ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

Although global brain science research has progressed rapidly in recent decades, several fundamental questions in neuroscience remain unresolved. In particular, the physical mechanism underlying neural signal transmission remains controversial, and the carriers responsible for neural information storage and retrieval have not yet been fully clarified. These unresolved issues motivate us to re-examine the processes of neural information generation, transmission, integration, storage, and retrieval from multiple perspectives. A key observation is that neural electromagnetic activities are closely associated with time. Their duration, temporal structure, and dynamic evolution play crucial roles in neural information processing. In this work, we analyze neural electromagnetic activities from the perspective of temporal scales (referred to here as the “time course”). By reviewing and integrating findings from previous studies, we examine the characteristic time requirements and dynamic features of neural processes occurring at different stages of information processing. These stages include neural signal generation, signal transmission along axons, synaptic integration, synaptic plasticity, and memory formation and retrieval. Based on this temporal analysis, we outline a framework describing neural electromagnetic activities across a wide range of time scales, spanning from microseconds to minutes, hours, or even longer periods associated with long-term memory, which suggests that neural information processing involves multiple physical processes operating at different time levels. Rapid electromagnetic events may occur on microsecond scales, whereas electrophysiological phenomena such as action potentials typically last on the order of milliseconds. Longer time scales are associated with synaptic plasticity and memory-related processes. From this perspective, we propose that the physical carrier of neural information may be transient electromagnetic pulses with durations on the microsecond scale. In this framework, action potentials can be interpreted as the macroscopic electrophysiological manifestation of underlying electromagnetic processes triggered by ionic currents across neuronal membranes. Rather than being the fundamental neural signal itself, the action potential may represent a measurable membrane-level response associated with the successful activation of these electromagnetic events. Moreover, we discuss a possible mechanism for long-term memory storage. Considering the apparent temporal contradiction between the millisecond-scale excitation of neurons and the long-term persistence of memories, we believe that long-term memory information may be stored within neural network topologies formed by electrical synapse coupling. Such structures, referred to as electrically coupled memory networks (ECMNs), may enable neurons within the same network to respond rapidly and synchronously to stimuli, thereby facilitating efficient memory retrieval. Overall, this study emphasizes the importance of considering the temporal organization of neural electromagnetic activities when interpreting neural signaling mechanisms. It may provide new insights into the physical nature of neural information carriers and the mechanisms of memory storage and retrieval. Furthermore, highlighting the potential role of electromagnetic interactions in neural activity may contribute to the development of new theoretical frameworks and experimental approaches in neuroscience. Such perspectives may also offer valuable references for future research on neural coding, brain function mechanisms, and neuromodulation technologies.

ObjectiveTo investigate the effects of different doses of uncooked corn starch （UCCS）， type 2 resistant starch， on intestinal mucosal barrier function in mice and to explore the potentional underlying mechanisms. MethodsTwenty C57BL/6 mice were randomly assigned to four groups and fed either a standard diet （control group） or diets supplemented with low （188.8 g/kg）， medium （314.8 g/kg）， or high （440.6 g/kg） doses of UCCS for 8 weeks. Body weight and disease activity index （DAI） were monitored. At the endpoint， colon length was measured； histopathological changes in were assessed via HE staining. The expression of tight junction proteins （ZO-1， E-cadherin， and Villin） in the colonic mucosa were detected using immunofluorescence. Serum inflammatory cytokines （IL-6， TNF-α， IL-1β， MIP-1α/CCL3） and fecal calprotectin levels were measured by ELISA. Gut microbiota alterations were analyzed via 16S rRNA gene sequencing and PICRUSt2 functional prediction. ResultsCompared with the control group， UCCS intervention across all doses significantly shortened colon length （P=0.000 5） and increased colonic inflammation scores （P=0.013 3）. Immunofluorescence revealed a significantly reduction in the expression and co-localization of ZO-1 and Villin in the colonic mucosa （P＜0.05）. Systemic inflammation was evidenced by significantly elevated serum levels of IL-6 （P=0.006 4）， TNF-α （P=0.000 1）， IL-1β （P=0.001 4）， and MIP-1α/CCL3 （P＜0.000 1）. Fecal calprotectin levels were also significantly increased during the early phase （weeks 1-2， P＜0.05）. 16S rRNA sequencing showed that UCCS significantly altered the β-diversity of the gut microbiota （P＜0.05）， characterized by the enrichment of butyrate-producing Clostridia_UCG-014， and the opportunistic pathogen Desulfovibrio， alongside a decreased abundance of immunomodulatory genera Akkermansia and Dubosiella. PICRUSt2 analysis suggested that UCCS modulated metabolic pathways related to energy metabolism， glutathione metabolism， and sulfur cycling. ConclusionLong-term or high-dose intake of UCCS may disrupt gut microbiota homeostasis and trigger inflammation response， thereby damaging the intestinal mucosal barrier. These findings suggest that the clinical or dietary application of UCCS should be cautioned regarding dose-dependent risks of intestinal injury.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

AIM: To assess the clinical efficacy and safety of epithelial-off accelerated corneal collagen cross-linking(CXL)in the management of progressive keratoconus over 1 a period.METHODS:A retrospective pre-post self-controlled study. Data were collected from complete cases of 63 patients(84 eyes)with progressive keratoconus who underwent epithelial-off accelerated CXL between August 2018 and September 2021. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction, corneal transparency, maximum keratometry(Kmax)of the anterior corneal surface, minimum corneal thickness, endothelial cell counts, and intraocular pressure(IOP)were analyzed preoperatively and at 1, 3, 6, and 12 mo postoperatively.RESULTS:No significant differences were observed in UCVA and spherical power before and after surgery(all P>0.05). However, there were significant differences in BCVA, cylinder power, Kmax, minimum corneal thickness, and IOP(all P<0.05). At 12 mo postoperatively, there were no significant differences in BCVA, cylinder power, minimum corneal thickness, and IOP compared with preoperative values(all P>0.05), while Kmax was decreased compared with preoperative value(P<0.05). At 1 mo postoperatively, the corneal endothelial cell count(2519.87±345.28 cells/mm2)was decreased compared with preoperative value(2693.63±313.39 cells/mm2; P<0.001). At 1 wk postoperatively, 22 eyes developed corneal haze(grade 0.5 to 1), and 15 eyes presented with linear corneal stromal opacity at 1 mo postoperatively. In 7 eyes, corneal opacity subsided within 3 to 6 mo after the operation, however, 5 eyes still exhibited corneal nebula or macula without affecting visual acuity.CONCLUSION: After epithelial-off accelerated CXL, the UCVA, BCVA and spherical diopter of patients remained stable over time. The astigmatism and corneal curvature temporarily increased and then gradually decreased. The cornea minimum thickness decreased initially but subsequently returned to preoperative levels. The corneal curvature at 6 and 12 mo after surgery was significantly lower than that before surgery, which could effectively prevent the progression of keratoconus. Despite potential localized corneal opacity and macular complications, as well as a possible decrease in corneal endothelial cell count, BCVA remained unaffected, demonstrating favorable safety outcomes.

AIM: To assess the clinical efficacy and safety of epithelial-off accelerated corneal collagen cross-linking(CXL)in the management of progressive keratoconus over 1 a period.METHODS:A retrospective pre-post self-controlled study. Data were collected from complete cases of 63 patients(84 eyes)with progressive keratoconus who underwent epithelial-off accelerated CXL between August 2018 and September 2021. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction, corneal transparency, maximum keratometry(Kmax)of the anterior corneal surface, minimum corneal thickness, endothelial cell counts, and intraocular pressure(IOP)were analyzed preoperatively and at 1, 3, 6, and 12 mo postoperatively.RESULTS:No significant differences were observed in UCVA and spherical power before and after surgery(all P>0.05). However, there were significant differences in BCVA, cylinder power, Kmax, minimum corneal thickness, and IOP(all P<0.05). At 12 mo postoperatively, there were no significant differences in BCVA, cylinder power, minimum corneal thickness, and IOP compared with preoperative values(all P>0.05), while Kmax was decreased compared with preoperative value(P<0.05). At 1 mo postoperatively, the corneal endothelial cell count(2519.87±345.28 cells/mm2)was decreased compared with preoperative value(2693.63±313.39 cells/mm2; P<0.001). At 1 wk postoperatively, 22 eyes developed corneal haze(grade 0.5 to 1), and 15 eyes presented with linear corneal stromal opacity at 1 mo postoperatively. In 7 eyes, corneal opacity subsided within 3 to 6 mo after the operation, however, 5 eyes still exhibited corneal nebula or macula without affecting visual acuity.CONCLUSION: After epithelial-off accelerated CXL, the UCVA, BCVA and spherical diopter of patients remained stable over time. The astigmatism and corneal curvature temporarily increased and then gradually decreased. The cornea minimum thickness decreased initially but subsequently returned to preoperative levels. The corneal curvature at 6 and 12 mo after surgery was significantly lower than that before surgery, which could effectively prevent the progression of keratoconus. Despite potential localized corneal opacity and macular complications, as well as a possible decrease in corneal endothelial cell count, BCVA remained unaffected, demonstrating favorable safety outcomes.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.

OBJECTIVE To investigate the current status of monitoring indicators related to the"Perioperative In-fection Control"in medical institutions above the secondary level in Guizhou Province,and to delve into the imple-mentation of key measures for infection prevention and control during the perioperative period for patients under-going surgical operations.METHODS Based on the"Implementation Plan for the'Perioperative Infection Control'Initiative in Guizhou Province",a"Case Investigation Form on Key Measures for Infection Prevention and Control During the Perioperative Period for Patients Undergoing Surgical Operation"was developed.A total of 138 medi-cal institutions participated in the case investigation,and a total of 2 128 cases were investigated.RESULTS The overall monitoring indicators for the"Perioperative Infection Control"initiative in the 138 medical institutions a-bove the secondary level in Guizhou Province were at a relatively low level.The skin cleansing compliance rate was 80.32％,the hair removal compliance rate was 16.43％,the prophylactic antibacterial drug administration rate within 0.5-1 hour before surgery was 55.94％and the antibacterial drug discontinuation rate within 24 hours after prophylactic medication for type Ⅰ incision surgeries was 56.48％.The hair removal compliance rate was higher in tertiary medical institutions(19.21％)than in secondary medical institutions(14.34％)(P=0.039).The distri-bution of the four monitoring indicators varied in clinical departments and surgery types,with statistically signifi-cant differences(P＜0.05).The preferred method for surgical site skin cleansing in medical institutions across the province was local wiping,primarily with clean water(57.21％).The primary method for hair removal was razors(68.82％),and hair removal on the day of surgery was most common(61.75％).CONCLUSIONS Conduc-ting a survey on the current status of"Perioperative Infection Control"initiative monitoring indicators in medi-cal institutions in Guizhou Province helps to understand the implementation of key measures for perioperative in-fection prevention and control and set intervention targets,thus providing references for establishing a dynam-ic monitoring indicator change mechanism.

The aim of this study was to understand the internal genetic diversity and population history dynamics of ticks in Inner Mongolia,to provide data for designing effective vector control programs and revealing ticks'transmission mechanisms.From 2022 to 2023,the manual collection method was used to collect samples in Inner Mongolia.The 16S rDNA and COI gene sequences of ticks were used to identify Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus,and analyze the sequence characteristics and genetic diversity within the populations.Base composition analysis indicated that the average A+T content of the 16S rDNA gene and CO I gene in the three ticks was significantly higher than that of C+G.Moreover,22 haplotypes of the COI gene and 12 haplotypes of the 16S rDNA sequence were identified in Hyalomma marginatum.Eleven haplotypes were identified according to the COI gene,and nine haplotypes were identified according to the16S rDNA sequence of Haemaphysalis concinna.Two haplotypes were identified on the basis of the COI gene,and six haplotypes were identified on the basis of the 16S rDNA sequence of Ar gas persicus.The minimum 16S rDNA haplotype diversity was 0.264 for Ar gas persicus and 0.579 for the other two species.The nucleotide diversity of the three tick species was less than 0.05.Tajima's val-ue and Fu's Fs value of the neutrality test were negative.Base saturation substitution analysis indicated that neither of the two genes in the three tick species reached saturation.The phylogenetic tree revealed that Hyalomma marginatum,Haema physalis concinna,and Ar gas persicus in Inner Mongolia independently aggregated into branches.In conclusion,the base content of Hyalomma marginatum,Haemaphysalis concinna,and Argas persicus genes in Inner Mongolia was consist-ent with the characteristics of insect mitochondrial DNA content.Furthermore,the three tick populations showed rapid evolu-tionary population expansion,and the phylogeny of three tick species showed independent aggregation into clades,with no pop-ulation isolation.