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Impact of agricultural industry transformation based on deep learning model evaluation and metaheuristic algorithms under dual carbon strategy
Design, antiproliferative potency, and in silico studies of novel 5-methylfuran-3-yl)thio)-3-phenylquinazolin-4(3H)-one based derivatives as potential EGFR inhibitors
Abstract Quinazolinone derivatives have been broadly studied as anti-cancer drug candidates due to their potential to inhibit key signaling pathways involved in tumor progression. In the current study, new 2-[(4-substituted-5-methylfuran-3-yl)thio]-3-phenylquinazolin-4(3H)-one derivatives (2–10) were designed and assessed for anti-cancer activity. Cytotoxicity of the compounds was tested against normal WI-38 cells and cancer cell lines HepG-2 (liver), MCF-7 (breast), and HCT-116 (colorectal). In addition, their inhibitory effects on EGFR and VEGFR-2, key targets for tumor growth and angiogenesis, were assessed. Compounds 6b and 10 showed significant cytotoxic activity, with 6b (IC₅₀ = 0.19 ± 0.03 μM) being the most effective EGFR inhibitor, over 10 (IC₅₀ = 0.51 ± 0.04 μM) and as potent as erlotinib (IC₅₀ = 0.23 ± 0.02 μM). Flow cytometry revealed that 6b induced apoptosis in 35.29% of MCF-7 cells and G₂/M phase cell cycle arrest, much better than that of untreated cells (6.81%). In silico ADMET prediction and molecular docking confirmed high EGFR binding affinity and favorable pharmacokinetic properties. Overall, compound 6b showed promising anti-cancer activity via EGFR inhibition, apoptosis, and cell cycle arrest and is a good lead for further development as an EGFR-targeted agent.
A novel dynamic scheduling model for application in multimode approach
In silico analysis of atrial fibrillation and hypertension mechanism of action secondary to ibrutinib/acalabrutinib in chronic lymphocytic leukemia
Abstract Ibrutinib and acalabrutinib are first- and next-generation Bruton Tyrosine Kinase inhibitors (BTKi), respectively, approved for chronic lymphocytic leukemia (CLL). Ibrutinib has been associated with cardiovascular events, including atrial fibrillation (AF) and hypertension. Acalabrutinib has demonstrated non-inferior progression-free survival than ibrutinib in relapsed/refractory CLL patients, with a lower cardiovascular event incidence. These adverse events seem to be derived from off-targets rather than BTK inhibition. Machine learning algorithms were applied to identify targets likely to trigger AF and hypertension in simulated CLL patients receiving acalabrutinib or ibrutinib. Common ibrutinib and acalabrutinib off-targets showed association with AF through structural remodeling and electrophysiology/ectopic activity mechanisms (TEC and ERBB4). There was association with hypertension through inflammation (ERBB4) and oxidative stress and endothelial dysfunction (ERBB4 and RIPK2). Ibrutinib-specific off-targets showed association with AF through structural remodeling (HCK, FGR, LYN, FYN, YES1, and FLT3) and electrophysiology activity (LYN and SRC), and with hypertension through inflammation (LCK, JAK3, and FLT3) and oxidative stress and endothelial dysfunction (ERBB2, BLK, SRC, and CSK). No acalabrutinib-specific off-targets were identified for AF or hypertension. This study supports that BTKi off-target selectivity may justify the different AF and hypertension incidences, suggesting their association with several ibrutinib-specific off-targets and identifying no acalabrutinib-specific ones.
Spatiotemporal orchestration of mitosis by cyclin-dependent kinase
Abstract Mitotic onset is a critical transition for eukaryotic cell proliferation. The commonly held view of mitotic control is that the master regulator, cyclin-dependent kinase (CDK), is first activated in the cytoplasm, at the centrosome, initiating mitosis 1–3 . Bistability in CDK activation ensures that the transition is irreversible, but how this unfolds in a spatially compartmentalized cell is unknown 4–8 . Here, using fission yeast, we show that CDK is first activated in the nucleus, and that the bistable responses differ markedly between the nucleus and the cytoplasm, with a stronger response in the nucleus driving mitotic signal propagation from there to the cytoplasm. Abolishing cyclin–CDK localization to the centrosome led to activation occurring only in the nucleus, spatially uncoupling the nucleus and cytoplasm mitotically, suggesting that centrosomal cyclin–CDK acts as a ‘signal relayer’. We propose that the key mitotic regulatory system operates in the nucleus in proximity to DNA, which enables incomplete DNA replication and DNA damage to be effectively monitored to preserve genome integrity and to integrate ploidy within the CDK control network. This spatiotemporal regulatory framework establishes core principles for control of the onset of mitosis and highlights that the CDK control system operates within distinct regulatory domains in the nucleus and cytoplasm.
Dopaminergic action prediction errors serve as a value-free teaching signal
Abstract Choice behaviour of animals is characterized by two main tendencies: taking actions that led to rewards and repeating past actions 1,2 . Theory suggests that these strategies may be reinforced by different types of dopaminergic teaching signals: reward prediction error to reinforce value-based associations and movement-based action prediction errors to reinforce value-free repetitive associations 3–6 . Here we use an auditory discrimination task in mice to show that movement-related dopamine activity in the tail of the striatum encodes the hypothesized action prediction error signal. Causal manipulations reveal that this prediction error serves as a value-free teaching signal that supports learning by reinforcing repeated associations. Computational modelling and experiments demonstrate that action prediction errors alone cannot support reward-guided learning, but when paired with the reward prediction error circuitry they serve to consolidate stable sound–action associations in a value-free manner. Together we show that there are two types of dopaminergic prediction errors that work in tandem to support learning, each reinforcing different types of association in different striatal areas.
Whole genome sequence of petroleum hydrocarbon degrading novel strain Microbacter sp. EMBS2025 isolated from Chilika Lake, Odisha, India
Modification mechanism of silver nanoparticles-functionalized MW-CNT and GGBFS and CQDs on the structural properties of geopolymer reinforced-composite beam
Enhancing power efficiency in BLDC motor drives for drones using multiview learning with hybrid optimization algorithms
Ancient DNA reveals a two-clanned matrilineal community in Neolithic China
Abstract Studies of ancient DNA from cemeteries provide valuable insights into early human societies, and have strongly indicated patrilocality1–10. Here, we analysed ancient DNA alongside archaeological contexts and multiple stable isotopic data from 60 individuals in 2 separate cemeteries at the Fujia archaeological site in eastern China, dating between 2750 and 2500 bce. Our findings suggest the existence of an early-described matrilineal community in the Neolithic period, characterized by high endogamy and a population practicing millet agriculture near the coast. Evidence of intermarriage between individuals in the two cemeteries and the presence of both primary and secondary burials, organized strictly according to maternal clans, underscore a strong sense of social cohesion and identity at Fujia. Bayesian modelling of radiocarbon dates indicates that the two cemeteries were used for approximately 250 years, implying a stable matrilineal lineage spanning at least 10 generations. This study contributes to the ongoing debate in anthropology and archaeology11, not only suggesting the existence of a matrilineal society in early human history but also revealing a pair of Neolithic cemeteries organized around two matrilineal clans, furthering our understanding of the early evolution of human societies through kinship systems.
Activated eosinophil plays a role in promoting fibrosis in endometriotic lesion
Profiling of the microRNA transcriptome in feline whole blood
Abstract Circulating microRNAs (miRNAs) are potential biomarkers for numerous diseases. Characterization of the whole blood (WB) miRNA-transcriptome (miRNome) in cats is lacking, which limits the potential use of miRNAs as biomarkers for diseases such as feline cardiovascular disease. The aims of the present study were to profile and evaluate circulating miRNAs in feline WB by high-throughput sequencing of the total miRNome in WB from twelve domestic mixed breed (DOM) and Norwegian Forest (NFO) cats stringently diagnosed with or without preclinical hypertrophic cardiomyopathy (HCM). A total of 459 mature miRNAs were identified in feline WB, of which 40 were potential novel feline miRNAs. A majority, 85.3%, of the miRNAs showed sequence similarity with human miRNAs. An effect of breed was found, with up to thirteen WB miRNAs being differentially abundant between breeds. The majority of the significant breed-specific miRNAs in feline WB could be associated with regulation of haematopoietic cells. One miRNA, miR-204-5p, was potentially associated with preclinical HCM in NFO cats, but the results need to be confirmed in a larger and sex-unbiased cohort. In conclusion, here we used miRNome-sequencing to identify hundreds of circulating miRNAs in feline WB. Breed should be considered when evaluating the miRNome in feline WB.
BSVA: blockchain-enabled secured vertical aggregation algorithm for transactions management in drug traceability framework
Abstract The pharmaceutical supply chain has a critical component, the Drug Traceability System, which tracks drugs from manufacturers for further processing and distribution. The integration of blockchain technology yields a secure solution for monitoring drugs throughout the supply chain management process. The paper proposes a novel Blockchain-enabled Secured Vertical Aggregation Algorithm (BSVA) by leveraging the Hyperledger model. The proposed model minimizes the requirement for a centralized authority to ensure privacy while also enhancing scalability to reduce response time in the process of managing transactions on the Blockchain. The Certificate Authority is used to maintain a secure data-sharing process. The robust aggregation is used for the local models to process the chain code, ensuring the successful execution of the secured transaction. The smart contract is deployed into a blockchain model as the block is stored and linked to the distributed Ledger. The decentralized framework is used by chain code, which guarantees that transactions are highly transparency. The performance parameters demonstrate the efficiency of the proposed model by enhancing the overall performance of the drug traceability system, as the proposed algorithm ensures the integrity of pharmaceutical products throughout the supply chain.
Dual prompt personalized federated learning in foundation models
Deciphering anti-colorectal cancer potential of Avicennia alba bioactives via network pharmacology and in vitro validation
Publisher Correction: Targeting GRPR for sex hormone-dependent cancer after loss of E-cadherin
Temperature and AC electrical properties effects on phosphate natural mixture, Abu Tartur plateau, Western Desert, Egypt
Abstract The research is focused on examining electrical properties (conductivity and dielectric constant), mineralogy, and geochemical behaviors of natural phosphate mixtures, Abu Tartur plateau, Western Desert Egypt. Abu Tartur plateau has a rich supply of phosphorus deposits. Phosphate deposits mostly consist of fluorapatite (Ca 5 (PO 4 ) 3 F). Our objective is to evaluate the changes in AC electrical properties, emphasizing the effects of temperature, and frequency variations. Electrical properties expand with temperature due to greater mobility of charge carriers at higher frequencies and at higher temperatures. Electrical characteristics were subjected to a temperature range of 60–700 0 C and frequencies of 42 Hz–5 MHz. Electrical properties of phosphate mixtures have a non-linear association with temperature and are highly dependent on frequency. As temperature rises, the conductivity of the mixture also increases, as evidenced by the temperature coefficient. The completion of these investigations will lead to a greater understanding of the geological and geochemical processes that lead to phosphate formation deposits, as well as the development of more effective industrial methods and material attributes. Temperature and conductivity are connected because dissolved ions increase both temperature and conductivity. Both conductivity and temperature are influenced by dissolved ions, hence they are coupled. Heterogeneity fluctuation can have a significant impact on the electrical characteristics of materials. Due to heterogeneity, the change in electrical characteristics is not monotonically affected by increasing conductor concentration. Presence of electrical features becomes more noticeable as temperature concentration increases. AC electrical conductivity of a phosphate natural combination from Abu Tartur and its fluctuation with temperature is inadequate and this work seeks to close this information gap.
Predicting pathological response of resectable esophageal squamous cell carcinoma to neoadjuvant anti-PD-1 with chemotherapy using serum inflammation indexes
Abstract Background Inflammatory indexes are increasingly being considered to predict treatment response in tumors. This study aimed to investigate the efficacy of serum inflammatory indexes in predicting pathological response in patients with esophageal squamous cell carcinoma (ESCC) receiving anti-PD-1 neoadjuvant immunochemotherapy (NICT). Methods We retrospectively collected clinical and laboratory data from 116 ESCC patients who received NICT. We set three outcome variables: pathologic complete response (PCR), good response (GR), and response (R). We assessed between-group differences in inflammation indexes and their diagnostic efficacy. Independent diagnostic markers were filtered using least absolute shrinkage and selection operator (LASSO) logistic regression and multivariable analysis, and the corresponding nomograms for PCR and GR were constructed, respectively. Receiver operating characteristic curves (ROC) and calibration curves assessed the efficiency and accuracy of the models. Decision curve analysis (DCA) and clinical impact curves (CIC) evaluated the clinical value. Moreover, we internally validated the predictive model with a random sample of 30% of patients. Results The prognostic nutritional index (PNI) predicted a cutoff value of 53.585 for PCR with an area under curve (AUC) value of 0.720, a cutoff value of 47.85 for GR with an AUC of 0.723, a cutoff value of 47.85 for R with an AUC of 0.629. Smoking and PNI were independent predictors of PCR, platelet-to-lymphocyte ratio (PLR) and PNI were independent predictors of GR, and PNI was an independent predictor of R. We built PNI-based nomograms to predict PCR and GR with AUC values of 0.795 and 0.763 for the training cohort and 0.907 and 0.757 for the validation cohort, respectively. The predicted and actual results of the calibration curves for both the training and validation groups showed good agreement, with Brier scores below 0.25. Conclusion High PNI value is a shared independent predictor of achieving PCR, GR, and R in ESCC patients receiving anti-PD1 NICT. PNI-based diagnostic models can be used as a practical tool to identify ideal patients for personalized clinical decisions.
Biochemical characterization of a novel purified lectin extracted from Pleurotus ostreatus mushroom for its antiviral activity
Abstract Viruses are responsible for numerous serious outbreaks and pandemics worldwide. In this context, lectins, which are carbohydrate-binding proteins, have garnered attention due to their antiviral properties against RNA and DNA viruses. The antiviral potential of the purified and well-characterized lectin from Pleurotus ostreatus (POL) was assessed against various viruses. POL showed potent antiviral activity against HCV with IC50 values of 68.75 nM and 52.13 nM for determining the blocking and neutralizing infectivity, respectively. POL exhibited IC50 values of 42.75 and 14.88 nM against HBV through treatment and blocking mechanisms, respectively. Notably, POL demonstrated a 58.80% binding capacity to cell-surface CD81, while the IC50 values for targeting the scavenger receptor class B-type I (SR-B1), HCV-NS3/4A protease inhibition, and anti-HBV polymerase activity were established at 10.08, 10.98, and 4.22 nM, respectively. The outcomes of this investigation offer crucial insights into the mechanisms through which POL effectively inhibits infection caused by different viruses. These findings have the potential to inform the development of antiviral strategies and therapeutic interventions.