The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

The macrophages,as a crucial component of the body's immune system,can be polarized into M1 and M2 types by different cellular molecules in various environments,and contribute to the progression of various diseases.In inflammatory responses,the M1 macrophages are primarily regarded as the pro-inflammatory cells,facilitate the inflammation progression,tissue destruction,and bone resorption,while M2 macrophages,as inflammatory cells,participate in tissue healing and bone repairment.In the tumor microenvironment,the roles of M1 and M2 macrophages are reversed.The periodontitis,pulpitis,and oral squamous cell carcinoma(OSCC)are the most prevalent inflammation and tumor in the oral cavity.Therefore,this article summarizes the relevant researches from home and abroad on the polarization of macrophages in oral inflammatory responses such as periodontitis,peri-implantitis,and pulpitis,bone remodeling during orthodontic treatment,and OSCC,and elucidate the metabolic activities of macrophages in infiammation,tumor,and bone remodeling and the mechanism of regulating the onset and development of diseases by the macrophage polarization,and provides new perspectives for the clinical treatment.

Objective To investigate the predictive value of lactic acid to albumin ratio in the in-hospital mortality of the patients with intra-abdominal infection sepsis in ICU.Methods The clinical data in 175 pa-tients with sepsis caused by intra-abdominal infection admitted and treated in the intensive care medicine de-partment of this hospital from January 2018 to December 2021 were retrospectively analyzed.The patients were divided into the survival group (n=94) and death group (n=81) according to whether or not having in-hospital death.The general data,blood lactic acid and albumin levels of the patients at admission were collect-ed,and the LAR value was calculated.The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of LAR for the in-hospital mortality of sepsis patients in ICU.The Cox regression analysis and Kaplan-Meier curves were used to analyze the independent correlation between LAR and ICU mortality. Results There were statistically significant differences in the acute physiology and chronic health scoring sys-tem Ⅱ (APACHⅡ) score,sequential organ failure assessment (SOFA) score,mean arterial pressure,oxygen-ation index,PCT,lactic acid,albumin,LAR and the proportion of surgical patients between the two groups (P<0.05).The area under the curve (AUC) of LAR for predicting the prognosis in the patients with ICU sepsis was 0.765 (95％CI:0.695-0.835),which was higher than that of the APACHEⅡscore,SOFA score,lactic acid and PCT.With LAR=1.295 as the cutoff value,the sensitivity and specificity for its prediction were 0.679 and 0.707,respectively.The Kaplan-Meier curve showed that the ICU motality rate in high LAR (LAR≥1.29) was higher than that in low LAR,and the difference was statistically significant(63.2％ vs. 41.5％,P<0.05).The Cox regression analysis results showed that the mortality in sepsis showed the increas-ing trend with the LAR level increase (P<0.05).Conclusion LAR is an influencing factor of the death in the intra-abdominal infection sepsis in ICU,which could effectively predict the risk of in-hospital death of the patients.

Objective To systematically evaluate the value of optical coherence tomography angiogra-phy (OCTA) for detecting the vessel density (VD) changes after open-angle glaucoma (OAG) surgery.Meth-ods The studies on OCTA for detecting the VD changes after OAG surgery were searched in the CNKI,WanFang,VIP,SinoMed,PubMed,Embase and Web of Science databases from the database establishment to May 2024.Literature screening,data extraction and risk of bias assessment of included studies were conducted independently by two reviewers.Descriptive analysis was adopoted for the systematic evaluation,the meta a-nalysis was conducted by using the R software and mean difference (MD) and its 95％CI were calculated.Re-sults A total of 13 studies were included,involving 472 patients with 500 tested eyes.The results of meta-a-nalysis showed that compared with pre-surgery,VD around the optic nerve head (ONH) and in nasal superi-or,temporal inferior,temporal superior,superior temporal and superior nasal regions at postoperative 6 months were significantly decreased.VD in the perimacular,perimacular superior hemisphere,permacular su-perior hemisphere,perimacular superior and permacular superior regions at postoperative 6 months were sig-nificantly increased.Conclusion OCTA could effectively detect the postoperative VD changes in the patients with OAG and predict postoperative visual function changes in glaucoma,and could serve as an effective test means for assessing the clinical treatment effect of the patients with OAG.

Objective:To explore the function and mechanism of transcription factor En1 in esophageal squamous cell carcinoma (ESCC).Methods:The correlations of En1 with prognosis were analyzed using the overall survival data of 9 397 pan-cancer patients and progression-free survival data of 4 349 pan-cancer patients from The Cancer Genome Atlas (TCGA) database. The En1 expression data in 53 and 155 cases of ESCC and their paired adjacent tissues were from Gene Expression Omnibus (GEO) database and National Genomics Data Center-Genome Sequence Archive(NGDC-GSA)database. Lentivirus was used to generate En1 stable knockout cell lines KYSE180 and KYSE450. The proliferation ability of the cells was detected by cell counting kit 8 and clone formation assay. The migration ability of the cells was detected by Transwell assay. The effect of En1 on the proliferation of ESCC was detected by xenograft experiment in BALB/c-nu/nu mice. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of En1, glioma-associated oncogene family zinc finger 1 (GLI1), glioma-associated oncogene family zinc finger 2 (GLI2) and smoothened (SMO).Results:Pan-cancer data from TCGA showed that patients with low En1 expression had longer overall survival and progression-free survival than patients with high En1 expression ( P< 0.001). Data from GEO and GSA databases also showed a high expression level of En1 in ESCC tissues compared with paired tissues ( P＜0.001). Proliferation was inhibited after knockout of En1 in KYSE180 and KYSE450 cells ( P＜0.001). The colony formation numbers decreased. The colony formation numbers of KYSE180 cells in the shEn1#1 group and the shEn1#2 group were 138.33±23.07 and 127.00±19.70, respectively, significantly lower than that of the shNC group 340.67±12.06 ( P<0.001). The colony formation numbers of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were 65.33±2.52 and 9.00±3.00, respectively, significantly lower than that of the shNC group 139.00±13.00 ( P<0.001). The migration numbers was inhibited after knockout of En1 [the Transwell numbers of KYSE180 cells in the shEn1#1 group and the shEn1#2 group were 66.67±12.66 and 71.33±11.02, respectively, significantly lower than that of the shNC group 334.67±16.56 ( P<0.001). The Transwell numbers of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were 112.33±14.57 and 54.33±5.51, respectively, significantly lower than that of the shNC group 253.33±21.03 ( P<0.001)]. Xenograft model showed a slower growth rate of shEn1#1 and shEn1#2 cell lines ( P＜0.001). The tumor weights of KYSE450 cells in the shEn1#1 group and the shEn1#2 group were (0.046±0.026)g and (0.047±0.025)g, respectively, significantly lower than that of the shNC group (0.130±0.038)g ( P＜0.001). After knockdown of En1, the relative expression levels of GLI1 in KYSE180 cells of the shEn1#1 group and the shEn1#2 group were 0.326±0.162 and 0.322±0.133, and the relative expression levels of GLI1 in KYSE450 cells of the shEn1#1 and shEn1#2 groups were 0.131±0.006 and 0.352±0.050, respectively, which were all lower than that in the shNC group ( P＜0.01). After knockdown of En1, overexpression of GLI1 attenuated the inhibitory effect of knockdown of En1 on cell proliferation ( P＜0.001), colony formation[the colony formation numbers of the shEn1#1-GLI1 group were 151.00±9.54, higher than 102.33±10.02 ( P=0.004) of the shEn1#1-vector group] and migration [the migration numbers of the shEn1#1-GLI1 group were 193.67±10.07, higher than 109.33±11.50 ( P<0.001) in the shEn1#1-vector group]. In clinical samples of ESCC, major regulatory factors of the Hedgehog pathway were up-regulated and the pathway was activated. Conclusion:En1 promotes the proliferation and migration of ESCC cells by regulating the Hedgehog pathway and can be used as a new potential target for targeted therapy of ESCC.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.

Objective:To explore the clinical efficacy of endoscopic sleeve gastrectomy (ESG) in the treatment of obesity.Method:A 26 year old female patient was admitted on October 20, 2022 due to a progressive increase in weight for 2 years. Her body mass index (BMI) was 30.04 kg/m 2, body fat percentage was 39.2%, and visceral fat grade was 15. ESG was performed using the OverStitch SX endoscopic suture system. Result:The surgery was successful, with approximately 5 ml of intraoperative bleeding.The patient discharged on the first day after surgery. Two weeks after surgery, small bowel follow-through showed a tubular shape of the stomach. At 6 months after surgery, the BMI was 25.2 kg/m 2, body fat percentage was 32%, visceral fat grade was 10. The total body weight loss rate (%TBWL) at 6 months after surgery was 16%, and the excess weight loss rate (%EWL) was 54.5%. Conclusion:ESG is effective for the treatment of obesity.

Objective This study aimed to observe the outcomes of iRoot BP Plus full pulpotomy in primary molars with partial irreversible pulpitis retrospectively.Methods Collect 102 cases of primary molars with partial irreversible pulpitis undergoing iRoot BP Plus full pulpotomy from January 2019 to August 2023,with a follow-up period of 24-47 months.Based on the presence of irreversible pulpitis symptoms before surgery,the included cases will be divided into asymptomatic group(n=53)and symptomatic group(n=49).Observe the clinical and imaging success rates of both groups.Results Clinical success rates were 96.2%and 97.9%in asymptomatic and symptomatic groups,and ra-diographic success rates were 96.2%and 93.9%respec-tively.Conclusion iRoot BP Plus full pulpotomy can be used for the treatment of primary molars with partial irreversible pulpitis under an enhanced pulpotomy protocol.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.