ABSTRACT
Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.
Subject(s)
Antiviral Agents , DNA, Viral , Guanine , Hepatitis B virus , Hepatitis B, Chronic , Viremia , Humans , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/complications , Male , Guanine/analogs & derivatives , Guanine/therapeutic use , Female , Adult , Risk Factors , Antiviral Agents/therapeutic use , Retrospective Studies , Middle Aged , Hepatitis B virus/genetics , Hepatitis B virus/drug effects , DNA, Viral/blood , Hepatitis B e Antigens/blood , Liver Cirrhosis/virology , Viral Load/drug effectsABSTRACT
In recent years, ground-level-ozoneï¼O3ï¼ pollution in urban areas in the Bohai Rim has attracted wide attention. Based on the analysis of the spatiotemporal distribution characteristics of O3 concentration in Dongying, a representative city in the Bohai Rim from 2017 to 2022, the effects of meteorological factors and sea-land breeze circulation on O3 concentration were evaluated. The results showed thatï¼ â From 2017 to 2022, the annual assessment value of O3 concentration in Dongying showed a fluctuating upward trend, and the pollution days with O3 as the primary pollutant increased. O3 pollution mainly occurred in spring, summer, and autumn, with the most severe O3 pollution episodes typically occurring in May and June, and the duration of O3 pollution season tended to be longer. The monthly variation in the daily maximum 8-h average ozone ï¼MDA8 O3ï¼ presented a bimodal distribution, with significant increases in the 5th and 25th percentiles, and the spatial distribution was "high in the north and south, low in the middle." In addition, the nocturnal O3 concentration in recent years in Dongying also showed a significant increase trend. â¡ Meteorological factors greatly influenced O3 concentration in Dongying. When the temperature was greater than 30â, the relative humidity was less than 50%, and the wind direction was south-southwest or east-northeast, a high O3 value was more likely to occur. Meteorological factors contributed 30% of the MDA8 O3 variation in Dongying during the study period. In the case of moderate and severe O3 pollution, the contribution of meteorological factors to the change in MDA8 O3 could be as high as 40%. ⢠To some extent, sea-land breeze contributed to the occurrence of MDA8 O3 exceeding the secondary standard limit value of the National Ambient Air Quality Standard. In the afternoon, the hourly concentration of O3 during the sea-land breeze days was approximately 20 µg·m-3 higher than that during the non-sea-land breeze days. On the days of moderate and severe O3 pollution, the O3 concentration during the sea-land breeze days from 10ï¼00 to 16ï¼00 was higher than that during non-sea-land breeze days, and the O3 concentration was also at a high level from 20ï¼00 to 23ï¼00 on sea-land breeze days. In the O3 pollution season, the sea-land breeze could significantly affect the O3 level in coastal cities, which could bring significant challenges for O3 pollution prevention and control in this region. In the future, cities in the Bohai Rim need to further strengthen regional joint prevention and control of O3 pollution and increase emission reduction efforts of nitrogen oxides and volatile organic compounds. This strategy could effectively lower pollutant concentrations within the land breeze air mass, consequently reducing the impact of the sea breeze air mass on air quality in cities in the Bohai Rim.
ABSTRACT
Anchoring Pt onto multi-heteroatom doped carbon materials has been recognized as an effective approach to improve the performance of electrocatalytic methanol oxidation. However, distinct contributions and specific behavior mechanisms of different heteroatoms, notably N and P, the specific behavior mechanisms in synergistically promoting Pt NPs remain elusive. In this work, we construct 1D N and P co-doped carbon nanotube (N, P-CNTs) supports with abundant defect anchors for Pt. The as-prepared Pt/N, P-CNTs exhibit outstanding activity and exceptional stability in methanol oxidation reaction (MOR), achieving high mass activity up to 6481.3 mA mg-1Pt. Moreover, they can retain 90.5 % of their initial current density even after 800 cycles tests. Detailed characterizations and theoretical calculations indicate that the robust strong metal-support interactions (SMSI) effect caused by N doping within the unique N and P co-doped coordination structure controllably regulate the coordination environment of Pt, reduce the d-band center of Pt, thus promoting the adsorption and decomposition of CH3OH. However, P doping weakens the adsorption strength of CO on the Pt active site by sacrificing partial electron transfer, accelerating the oxidative conversion of the CO-like poisoning species (COads). Significantly, the synergistic mechanism of N and P species on the modification of Pt's electronic structure and its subsequent impact on the electrocatalytic methanol oxidation behaviors on the Pt surface was thoroughly elucidated, providing a constructive route for designing robust MOR electrocatalysts with high MOR activity and durability.
ABSTRACT
Nitrite-oxidizing bacteria (NOB) are undesirable in the anaerobic ammonium oxidation (anammox)-driven nitrogen removal technologies in the modern wastewater treatment plants (WWTPs). Diverse strategies have been developed to suppress NOB based on their physiological properties that we have understood. But our knowledge of the diversity and mechanisms employed by NOB for survival in the modern WWTPs remains limited. Here, Three NOB species (NOB01-03) were recovered from the metagenomic datasets of a full-scale WWTP treating duck breeding wastewater. Among them, NOB01 and NOB02 were classified as newly identified lineage VII, tentatively named Candidatus (Ca.) Nitrospira NOB01 and Ca. Nitrospira NOB02. Analyses of genomes and in situ transcriptomes revealed that these two novel NOB were active and showed a high metabolic versatility. The transcriptional activity of Ca. Nitrospira could be detected in all tanks with quite different dissolved oxygen (DO) (0.01-5.01 mg/L), illustrating Ca. Nitrospira can survive in fluctuating DO conditions. The much lower Ca. Nitrospira abundance on the anammox bacteria-enriched sponge carrier likely originated from the intensification substrate (NO2 -) competition from anammox and denitrifying bacteria. In particular, a highlight is that Ca. Nitrospira encoded and treanscribed cyanate hydratase (CynS), amine oxidase, urease (UreC), and copper-containing nitrite reductase (NirK) related to ammonium and NO production, driving NOB to interact with the co-existed AOB and anammox bacteria. Ca. Nitrospira strains NOB01 and NOB02 showed quite different niche preference in the same aerobic tank, which dominanted the NOB communities in activated sludge and biofilm, respectively. In addition to the common rTCA cycle for CO2 fixation, a reductive glycine pathway (RGP) was encoded and transcribed by NOB02 likely for CO2 fixation purpose. Additionally, a 3b group hydrogenase and respiratory nitrate reductase were uniquely encoded and transcribed by NOB02, which likely confer a survival advantage to this strain in the fluctuant activated sludge niche. The discovery of this new genus significantly broadens our understanding of the ecophysiology of NOB. Furthermore, the impressive metabolic versatility of the novel NOB revealed in this study advances our understanding of the survival strategy of NOB and provides valuable insight for suppressing NOB in the anammox-based WWTP.
ABSTRACT
There is a significant difference between the simulation effect and the actual effect in the design process of maize straw-breaking equipment due to the lack of accurate simulation model parameters in the breaking and processing of maize straw. This article used a combination of physical experiments, virtual simulation, and machine learning to calibrate the simulation parameters of maize straw. A bimodal-distribution discrete element model of maize straw was established based on the intrinsic and contact parameters measured via physical experiments. The significance analysis of the simulation parameters was conducted via the Plackett-Burman experiment. The Poisson ratio, shear modulus, and normal stiffness of the maize straw significantly impacted the peak compression force of the maize straw and steel plate. The steepest-climb test was carried out for the significance parameter, and the relative error between the peak compression force in the simulation test and the peak compression force in the physical test was used as the evaluation index. It was found that the optimal range intervals for the Poisson ratio, shear modulus, and normal stiffness of the maize straw were 0.32-0.36, 1.24 × 108-1.72 × 108 Pa, and 5.9 × 106-6.7 × 106 N/m3, respectively. Using the experimental data of the central composite design as the dataset, a GA-BP neural network prediction model for the peak compression force of maize straw was established, analyzed, and evaluated. The GA-BP prediction model's accuracy was verified via experiments. It was found that the ideal combination of parameters was a Poisson ratio of 0.357, a shear modulus of 1.511 × 108 Pa, and a normal stiffness of 6.285 × 106 N/m3 for the maize straw. The results provide a basis for analyzing the damage mechanism of maize straw during the grinding process.
Subject(s)
Algorithms , Zea mays , Zea mays/chemistry , Calibration , Neural Networks, Computer , Computer SimulationABSTRACT
Microbial metabolism in landfill leachate systems is critically important in driving the degradation reactions of organic pollutants, including the emerging pollutant bisphenol A (BPA). However, little research has addressed the microbial degradation of BPA in landfill leachate and its interactions with nitrogen (N), sulfur (S), and methane (CH4) metabolism on a global scale. To this end, in this study on a global scale, an extremely high concentration of BPA was detected throughout the global landfill leachates. Subsequent reconstructive analyses of metagenomic datasets from 113 sites worldwide revealed that the predominant BPA-degrading microflora included Proteobacteria, Firmicutes, and Bacteroidota. Further metabolic analyses revealed that all four biochemical pathways involved in the degradation of BPA were achieved through biochemical cooperation between different bacterial members of the community. In addition, BPA degraders have also been found to actively collaborate synergistically with non-BPA degraders in the N and S removal as well as CH4 catabolism in landfill leachates. Collectively, this study not only provides insights into the dominant microbial communities and specific types of BPA-degrading microbial members in the community of landfill leachates worldwide, but also reveals the synergistic interactions between BPA mineralization and N, S, and CH4 metabolism. These findings offer valuable and important insights for future comprehensive and in-depth investigations into BPA metabolism in different environments.
Subject(s)
Benzhydryl Compounds , Biodegradation, Environmental , Metagenomics , Methane , Nitrogen , Phenols , Sulfur , Water Pollutants, Chemical , Phenols/metabolism , Water Pollutants, Chemical/metabolism , Benzhydryl Compounds/metabolism , Methane/metabolism , Sulfur/metabolism , Sulfur/chemistry , Nitrogen/metabolism , Waste Disposal Facilities , Bacteria/metabolism , Bacteria/genetics , Bacteria/classificationABSTRACT
OBJECTIVES: Hepatic inflammation, the driver of fibrosis progression in liver disease, can impact the accuracy of liver stiffness measurement (LSM). We wondered whether the decline in LSM value during the early antiviral phase was mainly attributed to the control of hepatic inflammation or the regression of fibrosis in patients with fibrotic/cirrhotic chronic hepatitis B (CHB). PATIENTS AND METHODS: The study cohort was composed of 82 patients with CHB who underwent antiviral and antifibrotic therapy at the Fifth Medical Center of PLA General Hospital. All patients had liver biopsies at both baseline and 72 weeks posttherapy. Liver pathology and clinical data, including the LSM value, were collected. RESULTS: After 72 weeks of treatment, both the histologic activity index score and fibrosis score, as well as the LSM value, were significantly decreased (P < 0.001), compared with their baseline values. The pretreatment correlation of LSM value with either histologic activity index score (r = 0.526 vs r = 0.286) or fibrosis score (r = 0.677 vs r = 0.587) was attenuated at 72 weeks. Notably, logistic regression analysis revealed that the improvement in inflammation (odds ratio = 1.018, 95% CI: 1.002-1.031, P = 0.023) but not fibrosis (odds ratio = 0.994, 95% CI: 0.980-1.009, P = 0.414), had an impact on the change in LSM values between baseline and at 72-week treatment. CONCLUSIONS: The findings of this study suggest that in patients with fibrotic CHB receiving antiviral medication, the early phase reduction in LSM value was related to improved hepatic inflammation rather than fibrosis regression.
ABSTRACT
BACKGROUND AND AIMS: The risk of hepatocellular carcinoma (HCC) occurrence following antiviral therapy in patients with chronic hepatitis C (CHC) remains unclear. The current study aims to compare: (1) the HCC occurrence rate following sustained virological response (SVR) versus non-response (NR); (2) the HCC occurrence rate following direct-acting antiviral (DAA) therapy versus interferon (IFN)-based therapy, and (3) the HCC occurrence rate in SVR patients with or without cirrhosis. METHODS: A search was performed for articles published between January 2017 and July 2022. Studies were included if they assessed HCC occurrence rate in CHC patients following anti-HCV therapy. Random effects meta-analysis was used to synthesize the results from individual studies. RESULTS: A total of 23 studies including 29,395 patients (IFN-based = 6, DAA = 17; prospective = 10, retrospective = 13) were included in the review. HCC occurrence was significantly lower in CHC with SVR (1.54 per 100 person-years (py, 95% CI 1.52, 1.57) than those in non-responders (7.80 py, 95% CI 7.61, 7.99). Stratified by HCV treatment regimens, HCC occurrence following SVR was 1.17 per 100 py (95% CI 1.11, 1.22) and 1.60 per 100 py (95% CI 1.58, 1.63) in IFN- and DAA treatment-based studies. HCC occurrence was 0.85 per 100 py (95% CI 0.85, 0.86) in the non-cirrhosis population and rose to 2.47 per 100 py (95% CI 2.42, 2.52) in the cirrhosis population. Further meta-regression analysis showed that treatment types were not associated with a higher HCC occurrence rate, while cirrhosis status was an important factor of HCC occurrence rate. CONCLUSION: HCC occurrence was significantly lower in the SVR population than in the NR population. HCC risk following SVR occurred three times more frequently in patients with cirrhosis than patients without cirrhosis. However, we found no significant difference in HCC occurrence risk following SVR between DAA and IFN therapies. CLINICAL TRIAL NUMBER: CRD42023473033.
ABSTRACT
INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.
Subject(s)
Carvedilol , Hypertension, Portal , Liver Cirrhosis , Carvedilol/therapeutic use , Carvedilol/pharmacology , Humans , Hypertension, Portal/drug therapy , Hypertension, Portal/etiology , Liver Cirrhosis/complications , Double-Blind Method , China/epidemiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Adrenergic beta-Antagonists/therapeutic use , Female , Liver/drug effects , Liver/physiopathology , Portal Pressure/drug effects , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/prevention & control , Elasticity Imaging Techniques , Adult , MaleABSTRACT
Growing demand for wound care resulting from the increasing chronic diseases and trauma brings intense pressure to global medical health service system. Artificial skin provides mechanical and microenvironmental support for wound, which is crucial in wound healing and tissue regeneration. However, challenges still remain in the clinical application of artificial skin since the lack of the synergy effect of necessary performance. In this study, a multi-functional artificial skin is fabricated through microfluidic spinning technology by using core-shell gel nanofiber scaffolds (NFSs). This strategy can precisely manipulate the microstructure of artificial skin under microscale. The as-prepared artificial skin demonstrates superior characteristics including surface wettability, breathability, high mechanical strength, strain sensitivity, biocompatibility and biodegradability. Notably, this artificial skin has the capability to deliver medications in a controlled and sustained manner, thereby accelerating the wound healing process. This innovative approach paves the way for the development of a new generation of artificial skin and introduces a novel concept for the structural design of the unique core-shell gel NFSs.
ABSTRACT
Cancers evolve in a dynamic ecosystem. Thus, characterizing cancer's ecological dynamics is crucial to understanding cancer evolution and can lead to discovering novel biomarkers to predict disease progression. Ductal carcinoma in situ (DCIS) is an early-stage breast cancer characterized by abnormal epithelial cell growth confined within the milk ducts. Although there has been extensive research on genetic and epigenetic causes of breast carcinogenesis, none of these studies have successfully identified a biomarker for the progression and/or upstaging of DCIS. In this study, we show that ecological habitat analysis of hypoxia and acidosis biomarkers can significantly improve prediction of DCIS upstaging. First, we developed a novel eco-evolutionary designed approach to define habitats in the tumor intra-ductal microenvironment based on oxygen diffusion distance in our DCIS cohort of 84 patients. Then, we identify cancer cells with metabolic phenotypes attributed to their habitat conditions, such as the expression of CA9 indicating hypoxia responding phenotype, and LAMP2b indicating a hypoxia-induced acid adaptation. Traditionally these markers have shown limited predictive capabilities for DCIS upstaging, if any. However, when analyzed from an ecological perspective, their power to differentiate between indolent and upstaged DCIS increased significantly. Second, using eco-evolutionary guided computational and digital pathology techniques, we discovered distinct spatial patterns of these biomarkers and used the distribution of such patterns to predict patient upstaging. The patterns were characterized by both cellular features and spatial features. With a 5-fold validation on the biopsy cohort, we trained a random forest classifier to achieve the area under curve(AUC) of 0.74. Our results affirm the importance of using eco-evolutionary-designed approaches in biomarkers discovery studies in the era of digital pathology by demonstrating the role of eco-evolution dynamics in predicting cancer progression.
ABSTRACT
Accurate weed detection is essential for the precise control of weeds in wheat fields, but weeds and wheat are sheltered from each other, and there is no clear size specification, making it difficult to accurately detect weeds in wheat. To achieve the precise identification of weeds, wheat weed datasets were constructed, and a wheat field weed detection model, YOLOv8-MBM, based on improved YOLOv8s, was proposed. In this study, a lightweight visual converter (MobileViTv3) was introduced into the C2f module to enhance the detection accuracy of the model by integrating input, local (CNN), and global (ViT) features. Secondly, a bidirectional feature pyramid network (BiFPN) was introduced to enhance the performance of multi-scale feature fusion. Furthermore, to address the weak generalization and slow convergence speed of the CIoU loss function for detection tasks, the bounding box regression loss function (MPDIOU) was used instead of the CIoU loss function to improve the convergence speed of the model and further enhance the detection performance. Finally, the model performance was tested on the wheat weed datasets. The experiments show that the YOLOv8-MBM proposed in this paper is superior to Fast R-CNN, YOLOv3, YOLOv4-tiny, YOLOv5s, YOLOv7, YOLOv9, and other mainstream models in regards to detection performance. The accuracy of the improved model reaches 92.7%. Compared with the original YOLOv8s model, the precision, recall, mAP1, and mAP2 are increased by 10.6%, 8.9%, 9.7%, and 9.3%, respectively. In summary, the YOLOv8-MBM model successfully meets the requirements for accurate weed detection in wheat fields.
Subject(s)
Plant Weeds , Triticum , Triticum/physiology , Plant Weeds/physiology , Neural Networks, Computer , AlgorithmsABSTRACT
The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al2O3), boron nitride (BN), and alumina/boron nitride hybrid (Al2O3/BN) fillers were used to prepare Al2O3@POE, BN@POE, and BN/Al2O3@POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.
ABSTRACT
Stress is an emotional state caused by an unexpected external environmental change or stimulus, and several experiments have demonstrated its negative impact on ovarian function, ultimately affecting reproductive ability. Melatonin (MT) has been shown to facilitate oocyte maturation and enhance ovarian function by regulating mitochondrial function. However, the specific effect and underlying molecular mechanisms of MT on stress-induced ovarian dysfunction remain largely unknown. In this study, we established a mouse model of chronic unpredictable mild stress (CUMS) to investigate its impact on ovarian function. Our findings revealed that CUMS led to premature ovarian insufficiency (POI) in mice, characterized by a reduction in follicle numbers and decreased levels of anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP15). Furthermore, CUMS caused decreased expression of mitochondrial fission protein 1 (FIS1) and enhanced level of mitochondrial fusion protein optic atrophy 1(OPA1), mitofusin1(MFN1), as well as nucleus-encoded protein succinate dehydrogenase complex A (SDHA), reflecting mitochondrial dyshomeostasis. Additionally, CUMS resulted in excessive autophagy and apoptosis. However, MT reversed these effects and improved ovarian damage. Importantly, the protective effects of MT were mediated through the inhibition of the eIF2α-AFT4 pathway. Overall, this study provides valuable insights into the treatment of POI caused by CUMS.
ABSTRACT
To facilitate effective training for freestyle skiers on artificial dry ski slopes, it is crucial to reduce the friction coefficient of the slopes and closely match it with that of snow. Traditional lubrication methods, such as water or soapy water, come with multiple disadvantages, including water waste, which leads to environmental pollution, short-lived effectiveness, and high costs. In this study, we have successfully developed a method for the scalable preparation of a liquid-infused coating (LIC) by tandem spraying inexpensive and environmentally friendly SiO2 particles and silicone oil lubricants. Experimental results showed that the resulting LIC is capable of imparting slippery properties to various surfaces, regardless of the surface chemistry. Moreover, the presence of LIC could reduce the friction coefficient significantly. By carefully regulating the surface composition, we achieved a friction coefficient of 0.059 between a snowboard and the LIC-functionalized ski slope, closely matching that between the snowboard and snow in a typical skiing competition venue (â¼0.06). We successfully applied LIC onto 103 m2 dry ski slopes, providing a training ground for professional freestyle skiers.
ABSTRACT
Botrytis cinerea is an important fungal pathogen that causes gray mold disease in plants. Previously, Bacillus velezensis TCS001 live culture presented broad-spectrum antifungal activity against various plant pathogenic fungi and oomycetes, particularly B. cinerea. Here, the bioactivity of lipopeptides produced by TCS001 against B. cinerea was investigated. The IC50 values of the crude lipopeptide extract (CLE) from TCS001 to suppress mycelial growth and conidial germination were 14.20 and 49.39 mg/L, respectively. SEM and TEM imaging revealed that CLE caused morphological deformities and ultrastructural changes in the mycelium. Transcriptomic analyses combined with ΔBcpsd mutant construction demonstrated that the CLE could confer antifungal activity via suppressing Bcpsd expression in the pathogen. In addition, the CLE activated the plant immune system by increasing the content of defense-related enzymes and the expression of marker genes in immunity signaling pathways in cucumber plants. Therefore, TCS001 CLE could be potentially developed into biopesticides for the biocontrol of gray mold disease.
Subject(s)
Bacillus , Botrytis , Cucumis sativus , Lipopeptides , Plant Diseases , Botrytis/drug effects , Bacillus/chemistry , Bacillus/genetics , Bacillus/metabolism , Lipopeptides/pharmacology , Lipopeptides/metabolism , Plant Diseases/microbiology , Cucumis sativus/microbiology , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemistry , Gene Expression Profiling , Spores, Fungal/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Transcriptome , Mycelium/drug effects , Mycelium/chemistry , Mycelium/growth & developmentABSTRACT
ABSTRACT: Compounds isolated from Epimedium include the total flavonoids of Epimedium, icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium, its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
ABSTRACT
AIM: To report the efficacy and safety of ensartinib, an anaplastic lymphoma kinase (ALK) inhibitor, in treating patients with ALK-positive advanced lung squamous cell carcinoma (LUSC) or lung adenosquamous carcinoma (LASC) in China. METHODS: This retrospective study analyzed data for 36 advanced-stage patients with ALK-positive LUSC (cohort A) and 13 patients with ALK-positive LASC (cohort B) between December 16, 2020 and December 16, 2021. All patients received once-daily ensartinib 225 mg. Outcome analysis included the demographic characteristics, tumor response, progression-free survival (PFS), and treatment-related adverse events (TRAE). RESULTS: Among the 49 patients, the majority were under 65 years old (73.5%), non-smokers (85.7%), had an Eastern Cooperative Oncology Group Performance Status of 0-1 (77.6%), and were at stage IV (71.4%). All patients were included in the efficacy and safety analysis. Seven PFS events were reported in cohort A while no patients experienced PFS events in cohort B. The median PFS was not estimable for both cohorts. In cohort A, the objective response rate (ORR) was 63.9%, and the disease control rate (DCR) was 83.3%. In the cohort B, the ORR was 76.9% and the DCR was 100.0%. Rash was the only TRAE reported in the cohort A (8.3%) and cohort B (23.1%). No patients had grade 3 or higher TRAE. CONCLUSION: Ensartinib has been tentatively proven favorable efficacy and tolerability in the treatment of patients with ALK-positive advanced LUSC or LASC in the real-world. However, confirmatory studies are still needed in larger sample sizes.
ABSTRACT
The concentration prediction of PM2.5 plays a vital role in controlling the air and improving the environment. This paper proposes a prediction model (namely EEMD-ALSTM) based on Ensemble Empirical Mode Decomposition (EEMD), Attention Mechanism and Long Short-Term Memory network (LSTM). Through the combination of decomposition and LSTM, attention mechanism is introduced to realize the prediction of PM2.5 concentration. The advantage of EEMD-ALSTM model is that it decomposes and combines the original data using the method of ensemble empirical mode decomposition, reduces the high nonlinearity of the original data, and Specially reintroduction the attention mechanism, which enhances the extraction and retention of data features by the model. Through experimental comparison, it was found that the EEMD-ALSTM model reduced its MAE and RMSE by about 15% while maintaining the same R2 correlation coefficient, and the stability of the model in the prediction process was also improved significantly.