Realm of hepatitis E: Challenges and opportunities.

Hepatitis E virus (HEV), responsible for widespread viral hepatitis, infects approximately 2.3 billion individuals globally, with a significant mortality burden in Asia. The virus, primarily transmitted through contaminated water and undercooked meat, is often underdiagnosed, particularly in immunocompromised patients. Current HEV treatments, while effective, are limited by adverse effects, necessitating research into safer alternatives. Moreover, HEV's extrahepatic manifestations, impacting the nervous and renal systems, remain poorly understood. This study underscores the imperative for enhanced HEV research, improved diagnostic methods, and more effective treatments, coupled with increased public health awareness and preventive strategies.

Inverse design of mid-infrared diamond waveguide beam splitter.

Diamond is a supreme material for mid-infrared (MIR) integrated photonics as it has a transparency window up to 20 µm that covers the entire fingerprint region. However, its relatively low refractive index poses a challenge in designing an MIR diamond functional device with both small footprint and high transmission efficiency. Here we propose and demonstrate the inverse design of an MIR diamond waveguide beam splitter operating at the wavelength of 15 µm with a small footprint of ∼15 µm × âˆ¼15 µm and a total transmission efficiency above 95%. Our work paves a new avenue for the design of compact and high-efficiency MIR diamond photonic devices.

Clinical analysis of the effect of helicobacter pylori infection on immune function in children with peptic ulcer.

Objective: To study whether children with peptic ulcer would have abnormalities in cellular and humoral immune functions, and whether Helicobacter pylori (Hp) infection would affect the immune function of children with peptic ulcer. Methods: This is a retrospective study. The subjects of study were 72 children with diagnosed and cured peptic ulcer (ulcer group), and 50 healthy children with physical examination (control group) at Baoding Hospital, Beijing Children's Hospital Affiliated to Capital Medical University from June 2020 to December 2022. Further detection was conducted on T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+ ratio) and immunoglobulin levels. Results: Of the 72 children with peptic ulcer, 53(73.6%) were positive for Hp (Hp-positive group) and 19 (26.4%) were negative (Hp-negative group). The levels of CD3+, CD4+, and CD4+/CD8+ ratio in the control group were significantly higher than those in the ulcer group, with statistically significant difference (P<0.05); while the level of IgG in the control group was lower than that in the ulcer group, with statistically significant difference (P<0.05). Meanwhile, there were statistically significant differences in that the levels of CD3+, CD4+ and CD8+ were increased in Hp-positive group than those in Hp-negative group before treatment (P<0.05); while CD4+/CD8+ ratio was lower in the former group than that in the latter group, with statistically significant difference (P<0.05). Conclusion: Hp infection can induce the elevation of T lymphocyte subsets. The development of peptic ulcer has an intimate association with the disorder of cellular and humoral immune functions.

The role of Phafin proteins in cell signaling pathways and diseases.

Membrane-associated proteins are important membrane readers that mediate and facilitate the signaling and trafficking pathways in eukaryotic membrane-bound compartments. The protein members in the Phafin family are membrane readers containing two phosphoinositide recognition domains: the Pleckstrin Homology domain and the FYVE (Fab1, YOTB, Vac1, and early endosome antigen 1) domain. Phafin proteins, categorized into two subfamilies, Phafin1 and Phafin2, associate with cellular membranes through interactions involving membrane-embedded phosphoinositides and phosphoinositide-binding domains. These membrane-associated Phafin proteins play pivotal roles by recruiting binding partners and forming complexes, which contribute significantly to apoptotic, autophagic, and macropinocytotic pathways. Elevated expression levels of Phafin1 and Phafin2 are observed in various cancers. A recent study highlights a significant increase in Phafin1 protein levels in the lungs of idiopathic pulmonary fibrosis patients compared to normal subjects, suggesting a crucial role for Phafin1 in the pathogenesis of pulmonary fibrosis. Additionally, phosphatidylinositol-3-phosphate-binding 2 (Pib2), a close relative of the Phafin1 protein, functions as an amino acid sensor activating the TOCR1 pathway in yeasts. This review focuses on delineating the involvement of Phafin proteins in cellular signaling and their implications in diseases and briefly discusses the latest research findings concerning Pib2.

Sources and control of impurity during one-pot enzymatic production of dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA) has a promising market due to its capacity to regulate human hormone levels as well as preventing and treating various diseases. We have established a chemical esterification coupled biocatalytic-based scheme by lipase-catalyzed 4-androstene-3,17-dione (4-AD) hydrolysis to obtain the intermediate product 5-androstene-3,17-dione (5-AD), which was then asymmetrically reduced by a ketoreductase from Sphingomonas wittichii (SwiKR). Co-enzyme required for KR is regenerated by a glucose dehydrogenase (GDH) from Bacillus subtilis. This scheme is more environmentally friendly and more efficient than the current DHEA synthesis pathway. However, a significant amount of 4-AD as by-product was detected during the catalytic process. Focused on the control of by-products, we investigated the source of 4-AD and identified that it is mainly derived from the isomerization activity of SwiKR and GDH. Increasing the proportion of glucose in the catalytic system as well as optimizing the catalytic conditions drastically reduced 4-AD from 24.7 to 6.5% of total substrate amount, and the final yield of DHEA achieved 40.1 g/L. Furthermore, this is the first time that both SwiKR and GDH have been proved to be promiscuous enzymes with dehydrogenase and ketosteroid isomerase (KSI) activities, expanding knowledge of the substrate diversity of the short-chain dehydrogenase family enzymes. KEY POINTS: • A strategy of coupling lipase, ketoreductase, and glucose dehydrogenase in producing DHEA from 4-AD • Both SwiKR and GDH are identified with ketosteroid isomerase activity. • Development of catalytic strategy to control by-product and achieve highly selective DHEA production.

Classification of brain tumor types through MRIs using parallel CNNs and firefly optimization.

Image segmentation is a critical and challenging endeavor in the field of medicine. A magnetic resonance imaging (MRI) scan is a helpful method for locating any abnormal brain tissue these days. It is a difficult undertaking for radiologists to diagnose and classify the tumor from several pictures. This work develops an intelligent method for accurately identifying brain tumors. This research investigates the identification of brain tumor types from MRI data using convolutional neural networks and optimization strategies. Two novel approaches are presented: the first is a novel segmentation technique based on firefly optimization (FFO) that assesses segmentation quality based on many parameters, and the other is a combination of two types of convolutional neural networks to categorize tumor traits and identify the kind of tumor. These upgrades are intended to raise the general efficacy of the MRI scan technique and increase identification accuracy. Using MRI scans from BBRATS2018, the testing is carried out, and the suggested approach has shown improved performance with an average accuracy of 98.6%.

Methylisothiazolinone pollution inhibited root stem cells and regeneration through auxin transport modification in Arabidopsis thaliana.

Methylisothiazolinone (MIT) is a widely used preservative and biocide to prevent product degradation, yet its potential impact on plant growth remains poorly understood. In this study, we investigated MIT's toxic effects on Arabidopsis thaliana root growth. Exposure to MIT significantly inhibited Arabidopsis root growth, associated with reduced root meristem size and root meristem cell numbers. We explored the polar auxin transport pathway and stem cell regulation as key factors in root meristem function. Our findings demonstrated that MIT suppressed the expression of the auxin efflux carrier PIN1 and major root stem cell regulators (PLT1, PLT2, SHR, and SCR). Additionally, MIT hindered root regeneration by downregulating the quiescent center (QC) marker WOX5. Transcriptome analysis revealed MIT-induced alterations in gene expression related to oxidative stress, with physiological experiments confirming elevated reactive oxygen species (ROS) levels and increased cell death in root tips at concentrations exceeding 50 µM. In summary, this study provides critical insights into MIT's toxicity on plant root development and regeneration, primarily linked to modifications in polar auxin transport and downregulation of genes associated with root stem cell regulation.

Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway.

Introduction: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods: C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results: Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion: Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut-liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

High-entropy selenides derived from Prussian blue analogues as electrode materials for sodium-ion batteries.

Transition metal selenides (TMS) have received much attention as anode materials for sodium-ion batteries (SIBs) because of their high theoretical capacity and excellent redox reversibility. However, their further development is constrained by the dissolution of transition metal ions and substantial volume changes experienced during cycling. Herein, the high-entropy Prussian blue analogues were selenized by the vapor infiltration method, resulting in the formation of a core-shell structured high-entropy selenides (HESe-6). The core-shell structure with voids and abundant selenium vacancies on the surface effectively mitigates bulk expansion and enhances electronic conductivity. Furthermore, the high-entropy property endows an ultra-stable crystal structure and inhibits the dissolution of metal ions. The ex-situ EIS and in-situ XRD results show that HESe-6 is able to be reversibly transformed into highly conductive ultrafine metal particles upon Na+ embedding, providing more Na+ reactive active sites. In addition, despite the incorporation of up to seven different elements, it exhibits minimal phase transitions during discharge/charge cycles, effectively mitigating stress accumulation. HESe-6 could retain an ultralong-term stability of 765.83 mAh g-1 after 1000 loops even at 1 A g-1. Furthermore, when coupled with the Na3V2(PO4)2O2F cathode, it maintains a satisfactory charge energy density of 303 Wh kg-1 after 300 cycles, which shows promising application prospect in the future.

New insights into membrane fouling in coagulation-ultrafiltration by cake characteristics analysis: A case study with PACl-Al13 and PACl.

Membrane fouling is a bottleneck issue that hindered the further application of ultrafiltration technology. To alleviate membrane fouling, coagulation-ultrafiltration (C-UF) process using polyaluminum chloride (PACl) and PACl-Al13 with high proportion of Al13O4(OH)247+ as coagulants, respectively, were investigated at various pH conditions. Results indicated that an increase in solution pH contributed to larger floc size and looser floc structure for both PACl and PACl-Al13. It was conducive to the formation of more porous cake, as evidenced by mean pore area and pore area distribution of cake, leading to lower reversible fouling. Furthermore, humic acid (HA) removal presented a trend of first increasing and then decreasing with the increase of pH. The optimal HA removal was achieved at pH 6 regardless of coagulant type, suggesting that the slightest irreversible fouling should be occurred at this point. Interestingly, the irreversible fouling with PACl coagulant achieved a minimum value at pH 9, while the minimal irreversible fouling with PACl-Al13 was observed at pH 6. We speculated that the cake formed by PACl could further intercept HA prior to UF process at alkaline pH. Furthermore, compared with PACl, PACl-Al13 had a stronger charge neutralization ability, thus contributing to more compact floc structure and higher HA removal at various pH conditions. By UF fractionation measurement, higher HA removal for PACl-Al13 was due to higher removal of HA with molecular weight less than 50 kDa.

Disproportionality Analysis of Nusinersen in the Food and Drug Administration Adverse Event Reporting System: A Real-World Postmarketing Pharmacovigilance Assessment.

BACKGROUND: Nusinersen is the first drug for precise targeted therapy of spinal muscular atrophy, a rare disease that occurs in one of 10,000 to 20,000 live births. Therefore, thorough and comprehensive reports on the safety of nusinersen in large, real-world populations are necessary. This study aimed to mine the adverse event (AE) signals related to nusinersen through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: We extracted reports of AEs with nusinersen as the primary suspect from FAERS between December 2016 and March 2023. Reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) were used for AE signal detection. RESULTS: We extracted a total of 4807 suspected AE cases with nusinersen as the primary suspect from the FAERS database. Among them, 106 positive signals were obtained using the ROR and BCPNN. The highest frequency reported systemic organ class was general disorders and administration site conditions. Common clinical AEs of nusinersen were detected in the FAERS database, such as pneumonia, vomiting, back pain, headache, pyrexia, and post-lumbar puncture syndrome. In addition, we identified potential unexpected serious AEs through disproportionality analysis, including sepsis, seizure, epilepsy, brain injury, cardiorespiratory arrest, and cardiac arrest. CONCLUSIONS: Analyzing large amounts of real-world data from the FAERS database, we identified potential new AEs of nusinersen by disproportionate analysis. It is advantageous for health care professionals and pharmacists to concentrate on effectively managing high-risk AEs of nusinersen, improve medication levels in clinical settings, and uphold patient medication safety.

Huangqin Qingre Chubi Capsule inhibits rheumatoid arthritis by regulating intestinal flora and improving intestinal barrier.

Background: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified. Materials and methods: In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA. Results: Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1ß and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology. Conclusion: The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA's new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

OBJECTIVE: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test. METHODS: Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48 months; 19 demonstrated typical development, mean age: 61.16 ± 8.11 months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval. RESULTS: The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors. CONCLUSIONS: This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis.

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Memory inflation: Beyond the acute phase of viral infection.

Memory inflation is confirmed as the most commonly dysregulation of host immunity with antigen-independent manner in mammals after viral infection. By generating large numbers of effector/memory and terminal differentiated effector memory CD8+ T cells with diminished naïve subsets, memory inflation is believed to play critical roles in connecting the viral infection and the onset of multiple diseases. Here, we reviewed the current understanding of memory inflated CD8+ T cells in their distinct phenotypic features that different from exhausted subsets; the intrinsic and extrinsic roles in regulating the formation of memory inflation; and the key proteins in maintaining the expansion and proliferation of inflationary populations. More importantly, based on the evidences from both clinic and animal models, we summarized the potential mechanisms of memory inflation to trigger autoimmune neuropathies, such as Guillain-Barré syndrome and multiple sclerosis; the correlations of memory inflation between tumorigenesis and resistance of tumour immunotherapies; as well as the effects of memory inflation to facilitate vascular disease progression. To sum up, better understanding of memory inflation could provide us an opportunity to beyond the acute phase of viral infection, and shed a light on the long-term influences of CD8+ T cell heterogeneity in dampen host immune homeostasis.

Genetics of causal relationships between circulating inflammatory proteins and postherpetic neuralgia: a bidirectional Mendelian randomization study.

Objective: According to data from several observational studies, there is a strong association between circulating inflammatory cytokines and postherpetic neuralgia (PHN), but it is not clear whether this association is causal or confounding; therefore, the main aim of the present study was to analyze whether circulating inflammatory proteins have a bidirectional relationship with PHN at the genetic inheritance level using a Mendelian randomization (MR) study. Methods: The Genome-Wide Association Study (GWAS) database was used for our analysis. We gathered data on inflammation-related genetic variation from three GWASs of human cytokines. These proteins included 91 circulating inflammatory proteins, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein 1b (MIP-1b), and CXC chemokine 13 (CXCL13). The PHN dataset was obtained from the FinnGen biobank analysis round 5, and consisted of 1,413 cases and 275,212 controls. We conducted a two-sample bidirectional MR study using the TwoSampleMR and MRPRESSO R packages (version R.4.3.1). Our main analytical method was inverse variance weighting (IVW), and we performed sensitivity analyses to assess heterogeneity and pleiotropy, as well as the potential influence of individual SNPs, to validate our findings. Results: According to our forward analysis, five circulating inflammatory proteins were causally associated with the development of PHN: interleukin (IL)-18 was positively associated with PHN, and IL-13, fibroblast growth factor 19 (FGF-19), MIP-1b, and stem cell growth factor (SCF) showed reverse causality with PHN. Conversely, we found that PHN was closely associated with 12 inflammatory cytokines, but no significant correlation was found among the other inflammatory factors. Among them, only IL-18 had a bidirectional causal relationship with PHN. Conclusion: Our research advances the current understanding of the role of certain inflammatory biomarker pathways in the development of PHN. Additional verification is required to evaluate the viability of these proteins as targeted inflammatory factors for PHN-based treatments.

Conversion of cobalt from spent LIBs to Co3O4 electrode material for application in supercapacitors.

The cathode material of lithium-ion batteries (LIBs) is endowed with valuable metals, such as cobalt. The improper treatment of these batteries pollutes the environment and causes enormous resource waste. Therefore, the recovery of valuable metals from spent LIBs has attracted widespread attention. In this study, Co3O4 electrode materials were prepared by a simple homogeneous precipitation method and heat treatment using a leaching solution of spent LIBs-positive electrode material as the cobalt source. The crystal structure and morphology of the products were examined at different annealing temperatures, and their electrochemical performance was analyzed. The results show that low-temperature annealing contributes to grain refinement. The Co3O4 material prepared at 300°C annealing temperature has a rod-like structure with distinct pores and a specific surface area of 58.98 m2 g-1. Furthermore, electrochemical performance testing reveals that Co3O4 prepared at 300°C displays the best electrochemical performance as an electrode material, with a specific capacitance of 97.93 F g-1 and a cycle retention rate of 79.12% after 500 charge-discharge cycles. These findings demonstrate the feasibility of recycling valuable metal cobalt from spent LIBs cathode materials to produce Co3O4 materials for use as supercapacitor electrode materials, opening up new avenues for the recycling and utilisation of spent LIBs.

Hydrogel activation of Mincle receptors for tumor cell processing: A novel approach in cancer immunotherapy.

An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8+ T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment.

CAG peptide functionalized graphene quantum dots-cationic polymer composite gene carriers.

In this study, a targeted graphene quantum dot-cationic polymer composite gene vector with endothelial cell-targeting CAG peptide was successfully designed and prepared. This vector could efficiently bind and deliver the therapeutic gene pZNF580 to endothelial cells (HUVECs). At a concentration of less than 40 µg mL-1, the results of the CCK-8 assay showed that the relative cell viability of each composite gene vector was greater than 80%, and the results of the flow cytometry assay showed that C-GQDs-PEI-PEG-CAG/pZNF580 (88.96%) and N-GQDs-PEI-PLGA-PEG-CAG/pZNF580 (87.70%) treated groups showed significantly higher cell viability than the positive control group Lip2000/pZNF580 (56.76%). The results of in vitro cell transfection and western blot experiments confirmed that the composite gene vector was able to deliver pZNF580 efficiently and enable the high expression of the ZNF580 protein in HUVECs. The results of the EdU assay, wound healing and Transwell experiments indicated that the composite gene vector/pZNF580 nanoparticles (NPs) could significantly promote the proliferation and migration. The results of the EdU method showed that the proliferative ability of C-GQDs-PEI-PLGA/pZNF580 (84.96 ± 1.99%) and N-GQDs-PEI-PLGA/pZNF580 (85.01 ± 1.31%) treatment groups for HUVECs was significantly higher than that of the positive control group Lip2000/pZNF580 (77.89 ± 2.18%). The results of the scratch assay showed that the cell migration rate of C-GQDs-PEI-PLGA-PEG-CAG/pZNF580 (93.08 ± 1.97%) and N-GQDs-PEI-PLGA-PEG-CAG/pZNF580 (91.99 ± 1.52%) groups was significantly higher than that of the positive control group Lip2000/pZNF580 (85.03 ± 2.21%). In addition, the results of the in vitro angiogenesis assay showed that the C-GQDs-PEI-PLGA-PEG-CAG/pZNF580 and N-GQDs-PEI-PLGA-PEG-CAG/pZNF580 groups had significantly higher angiogenesis-promoting ability than the positive control group, Lip2000/pZNF580.The present study provides a highly efficient and low-toxic method to promote endothelial cell migration in the field of regenerative medicine and a low-toxicity strategy to promote endothelial layer formation, which provides new possibilities for future vascular regeneration therapy.