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The purpose of this study is to identify the therapeutic effect of electroacupuncture (EA) on cerebral ischemia-reperfusion (I/R) injury, and to clarify the regulatory mechanism related to telomerase reverse transcriptase (TERT)-mediated telomerase activity. A Middle cerebral artery occlusion/reperfusion (MCAO/R) animal model was constructed and rats were treated by EA invention at the Baihui (GV20) and Fengchi (GB20) acupoints. Neurological deficits were assessed via rotarod test and Morris water maze test. 2,3,5-Triphenyltertrazolium chloride (TTC) staining was performed to evaluate infarct volume. Histological changes were observed under H&E staining and Nissl staining. TERT expression was examined using qRT-PCR and western blot. Telomerase activity was assessed with TRAP method. Neuron apoptosis and senescence were assessed by TUNEL and immunofluorescence assays. Inflammatory cytokines and oxidative stress-indicators were examined using commercial kits. EA intervention at both GV20 and GB20 acupoints reduced infarct volumes (2.48 ± 1.89 vs. 29.56 ± 2.55), elevated the telomerase activity (0.84 ± 0.08 vs. 0.34 ± 0.09), and upregulated the levels of total TERT protein (0.61 ± 0.09 vs. 0.21 ± 0.05) and mitochondrial TERT (Mito-TERT; 0.54 ± 0.03 vs. 0.27 ± 0.03) in hippocampus tissues of MCAO/R rats. EA intervention attenuated motor dysfunction (112.00 ± 6.69 vs. 30.02 ± 2.60) and improved spatial learning (23.87 ± 1.90 vs. 16.23 ± 1.45) and memory ability (8.38 ± 1.06 vs. 4.13 ± 1.13) of rats with cerebral I/R injury. In addition, EA intervention significantly attenuated histopathological changes of injured neurons, mitigated neuron apoptosis (32.27 ± 5.52 vs. 65.83 ± 4.31) and senescence in MCAO/R rats, as well as inhibited excessive production of inflammatory cytokines and attenuated oxidative stress. However, the above therapeutic efficiency of EA intervention in MCAO/R rats was partly eliminated by TERT knockdown. EA intervention at GB20 and GV20 acupoints exerted a protective role in cerebral I/R injury partly through restoring TERT function, implying the clinical potential of EA treatment in the treatment of ischemic stroke.
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INTRODUCTION: Asciminib is primarily utilized for treating Philadelphia chromosome-positive chronic myeloid leukemia in its chronic phase among patients harboring the T315I mutation or those who have been previously treated with at least two tyrosine kinase inhibitors. The safety profile of asciminib across a broad patient population over an extended timeframe remains unverified. This study uses a real-world pharmacovigilance database to evaluate the adverse events (AEs) linked with asciminib, providing valuable insights for clinical drug safety. METHODS: Data from the FDA Adverse Event Reporting System (FAERS) database, spanning from October 2021 to December 2023, served as the basis for this analysis. The extent of disproportional events was assessed using sophisticated metrics such as the reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. RESULTS: Within the specified period, the FAERS database documented 3,913,574 AE reports, with asciminib being associated with 966 incidents. Reactions to asciminib spanned 27 system organ categories. Utilizing four distinct analytical algorithms, 663 significant preferred terms exhibiting disproportional frequencies were identified. Notably, this investigation uncovered 26 significant AEs linked to off-label asciminib use, encompassing conditions such as gynecomastia, nephrotic syndrome, orchitis, pyelonephritis, hepatotoxicity, and pancreatitis. The median onset time for asciminib-related AEs was 52.5 days, ranging from 17 to 122.75 days. CONCLUSION: The study sheds light on additional potential AEs associated with asciminib use, warranting further research to confirm these findings.
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Duck hepatitis A virus type 3 (DHAV-3) is an infectious virus that is highly fatal to ducklings and causes significant economic losses in the duck industry worldwide. Biosecurity and vaccination are required to control the pathogen. In the present study, we attenuated a lowly pathogenic DHAV-3 clinical isolate, named as HB, by serial passaging in duck embryos, and followed by several adaptive proliferations in specific-pathogen-free (SPF) chicken embryos. The virulence of DHAV-3 at different passages was assessed by infecting 3-day-old ducklings. We found that the HB strain lost pathogenicity to ducklings from the 55th passage onwards. The 80th passage strain (HB80), which achieved good growth capacity in duck embryos with a viral titer of 108.17 50% egg lethal dose per milliliter (ELD50/mL), was selected as a live attenuated vaccine candidate. The HB80 strain did not induce clinical symptoms or pathological lesions in 3-day-old ducklings and showed no virulence reversion after 5 rounds of in vivo back-passage. The minimum effective dose of HB80 was determined to be 104.5 ELD50 by hypodermic inoculation of the neck. Importantly, a single dose of HB80 elicited good immune responses and provided complete protection against challenge with the lethal DHAV-3 strain. Compared with the genomic sequence of the parental HB strain, HB80 had 7 amino acid substitutions, two of them are in the hypervariable region of the VP1 and polymerase-encoding 3D regions, which may play a role in virulence attenuation. Our data suggest that the attenuated HB80 strain is a promising vaccine candidate for the prevention of DHAV-3 infections in China. HB80 has been registered as a New Veterinary Drug Registration Certificate by the Chinese Ministry of Agriculture and Rural Affairs (MARA), and is the first live attenuated DHAV-3 vaccine strain to be officially licensed in China.
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OBJECTIVE: To assess the clinical utility of ultrasound in predicting the risk of carotid vulnerable plaque rupture using pathological intraplaque hemorrhage as the gold standard. METHODS: A total of 118 patients who underwent endarterectomy due to symptomatic carotid artery stenosis were enrolled. Conventional ultrasound assessed the plaque thickness, area stenosis rate, echo, and surface morphology. Neovascularization were assessed by contrast-enhanced ultrasound (CEUS) and tracing intraplaque nonenhanced areas. According to neovascularization grade (0-4), plaques were classified as low-, intermediate-, and high risk. Fresh intraplaque hemorrhage within the pathology was adopted as the gold standard for diagnosing plaque rupture risk. Thus, we divided patients into ruptured risk and nonruptured risk groups to assess the value of crucial factors for plaque rupture risk using ultrasound. RESULTS: Of the 118 patients, hypertension accounted for 71.2%, hyperlipidemia 68.6%, diabetes 52.5%, and statin history 64.4%. In the rupture risk group, diabetes, smoking, and stenosis rate were significantly higher than the nonrupture risk group (P < .001); plaque thickness ≥4 mm (P > .05); and mainly hypoechoic with irregular surface morphology (P < .001), nonenhanced areas in the plaques (P < .001), and neovascularization >grade 2 (P < .001). Compared with the low-risk group, plaque rupture risk was 7.219 times higher in the medium-risk group and 18.333 times higher in the high-risk group. The kappa value of the interobserver consistency of crucial ultrasound parameters was >0.75, and the intraclass correlation coefficient was 0.919 (P < .01). CONCLUSIONS: Both conventional ultrasound and CEUS have significant clinical importance in the prediction of rupture risk in vulnerable carotid plaques, thereby enabling stroke risk stratification and the assessment of plaque rupture risk.
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Anoectochilus roxburghii is a well-known and valuable traditional Chinese herb due to various medicinal and functional benefits. In-depth investigation is necessary to discover active ingredients and expand its application. In this study, four new compounds (1-4) along with ten known compounds (5-14) were isolated from the ethanol extract of A.roxburghii. Their structures were elucidated by spectroscopic data interpretation. The isolates were screened for their inhibitory activities on the production of NO in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Among them, compounds 5, 6, 9, 10, 12, 13 and 14 exhibited significant anti-inflammatory activity through inhibiting the release of NO.
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BACKGROUND: Tamoxifen (TAM) is recommended as the first-line strategy for men with estrogen receptor (ER)-positive early breast cancer who are candidates for adjuvant endocrine therapy in ASCO guideline. Our study aims to analyze the cost-effectiveness of receiving adjuvant endocrine therapy with TAM compared to no TAM, and to assess the cost-effectiveness of using TAM with high adherence over low adherence for ER-positive early male breast cancer in the USA. METHODS: Two Markov models comprising three mutually exclusive health states were constructed: (1) the first Markov model compared the cost-effectiveness of adding TAM with not using TAM (TAM versus Not-TAM); (2) the second model compared the cost-effectiveness of receiving TAM with high adherence and low adherence (High-adherence-TAM versus Low-adherence-TAM). The simulation time horizon for both models was the lifetime of patients. The efficacy and safety data of two models were elicited from the real-world studies. Model inputs were derived from the US website and published literature. The main outcomes of two models both included the total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: In the first model, TAM yielded an ICER of $5707.29 per QALY compared to Not-TAM, which was substantially below the WTP threshold of $50,000.00 per QALY in the USA. Probabilistic sensitivity analysis results demonstrated a 100.00% probability of cost-effectiveness for this strategy. In the second model, High-adherence-TAM was dominated absolutely compared to Low-adherence-TAM. The High-adherence-TAM was cost-effective with a 99.70% probability over Low-adherence-TAM when WTP was set as $50,000.00/QALY. All of these parameters within their plausible ranges did not reversely change the results of our models. CONCLUSIONS: Our study will offer valuable guidance for physicians or patients when making treatment decisions and provide an effective reference for decision-making to consider the appropriate allocation of funds to this special group.
Subject(s)
Antineoplastic Agents, Hormonal , Breast Neoplasms, Male , Cost-Benefit Analysis , Markov Chains , Quality-Adjusted Life Years , Tamoxifen , Humans , Tamoxifen/therapeutic use , Tamoxifen/economics , Male , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/economics , Breast Neoplasms, Male/drug therapy , Breast Neoplasms, Male/economics , Chemotherapy, Adjuvant/economics , Chemotherapy, Adjuvant/methods , Middle Aged , Aged , Receptors, Estrogen/metabolism , Medication Adherence/statistics & numerical data , United StatesABSTRACT
High levels of urinary lactate are an increased risk of progression in patients with diabetic kidney disease (DKD). However, it is still unveiled how lactate drive DKD. Epithelial-mesenchymal transition (EMT), which is characterized by the loss of epithelial cells polarity and cell-cell adhesion, and the acquisition of mesenchymal-like phenotypes, is widely recognized a critical contributor to DKD. Here, we found a switch from oxidative phosphorylation (OXPHOS) toward glycolysis in AGEs-induced renal tubular epithelial cells, thus leading to elevated levels of renal lactic acid. We demonstrated that reducing the lactate levels markedly delayed EMT progression and improved renal tubular fibrosis in DKD. Mechanically, we observed lactate increased the levels of histone H3 lysine 14 lactylation (H3K14la) in DKD. ChIP-seq & RNA-seq results showed histone lactylation contributed to EMT process by facilitating KLF5 expression. Moreover, KLF5 recognized the promotor of cdh1 and inhibited its transcription, which accelerated EMT of DKD. Additionally, nephro-specific knockdown and pharmacological inhibition of KLF5 diminished EMT development and attenuated DKD fibrosis. Thus, our study provides better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD by disruption of the lactate-drived H3K14la/KLF5 pathway.
Subject(s)
Diabetic Nephropathies , Epithelial-Mesenchymal Transition , Kruppel-Like Transcription Factors , Lactic Acid , Animals , Humans , Male , Mice , Cell Line , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Diabetic Nephropathies/genetics , Epigenesis, Genetic , Epithelial Cells/metabolism , Epithelial Cells/pathology , Fibrosis , Gene Expression Regulation , Histones/metabolism , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Lactic Acid/metabolism , Signal TransductionABSTRACT
Multiple uncertainties such as water quality processes, streamflow randomness affected by climate change, indicators' interrelation, and socio-economic development have brought significant risks in managing water quantity and quality (WQQ) for river basins. This research developed an integrated simulation-optimization modeling approach (ISMA) to tackle multiple uncertainties simultaneously. This approach combined water quality analysis simulation programming, Markov-Chain, generalized likelihood uncertainty estimation, and interval two-stage left-hand-side chance-constrained joint-probabilistic programming into an integration nonlinear modeling framework. A case study of multiple water intake projects in the Downstream and Delta of Dongjiang River Basin was used to demonstrate the proposed model. Results reveal that ISMA helps predict the trend of water quality changes and quantitatively analyze the interaction between WQQ. As the joint probability level increases, under strict water quality scenario system benefits would increase [3.23, 5.90] × 109 Yuan, comprehensive water scarcity based on quantity and quality would decrease [782.24, 945.82] × 106 m3, with an increase in water allocation and a decrease in pollutant generation. Compared to the deterministic and water quantity model, it allocates water efficiently and quantifies more economic losses and water scarcity. Therefore, this research has significant implications for improving water quality in basins, balancing the benefits and risks of water quality violations, and stabilizing socio-economic development.
Subject(s)
Rivers , Water Quality , Uncertainty , Water Supply , Models, Theoretical , Climate ChangeABSTRACT
Helicase POLQ-like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq-/-) could significantly reduce the efficiency of mouse primordial germ cell-like cell (PGCLC) induction. In addition, Helq-/- embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.
Subject(s)
Germ Cells , Animals , Humans , Male , Mice , Apoptosis/genetics , Cell Differentiation/genetics , DNA Helicases/genetics , DNA Helicases/metabolism , DNA Helicases/deficiency , Germ Cells/metabolism , Mice, KnockoutABSTRACT
The K+ uptake system KtrAB is essential for bacterial survival in low K+ environments. The activity of KtrAB is regulated by nucleotides and Na+. Previous studies proposed a putative gating mechanism of KtrB regulated by KtrA upon binding to ATP or ADP. However, how Na+ activates KtrAB and the Na+ binding site remain unknown. Here we present the cryo-EM structures of ATP- and ADP-bound KtrAB from Bacillus subtilis (BsKtrAB) both solved at 2.8 Å. A cryo-EM density at the intra-dimer interface of ATP-KtrA was identified as Na+, as supported by X-ray crystallography and ICP-MS. Thermostability assays and functional studies demonstrated that Na+ binding stabilizes the ATP-bound BsKtrAB complex and enhances its K+ flux activity. Comparing ATP- and ADP-BsKtrAB structures suggests that BsKtrB Arg417 and Phe91 serve as a channel gate. The synergism of ATP and Na+ in activating BsKtrAB is likely applicable to Na+-activated K+ channels in central nervous system.
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Bacillus subtilis , Bacterial Proteins , Cation Transport Proteins , Potassium , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Bacillus subtilis/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Binding Sites , Cation Transport Proteins/metabolism , Cation Transport Proteins/chemistry , Cryoelectron Microscopy , Crystallography, X-Ray , Models, Molecular , Potassium/metabolism , Protein Binding , Sodium/metabolismABSTRACT
Microbial metabolism is closely related to soil carbon dioxide emissions, which in turn is related to environmental issues such as global warming. Dissolved organic matter (DOM) affects many fundamental biogeochemical processes such as microbial metabolism involved in soil carbon cycle, not only directly by its availability, but also indirectly by its chemodiversity. However, the association between the DOM chemodiversity and bioavailability remains unclear. To address this knowledge gap, soils from two agro-ecological experimental sites subjected to various long-term fertilizations in subtropical area was collected. The chemodiversity of DOM was detected by multi-spectroscopic techniques including ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy and excitation emission matrices fluorescence spectroscopy. Results showed that long-term manure amendments significantly decreased microbial metabolic quotient (qCO2) by up to 57%. We also observed that long-term manure amendments significantly increased recalcitrant components of DOM (indicated by the aromaticity, humification index, the ratio of aromatic carbon to aliphatic carbon, and the relative abundances of humic-like components) and decreased labile components of DOM. Negatively correlation between the qCO2 and the proportion of recalcitrant components of DOM supported that accumulation in recalcitrant components of DOM increased microbial carbon utilization efficiency. Random forest models also showed the highest contribution of the relative abundances of humic-like components and the aromaticity of DOM in affecting qCO2. Both of the redundancy analysis and structural equation modeling further indicated the decisive role of soil pH in influencing the DOM chemodiversity. Soil pH explained 56.7% of the variation in the chemodiversity of DOM. The accumulation of recalcitrant components in DOM with increasing soil pH might be attributed to the accelerated microbial consumption of bioavailability components and/or to the negative impact on the solubility of bioavailability components. Overall, this research highlights the significance of long-term manure amendments in regulating qCO2 by altering the chemodiversity of soil DOM.
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Manure , Soil Microbiology , Soil , Soil/chemistry , Fertilizers , Humic Substances , Agriculture/methods , Carbon Cycle , Environmental MonitoringABSTRACT
BACKGROUND: This study aimed to investigate whether physical activity (PA) is associated with a lower risk of subsequently developing chronic obstructive pulmonary disease (COPD). METHODS: We conducted this population-based longitudinal follow-up study in a community in Taiwan. This study recruited 61,446 subjects who had participated in the Keelung Community-based Integrated Screening Program (KCIS) between 2005 and 2012. During their participation in KCIS, they were provided with structured questionnaires to collect their baseline characteristics, including weekly PA time. After excluding subjects diagnosed with COPD before they joined KCIS and/or who provided incomplete lifestyle data, 59,457 subjects remained, and were classified into three groups based on their weekly PA time: i.e., as NPA (no regular PA), LPA (low PA, <90 min/week) and HPA (high PA, ≥90 min/week). The primary outcome was a new diagnosis of COPD, followed up until the end of 2015 or their death. Cox proportional-hazard regression was used to assess the impact of PA on the risk of COPD. RESULTS: The risk of COPD was more than 20% lower in the LPA and HPA groups than in the NPA group. Specifically, the adjusted hazard ratio for the risk of COPD was 0.72 in the LPA group (95% CI, 0.61-0.85, p < 0.001) and 0.79 in the HPA group (95% CI, 0.69-0.90, p < 0.001). CONCLUSIONS: Our research uncovered an inverse relationship between PA and COPD. The findings suggest that PA might be useful as a strategy for the primary prevention of COPD.
Subject(s)
Exercise , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Taiwan/epidemiology , Male , Female , Middle Aged , Longitudinal Studies , Follow-Up Studies , Aged , Risk Factors , AdultABSTRACT
OBJECTIVE: Dexmedetomidine (DEX) can strengthen the analgesic effects of local anesthetics (LAs) when used as an adjuvant through intrathecal, perineural, and intraperitoneal routes. Many studies have used intraperitoneal instillation of DEX with LAs in laparoscopic cholecystectomy (LC) to relieve postoperative pain. We performed a systematic review and meta-analysis to synthesize evidence of the efficacy and safety of intraperitoneal instillation of DEX as an adjuvant of LAs in patients undergoing LC. METHODS: A comprehensive literature search of the MEDLINE, PubMed, EMBASE, and Cochrane Library databases was performed to identify randomized controlled trials in which patients received intraperitoneal instillation of DEX combined with LAs during LC. A meta-analysis and sensitivity analysis of the results were conducted. We also performed a subgroup analysis to investigate the source of heterogeneity. The Egger test was used to check for publication bias. RESULTS: Eleven randomized controlled trials involving 890 patients were analyzed. We found that the addition of DEX to LAs significantly decreased pain scores at six postoperative time points (0.5, 1, 2, 4, 12, and 24 h) and significantly prolonged the time to the first analgesic request by patients. In addition, 24-hour postoperative analgesic consumption was decreased in the experimental group, and no significant difference in the incidence of nausea and vomiting was observed. CONCLUSION: Our findings indicate that intraperitoneal instillation of DEX with LAs can reduce postoperative pain and prolong the time to first request analgesia after LC.
Subject(s)
Anesthetics, Local , Cholecystectomy, Laparoscopic , Dexmedetomidine , Pain, Postoperative , Randomized Controlled Trials as Topic , Dexmedetomidine/administration & dosage , Humans , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Anesthetics, Local/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Pain Measurement , Instillation, Drug , Drug Therapy, CombinationABSTRACT
Liming, as a common amelioration practice worldwide, has the potential to alleviate soil acidification and ensure crop production. However, the impacts of long-term liming on the temperature sensitivity (Q10) of soil organic carbon (SOC) mineralization and its response to labile C input remain unclear. To fill the knowledge gap, soil samples were collected from a long-term (â¼10 years) field trial with unlimed and limed (CaO) plots. These soil samples were incubated at 15 °C and 25 °C for 42 days, amended without and with 13C-labeled glucose. Results showed that compared to the unlimed soil (3.6-8.6 mg C g-1 SOC), liming increased SOC mineralization (6.1-11.2 mg C g-1 SOC). However, liming significantly mitigated the positive response of SOC mineralization to warming, resulting in a lower Q10. Long-term liming increased bacterial richness and Shannon diversity as well as their response to warming which were associated with the decreased Q10. Furthermore, the decreased Q10 due to liming was attributed to the decreased response of bacterial oligotrophs/copiotrophs ratio, ß-glucosidase and xylosidase activities to warming. Labile C addition had a strong impact on Q10 in the unlimed soil, but only a marginal influence in the limed soil. Overall, our research highlights that acidification amelioration by long-term liming has the potential to alleviate the positive response of SOC mineralization to warming and labile C input, thereby facilitating SOC stability in agroecosystems, especially for acidic soils in subtropical regions.
Subject(s)
Calcium Compounds , Carbon , Soil , Soil Microbiology , OxidesABSTRACT
Antibacterial and active packaging materials have gained significant research attention in response to the growing interest in food packaging. In this investigation, we developed hydrogel packaging materials with antibacterial and antioxidant properties by incorporating chitooligosaccharide (COS) and fish skin gelatin (FSG) nanofiber membranes, which readily absorbed water and exhibited swelling characteristics. The nanofiber membranes were fabricated by electrospinning technology, embedding COS within FSG, and subsequently crosslinked through the Maillard reaction facilitated by the addition of glucose. The behavior of conductivity, viscosity, and surface tension in the spinning solutions was analyzed to understand their variation patterns. Scanning electron microscopy (SEM) results revealed that the crosslinked COS/FSG nanofiber membranes possessed a uniform yet disordered fiber structure, with the diameter of the nanofibers increasing as the COS content increased. Remarkably, when the COS content reached 25 %, the COS/FSG nanofiber membranes (CF-C-25) exhibited a suitable fiber diameter of 437.16 ± 63.20 nm. Furthermore, the thermal crosslinking process involving glucose supplementation enhanced the hydrophobicity of CF-C-25. Upon hydration, the CF-H-25 hydrogel displayed a distinctive porous structure, exhibiting a remarkable swelling rate of 954 %. Notably, the inclusion of COS significantly augmented the antibacterial and antioxidant properties of the hydrogel-based nanofiber membranes. CF-H-25 demonstrated an impressive growth inhibition of 90.56 ± 5.91 % against E. coli, coupled with excellent antioxidant capabilities. In continuation, we performed a comprehensive analysis of the total colony count, pH, TVB-N, and TBA of crucian carp. The CF-H-25 hydrogel proved highly effective in extending the shelf life of crucian carp by 2-4 days, suggesting its potential application as an edible membrane for aquatic product packaging.
Subject(s)
Chitosan , Nanofibers , Oligosaccharides , Sulfanilamides , Animals , Nanofibers/chemistry , Gelatin/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Escherichia coli , Hydrogels/pharmacology , Anti-Bacterial Agents/pharmacology , Chitin , GlucoseABSTRACT
Brentuximab vedotin (BV) has obtained approval for the therapeutic management of classical Hodgkin lymphoma as well as systemic anaplastic large cell lymphoma. Given the inherent constraints of conventional clinical trials, the correlation between BV and cardiac adverse events (AEs) remains enigmatic. The objective of this investigation is to comprehensively assess cardiac AEs attributed to BV by employing advanced data mining techniques, utilizing the FDA Adverse Event Reporting System (FAERS). The indices for the assessment of disproportionality encompass the reporting odds ratio (ROR), the proportional reporting ratio, the information component, and the empirical Bayesian geometric mean. Employing these sophisticated metrics, we gauged the extent of disproportionate occurrences. The dataset was sourced from the FAERS from the first quarter of 2012 to first quarter of 2023, facilitating a comprehensive analysis of the potential correlation between BV and cardiac AEs. This scrutiny encompassed a comparative analysis of both cardiac and non-cardiac AEs. A total of 495 cases of BV's cardiac AEs were discerned, with the identification of 31 preferred terms (PTs). Among these, 8 PTs emerged as conspicuous signals of cardiac AEs, notably encompassing ventricular hypokinesia (ROR 7.59), tachyarrhythmia (ROR 7.06), sinus tachycardia (ROR 6.18), cardiopulmonary failure (ROR 4.44), pericardial effusion (ROR 4.32), acute coronary syndrome (ROR 4.02), cardiomyopathy (ROR 3.30), and tachycardia (ROR 2.76). The manifestation of severe outcomes demonstrates a discernible correlation with the cardiac AEs (P < 0.001). Our investigation furnishes invaluable insights for healthcare practitioners to proactively mitigate the incidence of BV-associated cardiac AEs.
Subject(s)
Adverse Drug Reaction Reporting Systems , Brentuximab Vedotin , United States Food and Drug Administration , Humans , Brentuximab Vedotin/adverse effects , Adverse Drug Reaction Reporting Systems/statistics & numerical data , United States/epidemiology , Databases, Factual , Cardiotoxicity , Male , Female , Antineoplastic Agents, Immunological/adverse effects , Middle Aged , Bayes Theorem , Data MiningABSTRACT
Biochar application is widely studied to mitigate the threats of soil degradation to food security and climate change. However, there are big variations in the effects of biochar application on crops, soils, and the atmosphere during crop production. This study provides a global dataset of biochar application effects on crop yield, soil properties, and greenhouse emissions. The dataset is extracted and integrated from 367 peer-reviewed studies with 891 independent field, laboratory, and incubation experiments across 37 countries. This dataset includes 21 variables before and after biochar application (including soil properties, crop yield, greenhouse gas emissions, etc.) of 2438 items, focusing on two main biochar application types: biochar application alone and combined with fertilizers. Background information on climate conditions, initial soil properties, management practices, and characteristics of biochar sources and production is also contained in the dataset. This dataset facilitates a comprehensive understanding of the impact of biochar application, supports the utilization of agricultural wastes for biochar production, and assists researchers in refining experimental protocols for further studies.
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Water-related issues in transboundary basins are generally complicated by the challenges of climate change, the historical evolution of the basin characteristics, and the different interests of the riparian countries. Therefore, dealing with water-sharing and water cooperation problems among basin countries needs to be based on multi-factor system analysis in the context of regional water, energy, food (land) resources, and ecosystems. In the present study, the Aral Sea basin in Central Asia, where transboundary water problems are extremely prominent and complex, was selected as the research area. Firstly, the characteristics of the water-energy-food-ecosystem nexus of the Aral Sea basin are analyzed. Then, based on the game theory, a multi-objective game model is constructed, and the multi-objective evolutionary game process and evolutionary stable strategies (ESSs) of both the upstream and downstream countries are explored. Finally, the evolutionary stable strategy under the intervention of the basin commission is simulated. The results show that there are obvious reciprocal feedbacks among water, land, energy, and ecosystem in the Aral Sea basin, and the uneven distribution of natural resources, fragile ecosystems, and conflicting demands of multiple actors lead to the unstable evolution of the nexus. Driven by the maximization of upstream and downstream countries' respective interests, the optimal stabilization strategy of the system cannot be realized. Whereas, the introduction of the basin commission intervention and its restraint mechanism is conducive to promoting cooperation and maximizing the overall benefits of the basin. The incentives and penalties of the basin commission have significant effects on whether the system can reach Pareto optimality, and higher incentive coefficient and penalty coefficient help the system converge to the ideal state more quickly. The evolution of the water-energy-food-ecosystem nexus based on the perspective of the whole basin can provide theoretical support for dealing with the transboundary water conflicts, and the cooperation strategy aiming at maximizing the overall benefits of the basin can provide decision-making basis for promoting transboundary water cooperation and synergistic development of the water-energy-food-ecosystem nexus.
Subject(s)
Ecosystem , Water , Water Supply , Water Pollution , AsiaABSTRACT
Riemerella anatipestifer (RA) is an important pathogen of waterfowl, with multiple serotypes and a lack of cross-protection between each serotype, which leads to the continued widespread in the world and causing significant economic losses to the duck industry. Thus, prevention and inhibition of RA infection are of great concern. Previous research has established that Lactobacillus plantarum supernatant (LPS) can prevents the pathogenic bacteria infection. However, LPS whether inhibits RA and underlying mechanisms have not yet been clarified. In this study, we investigated the direct and indirect effects of LPS-ZG7 against RA infection in Muscovy ducks. The results demonstrated that LPS-ZG7 prevented RA growth in the presence of pH-neutralized, and the inhibition was relatively stable and unaffected by heat, acid-base and ultraviolet light (UV). Following flow cytometry data found that LPS-ZG7 increased RA membrane permeability and leakage of intracellular molecules. And scanning electron microscopy revealed LPS-ZG7 damaged the RA membrane integrity and leading to RA death. Furthermore, quantitative real time polymerase chain reaction (qPCR) analysis represented that LPS-ZG7 upregulated mucosal tight junction proteins occludin, claudin-1, and Zo-1 in Muscovy ducks, and increasing mucosal transport channels SGLT-1, PepT1, AQP2, AQP3, and AQP10 in duodenum, jejunum, and colon, then decreased the intestinal permeability and intestinal barrier disruption which were caused from RA. From the data, it is apparent that LPS-ZG7 enhanced intestinal mucosal integrity by rising villus height, villus height-to-crypt depth ratio and lower crypt depth. LPS-ZG7 significantly decreased intestinal epithelia cells apoptosis caused by RA invasion, and enhanced intestinal permeability and contribute to barrier dysfunction, ultimately improving intestinal health of host, indirectly leading to reduce diarrhea rate and mortality caused by RA. Overall, this study strengthens the idea that LPS-ZG7 directly inhibited the RA growth by increased RA membrane permeability and damaged the RA membrane integrity, and then indirectly enhanced intestinal mucosal integrity, improved intestinal health of host and mediated intestinal antimicrobial defense.
Subject(s)
Anti-Infective Agents , Flavobacteriaceae Infections , Lactobacillus plantarum , Poultry Diseases , Riemerella , Animals , Ducks/microbiology , Lipopolysaccharides , Aquaporin 2 , Chickens , Flavobacteriaceae Infections/microbiology , Flavobacteriaceae Infections/veterinary , Poultry Diseases/prevention & control , Poultry Diseases/microbiologyABSTRACT
In order to meet the needs of intelligent development of coal mines in China for transparency of geological conditions, identifying small faults with a drop of about 3 m has become one of the important geological tasks in structural interpretation. However, the accuracy of conventional 3D seismic exploration data interpretation methods for detecting small faults is still low. On the basis of introducing the basic principles of S-transform time-frequency analysis, principal component analysis, and RGB fusion, this paper proposes a method for identifying small faults in coal fields using multi-scale seismic curvature attribute fusion. The method uses S-transform to perform time frequency analysis to obtain seismic data volumes with multiple frequencies and seismic data volumes at different frequencies correspond to different scales of underground geological information portrayal. Perform spectral analysis on seismic data, determine parameters such as the dominant frequency and frequency bandwidth of seismic signals, and extract the maximum positive curvature attributes of seismic data volumes at different frequencies. Then the principal component analysis (PCA) method is used to analyze the seismic attributes of different frequency seismic data, the GRB fusion method is used to fuse the first three principal components. The application results of actual seismic data show that the results of multi-scale seismic curvature attribute fusion have obvious advantages in identifying small faults, and can improve the accuracy and interpretation accuracy of small faults in seismic data.