The original version of this article (Yang et al., 2023) unfortunately contained a mistake. In Acknowledgments, the funding information for the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H160001) was wrong. The correct funding should be the Zhejiang Health Science and Technology Project (No. 2022KY682), China.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Objective To observe the effects of Qingdu Decoction on intestinal barrier function by regulating the miR-34c-mediated signaling pathway of human mast cells-derived exosomes;To explore its molecular mechanism in the treatment of acute-on-chronic liver failure(ACLF).Methods An inflammatory model was established by treating human mast cells with 1 μg/mL lipopolysaccharide.The mast cells were over-expressed with miR-34c using lentiviral transfection,and were divided into normal group,model group and miR-34c over-expression group.Exosomes were extracted from each group of mast cells.Human intestinal epithelial cells were divided into normal group,normal exosome group,model exosome group,miR-34c over-expression exosome group and Qingdu Decoction group(miR-34c overexpression exosomes+Qingdu Decoction),and corresponding treatment was given.The dual luciferase gene report confirmed the targeting relationship between miR-34c and myeloma associated oncogene zinc finger protein(MAZ).RT-qPCR was used to detect the expression of miR-34c in mast cells and intestinal epithelial cells,and Western blot was used to detect the expressions of MAZ,Occludin and ZO-1 protein.Results Compared with the normal group,the expression of miR-34c in mast cells treated with lipopolysaccharide and transfected with lentivirus significantly increased(P<0.01).The results of the dual luciferase reporter gene experiment showed that miR-34c could target and inhibit MAZ expression.The RT-qPCR results showed that compared with the normal group,the miR-34c expression in intestinal epithelial cells significantly increased in the model exosome group and miR-34c over-expression exosome group(P<0.05,P<0.01),while the miR-34c expression in Qingdu Decoction group significantly decreased compared with the miR-34c over-expression exosome group(P<0.01).The Western blot results showed that compared with the normal group,the expressions of MAZ,Occludin and ZO-1 proteins in the model exosome group and miR-34c over-expressing exosome group were significantly reduced(P<0.05,P<0.01),while the expressions of MAZ,Occludin and ZO-1 proteins in Qingdu Decoction group significantly increased compared with the miR-34c over-expressing exosome group(P<0.05).Conclusion The treatment of ACLF with Qingdu Decoction may be related to the regulation of the miR-34c-mediated signaling pathway in mast cell-derived exosomes and the up-regulation of intestinal epithelial tight junction protein expression.

Investigated the mechanisms by which baicalein regulates nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)to ameliorate lipopolysaccharide(LPS)-induced sepsis-asso-ciated acute kidney injury(AKI)in mice.Sixty male C57BL/6 mice were randomly divided into six groups:control,model,low-dose baicalein(50 mg/kg),medium-dose baicalein(100 mg/kg),high-dose baicalein(200 mg/kg),and high-dose baicalein+brusatol(4 mg/kg).Baicalein was adminis-tered orally for 7 days as a preventative measure.Sepsis was induced via intraperitoneal injection of LPS.Murine sepsis score(MSS)was assessed within 12 hours post-induction.Serum creatinine(Scr),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6)were measured using an automatic biochemical analyzer and enzyme-linked immunosorbent assays(ELISA),respectively.Histopathological changes in kidney tissues were ob-served via hematoxylin-eosin(HE)staining.Western blot analysis was employed to determine the protein expression levels of Nrf2,HO-1,caspase-8,TNF-α,IL-1β,and IL-6 in kidney tissues.Additionally,total superoxide dismutase(SOD)activity in kidney tissues was assessed using com-mercially available kits.Compared to the model group,baicalein treatment significantly improved renal histopathological changes,alleviated cellular damage,and reduced the levels of inflammatory cytokines(TNF-α,IL-1βand IL-6)(P＜0.01)and kidney injury markers(Scr and BUN)(P＜0.01).Moreover,baicalein treatment significantly increased the protein expression levels of Nrf2 and HO-1(P＜0.01)and enhanced antioxidant enzyme activity.In conclusion,baicalein may pro-tect against LPS-induced sepsis-associated AK1 in mice by modulating the Nrf2/HO-1 signaling pathway,thereby attenuating oxidative stress,reducing inflammation,and disrupting the vicious cycle between inflammation and oxidative stress.

Objective: To explore the association between negative life events and smartphone addiction among middle school students, so as to provide theoretical support and practical guidance for prevention and intervention of smartphone addiction among middle school students. Methods: Using cluster sampling, 8 890 students were selected to survey from 27 junior high schools and 3 senior high schools in a district of Shenzhen in 2022 (baseline) and 2023 (followup). Data were collected through selfresigned questionnaires on basic information, the Smartphone Addiction Scale-Short Version, and the Adolescent Selfrating Life Events Checklist. Mixedeffects models were employed to analyze the association. Results: Compared to 2022, the punishment scores of middle school students in 2023 [1.00 (0.00, 6.00) and 1.00 (0.00, 6.00)] decreased (Z=4.27), while the scores of interpersonal stress, learning stress and adaptation [4.00(0.00, 8.00), 4.00(0.00, 8.00); 4.00(1.00, 8.00), 5.00(2.00, 9.00); 2.00 (0.00, 6.00), 3.00 (0.00, 7.00)] increased (Z=-3.04, -8.36, -6.80) (P<0.01). Mixedeffects models revealed a positive doseresponse relationship between negative life events and smartphone addiction (OR=1.08-1.17, P<0.01). Stepwise regression showed independent positive effects of interpersonal stress (OR=1.05), academic stress (OR=1.03), and adaptation stress (OR=1.11) on smartphone addiction (P<0.01). Subgroup analysis of nonaddicted students in 2022 confirmed persistent associations for academic stress (OR=1.03) and adaptation (OR=1.07) (P<0.01). Conclusion Negative life events exhibit a positive doseresponse relationship with smartphone addiction, particularly interpersonal stress, academic stress, and adaptationrelated events.

Objective: To explore the longitudinal association between only-child status and smartphone addiction among middle school students, so as to provide a basis for establishing family intervention measures for smartphone addiction in middle school students. Methods: In October 2022 and October 2023, a preliminary survey and follow-up were conducted among 8 759 middle and high school students from 30 schools in a district of Shenzhen. A self-designed questionnaire was used to determine whether the students were the only-child, and the Chinese Version of the Smartphone Addiction Scale-Short Version (C-SAS-SV) was utilized to assess the students smartphone addiction status. A multilevel mixed-effects model and subgroup analysis were applied to examine the association between only-child status and smartphone addiction among middle school students. Results: During 2022 to 2023, the prevalence of smartphone addiction in the cohort of middle school students increased from 24.1% to 25.2%. Compared with only-child, non-only child were more likely to be addicted to smartphones (adjusted model: OR =1.2, 95% CI =1.1-1.4) and also scored higher on smartphone addiction (adjusted model: β =0.9, 95% CI =0.2-1.5)( P <0.05). Subgroup analysis further revealed that compared to baseline, non-only child demonstrated an increased prevalence of smartphone addiction (adjusted model: OR = 1.2 , 95% CI =1.0-1.5) and higher addiction scores (adjusted model: β =0.8, 95% CI =0.2-1.5) after one year( P <0.05). Conclusions Non-only child face higher risk of smartphone addiction. Under the current population policy, it is crucial to address smartphone addiction among middle school students who is not only child.

Objective: To explore the potential causal association between adolescent compulsive behaviour and smartphone addiction based on longitudinal data, so as to provide reference for the establishment of adolescent smartphone addiction interventions. Methods: A preliminary survey and follow-up were conducted on 8 907 middle and high school students in a district of Shenzhen in 2022 and 2023, respectively. Compulsive behaviours were measured by using the Mental Health Inventory for Middle School Students-60 Items (MMHI-60), smartphone addiction was assessed by using the Smartphone Addiction Scale-Short Version ( SAS- SV), and the associations between compulsive behaviours and smartphone addiction were analysed by using multilevel mixed-effects models and subgroup analyses. Results: Smartphone addiction detection rates among middle school students were significantly associated with genders, father s education level, mother s education level, study load subgroups, and whether or not they were single-parent families, and there were statistical differences ( χ 2=17.21-175.34, P <0.05). Students with compulsive behaviours were 2.98 times more likely to develop smartphone addiction than those without compulsive behaviours ( OR=2.98, 95%CI=2.77-3.22, P <0.05). Subgroup analysis of middle school students without smartphone addiction in the first year found that compulsive behaviours significantly predicted smartphone addiction ( OR= 1.76 , 95%CI=1.54-2.01, P <0.05). Conclusion There is a potential causal association between obsessive-compulsive behaviours and smartphone addiction in middle school students, and obsessive-compulsive behaviours in middle school students could significantly predicted the occurrence of smartphone addiction.

Objective:To investigate the application of time series models in forecasting pre-hospital emergency ambulance trips in Handan City and develop the LPro ensemble model for improved prediction accuracy to support emergency resource allocation.Methods:Pre-hospital emergency data from Handan Emergency Medical Command Center (2019-2023) were retrospectively analyzed. From 324 799 original records, 289 949 valid records were included after cleaning. The training set (2019-2022: 215 918 records) included 35 527 records in 2019, 52 015 in 2020, 61 836 in 2021, and 66 540 in 2022. The validation set (2023) contained 74 031 records. ARIMA, linear trend seasonal, exponential smoothing, and Prophet models were fitted to the training set. The LPro ensemble model was constructed using MAPE-based weighting (linear trend seasonal model: 0.38, Prophet: 0.62). Performance metrics included MAPE, RMSE, MAE, and R 2. Results:Data showed annual growth (compound annual growth rate 23.27%) and seasonal patterns (October peaks, February troughs). Ambulance dispatches increased annually with monthly cyclical patterns. For 2023 validation predictions: ARIMA (MAPE 8.76%, RMSE 619, MAE 491, R 2 0.4563), linear trend seasonal (MAPE 9.83%, RMSE 671, MAE 545, R 2 0.3608), Prophet (MAPE 8.43%, RMSE 562, MAE 503, R 2 0.5513), exponential smoothing (MAPE 8.08%, RMSE 643, MAE 410, R 2 0.4124). LPro model showed superior performance (MAPE 7.05%, RMSE 491, MAE 393, R 2 0.6570), with 16.37% lower MAPE, 12.63% lower RMSE, 21.87% lower MAE, and 19.17% higher R 2 versus Prophet. Conclusion:The LPro ensemble model substantially enhances prediction accuracy and reliability, offering scientific support for emergency resource optimization and dispatch scheduling in Handan City.

MicroRNA(miRNA)serves as a novel regulatory factor in viral and bacterial co-infections,exhibiting dual regulatory roles during pathogen infections.On the one hand,it exerts protective effects by modulating viral replication cycles and host anti-infection immune responses.On the other hand,it can be exploited by pathogens to promote infection progression,including influencing viral replication,antiviral immune responses,and regulating bacterial adhesion and proliferation.Mixed viral and bacterial infections lead to high mortality rates.By binding to specific target gene mRNA,miRNA degrades or inhibits its translation,thereby regulating target gene expres-sion,which may ultimately serve as potential diagnostic and therapeutic targets.This paper reviews recent ad-vances in research on the role of miRNA in viral and bacterial infections,particularly its mechanisms in co-infec-tions,aiming to provide theoretical reference for further research on the infection mechanisms.

BACKGROUND:In recent years,it has been found that physical interventions play a significant role in influencing proliferation,differentiation,and migration of bone marrow mesenchymal stem cells.However,the current physical intervention still exists such as basic research data to be strengthened,unified parameter standards need to be further improved and other shortcomings.OBJECTIVE:To review the effects of physical interventions on the differentiation of bone marrow mesenchymal stem cells.METHODS:PubMed and CNKI databases were searched for relevant articles using"bone marrow mesenchymal stem cells(BMSC),bone marrow stromal cells,osteogenesis differentiation,chondrocytes differentiation,electrical stimulation,mechanical stimulation,hypoxia,electromagnetic fields,low intensity pulsed ultrasound"as English and Chinese search terms.A total of 58 articles were selected for review.RESULTS AND CONCLUSION:(1)Physical interventions have been applied to regulate the proliferation and differentiation of bone marrow mesenchymal stem cells by altering specific microenvironments,but the parameters have not yet been unified.The future investigation should further optimize and explore the best parameters and conditions of action of the relevant physical factors on the role of bone marrow mesenchymal stem cell proliferation and differentiation.(2)It is difficult to carry out the application of certain special physical environmental conditions through low-cost conventional means,pending subsequent research and development to further reduce the difficulty of constructing special physical conditions.(3)The use of physical factors to rationally intervene in differentiation and proliferation of bone marrow mesenchymal stem cells has not yet been widely applied in the clinic,and further research is needed to promote clinical translation in the future.