ABBV-744 alleviates LPS-induced neuroinflammation via regulation of BATF2-IRF4-STAT1/3/5 axis.

Suppression of neuroinflammation using small molecule compounds targeting the key pathways in microglial inflammation has attracted great interest. Recently, increasing attention has been gained to the role of the second bromodomain (BD2) of the bromodomain and extra-terminal (BET) proteins, while its effect and molecular mechanism on microglial inflammation has not yet been explored. In this study, we evaluated the therapeutic effects of ABBV-744, a BD2 high selective BET inhibitor, on lipopolysaccharide (LPS)-induced microglial inflammation in vitro and in vivo, and explored the key pathways by which ABBV-744 regulated microglia-mediated neuroinflammation. We found that pretreatment of ABBV-744 concentration-dependently inhibited the expression of LPS-induced inflammatory mediators/enzymes including NO, TNF-α, IL-1ß, IL-6, iNOS, and COX-2 in BV-2 microglial cells. These effects were validated in LPS-treated primary microglial cells. Furthermore, we observed that administration of ABBV-744 significantly alleviated LPS-induced activation of microglia and transcriptional levels of pro-inflammatory factors TNF-α and IL-1ß in mouse hippocampus and cortex. RNA-Sequencing (RNA-seq) analysis revealed that ABBV-744 induced 508 differentially expressed genes (DEGs) in LPS-stimulated BV-2 cells, and gene enrichment and gene expression network analysis verified its regulation on activated microglial genes and inflammatory pathways. We demonstrated that pretreatment of ABBV-744 significantly reduced the expression levels of basic leucine zipper ATF-like transcription factor 2 (BATF2) and interferon regulatory factor 4 (IRF4), and suppressed JAK-STAT signaling pathway in LPS-stimulated BV-2 cells and mice, suggesting that the anti-neuroinflammatory effect of ABBV-744 might be associated with regulation of BATF2-IRF4-STAT1/3/5 pathway, which was confirmed by gene knockdown experiments. This study demonstrates the effect of a BD2 high selective BET inhibitor, ABBV-744, against microglial inflammation, and reveals a BATF2-IRF4-STAT1/3/5 pathway in regulation of microglial inflammation, which might provide new clues for discovery of effective therapeutic strategy against neuroinflammation.

HLA-A+ tertiary lymphoid structures with reactivated tumor infiltrating lymphocytes are associated with a positive immunotherapy response in esophageal squamous cell carcinoma.

BACKGROUND: Immune checkpoint blockade (ICB) therapy provides remarkable clinical benefits for multiple cancer types. However, the overall response rate to ICB therapy remains low in esophageal squamous cell carcinoma (ESCC). This study aimed to identify biomarkers of ICB therapy for ESCC and interrogate its potential clinical relevance. METHODS: We investigated gene expression in 42 treatment-naïve ESCC tumor tissues and identified differentially expressed genes, tumor-infiltrating lymphocytes and immune-related genes signatures associated with differential immunotherapy responses. We systematically assessed the tumor microenvironment using the NanoString GeoMx digital spatial profiler, single-cell RNA-seq and multiplex immunohistochemistry in ESCC. Finally, we evaluated the associations between HLA-A-positive tertiary lymphoid structures (TLSs) and patients' responses to ICB in 60 ESCC patients. RESULTS: Tumor infiltrating B lymphocytes and several immune-related gene signatures, such as the antigen presenting machinery (APM) signature, are significantly elevated in ICB treatment responders. Multiplex immunohistochemistry identified the presence of HLA-A+ TLSs and showed that TLS-resident cells increasingly express HLA-A as TLSs mature. Most TLS-resident HLA-A+ cells are tumor-infiltrating T (TIL-T) or tumor-infiltrating B (TIL-B) lymphocytes. Digital spatial profiling of spatially distinct TIL-T lymphocytes and single-cell RNA-seq data from 60 ESCC tumor tissues revealed that CXCL13-expressing exhausted TIL-Ts inside TLSs are reactivated with elevated expression of the APM signature as TLSs mature. Finally, we demonstrated that HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, are associated with a clinical benefit from ICB treatment for ESCC. CONCLUSIONS: HLA-A+ TLSs are present in ESCC tumor tissues. TLS-resident TIL-Ts with elevated expression of the APM signature may be reactivated. HLA-A+ TLSs and their major cellular components, TIL-Ts and TIL-Bs, may serve as biomarkers for ICB-treated ESCC patients.

Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design.

Recent advances in cancer immunotherapy have highlighted the potential of neoantigen-based vaccines. However, the design of such vaccines is hindered by the possibility of weak binding affinity between the peptides and the patient's specific human leukocyte antigen (HLA) alleles, which may not elicit a robust adaptive immune response. Triggering cross-immunity by utilizing peptide mutations that have enhanced binding affinity to target HLA molecules, while preserving their homology with the original one, can be a promising avenue for neoantigen vaccine design. In this study, we introduced UltraMutate, a novel algorithm that combines Reinforcement Learning and Monte Carlo Tree Search, which identifies peptide mutations that not only exhibit enhanced binding affinities to target HLA molecules but also retains a high degree of homology with the original neoantigen. UltraMutate outperformed existing state-of-the-art methods in identifying affinity-enhancing mutations in an independent test set consisting of 3660 peptide-HLA pairs. UltraMutate further showed its applicability in the design of peptide vaccines for Human Papillomavirus and Human Cytomegalovirus, demonstrating its potential as a promising tool in the advancement of personalized immunotherapy.

Overcoming oxygen inhibition in UV photolithography for the fabrication of low-loss polymer waveguides.

Perfluorinated acrylate polymer materials exhibit low absorption loss at 1310 and 1550 nm, but molecular oxygen inhibits their photocuring. We propose a novel, to our knowledge, UV photolithography method incorporating a pre-exposure process for fabricating low-loss perfluorinated acrylate polymer waveguides. During the pre-exposure process, a partially cured thin layer forms on the core layer, effectively overcoming oxygen inhibition in subsequent lithography. Furthermore, the functional group contents of the polymerized materials were characterized by a Raman spectrometer to analyze the development reaction under the pre-exposure layer. Utilizing this improved method, we fabricated a straight waveguide with a length of 21 cm. The experiments showed that the propagation losses are 0.14 dB/cm at 1310 nm and 0.51 dB/cm at 1550 nm. The inter-channel cross talk for a core pitch of 250 µm was measured as low as -49 dB at 1310 nm. Error-free NRZ data transmission over this waveguide at 25 Gb/s was achieved, showcasing the potential in optical interconnect and communication applications.

miR-199a-5p modulates choroidal neovascularization by regulating Wnt7b/Wnt/ß-catenin signaling pathway.

Choroidal neovascularization (CNV) can be seen in many fundus diseases, and lead to fundus exudation, bleeding, or vision loss. miRNAs are vital regulator in CNV. miR-199a-5p has been proved to be involved in regulating vascular formation of endothelial cells, but its role in CNV remains unclear. This study aims to study the role of miR-199a-5p in CNV. Laser irradiation was used to induce CNV model. The lesion area of CNV was calculated by high-resolution angiography with fluorescein isothiocyanate-dextran. Wnt family member 7b (Wnt7b), ß-catenin, and Wnt pathway proteins was measured by western blot. Immunofluorescence was performed to test Wnt7b, ß-catenin, CD31, and p-p65. miR-199a-5p and Wnt7b mRNA were tested by reverse transcription real-time polymerase chain reaction. Cell count kit-8, wound healing, Transwell, tube formation, and flow cytometry were used to detect the function of miR-199a-5p and Wnt7b on human retinal microvascular endothelial cells (HRMEC). TargetScan database and dual-luciferase reporter assay verified the interaction between miR-199a-5p and Wnt7b. The results revealed that Wnt7b increased in CNV rats. Knocking down Wnt7b repressed cell proliferation, migration, invasion, and angiogenesis, and accelerated cell apoptosis of HRMEC. Dual-luciferase reporter assay verified that miR-199a-5p targeted Wnt7b. Overexpression of miR-199a-5p inhibited the angiogenesis of HRMEC and promoted cell apoptosis by inhibiting Wbt7b. In vivo experiment found that Wnt7b rescued the promotion of miR-199a-5p inhibition on CNV lesion of rats. In addition, Wnt7b positively regulated Wnt/ß-catenin signaling pathway and promoted the angiogenesis of HRMEC. In conclusion, overexpression of miR-199a-5p inhibited the angiogenesis of HRMEC by regulating Wnt7b/Wnt/ß-catenin signaling pathway, which may serve as a promising therapy target of CNV.

Alterations of intestinal mucosal barrier, cecal microbiota diversity, composition, and metabolites of yellow-feathered broilers under chronic corticosterone-induced stress: a possible mechanism underlying the anti-growth performance and glycolipid metabolism disorder.

This study aimed to explore alterations in growth performance, glycolipid metabolism disorders, intestinal mucosal barrier, cecal microbiota community, and metabolites in a chronic corticosterone (CORT)-induced stress (CCIS) broiler model. Results showed that compared with control (CON) broilers, in CCIS broilers: (i) the final body weight (BW), BW gain, and average daily gain were significantly reduced. (ii) The glycolipid metabolism disorder and impairement of intestinal immune barrier and physical barrier function were observed. (iii) Diversity and richness of cecal microbiota were obviously increased. From phylum to genus level, the abundances of Firmicutes and Faecalibacterium were significantly decreased, while the abundances of Proteobacteria, RuminococcaceaeUCG-005, and Escherichia coli (Shigella) were significantly increased. Microbial network analysis and function pathways prediction showed that cecal microbiota was mainly concentrated in translation, metabolism, nucleotide metabolism, and endocrine system. (iv) The main differential metabolites identified include steroids and their derivatives, amino acids, fatty acids, and carbohydrates; among which 37 metabolites were significantly upregulated, while 27 metabolites were significantly downregulated. These differential metabolites were mainly enriched in pathways related to steroid hormone biosynthesis and tyrosine metabolism. (v) Correlation between cecal microbiota and glycolipid metabolism indexes showed that BW and total cholesterol (TC) were positively correlated with Christensenellaceae_R.7_group and Escherichia_Shigella, respectively. Furthermore, the downregulated Faecalibacterium and Christensenellaceae were negatively correlated with the upregulated differentially expressed metabolites. These findings suggested that CCIS altered cecal microbiota composition and metabolites, which led to glycolipid metabolism disorder and impaired the nutritional metabolism and immune homeostasis, providing a theoretical basis for efforts to eliminate the harm of chronic stress to human health and animal production. IMPORTANCE: The study aimed to determine the influence of altered intestinal mucosal barrier, cecum flora community, and metabolites on anti-growth performance, glycolipid metabolism disorders of chronic corticosterone (CORT)-induced stress (CCIS) broilers. Compared with control (CON) broilers, in CCIS broilers: (i) anti-growth performance, glycolipid metabolism disorder, and impaired intestinal immune barrier and physical barrier function were observed. (ii) From phylum to genus level, the abundances of Firmicutes and Faecalibacterium were decreased; whereas, the abundances of Proteobacteria, RuminococcaceaeUCG-005, and Escherichia coli (Shigella) were increased. (iii) Differential metabolites in cecum were mainly enriched in steroid hormone biosynthesis and tyrosine metabolism. (iv) Body weight (BW) and total cholesterol (TC) were positively correlated with Christensenellaceae_R.7_group and Escherichia_Shigella, respectively, while downregulated Faecalibacterium and Christensenellaceae were negatively correlated with upregulated metabolites. Our findings suggest that CCIS induces anti-growth performance and glycolipid metabolism disorder by altering cecum flora and metabolites, providing a theoretical basis for efforts to eliminate the effect of chronic stress on human health and animal production.

High-bandwidth tilt-tip mirror with octagonal prism flexible mechanism.

The adaptive optical system requires a tilt-tip mirror (TTM) with high bandwidth to compensate for optical beam jitter caused by atmospheric turbulence in real time. This paper introduces a novel, to the best of our knowledge, design of a voice coil TTM using an octagonal flexible mechanism and optimizes its parameters through theoretical analysis and finite element simulations. The results show that its resonance frequency in the non-working direction is up to 1005.2 Hz, representing a 19.4% improvement in theoretical calculations and a 13.8% improvement in simulations compared to traditional cylindrical flexible mechanisms. Additionally, the non-working direction stiffness of the flexible support structure has been optimized, enhancing the third-order and higher resonance frequencies of the system to meet the high bandwidth requirements. A prototype of the TTM was developed based on this design, and its deflection angles and responses were measured in the laboratory, confirming the design's reliability. This low-cost, high-bandwidth TTM design facilitates miniaturization of adaptive optical systems, making it beneficial for applications in astronomical observations, laser communication, laser weapons, laser processing, and more.

AAAKB: A manually curated database for tracking and predicting genes of Abdominal aortic aneurysm (AAA).

Abdominal aortic aneurysm (AAA), an extremely dangerous vascular disease with high mortality, causes massive internal bleeding due to aneurysm rupture. To boost the research on AAA, efforts should be taken to organize and link the information about AAA-related genes and their functions. Currently, most researchers screen through genetic databases manually, which is cumbersome and time-consuming. Here, we developed "AAAKB" a manually curated knowledgebase containing genes, SNPs and pathways associated with AAA. In order to facilitate researchers to further explore the mechanism network of AAA, AAAKB provides predicted genes that are potentially associated with AAA. The prediction is based on the protein interaction information of genes collected in the database, and the random forest algorithm (RF) is used to build the prediction model. Some of these predicted genes are differentially expressed in patients with AAA, and some have been reported to play a role in other cardiovascular diseases, illustrating the utility of the knowledgebase in predicting novel genes. Also, AAAKB integrates a protein interaction visualization tool to quickly determine the shortest paths between target proteins. As the first knowledgebase to provide a comprehensive catalog of AAA-related genes, AAAKB will be an ideal research platform for AAA. Database URL: http://www.lqlgroup.cn:3838/AAAKB/.

High-precision calculation and experiments on the thermal blooming of high-energy lasers.

Thermal blooming (TB) is one of the important factors affecting the quality of high-energy laser beams. Reasonable simulation of thermal blooming is important to the application of a high-energy laser. However, reported investigations on TB simulation are mainly based on one method, such as the perturbation method or the phase screen method, which often leads to obvious errors in some conditions. In the paper, the reasonable ranges of optical generalized distortion parameters for both methods are determined based on the reported experimental data, which solves the problem of accurate TB simulations for the first time. In addition, the dynamic effect of thermal blooming is also calculated. Finally, the formula method is presented to extract the phase of thermal blooming distortion. We then use LC-SLM (Liquid crystal spatial light modulator) to emulate thermal blooming effect in the lab. The experimental results are more consistent with the numerical simulation results than conventional phase extraction methods. Our work provides a quantitatively and programmable way to accurately simulate TB with LC-SLM in the lab.

A novel AIE material for sensing of Erythromycin in pure water by hydrogen bond in portable test strips and cellular imaging applications.

Erythromycin could be used to treat various bacterial infection, but it was harmful to the colonic microflora. Therefore, it is highly desirable to develop a fluorescence probe that could selectively and sensitively detect Erythromycin in pure water. In this work, a fluorescent probe named EHMC, which exhibited aggregation-induced emission (AIE) characteristic in solid state and water/EtOH binary solvent was developed for "turn on" sensing Erythromycin in pure water with high selectivity and sensitivity (detection limit: 1.78 × 10-8 M). Also, there are fewer interference from other antibiotics in the detection process of probe EHMC for Erythromycin. Moreover, probe EHMC could as a portable test strips for highly selective detection of Erythromycin and identification of different concentrations of Erythromycin. In addition, living cells imaging experiments displayed that probe EHMC could detect Erythromycin in A549 cells and BEAS-2B cells successfully. Combined with the theoretical calculation results The sensing mechanisms that the CO in Erythromycin and OH in EHMC formed intermolecular hydrogen bond and further formed new aggregates were confirmed by job' plot, 1H NMR, FT-IR, ESI-MS, DLS and TEM and DFT calculation.

Current Development and Future Application Prospects of Plants-Derived Polyphenol Bioactive Substance Curcumin as a Novel Feed Additive in Livestock and Poultry.

Curcumin (CUR) is a kind of natural orange-yellow phenolic compound mainly extracted from the stems and roots of turmeric plants and other species in the genus Curcuma, furthermore, it is also the most important active ingredient exerting pharmacological functions in turmeric. In recent years, CUR has been frequently reported and has attracted widespread attention from scholars all over the world due to its numerous biological functions and good application prospects, such as anti-inflammatory, anticancer, antioxidant and providing lipid-lowering effects, etc. In addition, adding a certain dose of CUR to livestock and poultry feed is important for animal growth and development, which plays a key role in animal metabolism, reproduction, immunity and clinical health care. This review aims to summarize, based on the published papers and our own observations, the physical and chemical properties and the biological functions of the plant-derived bioactive ingredient CUR, especially regarding the latest research progress in regulating intestinal health as well as its current development and future application prospects in livestock and poultry as a novel feed additive, so as to provide theoretical and practical references for the further study of the application of CUR as a novel feed additive and a potential new antibiotic substitute, thereby improving the research field of plant-derived bioactive ingredients and promoting the healthy development of livestock and poultry.

Systematic benchmarking of nanopore Q20+ kit in SARS-CoV-2 whole genome sequencing.

Whole genome sequencing provides rapid insight into key information about the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), such as virus typing and key mutation site, and this information is important for precise prevention, control and tracing of coronavirus disease 2019 (COVID-19) outbreak in conjunction with the epidemiological information of the case. Nanopore sequencing is widely used around the world for its short sample-to-result time, simple experimental operation and long sequencing reads. However, because nanopore sequencing is a relatively new sequencing technology, many researchers still have doubts about its accuracy. The combination of the newly launched nanopore sequencing Q20+ kit (LSK112) and flow cell R10.4 is a qualitative improvement over the accuracy of the previous kits. In this study, we firstly used LSK112 kit with flow cell R10.4 to sequence the SARS-CoV-2 whole genome, and summarized the sequencing results of the combination of LSK112 kit and flow cell R10.4 for the 1200bp amplicons of SARS-CoV-2. We found that the proportion of sequences with an accuracy of more than 99% reached 30.1%, and the average sequence accuracy reached 98.34%, while the results of the original combination of LSK109 kit and flow cell R9.4.1 were 0.61% and 96.52%, respectively. The mutation site analysis showed that it was completely consistent with the final consensus sequence of next generation sequencing (NGS). The results showed that the combination of LSK112 kit and flow cell R10.4 allowed rapid whole-genome sequencing of SARS-CoV-2 without the need for verification of NGS.

The emerging roles and mechanisms of exosomal non-coding RNAs in the mutual regulation between adipose tissue and other related tissues in obesity and metabolic diseases.

Exosomes (EXs) are the major types of extracellular vesicles (EVs) of 30-100 nm diameter that can be secreted by most cells to the extracellular environment. EXs transport endogenous cargoes (proteins, lipids, RNAs, etc.) to target cells and thereby triggers the release of these bioactive components, which then play important roles in regulating numerous biological processes under both physiological and pathological conditions. Throughout the studies in recent years, growing evidences have shown that EXs-derived non-coding RNAs (EXs-ncRNAs) are emerging as key players in cell-to-cell communication between adipose tissue and other related tissues in obesity and metabolic diseases. In this review, we will summarize the recent findings about EXs-ncRNAs, especially focus on the following aspects: 1) the biogenesis of EXs and emerging roles of EXs-ncRNAs, 2) the role of EXs-ncRNAs (EXs-miRNAs, EXs-lncRNAs, EXs-circRNAs, etc.) that were secreted by adipose-related tissues in promoting the differentiation of preadipocytes into mature and fully functional adipocytes, and 3) the crosstalk between the adipose tissue derived EXs-ncRNAs and the development of insulin resistance, obesity and various cancers. This review aims to reveal the emerging roles and mechanisms of EXs-ncRNAs in the mutual regulation of adipose tissue and its related tissues in obesity and metabolic diseases, so as to provide references for elucidating the etiology of obesity and related metabolic diseases and screening novel therapeutic targets.

Synthesis of Ag-Cu co-doping sponge iron-based trimetal for boosting simultaneous degradation of combined pollutants.

To date, zero-valent iron (ZVI)-based technique has encountered a baffle, challenging simultaneous detoxification of refractory rhodamine B (RhB) and p-nitrophenol (PNP) possessing strong electronwithdrawing nitro-group. In this study, we synthesized Ag-Cu decorated sponge iron (s-Fe0)-based trimetal for simultaneous degradation of RhB and PNP. The results show that Cu-Ag co-doping s-Fe0 (s-Fe0-(Cu-Ag)) achieves approx. 90.6 % of maximized removal of RhB; the preferred s-Fe0-(5 wt%Cu-1 wt%Ag) assisted with 6 L/min aeration rate simultaneously declines RhB and PNP within 10 recycling tests; non-aeration process obtains a complete reduction of PNP as well as merely approx. 23.9 % removal of RhB. Moreover, the Cu-Ag microstructure covering s-Fe0-(Cu-Ag) has been characterized in detail. Furthermore, the electron spin resonance (ESR) spectra have been applied to investigate simultaneous generation of reactive oxygen species (ROSs) and hydrogen radicals ([H]abs) over s-Fe0-(Cu-Ag). To our best knowledge, this is the first study reporting the enhanced bifunctional catalysis of s-Fe0-(Cu-Ag)/O2 for simultaneous degradation of RhB and PNP.

Activation of MT1/MT2 to Protect Testes and Leydig Cells against Cisplatin-Induced Oxidative Stress through the SIRT1/Nrf2 Signaling Pathway.

There is growing concern that chemotherapy drugs can damage Leydig cells and inhibit the production of testosterone. Increasing evidence shows that melatonin benefits the reproductive process. This study mainly explores the protective effect and possible molecular mechanism of melatonin regarding cisplatin-induced oxidative stress in testicular tissue and Leydig cells. We found that there were only Leydig and Sertoli cells in the testes of gastrointestinal tumor patients with azoospermia caused by platinum chemotherapeutic drugs. Melatonin (Mel) receptor 1/melatonin receptor 2 (MT1/MT2) was mainly expressed in human and mouse Leydig cells of the testes. We also observed that the melatonin level in the peripheral blood decreased and oxidative stress occurred in mice treated with cisplatin or gastrointestinal tumor patients treated with platinum-based chemotherapeutic drugs. iTRAQ proteomics showed that SIRT1/Nrf2 signaling and MT1 proteins were downregulated in cisplatin-treated mouse testes. The STRING database predicted that MT1 might be able to regulate the SIRT1/Nrf2 signaling pathway. Melatonin reduced oxidative stress and upregulated SIRT1/Nrf2 signaling in cisplatin-treated mouse testes and Leydig cells. Most importantly, after inhibiting MT1/MT2, melatonin could not upregulate SIRT1/Nrf2 signaling in cisplatin-treated Leydig cells. The MT1/MT2 inhibitor aggravated the cisplatin-induced downregulation of SIRT1/Nrf2 signaling and increased the apoptosis of Leydig cells. We believe that melatonin stimulates SIRT1/Nrf2 signaling by activating MT1/MT2 to prevent the cisplatin-induced apoptosis of Leydig cells.

Melatonin Alleviates Venous Dysfunction in a Mouse Model of Iliac Vein Occlusion.

The iliac vein can be severely stenosed and occluded due to thrombosis, tumor compression, or an anatomical abnormality. Such occlusion could result in limb swelling, venous claudication, and persistent leg ulcers. Its devastating sequelae heavily impact patients lifestyles and the social economy. Due to a lack of a stable and easy-to-operate iliac vein occlusion (IVO) model, its underlying molecular mechanism and pathophysiological process has not been completely understood. Melatonin (MLT) plays a critical role in anti-inflammation, but the potential protective effect of melatonin on venous dysfunction induced by IVO has not been revealed. In this study, a mouse model of IVO was established to study the effects of MLT on injured veins. The results of laser speckle images and Evans blue showed that MLT inhibited venous permeability in an IVO mouse model. Furthermore, MLT suppressed inflammation of surrounding tissues close to the affected vein by inhibiting the mRNA levels of TNF-α, IL-1α, and MCP-1. In addition, endothelial injury was inhibited by MLT using zonula occludens protein-1 (ZO-1) staining. Taken together, we elucidated the therapeutic effect of MLT on vascular dysfunction induced by IVO, mainly by inhibiting the TNF-α, IL-1α, and MCP-1 mRNA levels, improving endothelial function, and inhibiting vascular leakage.

Mutations and Phylogenetic Analyses of SARS-CoV-2 Among Imported COVID-19 From Abroad in Nanjing, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a pandemic and is threatening human health globally. The rapid genome sequencing and bioinformatic analysis of SARS-CoV-2 have become a helpful tool in the battle against the COVID-19. Here, we report the genetic characteristics, variations and phylogenetic analysis of SARS-CoV-2 sequenced from 42 clinical specimens. The complete genomes sequencing of SARS-CoV-2 were performed using Oxford Nanopore sequencing. All genomes accumulated mutations compared to the Wuhan-Hu-1 (GenBank Accession No: MN908947.3). Our data of the 42 whole genomes revealed 16 different lineages. The B.1.1 lineage was the most frequent, and 5, 2, 2, 3, and 1 sequences were classified as lineages of B.1.1.7, B.1.351, P.1, B.1.617.2, and C.37, respectively. A total of 328 nucleotide mutation sites were found in 42 genomes, among which A23403G mutation (D614G amino acid change in the spike protein) was the most common substitution. The phylogenetic trees of 42 SARS-CoV-2 sequences and GISAID-available SARS-CoV-2 sequences were constructed and its taxonomic status was supported. These results will provide scientific basis for tracing the source and prevention and control of SARS-CoV-2 imported from abroad in Nanjing, China.

Curcumin represses lipid accumulation through inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis in porcine subcutaneous preadipocytes.

OBJECTIVE: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms. METHODS: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot. RESULTS: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 µM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 µM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis. CONCLUSION: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

Corrigendum: Systematic benchmarking of nanopore Q20+ kit in SARS-CoV-2 whole genome sequencing.

[This corrects the article DOI: 10.3389/fmicb.2022.973367.].

Comparison of Surface Subsidence Measured by Airborne and Satellite InSAR Over Permafrost Areas Near Yellowknife Canada.

In addition to spaceborne Interferometric Synthetic Aperture Radar (InSAR), airborne data such as those obtained by the Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) have also been utilized to measure surface subsidence in permafrost areas in recent years. Motivated by the integration of multiplatform InSAR data, we generated two UAVSAR interferograms and one Advanced Land Observing Satellite (ALOS)-2 L-band interferogram over a permafrost area near Yellowknife, Canada, then compared the surface subsidence in the thaw seasons of 2017. The correlation coefficient and the root mean square error (RMSE) of subsidence difference are calculated to compare the airborne and spaceborne InSAR measurements. The results demonstrate that the two UAVSAR measurements are self-consistent, with the correlation coefficient between independent airborne measurements ∼0.7. While the RMSE of the difference between surface subsidence measured by UAVSAR and ALOS2 is ∼2.0 cm, and the correlation coefficients are less than 0.41, that is, a noticeable deviation exists between the UAVSAR and ALOS2 results possibly due to different spatial resolution and the calibration processing of airborne and spaceborne InSAR data. In addition, both UAVSAR and ALOS2 interferograms show larger surface subsidence within taiga needleleaf forest regions than in regions of other biome types (including needleleaf forest, shrubland, and grassland). The results demonstrate that a scheme for the elimination of systematic differences needs to be developed before merging multisource InSAR results. This intercomparison will provide valuable insights for narrowing the gap between radar-based measurements and planning the integration of airborne and satellite InSAR measurements in permafrost environments.