Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Due to the immaturity of visualization and quantitative analysis methods,the utilization rate of level 3 characteristics is seriously insufficient.In this work,based on the wet-membrane method and scanning electrochemical microscopy(SECM),and the introduction of conductive black ink to enhance the visualization effect,a systematic level 3 feature quantitative method was developed.Firstly,the feasibility and effect of the multi-level characteristics extraction strategy of latent fingerprints was investigated.Then,the influences of various deposition conditions on the level 3 features were explored.The results showed that the higher the deposition pressure,the wider the ridges,and the smaller the pore size.Moreover,excessive oil content could cause the pore size to be smaller and even been covered.Subsequently,the quantitative method was established from various pore characteristics such as pore number,pore activity,pore size,pore-to-pore distance and pore-to-pore angle.The stability of the level 3 features(pore number,pore-to-pore distance and pore-to-pore angle)was confirmed via repeated experiments on the same fingerprint region.After stability test,the recognition ability of three indicators was investigated for different fingerprints,verifying the uniqueness of pore-to-pore distance and pore-to-pore angle.Finally,a multiple recognition strategy was proposed that combined frequency distribution fitting curves for pore-to-pore distance and angle with other level 3 details,and was successfully applied to incomplete fingerprint recognition.This ink-enhanced optical and electrochemical extraction method and quantitative analysis provided a new path for fingerprint recognition.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Introducing fingerprint level 3 features(especially sweat pores)in fingerprint recognition can significantly improve the value of fingerprints.However,conventional fingerprint visualization methods suffer from issues such as poor stability and reproducibility,insufficient resolution,and feature masking in detecting level 3 features.Electrospun membrane has unique advantages in latent fingerprint(LFP)detection due to its excellent adsorption performance and high specific surface area,and thus its application potential in LFP visualization urgently need to be explored.A novel pore visualization method based on core-shell structured PAN-Flu/PVP composite nanofibrous membrane was proposed in this work.Specifically,the PAN-Flu/PVP composite nanofibrous membrane was prepared via coaxial electrospinning technology,with polyacrylonitrile(PAN)loaded with fluorescein(Flu)as the core and polyvinylpyrrolidone(PVP)as the shell.The experimental results showed that the prepared PAN Flu/PVP composite nanofibrous membrane had a porous structure and excellent adsorption performance.Based on the water solubility of the outer shell PVP and the water induced fluorescence enhancement effect of the core Flu,high-resolution visualization of sweat pores could be achieved within 2 s.The optimization experiment showed that the best quality of sweat latent fingerprints was obtained when the Flu content was 4 mg/mL,the spinning time was 1 h,and the sweating time was 2 min.Through repeated fingerprinting and live fingerprint comparison experiment,the strong stability and high reproducibility of the as-produced membrane in displaying fingerprint sweat pores were finally verified.In summary,the development method could quickly,stably and accurately extract the spatial distribution and activity level of fingerprint sweat pores,which was of great significance for improving the utilization and value of fingerprints.

Aim To explore the mechanism by which dioscin regulates IL-17+γδT cells in the treatment of arthritis.Methods A collagen-induced arthritis(CIA)model was established in DBA/1 mice using bovine type Ⅱ collagen.The mice were randomly divid-ed into the CIA model group,methotrexate(MTX)positive control group,and dioscin low-dose(Dioscin-L),medium-dose(Dioscin-M),and high-dose(Dios-cin-H)groups.After intervention,the therapeutic effects were evaluated using scoring methods.Joint pathological damage was analyzed by hematoxylin and eosin(HE)staining.The levels of anti-collagen-spe-cific antibodies and the pro-inflammatory cytokine IL-17 were measured by ELISA.The expressions of γδT cells and their subtypes,as well as the secretion level of IL-17,were detected by flow cytometry.Results Dioscin significantly reduced the arthritis severity score in collagen-induced arthritis(CIA)mice,alleviated joint pathological damage,inhibited the production of IL-17 by splenic lymphocytes and the levels of anti-col-lagen-specific antibodies total IgG and IgG3,and de-creased the proportion of γδT cells in the lymph nodes,splenic γδT cells,and the Vδ4+T-cell subset.The level of IL-17 produced by the Vδ4 subtype in the lymph nodes of the intervention groups was lower than that in the model group,but the difference was not sta-tistically significant.Conclusion Dioscin has signifi-cant therapeutic effect on CIA,and its mechanism may be through the inhibition of γδT cells,but it is unlikely to be related to IL-17 derived from γδT cells.

Aim To generate a dual-reporter mouse model for tracing microglia and neurons to analyze their dynamic changes in real-time and to investigate the functional role of microglia-neuron interactions through microglial depletion.Methods Mi-croglia reporter mice were crossed with neuron reporter mice to generate Tmem119-e(2A-tdTomato-2A-DTR);Thy1-GFP dual-reporter mice.Genotyping was performed using tail DNA.Con-focal and two-photon microscopy were used to examine neuronal morphology.In vivo two-photon imaging was employed to observe the distribution of microglia and neurons in the brain.Diphtheria toxin(DT)was intraperitoneally injected to deplete microglia.Results The dual-reporter mice were successfully generated with the correct genotype.Both microglia and neurons were visu-alized,and microglia were specifically depleted by DT.Conclu-sions The successful establishment of a dual-reporter mouse model for tracing neurons and microglia will facilitate real-time in vivo observation of microglial and neuronal changes under physiological or pathological conditions,elucidating their specific roles in brain homeostasis.

Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyop-athy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg-1·d-1)and control group(n=20,Saline 100 mg·kg-1·d-1).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-dias-tolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis in-dex,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)％vs.(36.9±3.2)％],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P＜0.05 or＜0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)％vs.(45.1±0.9)％]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P＜0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.

Objective:To evaluate the safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) in the treatment of recurrent and refractory malignant tumors.Methods:The data of 14 patients admitted to Xiamen Humanity Hospital from September 2022 to April 2023 were prospectively collected, including 7 patients with primary brain malignancies and 7 patients with locally recurrent inoperable head and neck malignancies. All patients received intravenous infusion of boron drug (NBB-001, p-dihydroxyborylphe nylalanine, a patented freeze-dried formulation) at a total nominal dosage of 500 mg/kg (11 patients) or 750 mg/kg (3 patients), and were irradiated with neutrons (operating with NeuPex system). Adverse events after treatment were recorded and assessed. The primary efficacy endpoint was the 90 d objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS) and complete response rate (CRR). Data were compiled and analyzed by SAS 9.4 software. The rate and 95% CI were calculated using Clopper-Pearson method. Results:The median dose delivered to 80% of the target volume (D 80%) was 16.80 GyE (range: 8.93-23.79 GyE). The most common adverse reactions were hyperamylasemia, alopecia, and hyperprolactinemia. Five patients experienced 8 cases of grade 3 or above adverse events, including 1 case of grade 4 acute kidney injury and 7 cases of grade 3 adverse events. All adverse events were recovered after observation or treatment. At 90 d after treatment, the ORR of all patients was 9/14 (64%, 95% CI: 35%-87%), disease control rate (DCR) was 10/14 (71%, 95% CI: 42%-92%), CRR was 2/14 (14%, 95% CI: 2%-42%); and the best overall response during the entire course included an ORR of 10/14 (71% ,95% CI: 42%-92%), DCR of 13/14 (93%, 95% CI: 66%-100%), and CRR of 3/14 (21% ,95% CI: 5%-51%). The 1-year survival rate for head and neck malignancies was 71.4%, and the 2-year survival rate was 42.8%. The 1-year survival rate for recurrent brain malignancies was 42.8%. Conclusion:AB-BNCT demonstrates favorable safety and promising efficacy in treating primary brain malignancies and recurrent/refractory head and neck malignancies, representing a potential therapeutic option.