In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Cardiovascular disease(CVD)is the leading cause of death among patients with non-alcoholic fatty liver disease(NAFLD),which is also recognized as an independent risk factor for CVD.Exercise has emerged as a prom-ising therapeutic approach that can ameliorate a range of conditions,including those related to the cardiovascular and en-docrine systems.Recent research has highlighted the critical role of the integrated stress response(ISR)in the mecha-nisms and manifestations of these diseases.Notably,exercise influences ISR protein markers,regulates protein expres-sion,alleviates stress levels,and ultimately impacts disease onset and progression.Current studies suggest that the effects of ISR modulation through various exercise conditions differ for the heart and liver.However,evidence indicates that un-der specific circumstances,exercise can engage the PERK and GCN2 pathways to inhibit the ISR,thereby regulating glu-cose and lipid metabolism,apoptosis,and endoplasmic reticulum stress.These actions contribute to the protection of car-diac and hepatic function,ultimately improving outcomes in CVD and NAFLD.This review aims to provide novel insights and a theoretical foundation for the role of exercise in mitigating the onset of NAFLD,CVD,and related disorders.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Cardiovascular disease(CVD)is the leading cause of death among patients with non-alcoholic fatty liver disease(NAFLD),which is also recognized as an independent risk factor for CVD.Exercise has emerged as a prom-ising therapeutic approach that can ameliorate a range of conditions,including those related to the cardiovascular and en-docrine systems.Recent research has highlighted the critical role of the integrated stress response(ISR)in the mecha-nisms and manifestations of these diseases.Notably,exercise influences ISR protein markers,regulates protein expres-sion,alleviates stress levels,and ultimately impacts disease onset and progression.Current studies suggest that the effects of ISR modulation through various exercise conditions differ for the heart and liver.However,evidence indicates that un-der specific circumstances,exercise can engage the PERK and GCN2 pathways to inhibit the ISR,thereby regulating glu-cose and lipid metabolism,apoptosis,and endoplasmic reticulum stress.These actions contribute to the protection of car-diac and hepatic function,ultimately improving outcomes in CVD and NAFLD.This review aims to provide novel insights and a theoretical foundation for the role of exercise in mitigating the onset of NAFLD,CVD,and related disorders.

[Objective]To introduce Professor JI Laixi's experience in treating idiopathic asthenospermia by acupuncture based on the concept of"tonifying the kidney and harmonizing the heart and stomach".[Methods]By collecting and sorting out Professor JI's medical records and clinical narration of treating idiopathic asthenospermia with acupuncture therapy based on the concept of"tonifying the kidney and harmonizing the heart and stomach",the experience of Professor JI in treating this disease was comprehensively summarized and demonstrated with typical medical records.[Results]Professor JI believes that the disease is mainly located in the kidney,which is often related to the heart and stomach.Its pathogenesis is complicated,mainly due to the deficiency of kidney essence,and often accompanied with anxiety and/or disharmony of stomach Qi.In terms of treatment,it is necessary to focus on tonifying the kidney,and at the same time emphasize the overall concept,advocate"treating the kidney and calming the nerves"and"tonifying the kidney and regulating the stomach",so as to give consideration to diagnosis and treatment,make overall adjustment and gain full effect.In the medical record cited,the patient was diagnosed as infertility by combining auxiliary examination,tongue pulse and clinical symptoms.The main symptom was deficiency of kidney essence,also showing uneasiness and disharmony of stomach Qi.The acupuncture method of"Zhibian(BL 54)to Shuidao(ST 28)"was used to tonify the kidney and replenish essence,and acupuncture was supplemented by self-made"Anshen recipe"and"Gastropathy recipe"to soothe the nerves and harmonize the stomach.After four weeks of treatment,the patient's sperm quality returned to normal,while the clinical symptoms such as weakness of waist and legs and loss of appetite were also relieved significantly.After one year of following-up,the patient's wife was successfully pregnant.[Conclusion]Professor JI has rich clinical experience in treating idiopathic asthenospermia with acupuncture based on the concept of"primarily tonifying the kidney and simultaneously harmonizing the heart and stomach".The curative effect is remarkable,providing reference for the treatment of idiopathic asthenospermia.

The traditional web version of cancer screening information management platform can not fully meet the complex requirements of current early cancer diagnosis and treatment pro-grams,due to its functional limitation,low efficiency of data processing and difficulties in up-grading screening acceptability and effectiveness.This paper analyzes the informational require-ment for cancer early diagnosis and early treatment programs;introduces the design and construc-tion of an intellectualized management information platform;elaborates the roles of digital intelli-gence technology in the whole-process management,including intelligent health management;emphasizes the importance of improving the supervision and evaluation system for its high-quality development.The paper also discusses economic barriers and other issues related to the applica-tion of digital intelligence technology.

The traditional web version of cancer screening information management platform can not fully meet the complex requirements of current early cancer diagnosis and treatment pro-grams,due to its functional limitation,low efficiency of data processing and difficulties in up-grading screening acceptability and effectiveness.This paper analyzes the informational require-ment for cancer early diagnosis and early treatment programs;introduces the design and construc-tion of an intellectualized management information platform;elaborates the roles of digital intelli-gence technology in the whole-process management,including intelligent health management;emphasizes the importance of improving the supervision and evaluation system for its high-quality development.The paper also discusses economic barriers and other issues related to the applica-tion of digital intelligence technology.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

[Objective]To introduce Professor JI Laixi's experience in treating idiopathic asthenospermia by acupuncture based on the concept of"tonifying the kidney and harmonizing the heart and stomach".[Methods]By collecting and sorting out Professor JI's medical records and clinical narration of treating idiopathic asthenospermia with acupuncture therapy based on the concept of"tonifying the kidney and harmonizing the heart and stomach",the experience of Professor JI in treating this disease was comprehensively summarized and demonstrated with typical medical records.[Results]Professor JI believes that the disease is mainly located in the kidney,which is often related to the heart and stomach.Its pathogenesis is complicated,mainly due to the deficiency of kidney essence,and often accompanied with anxiety and/or disharmony of stomach Qi.In terms of treatment,it is necessary to focus on tonifying the kidney,and at the same time emphasize the overall concept,advocate"treating the kidney and calming the nerves"and"tonifying the kidney and regulating the stomach",so as to give consideration to diagnosis and treatment,make overall adjustment and gain full effect.In the medical record cited,the patient was diagnosed as infertility by combining auxiliary examination,tongue pulse and clinical symptoms.The main symptom was deficiency of kidney essence,also showing uneasiness and disharmony of stomach Qi.The acupuncture method of"Zhibian(BL 54)to Shuidao(ST 28)"was used to tonify the kidney and replenish essence,and acupuncture was supplemented by self-made"Anshen recipe"and"Gastropathy recipe"to soothe the nerves and harmonize the stomach.After four weeks of treatment,the patient's sperm quality returned to normal,while the clinical symptoms such as weakness of waist and legs and loss of appetite were also relieved significantly.After one year of following-up,the patient's wife was successfully pregnant.[Conclusion]Professor JI has rich clinical experience in treating idiopathic asthenospermia with acupuncture based on the concept of"primarily tonifying the kidney and simultaneously harmonizing the heart and stomach".The curative effect is remarkable,providing reference for the treatment of idiopathic asthenospermia.

ObjectiveTo evaluate the effect of transcranial direct current stimulation (tDCS) on the cognitive function and quality of life in patients with Parkinson's disease. MethodsRandomized controlled trials (RCTs) on tDCS for Parkinson's disease were searched in PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP and Wanfang Data from the inception to September, 2023. Control group was administered standard Parkinson's medications or placebo, physical therapy, and cognitive rehabilitation, while treatment group received tDCS additionally. The quality of the researches was evaluated using the Cochrane Risk of Bias Tool. Data synthesis and analysis were performed using RevMan 5.4 and Stata 17.0, with heterogeneity and sensitivity analyses. ResultsEight articles were included. tDCS significantly improved the scores of Montreal Cognitive Assessment (MD = 2.00, 95%CI 1.13 to 2.87, P < 0.001). However, there was no significant difference in the scores of Parkinson's Disease Questionnaire (MD = 0.73, 95%CI -5.78 to 7.23, P = 0.830), Beck Depression Inventory-Ⅱ(MD = -0.77, 95%CI -7.14 to 5.60, P = 0.810), and Unified Parkinson Disease Rating Scale-Ⅲ (MD = 1.60, 95%CI -0.77 to 3.97, P = 0.190). ConclusiontDCS may improve cognitive function of patients with Parkinson's disease.