Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

Energy metabolism regulation plays a pivotal role in metabolic engineering. It mainly achieves the balance of material and energy metabolism or maximizes the utilization of materials and energy by regulating the supply intensity and mode of ATP and reducing electron carriers in cells. On the one hand, the production efficiency can be increased by changing the distribution of material metabolic flow. On the other hand, the thermodynamic parameters of enzyme-catalyzed reactions can be altered to affect the reaction balance, and thus the production costs are reduced. Therefore, energy metabolism regulation is expected to become a favorable tool for the modification of microbial cell factories, thereby increasing the production of target metabolites and reducing production costs. This article introduces the commonly used energy metabolism regulation methods and their effects on cell factories, aiming to provide a reference for the efficient construction of microbial cell factories.
Energy Metabolism/physiology* ; Metabolic Engineering/methods* ; Adenosine Triphosphate/metabolism* ; Industrial Microbiology/methods*

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective To observe the expression of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)signal transducer in liver tissue of rats with bilateral ovarian castration(OVX)by electroacupuncture at Guanyuan(CV4)point,and explore the mechanism of electroacupuncture in up regulating PI3K/Akt signal pathway,regulating lipid metabolism,and reducing weight was investigated.Methods Thirty-two female SD rats were randomly divided into blank,sham operation,model and electroacupuncture group,with 8 rats in each group.Perimenopausal obesity(PMO)model was prepared by OVX in the model and the electroacupuncture group.After the model was successfully prepared,the electroacupuncture group was subjected to electroacupuncture at CV4(continuous wave,2 Hz,1 mA),once day,20 min once time,and for 14 consecutive days.The body mass of each group of rats was recorded during the whole experiment,and Lee's index was calculated during sampling.The pathological changes of liver were observed by HE staining.Serum levels of HDL,LDL and TG were detected by ELISA.Western blot analysis of PI3K,Akt,p-Akt protein expression and p-Akt/Akt in liver tissues.Results Compared with blank group and sham operation group,the body mass of rats in model group was significantly increased(P＜0.05),Lee's index was increased(P＜0.05),fat vacuoles appeared in liver,serum HDL level was decreased(P＜0.001),LDL and TG levels were increased(P＜0.01).PI3K,Akt,p-Akt,p-Akt/Akt were decreased in liver(P＜0.05).Compared with model group,body mass and Lee's index of rats in electroacupuncture group were decreased(P＜0.05),fat vacuoles in liver were decreased,HDL level was increased(P＜0.01),LDL and TG levels were decreased(P＜0.05,P＜0.01),PI3K,Akt and P-Akt were decreased(P＜0.05),and p-akt/Akt decreased(P＜0.01).Conclusion Electroacupuncture at CV4 can significantly up-regulate PI3K/Akt signaling pathway,improve lipid metabolism disorder and accumulation,and reduce body mass in OVX rats.

Objective This study aim to evaluate the therapeutic efficacy of ultrasound-guided acupuncture,specifically targeting the Tiaokou(ST38)acupoint through Chengshan(BL57)to elicit the Deqi sensation,in the context of acute scapulohumeral periarthritis.Methods Utilizing a randomized controlled trial design,a total of 60 subjects diagnosed with acute scapulohumeral periarthritis underwent random allocation into either the observation or control group,with 30 subjects in each.Under ultrasound guidance,acupuncture was administered unilaterally at the specific acupoint ST38 through BL57.The observation group received needling traversing the calf interosseous membrane,reaching the deep fascia of the tibialis posterior muscle,employing lifting and inserting twisting techniques to induce Deqi.In contrast,the control group received acupuncture targeting the sub-superficial fascia without needle manipulation or the requirement for Deqi.Both groups underwent a singular acupuncture session,with a standardized 20-minute needle retention period.Results Post-acupuncture intervention,the observation group exhibited a statistically significant total effective rate of 76.66％,greater than that in the control group at 30％(P＜0.01).Comparative analysis revealed substantial enhancements in the observation group,including improvements in VAS score,Constant shoulder joint function score,the highest △T of red external thermal imaging around the shoulder,and patients'subjective acupuncture sensation scores(P＜0.05).Additionally,within the observation group,post-treatment reductions were observed in VAS score and △ T of red external thermal imaging,coupled with an elevation in Constant shoulder joint function score(P＜0.01).Importantly,neither group manifested discernible adverse reactions.Conclusion Ultrasound-guided acupuncture,facilitating Deqi at Tiaokou(ST38),emerges as a clinically significant and secure intervention for acute scapulohumeral periarthritis.These findings substantiate its potential as a viable therapeutic modality,promoting broader clinical adoption.

Objective To observe the expression of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)signal transducer in liver tissue of rats with bilateral ovarian castration(OVX)by electroacupuncture at Guanyuan(CV4)point,and explore the mechanism of electroacupuncture in up regulating PI3K/Akt signal pathway,regulating lipid metabolism,and reducing weight was investigated.Methods Thirty-two female SD rats were randomly divided into blank,sham operation,model and electroacupuncture group,with 8 rats in each group.Perimenopausal obesity(PMO)model was prepared by OVX in the model and the electroacupuncture group.After the model was successfully prepared,the electroacupuncture group was subjected to electroacupuncture at CV4(continuous wave,2 Hz,1 mA),once day,20 min once time,and for 14 consecutive days.The body mass of each group of rats was recorded during the whole experiment,and Lee's index was calculated during sampling.The pathological changes of liver were observed by HE staining.Serum levels of HDL,LDL and TG were detected by ELISA.Western blot analysis of PI3K,Akt,p-Akt protein expression and p-Akt/Akt in liver tissues.Results Compared with blank group and sham operation group,the body mass of rats in model group was significantly increased(P＜0.05),Lee's index was increased(P＜0.05),fat vacuoles appeared in liver,serum HDL level was decreased(P＜0.001),LDL and TG levels were increased(P＜0.01).PI3K,Akt,p-Akt,p-Akt/Akt were decreased in liver(P＜0.05).Compared with model group,body mass and Lee's index of rats in electroacupuncture group were decreased(P＜0.05),fat vacuoles in liver were decreased,HDL level was increased(P＜0.01),LDL and TG levels were decreased(P＜0.05,P＜0.01),PI3K,Akt and P-Akt were decreased(P＜0.05),and p-akt/Akt decreased(P＜0.01).Conclusion Electroacupuncture at CV4 can significantly up-regulate PI3K/Akt signaling pathway,improve lipid metabolism disorder and accumulation,and reduce body mass in OVX rats.

Objective This study aim to evaluate the therapeutic efficacy of ultrasound-guided acupuncture,specifically targeting the Tiaokou(ST38)acupoint through Chengshan(BL57)to elicit the Deqi sensation,in the context of acute scapulohumeral periarthritis.Methods Utilizing a randomized controlled trial design,a total of 60 subjects diagnosed with acute scapulohumeral periarthritis underwent random allocation into either the observation or control group,with 30 subjects in each.Under ultrasound guidance,acupuncture was administered unilaterally at the specific acupoint ST38 through BL57.The observation group received needling traversing the calf interosseous membrane,reaching the deep fascia of the tibialis posterior muscle,employing lifting and inserting twisting techniques to induce Deqi.In contrast,the control group received acupuncture targeting the sub-superficial fascia without needle manipulation or the requirement for Deqi.Both groups underwent a singular acupuncture session,with a standardized 20-minute needle retention period.Results Post-acupuncture intervention,the observation group exhibited a statistically significant total effective rate of 76.66％,greater than that in the control group at 30％(P＜0.01).Comparative analysis revealed substantial enhancements in the observation group,including improvements in VAS score,Constant shoulder joint function score,the highest △T of red external thermal imaging around the shoulder,and patients'subjective acupuncture sensation scores(P＜0.05).Additionally,within the observation group,post-treatment reductions were observed in VAS score and △ T of red external thermal imaging,coupled with an elevation in Constant shoulder joint function score(P＜0.01).Importantly,neither group manifested discernible adverse reactions.Conclusion Ultrasound-guided acupuncture,facilitating Deqi at Tiaokou(ST38),emerges as a clinically significant and secure intervention for acute scapulohumeral periarthritis.These findings substantiate its potential as a viable therapeutic modality,promoting broader clinical adoption.