different study sites and among urban, suburban and rural areas. Danzhou had the highest mosquito biodiversity, with an α, ß, and Gini-Simpson biodiversity index of 8, 1.13 and 0.42, respectively. BGS traps captured Aedes mosquito at a higher efficiency than CDC light traps, whereas CDC light traps captured significantly more Anopheles and Armigeres mosquitoes than BGS traps. CONCLUSIONS: Mosquitoes were abundant on Hainan Island with clear seasonality and spatial heterogeneity. Population density, species composition, distribution, and species diversity were strongly affected by the natural environment. Different tools are required for the surveillance of different mosquito species.

MicroRNA-9 overexpression suppresses vulnerable atherosclerotic plaque and enhances vascular remodeling through negative regulation of the p38MAPK pathway via OLR1 in acute coronary syndrome.

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA-9 (miR-9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray-based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR-9. OLR1 was verified as a target gene of miR-9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE-/- mice, in which the agomir or antagomir of miR-9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response-related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR-9 and siRNA against OLR1, the p38-mitogen-activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor were reduced, but the high-density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR-9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1-mediated p38MAPK pathway.