The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
Humans ; Lung Neoplasms/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Chromatin Assembly Factor-1/metabolism* ; Animals ; Mice ; Male ; Female

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

BACKGROUND:Dexamethasone and hindlimb suspension are commonly used methods for modeling sarcopenia in animal experiments due to their short modeling time,ease of operation,and low cost.OBJECTIVE:To compare the differences in muscle mass,strength and functional phenotypes and molecular mechanisms between two mouse sarcopenia models induced by dexamethasone and hindlimb suspension.METHODS:Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group).The normal control group received no intervention.The dexamethasone group received daily intraperitoneal injections of 1 mg/kg/d dexamethasone sodium phosphate solution for 6 continuous days to establish sarcopenia models in mice,while mice in the hindlimb suspension group were suspended by tail harness for 16 hours,once per day,to establish sarcopenia models.Within 6 weeks after modeling,changes in body mass were monitored.After 6 weeks of modeling,mice were tested for limb grip strength,mobility(swimming test),skeletal muscle wet mass,and skeletal muscle pathological morphology.Expressions of skeletal muscle protein synthesis and catabolism indexes as well as the AMPK/FoXO3α signaling pathway were detected by RT-PCR and western blot.RESULTS AND CONCLUSION:(1)Two weeks after modeling,both dexamethasone and hindlimb suspension groups showed a significant decrease in body mass compared with the normal control group(P<0.001).After 6 weeks of modeling,grip strength of mice in both dexamethasone and hindlimb suspension groups was lower than that in the normal control group(P<0.001).The wet mass of gastrocnemius and extensor digitorum longus muscles and the cross-sectional area of gastrocnemius and soleus muscles in the dexamethasone group were lower than those in the normal control group(P<0.05).Compared with the hindlimb suspension group,the cross-sectional area of gastrocnemius muscle was significantly smaller in the dexamethasone group(P<0.05),while the cross-sectional area of soleus muscle was larger in the dexamethasone group(P<0.05).Mice in the dexamethasone group had reduced mobility when compared with those in the normal control group and the hindlimb suspension group(P<0.05).(3)Compared with the normal control group,PI3K,mTOR,AMPK,and PGC-1α mRNA expression and P-AMPK/AMPK protein were decreased in the two modeling groups(P<0.05),and FoXO3α mRNA expression and PGC-1α and FoXO3 protein expression were elevated(P<0.05);in the dexamethasone group,Akt1 mRNA expression was decreased(P<0.05),while Atrogin-1 and MuRF-1 mRNA expression was elevated(P<0.05);in the hindlimb suspension group,Akt1 mRNA expression was elevated(P<0.05).(4)Compared with the dexamethasone group,mTOR,Akt1,and FoXO3α mRNA expression was elevated in the hindlimb suspension group(P<0.05),while Atrogin-1 and MuRF-1 mRNA expression was decreased(P<0.05).To conclude,both modeling methods could decrease the levels of mitochondrial energy metabolism in skeletal muscle,with the dexamethasone group mediating atrophy of skeletal muscle through the dual action of ubiquitin proteasome and energy metabolism pathways,and the hindlimb suspension group inducing atrophy of skeletal muscle by mediating the energy metabolism pathway through the AMPK/FoXO3α signaling pathway,subsequently causing a reduction in mass,strength,and function of skeletal muscle.

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

Drug repurposing offers a promising alternative to traditional drug development and significantly re-duces costs and timelines by identifying new therapeutic uses for existing drugs.However,the current approaches often rely on limited data sources and simplistic hypotheses,which restrict their ability to capture the multi-faceted nature of biological systems.This study introduces adaptive multi-view learning(AMVL),a novel methodology that integrates chemical-induced transcriptional profiles(CTPs),knowledge graph(KG)embeddings,and large language model(LLM)representations,to enhance drug repurposing predictions.AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning(MVL),matrix factorization,and ensemble optimization techniques to integrate heterogeneous multi-source data.Comprehensive evaluations on benchmark datasets(Fdata-set,Cdataset,and Ydataset)and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art(SOTA)methods,achieving superior accuracy in predicting drug-disease associations across multiple metrics.Literature-based validation further confirmed the model's predictive capabilities,with seven out of the top ten predictions corroborated by post-2011 evidence.To promote transparency and reproducibility,all data and codes used in this study were open-sourced,providing resources for pro-cessing CTPs,KG,and LLM-based similarity calculations,along with the complete AMVL algorithm and benchmarking procedures.By unifying diverse data modalities,AMVL offers a robust and scalable so-lution for accelerating drug discovery,fostering advancements in translational medicine and integrating multi-omics data.We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Objective To investigate the predictive value of albumin-bilirubin score(ALBI),tumor burden score(TBS)and lac-tate dehydrogenase(LDH)level in predicting the prognosis of HCC patients after radical hepatectomy.Methods The clinical data of pa-tients who underwent radical hepatectomy for primary liver cancer in the Department of General Surgery,The Second Hospital of Lanzhou University from January 2011 to January 2022 were retrospectively collected,including the patients'basic personal information,relevant laboratory tests,imaging data,pathological reports and follow-up data.This study involved 162 patients.The patients were divided into survival group and death group according to their survival status at the last follow-up,and the area under the receiver operating character-istic curve(AUC)was used to estimate the prediction accuracy of different models.Results During the study period,a total of 79 pa-tients(48.7％)died.The median survival time was 46.5months.AFP and LDH were identified as two independent risk factors for over-all survival after surgery by univariate and multivariate analysis(P＜0.05).The AUC of ALBI-TBS-LDH score for predicting death af-ter radical hepatectomy was higher than that of ALBI score and TBS score.According to the optimal Youden index,when the optimal diag-nostic cutoff value of ALBI-TBS-LDH score was-0.18,the sensitivity and specificity of predicting death were 63.4％and 71.8％,respectively.The 1-year,3-year and 5-year overall survival rates of patients with ALBI-TBS-LDH score＜-0.18 were 95.1％,80.5％and 39.0％,respectively;the 1-year,3-year and 5-year overall survival rates of patients with score≥-0.18 were 86.6％,59.7％and 22.4％,respectively,with statistically significant differences(P＜0.001).Conclusion The ALBI-TBS-LDH score can be used as a simple tool to evaluate the prognosis of HCC patients after liver resection,but its role still needs further research and verifica-tion.Patients with high ALBI-TBS-LDH scores have a higher incidence of postoperative death and a shorter survival time than those with low scores.

OBJECTIVE To investigate the role of Bai Ling Long Zao An Shen formula(BLLZ)in sleep improvement in an environmental stress-induced insomnia rat model and explore its underlying mechanisms.METHODS(1)Component analysis:the chemical constituents of the BLLZ extract were analyzed using ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS).(2)Eval-uation of the sedative and hypnotic effect:① Mice:50 ICR mice were randomly divided into normal control group,BLLZ-L group(5,10 and 20 g·kg-1)and diazepam group(DZP,3 mg·kg-1).After five days of intragastric administration,pentobarbital sodium-induced righting reflex and locomotor activity tests were performed.② Rats:8 SD rats were implanted with electrodes and allowed to recover for seven days before baseline EEG data was collected over 24 h.A crossover design(7 d washout period)was employed,with rats randomly assigned to the DZP(3 mg·kg-1)and BLLZ(20 g·kg-1)group.After five days of treatment,24 h EEG recordings were obtained.(3)Insomnia model and interventions:①8 SD rats were allowed to recover for seven days post-surgery,followed by 6 h(14:00-20:00)baseline EEG recording.A 3×3 crossover design was used to assign rats to model(environmental stress-induced insomnia),model+DZP,or model+BLLZ groups.After five days of treatment,insomnia was induced by frequent cage changes(14:00,16:00 and 18:00),and EEG changes were monitored.(4)Mechanistic study:32 SD rats were randomly divided into the normal control group,model group,and model+DZP group.After five days of treatment,hypothalamic tissues were collected for biochemi-cal analysis.γ-aminobutyric acid(GABA),glutamate(Glu),and dopamine(DA)levels were measured using biochemical kits while γ aminobutyric acid receptor subunit alpha-1(GABAA1),core clock proteins period circadian regulator 2(PER2)and circadian locomotor output cycles(CLOCK)protein expressions were assessed by Western blotting.RESULTS(1)Compared with the normal control group,the sleep latency of BLLZ 10 and 20 g·kg-1 and DZP groups was significantly shortened,and the locomotor activity of BLLZ 20 g·kg-1 and DZP groups was significantly reduced;BLLZ 20 g·kg-1 signifi-cantly increased the total sleep time,slow-wave sleep time,and average duration of sleep in normal rats,and significantly reduced the wakefulness time.(2)The total sleep time and slow-wave sleep time of the model group significantly decreased and the wakefulness time significantly increased compared with baseline.(3)Compared with the model group,the total sleep time and slow-wave sleep time of the model+BLLZ group and the model+DZP group were significantly increased,and the wakefulness time significantly shortened.(4)Compared with the normal control group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly increased and GABAA1 and PER2 protein expres-sion were significantly decreased in the model group;compared with the model group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly decreased,and the expression of GABAA1 and PER2 were significantly increased in the model+BLLLZ group and the model+DZP group.CONCLUSION BLLZ has sedative and hypnotic effects.It can prolong the total slow-wave sleep time by increasing the average duration of slow-wave sleep episodes,thereby increasing the total sleep time and improving environmental stress-induced insomnia.The mechanism may be related to the downregulation of the Glu/GABA ratio and DA levels as well as the enhancement of GABAA1 expressions and the regulation of hypothalamic core clock protein expressions.

Objective To explore the value of the minimum intensity projection(minIP)images generated by post-processing of susceptibility weighted imaging(SWI)and corrected phase image(CPI)in evaluating the asymmetrical prominent veins sign(APVS)in acute ischemic stroke.Methods A retrospective analysis was conducted on 86 patients with acute ischemic stroke.Group A underwent conventional SWI reconstruction to generate minIP images,while group B used CPI for re-reconstruction to produce minIP images.Both groups used the same scanning method but different post-processing techniques to generate two sets of images,with each group consisted of 86 patients.Two deputy chief physicians of imaging diagnostics scored subjectively with a double-blind 5-point method to compare the ability of the two groups to display APVS and analyze the display rate of APVS.Results The subjective scores of group B were significantly higher than those of group A,with a statistically significant difference(P<0.05).The display rates of APVS in groups A and B were 67.44%and 73.26%respectively.Group B had a higher display rate of APVS below the tentorium cerebelli than above it.Conclusion The minIP images generated by CPI post-processing can achieve the effects similar to phase difference enhanced imaging(PADRE),and is superior to SWI reconstruction method in displaying APVS.It can be used as a supplementary post-processing method when acute stroke shows poor APVS,which has practical clinical application value and can provide more imaging basis for clinical practice.

Objective To explore the value of the minimum intensity projection(minIP)images generated by post-processing of susceptibility weighted imaging(SWI)and corrected phase image(CPI)in evaluating the asymmetrical prominent veins sign(APVS)in acute ischemic stroke.Methods A retrospective analysis was conducted on 86 patients with acute ischemic stroke.Group A underwent conventional SWI reconstruction to generate minIP images,while group B used CPI for re-reconstruction to produce minIP images.Both groups used the same scanning method but different post-processing techniques to generate two sets of images,with each group consisted of 86 patients.Two deputy chief physicians of imaging diagnostics scored subjectively with a double-blind 5-point method to compare the ability of the two groups to display APVS and analyze the display rate of APVS.Results The subjective scores of group B were significantly higher than those of group A,with a statistically significant difference(P<0.05).The display rates of APVS in groups A and B were 67.44%and 73.26%respectively.Group B had a higher display rate of APVS below the tentorium cerebelli than above it.Conclusion The minIP images generated by CPI post-processing can achieve the effects similar to phase difference enhanced imaging(PADRE),and is superior to SWI reconstruction method in displaying APVS.It can be used as a supplementary post-processing method when acute stroke shows poor APVS,which has practical clinical application value and can provide more imaging basis for clinical practice.

Objective To investigate the predictive value of albumin-bilirubin score(ALBI),tumor burden score(TBS)and lac-tate dehydrogenase(LDH)level in predicting the prognosis of HCC patients after radical hepatectomy.Methods The clinical data of pa-tients who underwent radical hepatectomy for primary liver cancer in the Department of General Surgery,The Second Hospital of Lanzhou University from January 2011 to January 2022 were retrospectively collected,including the patients'basic personal information,relevant laboratory tests,imaging data,pathological reports and follow-up data.This study involved 162 patients.The patients were divided into survival group and death group according to their survival status at the last follow-up,and the area under the receiver operating character-istic curve(AUC)was used to estimate the prediction accuracy of different models.Results During the study period,a total of 79 pa-tients(48.7％)died.The median survival time was 46.5months.AFP and LDH were identified as two independent risk factors for over-all survival after surgery by univariate and multivariate analysis(P＜0.05).The AUC of ALBI-TBS-LDH score for predicting death af-ter radical hepatectomy was higher than that of ALBI score and TBS score.According to the optimal Youden index,when the optimal diag-nostic cutoff value of ALBI-TBS-LDH score was-0.18,the sensitivity and specificity of predicting death were 63.4％and 71.8％,respectively.The 1-year,3-year and 5-year overall survival rates of patients with ALBI-TBS-LDH score＜-0.18 were 95.1％,80.5％and 39.0％,respectively;the 1-year,3-year and 5-year overall survival rates of patients with score≥-0.18 were 86.6％,59.7％and 22.4％,respectively,with statistically significant differences(P＜0.001).Conclusion The ALBI-TBS-LDH score can be used as a simple tool to evaluate the prognosis of HCC patients after liver resection,but its role still needs further research and verifica-tion.Patients with high ALBI-TBS-LDH scores have a higher incidence of postoperative death and a shorter survival time than those with low scores.