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In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

The hydraulic behavior of the connection between the floor failure area and the aquifer water-conductive zone is considered to be the root cause of mine water inrush disasters. Therefore, unraveling the floor failure mechanism is particularly important for safe coal mining above the high-confined aquifer. This paper estimates the depth of the baseplate failure to be 18.4–27.3 m by combining network parallel electrical methods with drilling visualization technology. The FLAC3D-based numerical model considering the strain hardening of caved rock was established with rigorous calibration and verification. The results showed that the depth of damage to the floor is 23.1 m, and the dominating floor failure mechanism is shear failure caused by the vertical stress exceeding the rock bearing capacity. Moreover, the stress recovery process of the baseplate does not alter the failure morphology of the baseplate. Based on the above research findings, the in-situ floor control technique of the working face No. 4305 is proposed and practiced in the field. Field measurements show that floor control performance is satisfactory with water inflow in the goaf being roughly stable at 50 m3/h. Our results can provide useful reference for safe mining above confined aquifer and prevention and mitigation of water-related hazards.

Abstract Thick-coal-seam with complex structures and thick-hard roof in the initial mining phase pose various challenges, including a long weighting interval, strong rock pressure, poor top coal caving performance (TCCP), and significant coal loss. These problems directly affect the safety and efficiency of the mining operations. This study employs the principles of elastic thin plates and ellipsoidal bodies to unravel the formation mechanism of strong rock pressure in thick-hard roof and the influence of parting on the TCCP. In addition, a hydraulic fracturing technique is proposed for safe-efficient recovery during the initial mining phase. The reliability of this technique is verified through numerical simulations and field experiments. The research findings reveal the following. (1) The primary causes of strong rock pressure in the mining face are attributed to a long weighting interval and wide collapse range of the main roof, and the weighting interval is primarily influenced by the thickness and tensile strength of the main roof. (2)The key factor affecting the TCCP is the cantilever beam structure formed by the fracture of the thick-hard parting, as it intersects the ellipsoidal body during coal caving. The simultaneous fracturing of both the top coal and roof can reduce the weighting interval on the working face. This process effectively decreased the strength of the thick-hard parting within the top coal, while simultaneously enhancing its load strength and eliminating the cantilever structure resulting from the parting fracture. It not only reduces the first weighting intensity but also promotes the early and proper coal release, thereby enhancing the TCCP and ensuring safe-efficient mining during the initial mining phase. (3) Aiming at the difference in the strengths of the top coal and roof, a graded hydraulic fracturing technique and system were proposed. Fracturing boreholes with a diameter of 60 mm, spacing of 10 m, and height of 20.85 m, which can economically and effectively ensure the fracturing results. Field applications have demonstrated that fractured coal and rocks in fracturing areas exhibit well-developed fractures. During the initial mining phase, the weighting interval in the working face was reduced by 20 m, resulting in a decrease in the overburden pressure and 26.9% reduction in the lumpiness of the top coal. Additionally, the recovery rate increased by 31.19%.

Abstract Background Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. Results Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3′-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain‐of‐function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. Conclusions These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.

Horseshoe crabs are marine chelicerates which have existed for about 450 million years. Their long coexistence with microbial pathogens presumably is due to their efficient immune system. Herein, the first large-scale transcriptome and microRNA (miRNA) dataset of embryonic stages of the horseshoe crab Tachypleus tridentatus were presented. It provides a general overview of global gene expression changes during horseshoe crab’s early development. This study focuses on the stages 18–20 of the embryonic development of T. tridentatus, which are the first three major embryonic molt stages and involve the formation of several vital organs. We identified 138,260 unigenes, including 34 immune-related gene families such as pattern recognition receptors, signaling and transduction pathway genes, antimicrobial peptides, and coagulation cascade genes. Additionally, 1522 miRNAs (1046 known miRNAs and 476 novel miRNAs) were predicted to 29,584 target genes. Numerous mRNA-miRNA interactions were also identified. Results of Quantitative PCR proved that the immune genes such as Spaetzle, ankyrin-3, peptidoglycan-recognition protein, coagulogen, TNF-receptor-associated factor, and CD-9 antigen were negatively regulated by miR-5735, miR-200, miR-145, miR-199, miR-144, and miR-322, respectively. Futhermore, we confirmed the target regulatory relationship between miR-200 and ankyrin-3 by dual luciferase reporter gene assay. To better understand the complex developmental gene regulatory networks in T. tridentatus, the time-course gene expression data analysis is the first step. Our results provide a valuable resource for analyzing the functions of gene repertoires in embryonic developmental stages （Stage 18 to Stage 20）of horseshoe crab.

Neural representations induced by naturalistic stimuli offer insights into how humans respond to stimuli in daily life. Understanding neural mechanisms underlying naturalistic stimuli processing hinges on the precise identification and extraction of the shared neural patterns that are consistently present across individuals. Targeting the Electroencephalogram (EEG) technique, known for its rich spatial and temporal information, this study presents a framework for Contrastive Learning of Shared SpatioTemporal EEG Representations across individuals (CL-SSTER). CL-SSTER utilizes contrastive learning to maximize the similarity of EEG representations across individuals for identical stimuli, contrasting with those for varied stimuli. The network employs spatial and temporal convolutions to simultaneously learn the spatial and temporal patterns inherent in EEG. The versatility of CL-SSTER was demonstrated on three EEG datasets, including a synthetic dataset, a natural speech comprehension EEG dataset, and an emotional video watching EEG dataset. CL-SSTER attained the highest inter-subject correlation (ISC) values compared to the state-of-the-art ISC methods. The latent representations generated by CL-SSTER exhibited reliable spatiotemporal EEG patterns, which can be explained by properties of the naturalistic stimuli. CL-SSTER serves as an interpretable and scalable framework for the identification of inter-subject shared neural representations in naturalistic neuroscience.

Transglutaminase 2 (TG2) is a widely distributed multifunctional protein with various enzymatic and non-enzymatic activities. It is becoming increasingly evident that high levels of TG2 in tumors induce the occurrence of epithelial to mesenchymal transition (EMT) and the acquisition of stem cell-like phenotypes, promoting tumor metastasis and drug resistance. By regulating intracellular and extracellular signaling pathways, TG2 promotes breast cancer metastasis to lung, brain, liver and bone, as well as resistance to various chemotherapy drugs including docetaxel, doxorubicin, platinum and neratinib. More importantly, recent studies described the involvement of TG2 in PD-1/PD-L1 inhibitors resistance. An in-depth understanding of the role that TG2 plays in the progression of metastasis and drug resistance will offer new therapeutic targets for breast cancer treatment. This review covers the extensive and rapidly growing field of the role of TG2 in breast cancer. Based on the role of TG2 in EMT, we summarize TG2-related signaling pathways in breast cancer metastasis and drug resistance and discuss TG2 as a therapeutic target.

The CBL (Casitas B-lineage lymphoma) family, as a class of ubiquitin ligases, can regulate signal transduction and activate receptor tyrosine kinases through various tyrosine kinase-dependent pathways. There are three members of the family: c-CBL, CBL-b, and CBL-c. Numerous studies have demonstrated the important role of CBL in various cellular pathways, particularly those involved in the occurrence and progression of cancer, hematopoietic development, and regulation of T cell receptors. Therefore, the purpose of this review is to comprehensively summarize the function and regulatory role of CBL family proteins in different human tumors, as well as the progress of drug research targeting CBL family, so as to provide a broader clinical measurement strategy for the treatment of tumors.

Under the carbon peaking and carbon neutrality strategy, biomass has attracted much attention due to its characteristics of regeneration, low pollution and zero carbon emissions. The imperfects of biomass, such as the loose structure and low energy density, can be effectively solved by briquetting, and the resulted fuel pellets can be used as a substitute for fossil fuels, which is of great significance for the construction of new energy system. In the paper, the influencing factors of the hot briquetting process of biomass were summarized, and the evolution behavior and binding mechanism of biomass particles during the hot briquetting process were analyzed and discussed. Biomass briquetting process mainly includes cold briquetting and hot briquetting. Compared with cold briquetting process of biomass, hot briquetting with lower energy consumption can produce the biomass fuel pellets with higher quality. The moisture content (4%−15%) of the raw biomass has greater influence, the briquetting temperature (70−150 ℃) has relatively smaller effect on the density of the fuel pellets, and the briquetting pressure (60−130 MPa) and the particle size ( < 2.5 mm) of the raw material show the different impact on the density of the fuel pellets from different biomass. During the hot process, cellulose mainly plays the role of supporting skeleton, hemicellulose and lignin play the role of binder. In the microcosmic process of hot briquetting process, the inertia movement and subsequent viscoelastic-plastic deformation of the biomass particles occur and the mechanical interlock is formed between the particles. The brittle particles are broken and the natural viscous components are released, and thus, the bridge linkage between the particles is formed under the integrated effects of moisture, temperature and pressure. Mechanical interlocking and bridging reduce the distance between biomass molecules and promote the generation of intermolecular forces. Based on the above-mentioned mechanism of the hot briquetting of biomass, the quality of the resulted fuel pellets can be improved by biomass component adjustment, biomass blending or hydrothermal pretreatment. In the future, the molecular dynamics simulation method will be used to investigate the biomass briquetting process to obtain the molecular bonding mechanism of biomass components, which is conducive to further exploring the hot briquetting mechanism of biomass, and provide important guiding significance for the preparation of fuel pellets and molding materials from biomass.

In order to promote the technological development of ultrasonic vibration induced cracking of coal and rock masses, improving the efficiency of coalbed methane production and hard rock excavation in mines, it reviews the development history of ultrasonic technology, summarizing the application status and research progress of ultrasonic vibration in fracturing coal and rock mass, and the key obstructive technology problems and development trends of ultrasonic vibration in the field of coal and rock fracturing are clarified. ① The technical problems of traditional technologies in the fields of coal seam methane production and hard rock excavation in mines is summarized, introducing unique advantages and application fields of ultrasonic technology, besides the development stages and corresponding performances of ultrasonic generator and ultrasonic transducer are described; ② The equipment and process of ultrasonic vibration to promote coalbed methane desorption and permeability increase are induced, analyzing the current situation of promoting permeability increase of coalbed methane by ultrasonic vibration, and the mechanism of pressure reduction, acceleration, potential energy and kinetic energy increase of coalbed methane under ultrasonic cavitation effect, mechanical vibration effect and thermal effect to promote its desorption and permeability increase is expounded; ③ The equipment and process of ultrasonic vibration rock fragmentation are generalized, describing the progress of ultrasonic vibration crushing of hard rock, and it reveals the internal mechanism of hard rock breaking caused by mechanical vibration effect and thermal effect of ultrasonic vibration, such as fatigue damage, subcritical propagation of microcracks, uneven thermal expansion or mineral phase transformation of mineral particles, and deterioration of rock physical and mechanical properties; ④ In view of limitations of ultrasonic generator, transducer and ultrasonic vibration in coal and rock mass fracturing in mines, four suggestions are put forward for the research focus on the efficient application of ultrasonic vibration induced fracturing of coal and rock masses in the field in the future: research and development of high-performance explosion-proof ultrasonic generator and transducer, in-depth analysis of the mechanism of increasing permeability by ultrasonic vibration and design of pipeline technology framework, development and test of multi-function and multi-field coupling indoor ultrasonic vibration cracking coal and rock mass equipment, research and application of anti-interference ultrasonic vibration equipment in underground mines.

Abstract Background The possibility of adverse effects of medical treatment (AEMT) is increasing worldwide, but little is known about AEMT in China. This study analyzed the health burden of AEMT in China in recent years through the Global Burden of Disease Study (GBD) 2019 and compared it with the worldwide average level and those in different sociodemographic index (SDI) regions. Methods We calculated the age-standardized rate (ASR) of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), incidence and prevalence attributed to AEMT in China, worldwide and countries with different sociodemographic indices during 1990–2019 using the latest data and methods from the GBD 2019. Results From 1990 to 2019, the global age-standardized death rate (ASDR), DALYs, and YLLs for AEMT showed a significant downward trend and were negatively associated with the SDI. By 2040, the ASDR is expected to reach approximately 1.58 (95% UI: 1.33–1.80). From 1990 to 2019, there was no significant change in the global incidence of AEMT. The occurrence of AEMT was related to sex, and the incidence of AEMT was greater among females. In addition, the incidence of AEMT-related injuries and burdens, such as ASR of DALYs, ASR of YLLs and ASR of YLDs, was greater among women than among men. Very old and very young people were more likely to be exposed to AEMT. Conclusions From 1990 to 2019, progress was made worldwide in reducing the harm caused by AEMT. However, the incidence and prevalence of AEMT did not change significantly overall during this period. Therefore, the health sector should pay more attention to AEMT and take effective measures to reduce AEMT.

The potential role of peroxisome proliferator-activated receptor (PPAR) in regulating the biosynthesis of long-chain polyunsaturated fatty acids (LCPUFA) has not been explored in marine gastropod. In this study, we identified and characterized a PPAR gene from the abalone species Haliotis discus hannai Ino. This gene encodes a peptide consisting of 469 amino acids and comprises typical four domains: A/B domain, DNA-binding domain, D domain, and ligand-binding domain. Highest homology with that of the Patella depressa (51.08 %) from multiple alignments and phylogenetic tree analyses revealed it is a direct orthologue of the vertebrate PPAR. Tissue distribution analysis demonstrated that PPAR was highly expressed in muscle and gill, with lower expression observed in the kidney, female gonad, and hepatopancreas. Dual-luciferase reporter assays indicated that abalone PPAR significantly up-regulated the promoter activity of Δ5 fatty acyl desaturase (Δ5fad), a crucial enzyme in LCPUFA biosynthesis. Furthermore, C18PUFA significantly increased the expressions of Δ5fad and PPAR in the hepatopancreas of abalone compared to the control group fed with an LCPUFA-rich diet. These findings suggest that PPAR acts as a positive transcription factor for the fad gene, contributing to the transcriptional regulation of LCPUFA biosynthesis in abalone.

Due to the large mining area, the fully-mechanized top-caving mining with thick-hard roof is easy to form cantilever structure on the lateral roof of the working face, which on the one hand causes high stress level of adjacent roadway and serious deformation of roadway, on the other hand causes gas accumulation in corners, which brings severe challenges to safe and efficient mining of the mine. In this study, a mine facing such problems in Jincheng, China was taken as the research object. Based on the mechanical characteristics of coal and rock, the characteristics of overlying strata activity in the mining process of working face are mastered, and the dual effects of controlled transformation of lateral overlying strata structure on stress field and gas field were revealed. On this basis, roadway reinforcement and gas drainage schemes were put forward and applied. The results showed that the strength of the hard rock stratum was high in the triaxial stress environment, and it was not easily destroyed. However, once the strata exceed their strength threshold, they break down. In addition, the strength of coal is relatively low, and it is continuously deformed when the force exceeds its strength. The overlying strata structure after thick-hard roof fully-mechanized top-caving mining evolves in the following manner: “long cantilever length formed by the main roof being broken in the initial stage, voussoir beam formed by the upper hard roof being broken in the middle stage, and double cantilever beam formed by overlying strata compaction.” The stress carried by upper hard rock stratum is transferred to coal pillars, which is the main reason for the high stress environment of multi-purpose roadway with large coal pillars. The controlled transformation of lateral overlying strata structure by pre-splitting and roof cutting can realize the ''transfer-unloading'' of coal pillar stress and the ''plugging and driving'' of corner gas. Based on the hydraulic fracturing reconstruction of lateral overburden structure, the grouting reinforcement scheme of roadway and dynamic gas drainage scheme were put forward. The results demonstrated that after roof cutting, the maximum deformation of the surrounding rock in the multi-purpose roadway was reduced by approximately 90 %, and the maximum concentration of corner gas was decreased by 15.28 %. This approach successfully achieved a collaborative control effect on roadway surrounding rock stability and gas emission well within the safety limits.

Abstract Bacterial wound infections are a serious threat due to the emergence of antibiotic resistance. Herein, we report an innovative hybrid nanozyme independent of antibiotics for antimicrobial wound healing. The hybrid nanozymes are fabricated from ultra-small Au NPs via in-situ growth on metal-organic framework (MOF)-stabilised Fe3O4 NPs (Fe3O4@MOF@Au NPs, FMA NPs). The fabricated hybrid nanozymes displayed synergistic peroxidase (POD)-like activities. It showed a remarkable level of hydroxyl radicals (·OH) in the presence of a low dose of H2O2 (0.97 mM). Further, the hybrid FMA nanozymes exhibited excellent biocompatibility and favourable antibacterial effects against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. The animal experiments indicated that the hybrid nanozymes promoted wound repair with adequate biosafety. Thus, the well-designed hybrid nanozymes represent a potential strategy for healing bacterial wound infections, without any toxic side effects, suggesting possible applications in antimicrobial therapy.

The phenomenon of Asaro–Tiller–Grinfeld (ATG) instability is common in the molecular beam epitaxy (MBE) process. In order to investigate the ATG instability, a two-dimensional mathematical model is established, which considers elastic stress. The phase-field method is utilized to simulate the interface evolution and the stress distribution. Furthermore, the Allen–Cahn approach, coupled with the motion of the interface, is used to investigate the morphology evolution. The results show that the thin film becomes unstable when it reaches a critical value. The critical thickness of the thin film is about 5.08 nm. The interface breaks into several parts due to the effect of elastic stress. The validity and correctness of the model are verified by the relevant theoretical results. Moreover, the numerical model can provide the basis for optimizing the ATG instability phenomenon in the MBE process.

BackgroundPerchlorates, nitrates, and thiocyanates are prevalent environmental chemicals. Their potential association with arthritis remains unexplored. This study aimed to investigate the link between perchlorate, nitrate, and thiocyanate exposure and arthritis, as well as the potential role of inflammation in this context.MethodsUtilizing the National Health and Nutrition Examination Survey (NHANES) data spanning from 2005 to 2016, the study enrolled 6597 participants aged 20-59 (young and middle-aged), of which 1045 had arthritis. Employing multivariate logistic regression modeling, multiple linear regression models, restricted cubic spline analysis, Bayesian kernel machine regression (BKMR) modeling, and mediation analysis, we assessed these relationships.ResultsThere was a significant positive association between elevated urinary thiocyanate levels and arthritis risk [1.19 (1.11, 1.28)]. This association held true across subgroups of osteoarthritis (OA) [1.24 (1.10, 1.40)] and rheumatoid arthritis (RA) [1.33 (1.15, 1.55)]. Thiocyanate levels displayed a dose-dependent relationship with arthritis risk, showing a linear trend (nonlinear P > 0.05). Conversely, perchlorate and nitrate did not exhibit associations with arthritis risk. BKMR outcomes highlighted a positive correlation between a mixture of perchlorate, nitrate, and thiocyanate and arthritis risk, with thiocyanate being the predominant predictors. Moreover, BKMR and generalized linear model analyses unveiled no significant synergistic effect of urinary perchlorate, nitrate, and thiocyanate on arthritis risk. Furthermore, thiocyanate exposure has been linked to elevated levels of inflammatory indicators (white blood cell, neutrophils, lymphocytes, and systemic immune-inflammatory index (SII)).ConclusionHeightened thiocyanate exposure may be linked to elevated arthritis risk, either single or in combined effects. Additionally, thiocyanate exposure is associated with heightened inflammation levels.

In order to investigate the effects of elliptical defects on rock failure under ultrasonic vibrations, ultrasonic vibration tests and PFC2D numerical simulations were conducted on rocks with single elliptical defects. The research results indicated that the fracture fractal dimension, axial strain, and crack depth of specimens with elliptical defects at 45° and 90° were the smallest and largest, respectively. The corresponding strain and fractal dimension showed a positive linear and logarithmic function relationship with time. The maximum crack depth of 46.50 mm was observed on the specimens with an elliptical defect angle of 90°. Specimens with elliptical defects at 0°, 30°, 75°, and 90° exhibited more dense and frequent acoustic emission events than those with elliptical defects at 15°, 45°, and 60°. During the ultrasonic vibration process, the maximum total energy (87.86 kJ) and energy consumption coefficient (0.963) were observed on specimens with elliptical defect angles of 30° and 45°, respectively. The difference in the stress field led to varying degrees of plastic strain energy in the specimens, resulting in different forms of crack propagation and triggering differential acoustic emission events, ultimately leading to specimen failure with different crack shapes and depths. The fractal dimensions of elliptical defect specimens under ultrasonic vibration have a high degree of consistency with the changes in axial strain and failure depth, and the fractal dimension of defect specimens is positively correlated with the degree of failure of defect specimens.

In this paper, a one-dimensional (1-D) range profile of the hypersonic target enveloped by a plasma sheath is investigated. Firstly, the non-uniform property of the plasma sheath is studied and its impact on the wideband electromagnetic (EM) wave is analyzed. A wideband radar echo model for the plasma-sheath-enveloped hypersonic target is constructed. Then, by exploiting the relationship among the incident depth, reflection intensity, and plasma velocity, it reveals that distinct scatter points in various areas of the target will suffer from varying reflection intensity and coupled velocity, leading to severe defocusing in the range profile. To tackle this issue, a novel focusing algorithm combing the Fractional Fourier Transform (FRFT) with the CLEAN technique is developed, which independently calculates the coupled plasma velocity and compensates for the phase error via a series of iterative procedures. Finally, the influence of the plasma sheath on the 1-D range profile and the effectiveness of the proposed focusing algorithm are validated through simulations.

NK-lysin is a component of natural killer cells and cytotoxic T lymphocytes, and it plays an important role in the innate immune response of aquatic animals against various pathogens. In this study, a 640 base pair full-length cDNA sequence of the NK-lysin gene from black sea bass (Centropristis striata) (CsNKl) was obtained and analyzed. Tissue distribution results showed that CsNKl was widely distributed in various tissues of C. striata, but a significantly high expression level was detected in the spleen. CsNKl also exhibited time-dependent expression in different tissues after challenge with Vibrio harveyi. Two antimicrobial peptides (CsNKl-26 and CsNKl-28) were predicted from CsNKl proteins, and they demonstrated bactericidal functions against a variety of bacteria. Scanning electron microscopy analysis revealed that CsNKl-26 and CsNKl-28 played their bactericidal roles using the classical alpha-helix antimicrobial peptide route. These results illustrate the immune functions of CsNKl against V. harveyi, and they can be applied to developing disease control methods for fish.

Abstract Background Gestational diabetes Mellitus (GDM) is a common pregnancy-specific disease with high morbidity, which is linked to a high risk of obesity and diabetes in offspring. N6-methyladenosine modification of RNA is emerging as an important epigenetic mechanism that is widely manifested in many diseases. This study aimed to investigate the mechanism of m6A methylation in metabolic syndrome in offspring result from intrauterine hyperglycemia. Methods GDM mice were established by feeding a high-fat diet 1 weeks before pregnancy. The m6A RNA methylation quantification kit was used to detect liver tissue methylation levels. PCR array was used to determine the expression of the m6A methylation modification enzyme. Immunohistochemistry, qRT-PCR, and western blot were used to examine the expression of RBM15, METTL13, IGF2BP1, and IGF2BP2. Subsequently, methylated RNA immunoprecipitation sequencing combined with mRNA sequencing, followed by dot blot and glucose uptake tests, were performed. Results In this study, we found that offspring from a GDM mother were more vulnerable to glucose intolerance and insulin resistance. GC–MS revealed significant metabolic changes including saturated fatty acids and unsaturated fatty acids in liver of GDM offspring. We also demonstrated that global mRNA m6A methylation level was significantly increased in the fetal liver of GDM mice, indicating epigenetic change may have a strong relationship with the mechanism of metabolism syndrome. Concordantly, RBM15, the RNA binding methyltransferase, was upregulated in the liver. In vitro, RBM15 suppressed insulin sensitivity and increased insulin resistance through m6A-regulated epigenetic inhabitation of CLDN4. Moreover, MeRIP-sequencing and mRNA-sequencing revealed that differently regulated genes with differential m6A peaks were enriched in metabolic pathways. Conclusion Our study revealed the essential role of RBM15 in insulin resistance and the effect of RBM15-regulated m6A modification in the metabolic syndrome of offspring of GDM mice.

With the continuous development of advanced packaging technology in heterogeneous semiconductor integration, the delamination failure problem in a dynamic service environment has gradually become a key factor limiting the reliability of packaging devices. In this paper, the delamination failure mechanism of polymer-based packaging devices is clarified by summarizing the relevant literature and the latest research solutions are proposed. The results show that, at the microscopic scale, thermal stress and moisture damage are still the two main mechanisms of two-phase interface failure of encapsulation devices. Additionally, the application of emerging technologies such as RDL structure modification and self-healing polymers can significantly improve the thermal stress state of encapsulation devices and enhance their moisture resistance, which can improve the anti-delamination reliability of polymer-based encapsulation devices. In addition, this paper provides theoretical support for subsequent research and optimization of polymer-based packages by summarizing the microscopic failure mechanism of delamination at the two-phase interface and introducing the latest solutions.

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe–/– mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

During the mining of thick coal seams under the gully slope, the mining-induced fractures are prone to connect with the gully runoff, which may induce potential water hazards and affect underground production. Based on the occurrence characteristics of coal seams and the landform in the gully-developed mining area, the coal seam mining under the slope of Na’er Coal Mine and Baoshan Coal Mine was taken as the engineering background, the seasonal runoff of gullies was considered as the influencing factors of the safe mining, and the spatial relationship between the working face and the gully slope was analyzed when the mining-induced fractures were connected with the gully surface and caused the gully runoff water disaster. The research results show that the occurrence structure of the gully slope has a greater impact on the strata movement of the slope. When the key layer is incomplete, the horizontal sliding and local block overturning of the slope rock strata are strong; when the key layer is complete, the horizontal sliding and local block overturning of the slope rock strata are weakened. According to the safety distance of the working face and the generalized model of safety coal pillar setting, the method of setting the safety coal pillar was used to prevent the connection of slipping cracks of the rock strata at the slope bottom and the gully surface during the slope mining, thus preventing the occurrence of runoff hazards during the thick coal seams mining in the valley terrain. The results can provide a theoretical basis and technical support for the prevention and control of seasonal runoff hazards, as well as a reference for the prevention and control of mining-induced landslides, water conservation mining, and ecological environment protection.

Selenium (Se) is required for the normal growth and development of aquatic animals. However, excessive Se can have various toxic effects on aquatic animals. In this study, we performed transcriptome analysis to determine the mechanism by which immunity and growth of abalone are affected by toxic dietary concentrations of Se. Four experimental diets were administered to supplement organic Se at concentrations of 0.00 (Control), 0.15 (Se15), 0.30 (Se30), and 0.60 mg/kg (Se60) to provide 0.16 (insufficient), 0.32 (optimal), 0.44 (super nutritional), and 0.60 mg/kg (toxic) Se concentrations in the diet. After feeding for 100 days, the results of the Gene Ontology (GO) analysis showed that the enriched GO terms of differentially expressed genes (DEGs) in the Se15 and Se30 groups were mainly focused on the cellular components, whereas the GO terms enriched in the Se60 group were mainly related to the metabolism of nutrients and the activities of various enzymes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs of the Se30 group were mainly enriched in various disease pathways, whereas the DEGs of the Se60 treatment were associated with the metabolism of various nutrients. Further analysis of DEGs showed that toxic dietary concentrations of Se decreased the immunity of abalone by affecting the biosynthesis and metabolism pathways of various nutrients. Additionally, toxic dietary concentrations of Se retarded the growth of abalone by decreasing the expression of various genes associated with shell formation, including lustrin A, perlucin, perlustrin, dermatopontin, chitin synthase, and chitinase as well as the genes associated with muscle production, including collagen, myosin heavy chain, myosin essential light chain, and paramyosin. In conclusion, the mechanism of the decrease of immunity and growth of abalone by toxic dietary concentrations of Se has been preliminary revealed in this study.

BackgroundGestational diabetes mellitus (GDM) is a metabolic condition defined as glucose intolerance with first presentation during pregnancy. Many studies suggest that environmental exposures, including air pollution, contribute to the pathogenesis of GDM. Although hair metabolite profiles have been shown to reflect pollution exposure, few studies have examined the link between environmental exposures, the maternal hair metabolome and GDM. The aim of this study was to investigate the longitudinal relationship (from pre-conception through to the third trimester) between air pollution exposure, the hair metabolome and GDM in a Chinese cohort.MethodsA total of 1020 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) birth cohort were included in our study. Metabolites from maternal hair segments collected pre-conception, and in the first, second, and third trimesters were analysed using gas chromatography-mass spectrometry (GC-MS). Maternal exposure to air pollution was estimated by two methods, namely proximal and land use regression (LUR) models, using air quality data from the air quality monitoring station nearest to the participant’s home. Logistic regression and mixed models were applied to investigate associations between the air pollution exposure data and the GDM associated metabolites.ResultsOf the 276 hair metabolites identified, the concentrations of fourteen were significantly different between GDM cases and non-GDM controls, including some amino acids and their derivatives, fatty acids, organic acids, and exogenous compounds. Three of the metabolites found in significantly lower concentrations in the hair of women with GDM (2-hydroxybutyric acid, citramalic acid, and myristic acid) were also negatively associated with daily average concentrations of PM2.5, PM10, SO2, NO2, CO and the exposure estimates of PM2.5 and NO2, and positively associated with O3.ConclusionsThis study demonstrated that the maternal hair metabolome reflects the longitudinal metabolic changes that occur in response to environmental exposures and the development of GDM.

Molting is a key biological process in crustaceans, with impacts on their growth, development and reproduction. Extracellular vesicles (EVs) serve as bio-cargo carrying such as nucleic acids, proteins, and lipids which mediate intercellular communication and participate in various cell biological processes. In this study, we obtained hemocyte transcriptome data during the intermolt, premolt, and postmolt stages of the mud crab Scylla paramamosain. We analyzed the differentially expressed genes in the three stages of molt and identified a number of immune-related genes and structural cuticle genes. We then isolated and characterized the EVs from the hemolymph of S. paramamosain and sequenced their miRNA. In total, we characterized 89 EVs microRNAs (miRNAs) targeting 1447 genes that are potentially involved in the molting process of S. paramamosain. The EVs miRNAs mainly regulated the immune-related genes and affected the molting process by mediating ecdysone signaling and insulin signaling pathways during the mud crab molt cycle. This is the first study of EVs miRNAs and their interaction with mRNA to identify important candidate genes associated with, or regulating, the molting process. This study provides a better understanding of, and novel insights into, the molting cycle of crustaceans and offers baseline information for further studies in the mechanisms regulating molt.

Abalone (Haliotis discus hannai Ino) is one of the most vital economic shellfish cultured in China. However, bacterial and viral infection often leads to its high mortality and serious economic losses. In this study, transcriptome sequencing was performed on gill of abalone challenged by Vibrio parahaemolyticus for 0 h (control group, A0h), 8 h (A8h), and 48 h (A48h), respectively. Each library has an average of 53,361,675 clean reads. Approximately 85.71% reads were mapped to the reference genome of Haliotis discus hannai Ino. In comparison with A0h group, 7,656 and 2,789 genes were differentially expressed in the A8h and A48h groups, respectively. The differentially expressed genes (DEGs) were mostly enriched in oxidation–reduction process and oxidoreductase activity from GO analysis as well as immunity and metabolism-related pathways from Kyoto Encyclopedia of Genes and Genomes analysis. Cluster analysis demonstrated that all DEGs were categorized into eight subclusters by adopting the gene expression model. Specifically, a total of 1,070 significantly downregulated genes from two clusters were related to some metabolic pathways, ABC transporters, and cell adhesion. Moreover, 212 upregulated genes in one subcluster were enriched in several immune-related pathways, including nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway and apoptosis. Some members of the pattern recognition receptors family, which can initiate inflammatory signaling and induce apoptosis, were stimulated to upregulate in gill after challenge including C1q, perlucin, and low-density lipoprotein receptor–related protein. In addition, caspase-dependent apoptosis pathway was inactive, whereas caspase-independent apoptosis pathway was stimulating in response to Vibrio challenge. To eliminate invading pathogen, the immune effectors such as interleukin-17, matrix metalloproteinase, lysozyme, superoxide, and ferritin were also stimulated in gill. Moreover, this study also provides more information for comprehending the immunity and defense mechanisms against V. parahaemolyticus infection in abalone.

Abstract Background Gestational diabetes mellitus (GDM) is correlated with an increased risk of adverse perinatal outcomes for both the mother and offspring. Previous research has reported correlations between maternal dietary patterns and GDM, but such evidence for twin pregnancies is lacking. This study aimed to identify maternal dietary patterns in the second trimester and investigate their relationships with the risk of GDM among women who were pregnant with twins in China. Methods A longitudinal twin pregnancies birth cohort study of women who were pregnant with twins in China was conducted. Maternal dietary intake in the second trimester was recorded by using a food frequency questionnaire prior to the diagnosis of GDM among participants from the prospective twin pregnancies birth cohort in Chongqing City. GDM was diagnosed with a 75 g 2-h oral glucose tolerance test at 23–26 weeks of gestation. Dietary patterns were identified by principal components analysis, and the correlations between dietary pattern and GDM were examined using multivariable logistic regression analyses. Results Of the 324 participants, 101 (31.2%) were diagnosed with GDM. Four dietary patterns were identified: a vegetable-based pattern, a poultry-and-fruit-based pattern, a sweet-based pattern and a plant-protein-based pattern. Multivariate analysis showed that none of the dietary patterns were correlated with the risk of GDM among women who were pregnant with twins, but the sweet-based dietary pattern, which was associated with a higher GDM risk for quartile 4 versus quartile 1 (OR 2.69; 95% CI: 1.09, 6.66) among non-overweight women (prepregnancy BMI

Rock breakage is inevitable for creating openings in underground engineering operations. Ultrasonic vibration has been attracting extensive attention for such a practice considering its outstanding performance in rock breakage. In order to understand the fundamental failure mechanism of rocks subjected to ultrasonic vibrations, based on P-wave monitoring and the direct current electric method, we captured the evolution of the failure process of the red sandstone. In addition, we fundamentally analyse the failure mechanisms of the red sandstone using numerical simulation and microscopy scans. It was found that extensive fractures were initiated due to the ultrasonic vibration and the fractures propagated downwards forming a conical shape. The apparent resistivity became as high as 320000 Ω being 16 times the initial resistivity. The fracture propagated downwards as deep as 41 mm. The maximum damage parameter on the testing sample could be as high as 0.68, and it completely failed after 140 s of ultrasonic vibration duration. As a result of numerical simulation, it was found that the microfractures and pores in the testing sample were activated due to the stress wave resulting from the ultrasonic vibration leading to the fracture propagation and eventually complete failure. Through comparing the performance of uniaxial compressive loading and ultrasonic vibration techniques in rock damage, it was concluded the latter has a much higher capacity and competence in rock breakage.

Analysing the penetration and droplet deposition characteristics in the canopy of fruit trees is critical for optimising the operational parameters of air-assisted spraying equipment, achieving precise application of chemicals, and improving the effectiveness of fruit tree pest and disease control. We used a mobile LIDAR system to detect the tree canopy characteristics and optical porosity and conduct wind tunnel experiments to investigate the interaction between the tree canopy, the airflow field, and the droplet penetration ratio in the canopy of fruit trees. The results show that the relative wind velocity decreases rapidly during canopy penetration, and that the minimum value occurs at the back of the canopy. The smaller the optical porosity, the greater the reduction in wind velocity is. The quadratic exponential regression model had the highest coefficient of determination (R2) (0.9672) and the lowest root mean square error (RMSE) (5.56%). This paper provides information on optimising the spraying parameters, improving the pesticide utilisation rate, and selecting the optimum spraying conditions and application parameters.

Numerous nanocarriers have been developed to deliver drugs for the treatment of hepatocellular carcinoma. However, the lack of specific targeting ability, the low administration efficiency, and insufficient absorption by hepatocellular carcinoma cells, severely limits the therapeutic effect of the current drugs. Therefore, it is still of great clinical significance to develop highly efficient therapies with few side effects for the treatment of hepatocellular carcinoma. Herein, we developed a highly effective nanocarrier, cyclic RGD peptide-conjugated magnetic mesoporous nanoparticles (RGDSPIO@MSN NPs), to deliver the chemotherapeutic drug doxorubicin (DOX) to human hepatocellular carcinoma HepG2 cells, and further explored their synergistic apoptosis-promoting effects. The results showed that the prepared RGDSPIO@MSN NPs had good stability, biosafety and drug-loading capacity, and significantly improved the absorption of DOX by HepG2 cells, and that the RGDSPIO@MSN@DOX NPs could synergistically promote the apoptosis of HepG2 cells. Thus, this cyclic RGD peptide-modified magnetic mesoporous silicon therapeutic nanosystem can be regarded as a potentially effective strategy for the targeted treatment of hepatocellular carcinoma.

Sulfite is widely used as an antioxidant additive and preservative in food and beverages. Abnormal levels of sulfite in the body is related to a variety of diseases. There are strict rules for sulfite intake. Therefore, to monitor the sulfite level in physiological and pathological events, there is in urgent need to develop a rapid, accurate, sensitive, and non-invasive approach, which can also be of great significance for the improvement of the corresponding clinical diagnosis. With the development of fluorescent probes, many advantages of fluorescent probes for sulfite detection, such as real time imaging, simple operation, economy, fast response, non-invasive, and so on, have been gradually highlighted. In this review, we enumerated almost all the sulfite fluorescent probes over nearly a decade and summarized their respective characteristics, in order to provide a unified platform for their standardized evaluation. Meanwhile, we tried to systematically review the research progress of sulfite small-molecule fluorescent probes. Logically, we focused on the structures, reaction mechanisms, and applications of sulfite fluorescent probes. We hope that this review will be helpful for the investigators who are interested in sulfite-associated biological procedures.

Abstract The gut microbiome plays a fundamental role in host health and the fecal metabolome can be analysed to assess microbial activity and can be used as an intermediate phenotype monitoring the host-microbiome relationship. However, there is no established extraction protocol to study the fecal metabolome of giant pandas. The aim of this research is to optimize extraction of the fecal metabolome from adult and baby pandas for high throughput metabolomics analysis using gas chromatography-mass spectrometry (GC-MS). Fecal samples were collected from eight adult pandas and a pair of twin baby pandas. Six different extraction solvents were investigated and evaluated for their reproducibility, metabolite coverage, and extraction efficiency, particularly in relation to the biochemical compound classes such as amino acids, tricarboxylic acid (TCA) cycle intermediates, fatty acids, secondary metabolites, and vitamin and cofactors. Our GC-MS results demonstrated that the extraction solvents with isopropanol: acetonitrile: water (3:2:2 ratio) and 80% methanol were the most appropriate for studying the fecal metabolome of adult and baby giant pandas respectively. These extraction solvents can be used in future study protocols for the analysis of the fecal metabolome in giant pandas.

Plasma sheath poses a serious challenge to inverse synthetic aperture radar (ISAR) imaging of hypersonic targets. This paper investigated the distribution characteristics of the electron density and velocity field in the plasma sheath surrounding the hypersonic target in various flight scenes. The incident depth and reflective surface of electromagnetic (EM) waves with X-band, Ku-band, and Ka-band can be determined based on the plasma frequency. We established the echo model coupled with the velocity field of the plasma sheath on the reflective surface and obtained one-dimensional range profiles and ISAR images of the hypersonic target in various flight scenes. The simulation results indicated that the non-uniform velocity field on the reflective surface induced displacement and diffusion in the one-dimensional range profile, resulting in ISAR image distortion. A changing flight scene and radar frequency can have an impact on imaging results. Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity (SSIM) were utilized to assess the impact of plasma sheath on ISAR images. This study revealed the defocus mechanism of the ISAR image caused by the velocity field of the plasma sheath and provided a theoretical reference for the selection of radar frequency for hypersonic targets in various flight scenes.

Efficiency can be improved through the cooperation of a dual-robot during assembly. However, how to effectively plan a simple and smooth path in a dynamic environment is a prominent problem in the process of dual-robot cooperative assembly. In this paper, a method based on RRT-Connect algorithm for trajectory planning and post-processing for trajectory optimization is proposed. This method takes full advantage of the excellent solution ability of RRT-Connect algorithm in the complex environment so as to obtain the initial path successfully. Through post-processing, the problem of RRT-Connect non-convergence to target is optimized. We use two 6-DOF industrial robots to build an experimental platform and design a dual-robot cooperative assembly system. According to the given task, the system can generate the original collision-free path based on RRT-Connect algorithm. Then the original path is simplified by Floyd algorithm and smoothed by multi-segment Bezier curve. Finally, the time parameter is sequenced for all the path points based on the iterative method, and the effective trajectory is obtained. The experimental results show that the algorithm proposed in this paper can effectively plan and optimize the trajectory of dual-robot. Compared to other methods, this approach has a higher success rate and less planning time.

Members of the genus Crassicauda (Nematoda: Spirurida) are macroparasites infect the body tissues of whales and dolphins. However, limited information is available on morphological descriptions and phylogenetic studies of the worms. In present study, we report the first complete mitochondrial genome of Crassicauda magna from Neophocoena sunameri in Ningbo, Zhejiang Provence, China. The mitogenome has 13,605 base pairs (74.97% A + T content) and is made up of a total of 36 genes (12 protein-coding, 22 transfer RNAs, and 2 ribosomal RNAs). This study will provide useful molecular information for addressing taxonomic and evolutionary issues in Crassicauda sp..

Confirmation bias and peer pressure are regarded as the main psychology origins of personal opinion adjustment. Each show substantial impacts on the formation of collective decisions. Nevertheless, few attempts have been made to study how the interplay between these two mechanisms affects public opinion evolution on large-scale social networks. In this paper, we propose an agent-based model of opinion dynamics which incorporates the conjugate effect of confirmation bias (characterized by the population identity scope and initiative adaptation speed) and peer pressure (described by a susceptibility threshold and passive adaptation speed). First, a counterintuitive non-monotonous phenomenon arises in the homogeneous population: the number of opinion clusters first increases and then decreases to one as the population identity scope becomes larger. We then consider heterogeneous populations where “impressionable” individuals with large susceptibility to peer pressure and “confident” individuals with small susceptibility coexist. We find that even a small fraction of impressionable individuals could help eliminate public polarization when population identity scope is relatively large. In particular, the impact of impressionable agents would be greater if these agents are hubs. More intriguingly, while impressionable individuals have randomly distributed initial opinions, most of them would finally evolve to moderates. We highlight the emergence of these “impressionable moderates” who are easily influenced, yet are important in public opinion competition, which may inspire efficient strategies in winning competitive campaigns.

Objective: To explore the inhibitory and synergistic effects of 5-fluorouracil and curcumin on Hep-2 laryngeal cancer cells and clarify the effect of mesoporous silica nanoparticles as drug carriers. Methods: The inhibitory effects of 5-fluorouracil and curcumin on Hep-2 cells were detected using the CCK-8 assay. CompuSyn was used to calculate the synergistic effect of the 2 drugs. Flow cytometry was used to detect apoptosis and cell cycle arrest induced by 5-fluorouracil and curcumin. The drugs were loaded into mesoporous nanoparticles. Western blotting was used to detect the expression of related proteins after treatment. The growth of subcutaneous tumors in BALB/c nude after the intraperitoneal injection with drug-loaded mesoporous silica nanoparticles was recorded. Results: 5-Fluorouracil and curcumin synergistically induced apoptosis and cell cycle arrest in Hep-2 cells. Mesoporous silica nanoparticles as drug carriers enhanced the therapeutic effects of 5-fluorouracil and curcumin. Conclusions: Mesoporous silica nanoparticles are expected to be effective drug carriers that enhance the synergistic effects of 5-fluorouracil and curcumin on laryngeal cancer.

Endothelial dysfunction plays an important role in promoting the progression of disease genesis such as atherosclerosis and abdominal aortic aneurysm (AAA). The physiological unbalance of endothelial cells is a major pathological basis. In this present study, we investigated Brahma-related gene 1 (BRG1), a chromatin remodeling protein, was in mouse models of diabetic atherosclerosis and AAA, focusing on its role in endothelial dysfunction. We report that compared with their wild-type (WT, ApoE–/–; BRG1fl/fl) littermates, endothelium conditional BRG1 knockout mice (CKO, ApoE–/–; BRG1fl/fl; CDH5-cre) exhibited an alleviated phenotype of diabetic atherosclerosis. Immunohistochemically staining and real-time PCR analysis demonstrated fewer macrophages recruitment with a reduction of vascular inflammatory in CKO mice compared with WT mice. Further research in the Ang-II induced AAA model revealed that BRG1 deficiency had the protective effects on endothelium conditional BRG1 deletion, evidenced by the downregulation of pro-inflammatory mediators [interleukin (IL)-1β and IL-6, not tumor necrosis factor-α (TNF-α)] in the vessels of CKO mice compared with WT mice. In Ea.hy926 cell lines, anti-BRG1 small interfering RNA and PFI-3 treatment obviously alleviated tumor necrosis factor-α-induced IL-6 and CCL2 expression, and further research demonstrated that the BRG1 inhibition in endothelial cells not only decreased c-Fos expression but also blocked the c-Fos translocation into nuclei. In conclusion, our results suggest that endothelial BRG1 deficiency may protect the mice from diabetic atherosclerosis and AAA via inhibiting inflammatory response in vessels.

Active tuberculosis infection is a major health concern in the world. Each year, millions of people die of tuberculosis, especially in third-world countries. Though the World Health Organization has recently reported the rate of mortality by this disease is declining by 3% yearly, active tuberculosis infection is still endangering human health seriously. In addition, there are many people who have a latent tuberculosis infection, and these people do not seek treatment because they have no clinical symptoms. It is true that current specific laboratory examination approaches are capable of diagnosing active tuberculosis infection promptly and accurately. But sensitivity and specificity of current diagnostic approaches are at a low level. However, the development of new nanomaterials allows more scientists to combine diagnostic methods with nanotechnology. Recently, a novel Nanodisk mass spectrometry method has been reported. Mycobacterium tuberculosis-specific peptides are enriched using an antibody-conjugated nanodisk, allowing for rapid, quantitative detection of the serum-specific antigen for active tuberculosis infection. This method overcomes the shortcomings of poor sensitivity and long turnaround time associated with current diagnostic approaches. This review discusses the current status and progress of specific laboratory examination methods of active tuberculosis diagnosis and compares the newest diagnostic techniques.

Conventional compressive sensing (CS)-based imaging methods allow images to be reconstructed from a small amount of data, while they suffer from high computational burden even for a moderate scene. To address this problem, this paper presents a novel two-dimensional (2D) CS imaging algorithm for strip-map synthetic aperture radars (SARs) with zero squint angle. By introducing a 2D separable formulation to model the physical procedure of the SAR imaging, we separate the large measurement matrix into two small ones, and then the induced algorithm can deal with 2D signal directly instead of converting it into 1D vector. As a result, the computational load can be reduced significantly. Furthermore, thanks to its superior performance in maintaining contour information, the gradient space of the SAR image is exploited and the total variation (TV) constraint is incorporated to improve resolution performance. Due to the non-differentiable property of the TV regularizer, it is difficult to directly solve the induced TV regularization problem. To overcome this problem, an improved split Bregman method is presented by formulating the TV minimization problem into a sequence of unconstrained optimization problem and Bregman updates. It yields an accurate and simple solution. Finally, the synthesis and real experiment results demonstrate that the proposed algorithm remains competitive in terms of high resolution and high computational efficiency.

Halophila beccarii has been listed as a vulnerable species in ICNU. In this study, the complete plastid genome sequence of H. beccarii was successfully sequenced by the technology of Illumina. The whole plastid genome length was 168,585 bp and contained a typical quadripartite structure including one large single-copy (LSC) region (80,881 bp), one small single-copy (SSC) region (4,730bp) and a pair of inverted repeats (IR) regions (41,487bp). The GC content of this genome was 38.5%. The whole genome contained 132 genes including 88 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The phylogenetic analysis indicated that H. beccarii and Thalassia hemprichii formed a distinct clade.

BACKGROUND:Chromoblastomycosis is a chronic skin and subcutaneous fungal infection caused by dematiaceous fungi and is associated with low cure and high relapse rates. In southern China, Fonsecaea monophora and Fonsecaea pedrosoi are the main causative agents. PRINCIPAL FINDINGS:We treated 5 refractory and complex cases of chromoblastomycosis with 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with oral antifungal drugs. The lesions improved after 4 to 9 sessions of ALA-PDT treatment at an interval of one or two weeks, and in some cases, mycological testing results became negative. The isolates were assayed for susceptibility to antifungal drugs and ALA-PDT in vitro, revealing sensitivity to terbinafine, itraconazole and voriconazole, with ALA-PDT altering the cell wall and increasing reactive oxygen species production. CONCLUSIONS:These results provide the basis for the development of a new therapeutic approach, and ALA-PDT combined with oral antifungal drugs constitutes a promising alternative method for the treatment of refractory and complex cases of chromoblastomycosis.

Trans-differentiation of quiescent hepatic stellate cells (HSC) to myofibroblasts is a hallmark event in liver fibrosis. Previous studies have led to the discovery that myocardin-related transcription factor A (MRTF-A) is a key regulator of HSC trans-differentiation or, activation. In the present study we investigated the interplay between MRTF-A and c-Abl (encoded by Abl1), a tyrosine kinase, in this process. We report that hepatic expression levels of c-Abl were down-regulated in MRTF-A knockout (KO) mice compared to wild type (WT) littermates in several different models of liver fibrosis. MRTF-A deficiency also resulted in c-Abl down-regulation in freshly isolated HSCs from the fibrotic livers of mice. MRTF-A knockdown or inhibition repressed c-Abl in cultured HSCs in vitro. Further analyses revealed that MRTF-A directly bound to the Abl1 promoter to activate transcription by interacting with Sp1. Reciprocally, pharmaceutical inhibition of c-Abl suppressed MRTF-A activity. Mechanistically, c-Abl activated extracellular signal-regulated kinase (ERK), which in turn phosphorylated MRTF-A and promoted MRTF-A nuclear trans-localization. In conclusion, our data suggest that a c-Abl-MRTF-A positive feedback loop contributes to HSC activation and liver fibrosis.

Activation of hepatic stellate cells (HSC) is a hallmark event in liver fibrosis. Accumulation of reactive oxygen species (ROS) serves as a driving force for HSC activation. The regulatory subunits of the NOX complex, NCF1 (p47phox) and NCF2 (p67phox), are up-regulated during HSC activation contributing to ROS production and liver fibrosis. The transcriptional mechanism underlying NCF1/2 up-regulation is not clear. In the present study we investigated the role of serum response factor (SRF) in HSC activation focusing on the transcriptional regulation of NCF1/2. We report that compared to wild type littermates HSC-conditional SRF knockout (CKO) mice exhibited a mortified phenotype of liver fibrosis induced by thioacetamide (TAA) injection or feeding with a methionine-and-choline deficient diet (MCD). More importantly, SRF deletion attenuated ROS levels in HSCs in vivo. Similarly, SRF knockdown in cultured HSCs suppressed ROS production in vitro. Further analysis revealed that SRF deficiency resulted in repression of NCF1/NCF2 expression. Mechanistically, SRF regulated epigenetic transcriptional activation of NCF1/NCF2 by interacting with and recruiting the histone acetyltransferase KAT8 during HSC activation. In conclusion, we propose that SRF integrates transcriptional activation of NCF1/NCF2 and ROS production to promote liver fibrosis. Keywords: Transcriptional regulation, Serum response factor, Hepatic stellate cell, Reactive oxygen species, Liver fibrosis, Neutrophil cytosolic factor

Pingdingshan mining area is one of the typical deep mining areas in China, and most of the mines in this area are troubled by the difficulties of the deep-soft-rock roadway support. Based on the concept of synergistic interactions of the interior and exterior bearing structure of the surrounding rock and, considering the specific geological conditions of the research site, we establish the mechanical model of the interior and exterior bearing structure of the roadway. Based on numerical simulation, we reveal the influence of main factors, such as support strength and mechanical characteristics, of surrounding rock on the distribution and evolution of the interior and exterior bearing structure. We found that increasing the support strength and mechanical parameters of surrounding rock can make the exterior bearing structure close to the roadway enhance the bearing characteristics of the interior and exterior bearing structure and improve the roadway stability. The distribution characteristics of the interior and exterior bearing structure of the roadway under six different support strengths and six different grouting parameters were systematically investigated by field measurements. According to the field test results, an effective strategy for controlling the deep-soft-rock roadway is proposed, which provides a good reference for surrounding rock control of the deep-soft-rock roadway in the Pingdingshan mining area and mines with similar mining conditions.