Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

The focus of green analytical chemistry(GAC)is to minimize the negative impacts of analytical pro-cedures on human safety,human health,and the environment.Several factors,such as the reagents used,sample collection,sample processing,instruments,energy consumed,and the quantities of hazardous materials and waste generated during analytical procedures,need to be considered in the evaluation of the greenness of analytical assays.In this study,we propose a greenness evaluation metric for analytical methods(GEMAM).The new greenness metric is simple,flexible,and comprehensive.The evaluation criteria are based on both the 12 principles of GAC(SIGNIFICANCE)and the 10 factors of sample prep-aration,and the results are presented on a 0-10 scale.The GEMAM calculation process is easy to perform,and its results are easy to interpret.The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

This study aimed to identify,characterize,and functionally analyze the CYP450 gene fam-ily within Hyalomma asiaticum unfed nymphs(HasiUN)under regular physiological conditions,laying the groundwork for further study into the biosynthesis and metabolism of exogenous sub-stances associated with the CYP450 gene in HasiUN.Through our methods,we identified and characterized HasiUNCYP450 genes.We then annotated them using the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG).This was achieved with the help of bioinforma-tics,based on the transcriptome of 2-week-old HasiUN.Further on,we conducted a preliminary a-nalysis of tissue expression,distribution,and potential function with qRT-PCR and network inter-action predictions.Our analyses showed that 87 HasiUN CYP450 genes,ranging in size from 1089 to 1692 bp,encoded predominantly basic,hydrophilic,and unstable protein sequences.These se-quences had nearly identical numbers of transmembrane regions,both with and without a signal peptide.Phylogenetic and domain analyses indicated that HasiUN CYP450,having a complete CYP450 domain,were distributed among various clans,with most members found in clan 3.CYP20 clans,present in 13 species from 2 families and 7 genera,required either one-host or three-hosts to undergo their full life cycle.MEME analysis results hint at different clans having variations in the amount and combination of motifs.Expression level analysis showed that HasiUN CYP450 was expressed at different levels,with the highest distribution of normally expressed genes in clan 3 and low expression of all mito clan genes.Functional annotation revealed HasiUN CYP450 key as-sociation with biological processes,metabolism,and organismal systems according to the GO and KEGG annotations.Distribution results showed that HasiUN CYP20a1 was expressed in specific tissues,including salivary glands and ovaries.Functional analysis points to CYP20a1's role in UV-induced toxic metabolism,endocrine disruptor metabolism,and hazardous substance metabolism in the nervous system.Our research presents the first analysis of HasiUN CYP450 gene's biological characteristics and expression pattern under normal physiological conditions.Additionally,investi-gations into the distribution and function of a new category,HasiUN CYP20a1,were embarked upon.These findings establish a theoretical foundation for continued functional study of HasiUN CYP45 gene.

The focus of green analytical chemistry (GAC) is to minimize the negative impacts of analytical procedures on human safety, human health, and the environment. Several factors, such as the reagents used, sample collection, sample processing, instruments, energy consumed, and the quantities of hazardous materials and waste generated during analytical procedures, need to be considered in the evaluation of the greenness of analytical assays. In this study, we propose a greenness evaluation metric for analytical methods (GEMAM). The new greenness metric is simple, flexible, and comprehensive. The evaluation criteria are based on both the 12 principles of GAC (SIGNIFICANCE) and the 10 factors of sample preparation, and the results are presented on a 0-10 scale. The GEMAM calculation process is easy to perform, and its results are easy to interpret. The output of GEMAM is a pictogram that can provide both qualitative and quantitative information based on color and number.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objectives:Recently,domestical developed left ventricular assist devices(LVAD)have been frequently introduced into clinical practice.This study aims to report the anesthesia protocol and perioperative outcomes in Chinese patients receiving LVAD implantation surgery.Methods:This retrospective analysis included patients who underwent LVAD implantation at our center from June 2017 to November 2024.During and after separation from cardiopulmonary bypass,we optimized right heart function through careful adjustments in heart rate,rhythm,preload,myocardial contractility,and afterload.Vasoactive agents were administered as needed,and mechanical ventilation parameters were optimized.We implemented blood conservation strategies and established strict transfusion criteria to minimize allogenic blood transfusions.Results:A total of 100 patients were included in the analysis,with 54.0%classified as Interagency Registry for Mechanically Assisted Circulatory Support(INTERMACS)I or II.Before leaving the operating room,the mean arterial pressure(MAP),mean pulmonary arterial pressure(mPAP),central venous pressure(CVP),lactic acid levels,and urinary output after cardiopulmonary bypass were recorded as(74±7)mmHg,(25±7)mmHg,(7±3)mmHg,(2.3±1.9)mmol/L,and(8.2±5.4)ml/(kg·h),respectively.The transfusion rates for red blood cells and fresh frozen plasma were 20.0%and 28.0%.The in-hospital mortality rate was 3.0%,with a low incidence of severe complications including right heart failure(12%).Left ventricular ejection fraction increased from(23.7±4.8)%preoperatively to(25.3±10.5)%prior to discharge.Conclusions:Patients who received LVAD at our center exhibited low rates of postoperative mortality and complications and significant improvement in left heart function before discharge.

This study aimed to identify,characterize,and functionally analyze the CYP450 gene fam-ily within Hyalomma asiaticum unfed nymphs(HasiUN)under regular physiological conditions,laying the groundwork for further study into the biosynthesis and metabolism of exogenous sub-stances associated with the CYP450 gene in HasiUN.Through our methods,we identified and characterized HasiUNCYP450 genes.We then annotated them using the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG).This was achieved with the help of bioinforma-tics,based on the transcriptome of 2-week-old HasiUN.Further on,we conducted a preliminary a-nalysis of tissue expression,distribution,and potential function with qRT-PCR and network inter-action predictions.Our analyses showed that 87 HasiUN CYP450 genes,ranging in size from 1089 to 1692 bp,encoded predominantly basic,hydrophilic,and unstable protein sequences.These se-quences had nearly identical numbers of transmembrane regions,both with and without a signal peptide.Phylogenetic and domain analyses indicated that HasiUN CYP450,having a complete CYP450 domain,were distributed among various clans,with most members found in clan 3.CYP20 clans,present in 13 species from 2 families and 7 genera,required either one-host or three-hosts to undergo their full life cycle.MEME analysis results hint at different clans having variations in the amount and combination of motifs.Expression level analysis showed that HasiUN CYP450 was expressed at different levels,with the highest distribution of normally expressed genes in clan 3 and low expression of all mito clan genes.Functional annotation revealed HasiUN CYP450 key as-sociation with biological processes,metabolism,and organismal systems according to the GO and KEGG annotations.Distribution results showed that HasiUN CYP20a1 was expressed in specific tissues,including salivary glands and ovaries.Functional analysis points to CYP20a1's role in UV-induced toxic metabolism,endocrine disruptor metabolism,and hazardous substance metabolism in the nervous system.Our research presents the first analysis of HasiUN CYP450 gene's biological characteristics and expression pattern under normal physiological conditions.Additionally,investi-gations into the distribution and function of a new category,HasiUN CYP20a1,were embarked upon.These findings establish a theoretical foundation for continued functional study of HasiUN CYP45 gene.

Objectives:Recently,domestical developed left ventricular assist devices(LVAD)have been frequently introduced into clinical practice.This study aims to report the anesthesia protocol and perioperative outcomes in Chinese patients receiving LVAD implantation surgery.Methods:This retrospective analysis included patients who underwent LVAD implantation at our center from June 2017 to November 2024.During and after separation from cardiopulmonary bypass,we optimized right heart function through careful adjustments in heart rate,rhythm,preload,myocardial contractility,and afterload.Vasoactive agents were administered as needed,and mechanical ventilation parameters were optimized.We implemented blood conservation strategies and established strict transfusion criteria to minimize allogenic blood transfusions.Results:A total of 100 patients were included in the analysis,with 54.0%classified as Interagency Registry for Mechanically Assisted Circulatory Support(INTERMACS)I or II.Before leaving the operating room,the mean arterial pressure(MAP),mean pulmonary arterial pressure(mPAP),central venous pressure(CVP),lactic acid levels,and urinary output after cardiopulmonary bypass were recorded as(74±7)mmHg,(25±7)mmHg,(7±3)mmHg,(2.3±1.9)mmol/L,and(8.2±5.4)ml/(kg·h),respectively.The transfusion rates for red blood cells and fresh frozen plasma were 20.0%and 28.0%.The in-hospital mortality rate was 3.0%,with a low incidence of severe complications including right heart failure(12%).Left ventricular ejection fraction increased from(23.7±4.8)%preoperatively to(25.3±10.5)%prior to discharge.Conclusions:Patients who received LVAD at our center exhibited low rates of postoperative mortality and complications and significant improvement in left heart function before discharge.

Objective To investigate the current status of family resilience of children with cancer and analyze its influencing factors,to provide a basis for medical staff to formulate intervention plans.Methods Using a convenient sampling method,children with cancer who were hospitalized in 2 tertiary hospitals in Henan Province from January to April 2024 were selected for the survey.A general information questionnaire,family resilience assessment scale,quality of life family version,ZBI caregiver burden interview,and social support rating scale were used to understand the current status of family resilience of children with cancer and to explore the related influencing factors by univariate analysis and multiple stepwise linear regression analysis.Results A total of 280 questionnaires were distributed and 265 valid questionnaires were recovered,with a valid questionnaire recovery rate of 94.64％.The total score of family resilience for primary caregivers of children with cancer was(185.63±30.66).The multiple stepwise linear regression analysis results showed that the children's self-care ability,caregiver's work status,family care burden,and social support level were the influencing factors for family resilience of children with cancer(P＜0.05),and the explanatory variance was 51.3％.Conclusion The family resilience of children with cancer is at a medium level.The worse the children's self-care ability and the heavier the family care burden,the worse the family resilience;the caregiver's work status and good social support are helpful for the family resilience of children with cancer.Healthcare workers should develop intervention programs to address these factors to enhance the family resilience of children with cancer.

Stroke imposes a tremendous burden on patients'families and society due to its high rates of mortality,disability,and recurrence.Advances in neuroimaging technologies have provided critical theoretical foundations for investigating the pathophysiological mechanisms of stroke,as well as enabling early clinical intervention and personalized rehabilitation.This article reviewed the application of five commonly used magnetic resonance imaging(MRI)techniques in acupuncture therapy for stroke,including functional MRI(fMRI)for cerebral blood oxygen metabolism,magnetic resonance spectroscopy(MRS),diffusion MRI(dMRI),perfusion MRI(pMRI),and structural MRI(sMRI).By examining functional,metabolic,structural,and hemodynamic aspects,these imaging modalities offer evidence to validate the multi-target effect and efficacy of acupuncture in stroke treatment.