Large-scale snake genome analyses provide insights into vertebrate development.

Snakes are a remarkable squamate lineage with unique morphological adaptations, especially those related to the evolution of vertebrate skeletons, organs, and sensory systems. To clarify the genetic underpinnings of snake phenotypes, we assembled and analyzed 14 de novo genomes from 12 snake families. We also investigated the genetic basis of the morphological characteristics of snakes using functional experiments. We identified genes, regulatory elements, and structural variations that have potentially contributed to the evolution of limb loss, an elongated body plan, asymmetrical lungs, sensory systems, and digestive adaptations in snakes. We identified some of the genes and regulatory elements that might have shaped the evolution of vision, the skeletal system and diet in blind snakes, and thermoreception in infrared-sensitive snakes. Our study provides insights into the evolution and development of snakes and vertebrates.

IRF8 deficiency-induced myeloid-derived suppressor cell promote immune evasion in lung adenocarcinoma.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) have a low response rate to immune checkpoint blockade. It is highly important to explore the tumor immune escape mechanism of LUAD patients and expand the population of patients who may benefit from immunotherapy. METHODS: Based on 954 bulk RNA-seq data of LUAD patients and 15 single-cell RNA-seq data, the relationships between tumor immune dysfunction and exclusion (TIDE) scores and survival prognosis in each patient were calculated and evaluated, and the immune escape mechanism affecting the independent prognosis of LUAD patients was identified. Functional enrichment analysis explored the antitumour immune response and biological behavior of tumor cells among different LUAD groups. Single-cell annotation and pseudotemporal analysis were used to explore the target molecules and immune escape mechanisms of LUAD. RESULTS: Myeloid-derived suppressor cells (MDSCs) and IRF8 were identified as risk and protective factors for the independent prognosis of LUAD patients, respectively. In the tumor microenvironment of patients with high infiltration of MDSCs, the antitumor immune response is significantly suppressed, while tumor cell division, proliferation, and distant metastasis are significantly enhanced. Single-cell RNA-seq analysis revealed that IRF8 is an important regulator of MDSC differentiation in LUAD myeloid cells. In addition, IRF8 may regulate the differentiation of MDSCs through the IL6-JAK-STAT3 signalling pathway. CONCLUSIONS: IRF8 deficiency impairs the normal development of LUAD myeloid cells and induces their differentiation into MDSCs, thereby accelerating the immune escape of LUAD cells. IRF8-targeted activation to inhibit the formation of MDSCs may be a new target for immunotherapy in LUAD.

Establishment and application of a quadruplex real-time RT-qPCR assay for differentiation of TGEV, PEDV, PDCoV, and PoRVA.

Porcine viral diarrhea is a common ailment in clinical settings, causing significant economic losses to the swine industry. Notable culprits behind porcine viral diarrhea encompass transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and porcine rotavirus-A (PoRVA). Co-infections involving the viruses are a common occurrence in clinical settings, thereby amplifying the complexities associated with differential diagnosis. As a consequence, it is therefore necessary to develop a method that can detect and differentiate all four porcine diarrhea viruses (TGEV, PEDV, PDCoV, and PoRVA) with a high sensitivity and specificity. Presently, polymerase chain reaction (PCR) is the go-to method for pathogen detection. In comparison to conventional PCR, TaqMan real-time PCR offers heightened sensitivity, superior specificity, and enhanced accuracy. This study aimed to develop a quadruplex real-time RT-qPCR assay, utilizing TaqMan probes, for the distinctive detection of TGEV, PEDV, PDCoV, and PoRVA. The quadruplex real-time RT-qPCR assay, as devised in this study, exhibited the capacity to avoid the detection of unrelated pathogens and demonstrated commendable specificity, sensitivity, repeatability, and reproducibility, boasting a limit of detection (LOD) of 27 copies/µL. In a comparative analysis involving 5483 clinical samples, the results from the commercial RT-qPCR kit and the quadruplex RT-qPCR for TGEV, PEDV, PDCoV, and PoRVA detection were entirely consistent. Following sample collection from October to March in Guangxi Zhuang Autonomous Region, we assessed the prevalence of TGEV, PEDV, PDCoV, and PoRVA in piglet diarrhea samples, revealing positive detection rates of 0.2 % (11/5483), 8.82 % (485/5483), 1.22 % (67/5483), and 4.94 % (271/5483), respectively. The co-infection rates of PEDV/PoRVA, PEDV/PDCoV, TGEV/PED/PoRVA, and PDCoV/PoRVA were 0.39 %, 0.11 %, 0.01 %, and 0.03 %, respectively, with no detection of other co-infections, as determined by the quadruplex real-time RT-qPCR. This research not only established a valuable tool for the simultaneous differentiation of TGEV, PEDV, PDCoV, and PoRVA in practical applications but also provided crucial insights into the prevalence of these viral pathogens causing diarrhea in Guangxi.

CCDC92 promotes podocyte injury by regulating PA28α/ABCA1/cholesterol efflux axis in type 2 diabetic mice.

Podocyte lipotoxicity mediated by impaired cellular cholesterol efflux plays a crucial role in the development of diabetic kidney disease (DKD), and the identification of potential therapeutic targets that regulate podocyte cholesterol homeostasis has clinical significance. Coiled-coil domain containing 92 (CCDC92) is a novel molecule related to metabolic disorders and insulin resistance. However, whether the expression level of CCDC92 is changed in kidney parenchymal cells and the role of CCDC92 in podocytes remain unclear. In this study, we found that Ccdc92 was significantly induced in glomeruli from type 2 diabetic mice, especially in podocytes. Importantly, upregulation of Ccdc92 in glomeruli was positively correlated with an increased urine albumin-to-creatinine ratio (UACR) and podocyte loss. Functionally, podocyte-specific deletion of Ccdc92 attenuated proteinuria, glomerular expansion and podocyte injury in mice with DKD. We further demonstrated that Ccdc92 contributed to lipid accumulation by inhibiting cholesterol efflux, finally promoting podocyte injury. Mechanistically, Ccdc92 promoted the degradation of ABCA1 by regulating PA28α-mediated proteasome activity and then reduced cholesterol efflux. Thus, our studies indicate that Ccdc92 contributes to podocyte injury by regulating the PA28α/ABCA1/cholesterol efflux axis in DKD.

Characterizing the distribution pattern of traffic-related air pollutants in near-road neighborhoods.

In near-road neighborhoods, residents are more frequently exposed to traffic-related air pollution (TRAP), and they are increasingly aware of pollution levels. Given this consideration, this study adopted portable air pollutant sensors to conduct a mobile monitoring campaign in two near-road neighborhoods, one in an urban area and one in a suburban area of Shanghai, China. The campaign characterized spatiotemporal distributions of fine particulate matter (PM2.5) and black carbon (BC) to help identify appropriate mitigation measures in these near-road micro-environments. The study identified higher mean TRAP concentrations (up to 4.7-fold and 1.7-fold higher for PM2.5 and BC, respectively), lower spatial variability, and a stronger inter-pollutant correlation in winter compared to summer. The temporal variations of TRAP between peak hour and off-peak hour were also investigated. It was identified that district-level PM2.5 increments occurred from off-peak to peak hours, with BC concentrations attributed more to traffic emissions. In addition, the spatiotemporal distribution of TRAP inside neighborhoods revealed that PM2.5 concentrations presented great temporal variability but almost remained invariant in space, while the BC concentrations showed notable spatiotemporal variability. These findings provide valuable insights into the unique spatiotemporal distributions of TRAP in different near-road neighborhoods, highlighting the important role of hyperlocal monitoring in urban micro-environments to support tailored designing and implementing appropriate mitigation measures.

Intense Circularly Polarized Luminescence Induced by Chiral Supramolecular Assembly: The Importance of Intermolecular Electronic Coupling.

Herein we report on circularly polarized luminescence (CPL) emission originating from supramolecular chirality of organic microcrystals with a |glum| value up to 0.11. The microcrystals were prepared from highly emissive difluoroboron ß-diketonate (BF2dbk) dyes R-1 or S-1 with chiral binaphthol (BINOL) skeletons. R-1 and S-1 exhibit undetectable CPL signals in solution but manifest intense CPL emission in their chiral microcrystals. The chiral superstructures induced by BINOL skeletons were confirmed by XRD analysis. Spectral analysis and theoretical calculations indicate that intermolecular electronic coupling, mediated by the asymmetric stacking in the chiral superstructures, effectively alters excited-state electronic structures and facilitates electron transitions perpendicular to BF2bdk planes. The coupling increases cosθµ,m from 0.05 (monomer) to 0.86 (tetramer) and triggers intense optical activity of BF2bdk. The results demonstrate that optical activity of chromophores within assemblies can be regulated by both orientation and extent of intermolecular electronic couplings.

Quantifying traffic-related carbon emissions on elevated roads through on-road measurements.

Vehicles generally move smoothly and with high speeds on elevated roads, thereby producing specific traffic-related carbon emissions in contrast to ground roads. Hence, a portable emission measurement system was adopted to determine traffic-related carbon emissions. The on-road measurement results revealed that the instantaneous emissions of CO2 and CO from elevated vehicles were 17.8% and 21.9% higher than those from ground vehicles, respectively. Based on it, the vehicle specific power was confirmed to exhibit a positive exponential relationship with instantaneous CO2 and CO emissions. In addition to carbon emissions, carbon concentrations on roads were simultaneously measured. The average CO2 and CO emissions on elevated roads in urban areas were 1.2% and 6.9% higher than those on ground roads, individually. Finally, a numerical simulation was performed, and the results verified that elevated roads could deteriorate the air quality on ground roads but improve the air quality above them. What ought to be paid attention to is that the elevated roads present varied traffic behaviour and cause particular carbon emissions, indicating that comprehensive consideration and further balance among the traffic-related carbon emissions are necessary when building elevated roads to alleviate the traffic congestion in urban areas.

Characterizing nighttime vertical profiles of atmospheric particulate matter and ozone in a megacity of south China using unmanned aerial vehicle measurements.

Daytime atmospheric pollution has received wide attention, while the vertical structures of atmospheric pollutants at night play a crucial role in the photochemical process on the following day, which is still less reported. Focusing on Guangzhou, a megacity of South China, we established an unmanned aerial vehicle (UAV) equipped with micro detectors to collect consecutive high-resolution samples of fine particle (PM2.5), submicron particle (PM1.0), black carbon (BC) and ozone (O3) concentrations in the atmosphere, as well as the air temperature (AT) and relative humidity (RH) within a 500 m altitude during nighttime from Oct. 24th to Nov. 6th, 2018. The measurements showed that PM2.5, PM1.0, and BC decreased with altitude and were influenced by the nighttime shallow planetary boundary layer (PBL) where BC was more accumulated and fluctuated. In contrast, O3 was positively correlated with altitude. Backward trajectory clustering and Pasquill stability classification showed that advection and convection significantly influenced the vertical distribution of all pollutants, particularly particulate matter. External air masses carrying high concentrations of pollutants increased PM1.0 and PM2.5 levels by 145% and 455%, respectively, compared to unaffected periods. The ratio of BC to PM2.5 indicated that local emissions had a minor role in nighttime particulate matter. Vertical transport caused by atmospheric instability reduced the differences in pollutant concentrations at various heights. Geodetector and generalized additive model showed that RH and BC accumulation in the PBL were significant factors influencing vertical changes of the secondary aerosol intensity as indicated by the ratio of PM1.0 to PM2.5. The joint explanation of RH and atmospheric stability with other variables such as BC is essential to understand the generation of secondary aerosols. These findings provide insights into regional and local measures to prevent and control night-time particulate matter pollution.

Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1.

Endothelial microparticles (EMPs) can be released in chronic kidney disease (CKD). Plasma concentration of high inorganic phosphate (HP) is considered as a decisive determinant of vascular calcification in CKD. We therefore explored the role of HP-induced EMPs (HP-EMPs) in the vascular calcification and its potential mechanism. We observed the shape of HP-EMPs captured by vascular smooth muscle cells (VSMCs) dynamically changed from rare dots, rosettes, to semicircle or circle. Our results demonstrated that HP-EMPs could directly promote VSMC calcification, or accelerate HP-induced calcification through signal transducers and activators of transcription 3 (STAT3)/bone morphogenetic protein-2 (BMP2) signaling pathway. AEG-1 activity was increased through HP-EMPs-induced VSMC calcification, in arteries from uremic rats, or from uremic rats treated with HP-EMPs. AEG-1 deficiency blocked, whereas AEG-1 overexpression exacerbated, the calcium deposition of VSMCs. AEG-1, a target of miR-153-3p, could be suppressed by agomiR-153-3p. Notably, VSMC-specific enhance of miR-153-3p by tail vein injection of aptamer-agomiR-153-3p decreased calcium deposition in both uremia rats treated with HP-EMPs or not. HP-EMPs could directly induce VSMCs calcification and accelerate Pi-induced calcification, and AEG-1 may act as crucial regulator of HP-EMPs-induced vascular calcification. This study sheds light on the therapeutic agents that influence HP-EMPs production or AEG-1 activity, which may be of benefit to treat vascular calcification.

miRNA and mRNA expression analysis reveals the effects of continuous heat stress on antibacterial responses to Aeromonas hydrophila lipopolysaccharide (LPS) in grass carp (Ctenopharyngodon idella).

Grass carp (Ctenopharyngodon idella) is the largest economic fish in freshwater culture in China, which is predisposed to infectious diseases under high temperature. Under the background of global warming, the industrialization of the Pearl River Delta region has led to aggravated thermal pollution, which has increasingly serious impacts on the aquatic ecological environment. This will result in more frequent exposure of grass carp to overheated water temperatures. Previous studies have only identified the regulatory genes of fish that respond to pathogens or temperature stress, but the transcriptional response to both is unknown. In this study, the histopathological analysis showed heat stress exacerbated spleen damage induced by Aeromonas hydrophila. The transcriptional responses of the spleens from A. hydrophila lipopolysaccharide (LPS) -injected grass carp undergoing heat stress and at normal temperatures for 6, 24, and 72 h were investigated by mRNA and microRNA sequencing. We identified 28, 20, and 141 differentially expressed (DE) miRNAs and 126, 383, and 4841 DE mRNAs between the two groups after 6, 24, and 72 h, respectively. There were 67 DE genes mainly involved in the cytochrome P450 pathway, antioxidant defense, inflammatory response, pathogen recognition pathway, antigen processing and presentation, and the ubiquitin-proteasome system. There were 5 DE miRNAs involved in regulating apoptosis and inflammation. We further verified 17 DE mRNAs and 5 DE miRNAs using quantitative real-time PCR. Based on miRNAs and mRNAs analysis, continuous heat stress will affect the antibacterial responses of grass carp spleens, resulting in aggravation of spleen injury. Together, these results provide data for further understanding of the decreased tolerance of fish to pathogen infection in persistent high-temperature environments.

Identification of a broad-spectrum lytic Myoviridae bacteriophage using multidrug resistant Salmonella isolates from pig slaughterhouses as the indicator and its application in combating Salmonella infections.

BACKGROUND: Salmonella is a leading foodborne and zoonotic pathogen, and is widely distributed in different nodes of the pork supply chain. In recent years, the increasing prevalence of antimicrobial resistant Salmonella poses a threat to global public health. The purpose of this study is to the prevalence of antimicrobial resistant Salmonella in pig slaughterhouses in Hubei Province in China, and explore the effect of using lytic bacteriophages fighting against antimicrobial resistant Salmonella. RESULTS: We collected a total of 1289 samples including anal swabs of pigs (862/1289), environmental swabs (204/1289), carcass surface swabs (36/1289) and environmental agar plates (187/1289) from eleven slaughterhouses in seven cities in Hubei Province and recovered 106 Salmonella isolates. Antimicrobial susceptibility testing revealed that these isolates showed a high rate of antimicrobial resistance; over 99.06% (105/106) of them were multidrug resistant. To combat these drug resistant Salmonella, we isolated 37 lytic phages using 106 isolates as indicator bacteria. One of them, designated ph 2-2, which belonged to the Myoviridae family, displayed good capacity to kill Salmonella under different adverse conditions (exposure to different temperatures, pHs, UV, and/or 75% ethanol) and had a wide lytic spectrum. Evaluation in mouse models showed that ph 2-2 was safe and saved 80% (administrated by gavage) and 100% (administrated through intraperitoneal injection) mice from infections caused by Salmonella Typhimurium. CONCLUSIONS: The data presented herein demonstrated that Salmonella contamination remains a problem in some pig slaughter houses in China and Salmonella isolates recovered in slaughter houses displayed a high rate of antimicrobial resistance. In addition, broad-spectrum lytic bacteriophages may represent a good candidate for the development of anti-antimicrobial resistant Salmonella agents.

Isolation of Three Coliphages and the Evaluation of Their Phage Cocktail for Biocontrol of Shiga Toxin-Producing Escherichia coli O157 in Milk.

Shiga toxin-producing Escherichia coli (STEC) O157 is a well-known foodborne pathogen and a leading cause of many intestinal diseases. In this study, we explore the use of a phage cocktail to help control STEC O157 in broth and milk. We isolated three virulent phages from sanitary sewages using a STEC O157 as the indicator bacterium. Phenotypical characterizations revealed that these three phages belong to the Myoviridae family and were stable at different temperatures and pH. They displayed a short latent period between 10 and 20 min, and a burst size (32-65 per infected cell). No virulence factors and drug resistance genes were found in their genomes. Bacterial lysis assays showed that a phage cocktail comprising these three phages was more effective (at least 4.32 log reduction) against STEC O157 at 25 °C with multiplicity of infection (MOI) = 1000 in broth medium. At 4 °C, a 3.8 log reduction in the number of viable STEC O157 after 168-h treatment with phage cocktail at MOI = 1000 was observed in milk, compared to phage-free bacterial control group. Characterizations of phages suggest they could be developed into novel therapeutic agents to control STEC O157 in milk production.

RNA-seq analysis of extracellular vesicles from hyperphosphatemia-stimulated endothelial cells provides insight into the mechanism underlying vascular calcification.

BACKGROUND: Hyperphosphatemia (HP) is associated with vascular calcification (VC) in chronic kidney disease (CKD). However, relationship between HP-induced-endothelial extracellular vesicles (HP-EC-EVs) and VC is unclear, and miR expression in HP-EC-EVs has not been determined. METHODS: We isolated HP-EC-EVs from endothelial cells with HP and observed that HP-EC-EVs were up-taken by vascular smooth muscle cells (VSMCs). HP-EC-EVs inducing calcium deposition was characterized by Alizarin Red S, colourimetric analysis and ALP activity. To investigate the mechanism of HP-EC-EVs-induced VSMC calcification, RNA-sequencing for HP-EC-EVs was performed. RESULTS: We first demonstrated that HP-EC-EVs induced VSMC calcification in vitro. RNA-seq analysis of HP-EC-EVs illustrated that one known miR (hsa-miR-3182) was statistically up-regulated and twelve miRs were significantly down-regulated, which was verified by qRT-PCR. We predicted 58,209 and 74,469 target genes for those down- and up-regulated miRs respectively through miRDB, miRWalk and miRanda databases. GO terms showed that down- and up-regulated targets were mostly enriched in calcium-dependent cell-cell adhesion via plama membrane cell-adhesion molecules (GO:0,016,338, BP) and cell adhesion (GO:0,007,155, BP), plasma membrane (GO:0,005,886, CC), and metal ion binding (GO:0,046,914, MF) and ATP binding (GO:0,005,524, MF) respectively. Top-20 pathways by KEGG analysis included calcium signaling pathway, cAMP signaling pathway, and ABC transporters, which were closely related to VC. CONCLUSION: Our results indicated that those significantly altered miRs, which were packaged in HP-EC-EVs, may play an important role in VC by regulating related pathways. It may provide novel insight into the mechanism of CKD calcification.

Agent-based Modeling to Evaluate Human-Environment Interactions in Community Flood Risk Mitigation.

This article deals with household-level flood risk mitigation. We present an agent-based modeling framework to simulate the mechanism of natural hazard and human interactions, to allow evaluation of community flood risk, and to predict various adaptation outcomes. The framework considers each household as an autonomous, yet socially connected, agent. A Beta-Bernoulli Bayesian learning model is first applied to measure changes of agents' risk perceptions in response to stochastic storm surges. Then the risk appraisal behaviors of agents, as a function of willingness-to-pay for flood insurance, are measured. Using Miami-Dade County, Florida as a case study, we simulated four scenarios to evaluate the outcomes of alternative adaptation strategies. Results show that community damage decreases significantly after a few years when agents become cognizant of flood risks. Compared to insurance policies with pre-Flood Insurance Rate Maps subsidies, risk-based insurance policies are more effective in promoting community resilience, but it will decrease motivations to purchase flood insurance, especially for households outside of high-risk areas. We evaluated vital model parameters using a local sensitivity analysis. Simulation results demonstrate the importance of an integrated adaptation strategy in community flood risk management.

Causes and predictors of mortality from lupus nephritis in Southern Hunan, China.

OBJECTIVES: The objective of the study was to explore the causes and predictors of mortality in a cohort of LN with LN in southern Hunan, China. METHODS: We analyzed 236 patients with biopsy-proven LN during 2010-2018. Demographic data, laboratory data, SLEDAI scores, treatment strategies, and comorbidity were collected. Cox regression analysis was carried out to determine the independent predictors of mortality. RESULTS: The patients had mean disease duration of 67.9 ± 28.2 months. Class IV LN was the predominant biopsy class within the cohort (38.1%). After 1 year therapy, the majority of patients achieved complete remission (72.9%) and 44 (18.6%) patients achieved partial remission. The 5- and 10-years survival rates for our cohort were 94.4 and 85.2%, respectively. There were 18 deaths (7.6%), of which the main causes were infection (50%) alone and cardiovascular diseases (27.8%). Independent predictors of mortality in our cohort were: platelet-to-neutrophil ratio (PNR) [hazard ratio (HR) 5.910; confidence interval (CI) 1.253-27.875], onset age (HR 1.090; CI 1.035-1.147), and SLEDAI scores (HR 1.258; CI 1.068-1.482). CONCLUSION: We firstly revealed that PNR might be a promising predictor of mortality and reported the causes and prognostic predictors of mortality in LN from southern Hunan, China.

Measuring the impact of an exogenous factor: An exponential smoothing model of the response of shipping to COVID-19.

Following the outbreak of the COVID-19 pandemic, various lockdown strategies restrained global economic growth bringing a significant decline in maritime transportation. However, the previous studies have not adequately recognized the specific impacts of COVID-19 on maritime transportation. In this study, a series of analyses of the Baltic Dry Index (BDI), the China Coastal Bulk Freight Index (CCBFI) and of container throughputs with and without the impact of COVID-19 were carried out to assess changing trends in dry bulk and container transportation. The results show that global dry bulk transportation was largely affected by lockdown policies in the second month during COVID-19, and BDI presented a year-on-year decrease of approximately 35.5% from 2019 to 2020. The CCBFI showed an upward trend in the second month during COVID-19, one month ahead of the BDI. The container throughputs at Shanghai Port, the Ports of Hong Kong, the Ports of Singapore and the Ports of Los Angeles from 2019 to 2020 presented the largest year-on-year drops of approximately 19.6%, 7.1%, 10.6% and 30.9%, respectively. In addition, the authors developed exponential smoothing models of BDI, CCBFI, and container transportation, and calculated the percentage prediction error between the observed and predicted values to examine the impact of exogenous effects on the shipping industry due to the outbreak of COVID-19. The results are consistent with the conclusions obtained from the comparison of BDI, CCBFI, and container transportation during the same period in 2020 and 2019. Finally, on the basis of the findings, smart shipping and special support policies are proposed to reduce the negative impacts of COVID-19.

Diversity of actinobacteria in sediments of Qaidam Lake and Qinghai Lake, China.

Using 16S rRNA gene analysis and high-throughput, the diversity and community structure of actinobacteria in the sediments of Qaidam Lake and Qinghai Lake with different salinity and alkalinity in Qinghai-Xizang Plateau were studied, and the differences of actinobacteria community structure and their relationship with environmental factors were discussed. A total of 77 genera belonging to actinobacteria were found in the samples, of which 31 genera were found in the sediment samples of Qaidam Lake with 19 genera being dominant genera, such as Actinomycetes, Corynebacterium, Morella, Bifidobacterium, and 69 genera were found in the sediment samples of Qinghai Lake with 17 genera becoming dominant, such as Ilumattalaer, Actinotalea, Aquihaans and so on. The correlation analysis of environmental factors and community showed that the community structure of the two salt lakes was mainly affected by total salinity, total organic carbon) (TOC) and CO32-, among which TOC was the most influential factor. The functional differences of metabolic pathway enrichment analysis (KEGG) showed that there was a high abundance of metabolic-related functions in the two salt lakes. There were significant differences in the biosynthesis of energy metabolism and other secondary metabolites between the two salt lakes, which may be the main reason for the difference of actinomycete community. The results show that the actinobacteria diversity was rich in the plateau salt lakes, and affected by a variety of physicochemical factors. In addition, there were a large number of unculturable actinobacteria in the sediment, which provides a theoretical basis for the excavation and utilization of actinobacteria resources in salt lakes.

Hsa_circ_0016788 regulates hepatocellular carcinoma progression via miR-506-3p/poly-adenosine diphosphate-ribose polymerase.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of HCC, but the mechanism is still indistinct. In this work, we explored the roles of circRNA_0016788 in HCC. METHODS: The levels of hsa_circ_0016788, microRNA-506-3p (miR-506-3p), and mRNA of poly-adenosine diphosphate-ribose polymerase, member 14 (PARP14) were detected by quantitative real-time reverse transcription-polymerase chain reaction in HCC tissues. Meanwhile, the level of PARP14 was quantified by Western blot analysis. Besides, the cell functions were examined by commercial kit, Cell Counting Kit-8 assay, EdU assay, colony formation assay, flow cytometry assay, Western blot, and transwell assay. Furthermore, the interplay between miR-506-3p and hsa_circ_0016788 or PARP14 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of hsa_circ_0016788. RESULTS: The levels of hsa_circ_0016788 and PARP14 were upregulated, and the miR-506-3p level was decreased in HCC tissues in contrast to that in normal tissues. For functional analysis, hsa_circ_0016788 deficiency inhibited cell glycolysis metabolism, cell vitality, cell proliferation, colony formation, and invasion in HCC cells whereas promoted cell apoptosis. Moreover, miR-506-3p was confirmed to repress the progression of HCC cells by suppressing PARP14. In mechanism, hsa_circ_0016788 acted as a miR-506-3p sponge to regulate the level of PARP14. In addition, hsa_circ_0016788 knockdown also inhibited tumor growth in vivo. CONCLUSION: Hsa_circ_0016788 facilitates the development of HCC through increasing PARP14 expression by regulating miR-506-3p, which also offered an underlying targeted therapy for HCC treatment.

Secoiridoid dimers and their biogenetic precursors from the fruits of Cornus officinalis with potential therapeutic effects on type 2 diabetes.

Cornusdiridoid A-F (1-6), six unusual cornuside-morroniside secoiridoid dimers, and their possible new biogenetic precursor, 3″,5″-dehydroxycornuside (7), together with four known secoiridoids (8-11), were obtained from the fruits of Cornus officinalis. Their structures were elucidated on the basis of various spectroscopic and chemical methods. A plausible biosynthetic pathway of compounds 1-11 was proposed. The α-glucosidase inhibitory, antioxidant and anti-inflammatory activities of these isolates were evaluated. Some of them emerged out as potent antidiabetic, anti-inflammatory and free radical scavenging agents. Molecular docking was also carried out for antidiabetic target α-glucosidase to investigate the possible binding modes of the most potent α-glucosidase inhibitor, vincosamide (9). These results revealed that the secoiridoids from C. officinalis fruits may be served as new potential antidiabetic agents to prevent and treat type 2 diabetes.