Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.

AIM:To identify the expression characteristics of transfer RNA-derived small RNAs(tsRNAs)re-sponding to DNA damage in human hepatoblastoma HepG2 cells,and to investigate their potential functions.METHODS:Based on paired HepG2 cells and TP53 gene knockout HepG2 cells,we successfully constructed a DNA damage cellular model using adriamycin(ADR).Transcriptome analysis of small noncoding RNAs was performed to systematically identi-fy a set of tsRNAs responding to ADR and involved in p53 regulation.Functional enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes(KEGG).Additionally,after silencing the expression of target tsRNA genes,the biological functions of these tsRNAs in HepG2 cells were initially confirmed through CCK-8 assay and plate colo-ny formation assay.RESULTS:DNA damage induced a set of tsRNAs involved in p53 regulation,among which tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)and tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)showed the most significant up-regulation in HepG2 cells(P<0.05).Silencing of either tRF-5-1 or tRF-i-1 gene inhibited the proliferative activity of HepG2 cells(P<0.05).CONCLUSION:A group of tsRNAs responding to DNA damage can be identified in HepG2 cell model,and tsRNAs can promote the proliferative activity of HepG2 cells,suggesting that tsRNAs may play an important role in the de-velopment and progression of liver malignancies.

Objective To assess the safety of transeptal puncture(TSP)guided by transthoracic echocardiography(TEE)in percutaneous transcatheter closure of patent foramen ovale(PFO).Methods From March 2022 to December 2022,our department performed TSP guided by TEE in 45 patients with PFO who were unable to pass through the PFO with transcatheter standard technique.After guiding the delivery of the sheath,the foramen ovale was occluded.Results PFO closure with TSP technique guided by transthoracic echocardiography was successfully finished in all the 45 patients,with an operative time of(15.0±3.7)min.No complications such as arrhythmia or cardiac perforation happened immediately and at 12 h after surgery.All the patients recovered and were discharged on the next day after surgery.All the 45 patients were followed up by outpatient echocardiography and dynamic electrocardiogram at 3 months after surgery,and no complications such as intracardiac shunt,pericardial effusion,atrial fibrillation,aortic regurgitation,or arrhythmia were observed.Conclusion TSP guided by TEE is safe and feasible,and it can be used as a supplementary method for complex PFO.

Objective:To explore the effect of photobiomodulation (PBM) combined with umbilical cord mesenchymal stem cell transplantation on motor function recovery in rats with spinal cord injury.Methods:The mesenchymal stem cells were irradiated with a laser energy density of 1.5, 3, 6 and 12 J/cm 2. The optimal energy density was screened by the MTT method on the 3rd day. Before cell transplantation, 32 male SD rats were randomly divided into the spinal cord injury group, which was injected with normal saline without cells; the stem cell transplantation group, which was injected with stem cells in the injury model; the laser irradiation group, which was injected with cell-free saline and laser irradiation; and the combined treatment group, which was treated with cell transplantation and laser irradiation. BBB score and inclined plate test were performed on the 1st, 3rd, 7th, 14th and 21st day, and hematoxylin-eosin staining and Nissl staining were performed on the 21st day. Results:The laser irradiation with an energy density of 12 J/cm 2 can accelerate cell proliferation ( P<0.05). After the modeling, the BBB score of the combined treatment group was higher than that of the other groups (all P<0.05), and the motor function recovered significantly. In the inclined plate experiment, the performance of the combined treatment group and the laser irradiation group was also better than that of other groups. The results of hematoxylin-eosin staining showed that the cavity area in the combined treatment group was significantly reduced, and the inflammatory reaction was the lightest. The staining of Nissl bodies became deeper, and the spinal cord injury was significantly reduced. Conclusions:PBM can promote the recovery of motor function in rats with spinal cord injury after the transplantation of umbilical cord mesenchymal stem cells, and has an obvious therapeutic effect on spinal cord injury in rats. This study provides a basis for the treatment of spinal cord injury.

Background: Recent studies showed that the clinical outcome of moderately severe acute pancreatitis (MSAP) are different among different subgroups. Aims: To further subdivide MSAP, and explore the heterogeneity of MSAP subgroups. Methods: A retrospective analysis was performed on patients with acute pancreatitis (AP) from January 2016 to December 2020 at Northern Jiangsu People’s Hospital, including 538 patients with mild acute pancreatitis (MAP) and 461 patients with MSAP. MSAP patients were divided into four groups according to local complication and transient organ failure (TOF), including single acute peripancreatic fluid collection (APFC) without TOF group (group A), multiple APFC without TOF group (group B), other local complication without TOF group (group C) and TOF group (group D). The baseline data and the severity of AP among the four subgroups were compared. Meanwhile, the severity of disease between group A and MAP patients was also compared. Logistic regression analysis was used to evaluate the risk factors of MSAP. Results: Patients in group D were older than those in group A (P<0.05). There were statistically significant differences in different scoring systems among the four subgroups (P<0.05). The proportions of APACHE Ⅱ≥8, Glasgow≥3 and BISAP≥3 in group D were significantly higher than those in the other three groups (P<0.05). There were significant differences in levels of Ca

Objective To summarize the experience and effect of applying 3D printing to repair thoraco-abdominal aortic disease with fenestrated stent-graft or branch stent-graft technique.Methods From Oct 2017 to Sep 2018,22 patients with thoracic and abdominal aortic diseases,including aortic arterial dissection (9 patients) and aortic aneurysm (13 patients) were admitted.There were 19 males and 3 females,with mean age of (60 ± 13) years.Before the surgery 3D printing model guide plate was made according to CT,and then the pre-fenestrated stent-graft technique,branch stent-graft technique and other techniques were adopted in the surgery to perform endovascular repair.Resuits All of the operations were completed in one stage without open surgery.The average operation time was (5.67 ± l.23) hours without renal insufficiency and paraplegia,1 branch artery was lost during operation (1.4％) and 1 patient died (4.5％).Conclusion The application of 3D printing in the treatment of thoraco-abdominal aortic disease involving branches is more accurate than traditional measurement and localization.It had a safe and reliable short-term result.