Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

BACKGROUND:Based on the principle of vertical tooth movement,a personalized orthodontic appliance is created through digital design combined with 3D printing,so that the personalized orthodontic appliance forms a support system with the individual incisors.With the help of the absolute support of the micro-implant,the single tooth is precisely controlled in a three-dimensional direction.OBJECTIVE:To design personalized orthodontic appliances with 11,12,21,and 22 intrusion and extrusion based on biomechanical principles,and analyze the safety of the personalized orthodontic appliances in terms of their movement effect on the teeth by means of the three-dimensional finite element method.METHODS:Three-dimensional finite element models of alveolar bone-periodontium-maxillary incisors-personalized cantilever micro-implant-connecting plates-personalized brackets in the maxillary anterior region(teeth numbers 11,12,21,and 22)were established using Mimics,Geomagic Wrap,SolidWorks,and Ansys Workbench software,respectively.Personalized orthodontic appliances with low pressure movement and extended movement were set up at each tooth position.The stress level of each component of the personalized orthodontic appliances was analyzed,and the tooth displacement and periodontal stress distribution were calculated under loading of 300 g tensile or thrust force.RESULTS AND CONCLUSION:(1)The maximum equivalent force on the personalized intrusion mobile orthodontic appliance was 162.90 MPa,and the maximum equivalent force on the personalized extrusion mobile orthodontic appliance was 239.57 MPa.The maximum equivalent stress on both devices was located in the vertical portion of the personalized bracket loading attachment.The equivalent stresses on each part of the personalized orthodontic appliance were all within the yield strength,and they had good safety.(2)The initial displacement of the teeth under the action of the personalized orthodontic appliances showed a tendency towards overall intrusion or extrusion,with the displacement in the vertical direction far exceeding that in the horizontal and sagittal directions.The equivalent stress peak appeared at the root tip or neck of the periodontal membrane,and the equivalent stress concentration area appeared in the periodontal membrane of the root apical region.(3)The results show that the personalized orthodontic appliance allows 11,12,21,and 22 to approximate either intrusion movement or extrusion movement,initially confirming the effectiveness of the personalized vertical movement orthodontic appliance.

This study aims to investigate the isolate and identify of infectious bronchitis virus(IBV)in chickens,and study its genetic variation and pathogenicity.In 2023,two strains named CK/CH/HN/SQ202301 and CK/CH/HN/SQ202302 were obtained from suspected infectious bronchitis(IB)infected materials collected in a region of Henan Province,China.Further analysis showed that the two isolates belong to the G Ⅰ-13 and GⅥ genotypes,respectively.The cleavage sites of S protein were all RRSRR.The prediction of glycosylation sites showed that the two isolates had 18 and 12 N-glycosylation sites respectively,but no O-glycosylation site.Recombinant analysis shows that C2023-1 was a recombinant strain.Pathogenicity was assessed by infecting 1-day-old SPF chicks with the two isolates,and the results showed that C2023-1 strain infection could cause clini-cal symptoms such as depression and head shaking,as well as death in chicks,with a mortality rate of 37.5％.There were no clinical symptoms or deaths after infection with C2023-2 strain.Viral load test results showed that both isolates continued to detoxify until the 10th day,and had strong rep-lication capacity in the kidney,trachea and bursa of Fabricius.The results indicate significant differences in the genetic characteristics and pathogenicity of the two isolates due to their different genotypes.This study not only provides new epidemiological data on IB,which contributes to a bet-ter understanding of IBV's epidemiological features and control challenges,but also adds valuable bioinformatics resources for IBV by analyzing its variation mechanisms and biological information.

Objective To investigate the efficacy and safety of spinal endoscopic decompression through 45° puncture foraminal approach in treatment of L5/S1 lumbar disc herniation(LDH).Methods Clinical data of 130 patients with L5/S1 level LDH from January 2021 to January 2023 were retrospectively analyzed.These patients were divided into two groups based on the spinal endoscopic surgery approach.Observation group(67 patients)underwent spinal endoscopic decompression via 45° puncture,while the control group(63 patients)underwent spinal endoscopic decompression using the traditional transforaminal endoscopic spinal system(TESSYS)technique.Perioperative indicators such as operation time,X-ray fluoroscopy time,and hospital stay were recorded for both groups.Visual analogue scale(VAS)scores for low back pain and lower limb pain,as well as the Oswestry disability index(ODI)were assessed before surgery and at 1 day,3 months,6 months,and 12 months after operation.The overall efficacy was evaluated using the modified MacNab criterion at 12 months postoperatively.Results All the patients in both groups successfully underwent spinal endoscopic decompression.The observation group had significantly shorter average operation time and intraoperative X-ray fluoroscopy time compared to the control group,the differences were statistically significant(P＜0.05).There was no significant difference in hospital stay between the two groups(P=0.505).Compared to preoperative values,both groups showed a significant decreasing trend in VAS scores for low back pain,lower limb pain,and ODI at 1 day,3 months,6 months,and 12 months after operation,the differences were statistically significant(P＜0.05).The observation group had significantly low back pain VAS score,lower limb pain VAS score and ODI at 1 day and 3 months after operation compared to the control group(P＜0.05).There were no statistically significant differences in low back pain VAS score,lower limb pain VAS score and ODI between the two groups 6 and 12 months after operation(P＞0.05).At 12 months after operation,the excellent and good rate was 95.5％ in observation group and 85.7％ in control group,with no significant difference between the two groups(P=0.054).No surgery-related complications occurred in either group.During postoperative follow-up,6 patients(9.5％)in control group experienced recurrence of low back pain and lower limb pain due to recompression of nerve roots by residual herniated material,while no recurrence was observed in observation group,the difference was statistically significant(P=0.035).Conclusion Both the 45° puncture technique and the traditional TESSYS technique can achieve satisfactory decompression effects in patients with LDH at the L5/S1 segment undergoing transforaminal spinal endoscopic decompression surgery.However,the 45° puncture technique can shorten the operation time and X-ray fluoroscopy time,resulting in more pronounced early postoperative improvement and a lower recurrence rate.It is worthy clinical application.

AIM:This study aims to investigate the protective effect of α-lipoic acid(α-LA)against alcohol-induced damage in H9c2 rat cardiomyocytes and to explore the underlying mechanisms.METHODS:An alcohol-induced injury model of H9c2 cells was established,and the cells were divided into 4 groups:control group,alcohol group,α-LA group,and alcohol+α-LA group.Additionally,H9c2 cells overexpressing aldehyde dehydrogenase 2(ALDH2)were cre-ated and further divided into 6 groups:normal control group,normal cells treated with alcohol group,normal cells treated with alcohol+α-LA group,ALDH2 overexpression group,ALDH2-overexpressing cardiomyocytes treated with alcohol group,and ALDH2-overexpressing cardiomyocytes treated with alcohol+α-LA group.Cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine(EdU)staining.Reactive oxygen species(ROS)levels in each group were measured using di-hydroethidium(DHE)staining,while the expression levels of ALDH2,silent information regulator 1(SIRT1),heme oxy-genase 1(HO1)and P53 proteins were detected by Western blot analysis.RESULTS:(1)Alcohol exposure resulted in a decrease in the proliferation of H9c2 cells and an increase in intracellular oxidative stress,evidenced by elevated ROS levels and decreased expression of related proteins(ALDH2,SIRT1 and HO1).However,α-LA treatment significantly mitigated the decline in cell proliferation and the oxidative stress induced by alcohol.(2)Alcohol may induce cellular se-nescence,as demonstrated by the up-regulation of P53 expression,which were reversed by α-LA.(3)The H9c2 cells with high ALDH2 expression markedly improved the cell proliferation in the presence of alcohol,suppressed the ROS pro-duction,prevented the down-regulation of oxidative stress-related proteins(ALDH2,SIRT1 and HO1),and reversed the enhanced expression of the senescence marker P53.CONCLUSION:Treatment with α-LA may counteract oxidative stress and attenuate cellular senescence by activating ALDH2,thereby protecting cardiomyocytes from alcohol-induced damage.

To verify whether the two B-cell epitopes Pep1 and Pep4 in the FAdV-4 WZ fiber can be used as candidate epitopes for multivalent epitope vaccines,epitopes Pep1 and Pep4 were tandemly linked with the chicken infectious bronchitis virus strain M41 S1 protein gene in different patterns,and a recombinant fusion plasmid was constructed and expressed in E.coli BL21(DE3).It was confirmed by Western blot and ELISA tests that all four expressed fusion proteins reacted specific-ally with anti-M41 whole virus serum and WZ strain anti-Fiber 2-knob protein serum.After purifi-cation and immunization of BALB/c mice,specific antibodies against the peptide epitopes were de-tected in mouse sera.The results showed that the Pep4 epitope induced a stronger immune re-sponse than the Pep1 epitope.When Pep1 was connected with the amino and carboxyl termini of the fusion protein,respectively,both resulted in the production of the same level of anti-Pep1 anti-bodies in the immunized animals,whereas when Pep4 was connected with the carboxyl terminus of the fusion protein,the immunized animals produced a higher level of anti-Pep4-specific antibodies.This research indicates that the B cell epitopes Pep1 and Pep4 of the reactive WZ strain Fiber 2,when conjugated with proteins to form fusion proteins,can enhance the immunogenicity of Pep1 and Pep4 without affecting the antigenicity of the carrier protein.This study provides technical support and serves as a reference for the design and development of a multivalent epitope vaccine for FAdV-4.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.

To verify whether the two B-cell epitopes Pep1 and Pep4 in the FAdV-4 WZ fiber can be used as candidate epitopes for multivalent epitope vaccines,epitopes Pep1 and Pep4 were tandemly linked with the chicken infectious bronchitis virus strain M41 S1 protein gene in different patterns,and a recombinant fusion plasmid was constructed and expressed in E.coli BL21(DE3).It was confirmed by Western blot and ELISA tests that all four expressed fusion proteins reacted specific-ally with anti-M41 whole virus serum and WZ strain anti-Fiber 2-knob protein serum.After purifi-cation and immunization of BALB/c mice,specific antibodies against the peptide epitopes were de-tected in mouse sera.The results showed that the Pep4 epitope induced a stronger immune re-sponse than the Pep1 epitope.When Pep1 was connected with the amino and carboxyl termini of the fusion protein,respectively,both resulted in the production of the same level of anti-Pep1 anti-bodies in the immunized animals,whereas when Pep4 was connected with the carboxyl terminus of the fusion protein,the immunized animals produced a higher level of anti-Pep4-specific antibodies.This research indicates that the B cell epitopes Pep1 and Pep4 of the reactive WZ strain Fiber 2,when conjugated with proteins to form fusion proteins,can enhance the immunogenicity of Pep1 and Pep4 without affecting the antigenicity of the carrier protein.This study provides technical support and serves as a reference for the design and development of a multivalent epitope vaccine for FAdV-4.

Objective To investigate the efficacy and safety of spinal endoscopic decompression through 45° puncture foraminal approach in treatment of L5/S1 lumbar disc herniation(LDH).Methods Clinical data of 130 patients with L5/S1 level LDH from January 2021 to January 2023 were retrospectively analyzed.These patients were divided into two groups based on the spinal endoscopic surgery approach.Observation group(67 patients)underwent spinal endoscopic decompression via 45° puncture,while the control group(63 patients)underwent spinal endoscopic decompression using the traditional transforaminal endoscopic spinal system(TESSYS)technique.Perioperative indicators such as operation time,X-ray fluoroscopy time,and hospital stay were recorded for both groups.Visual analogue scale(VAS)scores for low back pain and lower limb pain,as well as the Oswestry disability index(ODI)were assessed before surgery and at 1 day,3 months,6 months,and 12 months after operation.The overall efficacy was evaluated using the modified MacNab criterion at 12 months postoperatively.Results All the patients in both groups successfully underwent spinal endoscopic decompression.The observation group had significantly shorter average operation time and intraoperative X-ray fluoroscopy time compared to the control group,the differences were statistically significant(P＜0.05).There was no significant difference in hospital stay between the two groups(P=0.505).Compared to preoperative values,both groups showed a significant decreasing trend in VAS scores for low back pain,lower limb pain,and ODI at 1 day,3 months,6 months,and 12 months after operation,the differences were statistically significant(P＜0.05).The observation group had significantly low back pain VAS score,lower limb pain VAS score and ODI at 1 day and 3 months after operation compared to the control group(P＜0.05).There were no statistically significant differences in low back pain VAS score,lower limb pain VAS score and ODI between the two groups 6 and 12 months after operation(P＞0.05).At 12 months after operation,the excellent and good rate was 95.5％ in observation group and 85.7％ in control group,with no significant difference between the two groups(P=0.054).No surgery-related complications occurred in either group.During postoperative follow-up,6 patients(9.5％)in control group experienced recurrence of low back pain and lower limb pain due to recompression of nerve roots by residual herniated material,while no recurrence was observed in observation group,the difference was statistically significant(P=0.035).Conclusion Both the 45° puncture technique and the traditional TESSYS technique can achieve satisfactory decompression effects in patients with LDH at the L5/S1 segment undergoing transforaminal spinal endoscopic decompression surgery.However,the 45° puncture technique can shorten the operation time and X-ray fluoroscopy time,resulting in more pronounced early postoperative improvement and a lower recurrence rate.It is worthy clinical application.

Objective:To explore the relationship between suicide attempts,school bullying,and psychological resilience in children and adolescents with major depressive disorder(MDD)and school bullying and psychological resilience.Methods:A total of 784 patients with MDD aged 10 to 18 years were included.The Chinese version of the Olweus Bullying Victimization Questionnaire,Adolescent Psychological Resilience Scale,and a suicide attempt assessment were utilized to evaluate school bullying,psychological resilience,and suicide attempt.Stepwise logistic regression was applied to identify the associated factors of suicide attempts.Results:The occurrence of suicide at-tempts in children and adolescents with MDD was positively associated with physical bullying(OR=1.85,95％CI:1.14-3.02)and indirect bullying(OR=1.48,95％CI:1.06-2.04),and negatively associated with higher levels of goal focus(OR=0.62,95％CI:0.45-0.85)and positive cognition(OR=0.62,95％CI:0.45-0.85)at higher levels.Conclusion:Bullying significantly increases the risk of suicide attempts in children and adolescents with MDD,while higher psychological resilience could mitigate this risk.