RATIONALE:Electroacupuncture (EA) has been widely used for depression treatment. Microbiota-gut-brain (MGB) axis plays a vital role in regulating emotional behaviors. However, the potential role of MGB axis in EA-mediated protective effects remains unclear. METHODS:The protective effects of EA in chronic unpredictable mild stress (CUMS) induced mice were evaluated, and the gut microbiota and metabolic profiles were analyzed. Fecal microbiota transplantation (FMT) was utilized to explore the role of MGB axis in the protective effects of EA. Analyses related to synaptic pruning mediated by microglia were conducted to explore the molecular mechanisms. RESULTS:In this study, EA treatment prevented depressive-like behaviors in CUMS mice. Mechanistically, EA ameliorated CUMS-induced gut microbiota dysbiosis and inflammation, and partially restored gut microbial metabolism, particularly affecting the abundance of Alistipes and taurine metabolism. Furthermore, EA significantly reduced systemic and hippocampal inflammation. It also attenuated aberrant synaptic pruning in the hippocampus. Moreover, FMT from CUMS mice induced depressive-like behaviors, gut inflammation and microglia-mediated aberrant synaptic pruning, whereas FMT from EA-treated donors exerted protective effects against these impairments. CONCLUSION:Collectively, our findings suggest that EA prevented CUMS-induced depression-like behaviors and support the involvement of the MGB axis in its protective effects.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that continues to pose a major clinical challenge, primarily due to the difficulty of early detection and the limited efficacy of existing therapeutic approaches. Immunotherapy, which has revolutionized the treatment of many other cancers, has shown limited success in PDAC, largely because of the complex and immunosuppressive features of its tumor microenvironment (TME). Consequently, strategies aimed at remodeling or modulating the TME have emerged as promising avenues for enhancing the therapeutical potential of immunotherapy in PDAC. MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as key regulators of gene expression with multi-target capabilities and relatively low toxicity. Increasing evidence demonstrates that miRNAs play critical roles in regulating immune responses and shaping the TME across diverse tumor types, highlighting their considerable potential in improving immunotherapeutic outcomes in PDAC. In this review, we summarize the functional roles of miRNAs in PDAC and discuss the advantages of miRNA-based therapeutics compared with conventional treatments. We further examine current immunotherapeutic strategies for PDAC and highlight how miRNAs regulate immune activity and TME dynamics, providing mechanistic insights into miRNA-mediated immunotherapy. Finally, we discuss the major challenges limiting clinical translation, including off-target effects, toxicity, and delivery barriers and outline emerging delivery platforms that may enhance therapeutic efficacy. Besides, we explore how emerging technologies, such as artificial intelligence (AI), miniature soft robotics, and advanced 3D imaging ecosystems can be integrated into miRNA-based therapeutic strategies. Together, these innovations may pave the way for more effective, personalized, and patient-centered miRNA-based immunotherapies for PDAC.

Prunella vulgaris L. (XiakuCao) is a traditional edible Chinese medicinal herb widely used for its purging properties. While its polysaccharides are known for diverse bioactivities, their potential in treating liver diseases remains closely linked to their specific structural features. Most reported polysaccharides from Prunella vulgaris L. have been complex heteropolysaccharides isolated by hot water. In this study, a new homogeneous polysaccharide, designated AO3-1, was isolated for the first time from Prunella vulgaris L. by ammonium oxalate solution after water treatment. Structural analysis revealed that AO3-1 is mainly composed of α-D-1, 4-GalpA, consistent with a typical pectic polysaccharide. Pharmacological evaluations demonstrated that AO3-1 has significant therapeutic effects in alleviating alcoholic liver injury (ALD), as indicated by the reduction of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the mitigation of hepatic steatosis (TG, TC, LDL-C and HDL-C). Notably, AO3-1 treatment suppressed systemic inflammation (IL-6, IL-1β and TNF-α) and effectively modulated intestinal microecology, suggesting a protective role mediated by the gut-liver axis. These findings provide the first evidence of a unique pectic polysaccharide from Prunella vulgaris L. with potent anti-ALD activity. Our study highlights the potential of AO3-1 as a novel functional food ingredient or therapeutic agent for managing alcoholic liver injury, offering a new strategy for the valorization of herbal processing by-products.

Alpha-mannosidosis (AMD) is a well-known lysosomal storage disorder caused by the loss of α-mannosidase activity due to the mutation of the MAN2B1 gene. Defective α-mannosidase cannot completely degrade the sugar chains of upstream input glycoproteins, leading to the accumulation of oligosaccharides with α-mannosidic linkages in lysosomes, finally causing AMD. However, till now, the upstream input mediating AMD remains elusive, which hinders the development of alternative therapeutic treatments. To address this question, we establish the first Drosophila model of AMD and, through genetic screen, identify three novel upstream factors named Jer1, Ga2, and LpR1. We demonstrate that knocking down either of them can rescue the lethal phenotype of AMD flies and they mediate upstream input of AMD through a Jer1-Ga2-LpR1 axis. Mechanistically, Jer1 recruits the E3 ligase Ga2, which mediates the ubiquitination of the glycoprotein LpR1 for subsequent lysosomal degradation. Therefore, knockdown of Jer1 or Ga2 downregulates LpR1 ubiquitination and prevents it from degradation in lysosomes, reducing the burden on lysosomes and alleviating the symptoms of AMD. Importantly, our study further demonstrates that IPP, UBE3C, and VLDLR, the mammalian counterparts of Jer1, Ga2, and LpR1, respectively, are functionally conserved during evolution, suggesting that they can be used as potential therapeutic targets for the treatment of AMD.

BACKGROUND:Breast cancer (BC) is one of the most frequent malignant tumors, with high morbidity and fatality rates. Abnormalities in the Hippo pathway or YAP overexpression alter the cell proliferation-apoptosis equilibrium, which promotes cancer progression. Ursolic acid (UA), a naturally occurring triterpenoid carboxylic acid, exhibits preventive and anticancer properties. This study aimed to evaluate the effects of UA on breast cancer via the Hippo-YAP pathway. RESULTS:The findings revealed that UA hindered YAP nuclear translocation and increased its phosphorylation, preventing YAP from entering the nucleus from the cytoplasm and thus failing to motivate transcriptional expression of the downstream proliferation-related target genes, including CYR61 (i.e. cysteine-rich 61) and CTGF (i.e. connective tissue growth factor). Moreover, YAP overexpression reversed the inhibitory impact of UA on breast cancer cell proliferation and migration, whereas siYAP increased the inhibitory effects of UA on breast cancer cell proliferation and migration. Additionally, UA inhibited tumor growth in mice xenografted with MCF-7 cells. CONCLUSION:UA reduces breast cancer growth via the Hippo-YAP pathway, providing a theoretical foundation for its anticancer activity and suggesting that UA may serve as a promising candidate for breast cancer therapy. © 2026 Society of Chemical Industry.

This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both NaV1.7, NaV1.8, and NaV1.9 and KV7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited NaV1.7, NaV1.8, and NaV1.9 channels with a particularly low half maximal inhibitory concentration (IC50) for NaV1.9 by promoting sodium channel inactivation, and also effectively increased KV7.2/7.3, KV7.2, and KV7.5 channels, excluding KV7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Bortezomib is a mainstay drug for the treatment of myeloma, a malignancy of plasma cells, but resistance frequently develops. Overcoming bortezomib resistance is urgently needed. In the present study, we found that acevaltrate, an active ingredient from a traditional Chinese medicine, exhibits potent activity in triggering pyroptosis in bortezomib-resistant myeloma cells. Mechanistically, acevaltrate induces myeloma cells pyroptosis in a Caspase-3 and GSDME-dependent manner. When Caspase-3 is inhibited by its specific inhibitor or GSDME is knocked out, myeloma cells fail to undergo pyroptosis triggered by acevaltrate. Moreover, acevaltrate promotes the production of reactive oxygen species and strikingly reduces mitochondrial membrane potential. Consistent with this finding, acevaltrate dissociates BAX from its inhibitor, Bcl-2, thereby promoting BAX translocalization to mitochondria. Furthermore, IFIT3, an IFN-inducible protein, is upregulated by acevaltrate. Interestingly, while IFIT3 fails to directly induce myeloma cells pyroptosis, it markedly enhances acevaltrate-induced pyroptosis. IFIT3 binds to Bcl-2 and prevents it from interacting with BAX. Lastly, acevaltrate effectively triggers pyroptosis in bortezomib-resistant myeloma cells. Pre-treatment with acevaltrate significantly restores the sensitivity of resistant myeloma cells to bortezomib. Therefore, acevaltrate strongly induces myeloma cell pyroptosis and overcomes bortezomib resistance. Given its potent activity against myeloma and its established safety profile, acevaltrate warrants further evaluation in clinical settings for its potential to overcome myeloma resistance to bortezomib.

Chronic migraine is a debilitating disorder often accompanied by gastrointestinal dysfunction. However, the targets and mechanisms underlying this interaction in migraine remain unclear. Wuzhuyu Decoction (WZYD), a traditional Chinese medicine, has shown efficacy in alleviating migraine and gastrointestinal symptoms. However, its mechanisms of brain-gut coordination remain unclear. This study investigates the mechanisms of WZYD on the brainstem and colon in chronic migraine model rats based on proteomics. A chronic migraine model was induced via meningeal inflammation, followed by WZYD administration. WZYD increased pain thresholds, reduced CGRP and Fos, while elevating 5-HT. Proteomic analysis identified proteins significantly regulated by WZYD in the brainstem and colon respectively, primarily involved in inflammation and signal transduction. UHPLC-Q-Exactive-MS/MS revealed blood-absorbed components of WZYD, and network analysis predicted 959 potential targets. Proteomics-based PPI analysis combined with network analysis of blood-absorbed components identified DDO, PRKACB, and MAPK8 as key potential targets regulated by WZYD. These findings were validated through molecular docking, mRNA and protein expression analysis. WZYD reduced Iba-1, TNF-α, IL-6, SP, DDO, PRKACB, and MAPK8, while elevating IL-10 and GLP-2 levels, mitigating neuroinflammation and intestinal inflammation. These findings suggest WZYD could alleviate chronic migraine by regulating key protein targets and coordinating anti-inflammatory responses in the brain and gut.

Background The prevalence of diabetic cognitive impairment (DCI) is significant, some studies have shown that it is related to mitochondrial respiratory chain homeostasis, but the specific mechanism is not clear. 2-hydroxyisobutyric acid (2-HIBA) is a novel short-chain fatty acid with potential applications in the treatment of metabolic diseases because it can regulate mitochondrial disorders. Our aim was to explore a novel mechanism of action for 2-HIBA in the treatment of DCI in mitochondrial respiratory chain homeostasis. Methods Metabolic substances and differentially active metabolic pathways in the serum of diseased mice were identified based on multi-omics analysis. The nanoLC-Obitrap-MS technology was utilized to detect the content of selected small molecules with differential metabolic activity in the hippocampus and mitochondria of mice to evaluate their permeability through the blood-brain barrier (BBB) and outer mitochondrial membrane. A combination of behavioral, proteomic, and molecular biology approaches was used to explore specific regulatory mechanisms and identify potential pharmacological targets. Additionally, using techniques such as protein thermal shift, drug affinity responsive target stability (DARTS), hydrolase stability, and surface plasmon resonance (SPR) experiments, we demonstrated the direct binding effects of small molecule metabolites with protein targets. Results 2-HIBA was found to directly ameliorate cognitive dysfunction in db/db mice by penetrating the blood-brain barrier and reversing the decrease in the protein content of NADH dehydrogenase 3 (MT-ND3) in the hippocampus through direct binding to ND3. This action helps maintain the stability of NAD+/NADH and regulate the mitochondrial respiratory chain balance. Furthermore, a combined medication plant agonist of 2-HIBA can enhance the expression of MT-ND3, thereby improving cognitive dysfunction in mice. Conclusion MT-ND3 is a crucial target for improving diabetic cognitive dysfunction, and 2-HIBA can directly bind to the MT-ND3 protein to alleviate the functional impairment of the mitochondrial respiratory chain in mice to treat DCI.

Background:Although the overall survival of multiple myeloma (MM) has improved significantly, patients with ultra-high-risk features (UHR-MM) had dismal outcomes. New therapies to address this unmet medical need are warranted. Equecabtagene autoleucel (eque-cel) has been approved for patients who have received at least three previous lines of therapy by the Chinese National Medical Products Administration. With good efficacy and safety profile in these patients, eque-cel is being explored in early relapse or newly diagnosed UHR-MM patients, Hereby, we report the primary real world data of eque-cel followed ASCT in UHR-MM patients. Methods:We conducted a retrospective chart review on UHR-MM patients who received eque-cel followed ASCT. UHR-MM are defined as: 1) Genetic ultra-high risk: del(17p)≥60%; or ≥2 high-risk cytogenetic abnormalities including TP53 mutation, del(17p)/P53 deletion, t(4;14), t(14;16), t(14;20), 1q21 gain/ amplification; 2) Primary refractory: Results:From August 2023 to April 2025, 12 UHR-MM patients completed ASCT followed by eque-cel infusion. Six patients received melphalan, five received bendamustine combining melphalan and one patient received fludarabine combining melphalan conditioning. Peripheral stem cell was administrated at (2.3-5.5) × 106 cells/kg, and eque-cel was administrated at 1 × 106 cells/kg for all 12 patients. The median age was 53 years (range: 36-67) and 11 (91.7%) were male. Eight patients (72.7%) had genetic ultra-high risk features, one patients (8.3%) were early progression, and two patients (16.7%) had primary PCL history. Two (16.7%) patients had extramedullary disease. With median 2 (range: 1-4) previous line of therapy, the median disease course is 10.5 months before ASCT. Eleven (91.7%) patients had received daratumumab based triplet or quadruplet therapy. All patients received bridging and 11 received maintenance therapy. Two patients, who had received eque-cel infusion within the preceding 6 months but did not achieve a complete response (CR), subsequently underwent consolidation therapy with eque-cel followed ASCT. With a median follow-up of 196 days (from ASCT date), seven patients (58.3%) experienced grade 1 and three patients (25.0%) experienced grade 2 CRS and fully recovered. Four patients were treated with glucocorticoids. No ICANS event was reported. As expected, AEs are dominated by hematological toxicities. All 12 patients achieved hematopoietic reconstitution within 1 months after ASCT, with a median time of 15 days for ANC reconstitution (≥0.5×109/L) and 11.5 days for PLT reconstitution (≥20×109/L) post ASCT. By July 1st, 2025, the ORR was 100%, with all 12 patients reached CR. All patients are MRD negative. Two patients received first eque-cel 3 month before ASCT, which achieved both VGPR. After ASCT and second eque-cel infusion, achieved sCR and MRD negative status on day 23 and day 190 post-ASCT, respectively. The early progression patient relapsed at 55 days post ASCT, all the other patients are keeping their response and under follow-up. The median DOR, PFS and OS were not reached by cutoff date. Robust CAR T-cell expansion was observed, with a median Tmax of 11 days (range 7~21). The median Cmax was 665.04 cells/μL. The pharmacokinetic profile is similar to that of eque-cel in R/RMM patients. Conclusion:Eque-cel followed ASCT demonstrated promising deep and durable response and was well tolerated in UHR-MM patients. CRS events are slight, hematopoietic reconstruction rate was 100%. We are looking forward to more patients gaining long-term benefit from this new treatment.

Traditional chemotherapy against colorectal cancer (CRC) is limited by systemic toxicity and side effects, highlighting the need for safe and effective drug delivery systems. In this study, β-glucan self-assembled nanotubes (β-gluSNTs) were developed as colon-targeted delivery platforms, which enable microbiota-triggered drug release in the colon. By encapsulating the typical chemotherapeutic agent doxorubicin (DOX) within these nanotubes, the obtained β-gluSNTs-DOX complex was oral administrated to against CRC in an orthotopic mouse model, with a tumor suppression rate reaching 42.55 ± 0.18 %. β-gluSNTs-DOX exhibited high drug-loading capacity (30.5 ± 0.16 %) and protected DOX from premature release in the upper gastrointestinal tract, resulting in enhanced drug accumulation at the colonic tumor site. Notably, due to encapsulation of DOX inside the β-gluSNTs, the β-glucan shell helps alleviate oral DOX-induced systemic toxicity, inflammation, and gut microbiota dysbiosis, while promoting M1 macrophage polarization and antitumor immunity, thereby synergistically enhancing the oral therapeutic efficacy of DOX. In summary, these findings suggest that β-glucan-based nanotubes represent a promising, low-toxicity, colon-targeted delivery system for CRC therapy with additional benefits in regulating the gut microbiota and tumor immune microenvironment.

Microalgae are microorganisms that possess highly efficient photosynthetic capabilities and versatile biosynthetic pathways, enabling the production of various bioactive compounds. In recent years, microalgae, as a group of unicellular organisms with high biosafety and diverse biological functions, have received widespread attention in biomaterials and medicine. Microalgae-derived extracts are rich in a variety of bioactive components, including carotenoids, proteins, polysaccharides, and unsaturated fatty acids. These components exhibit antiinflammatory and antioxidant properties, with their therapeutic value having been experimentally demonstrated. Additionally, the photosynthetic ability of microalgae allows in situ oxygen production, offering a novel strategy to counteract hypoxic microenvironments in disease treatment. This article summarizes common microalgae species and their bioactive compounds in biomedicine, while reviewing recent advances in cancer therapy, chronic wound healing, and cerebral diseases. It aims to summarize the theories and research directions of novel biomaterials and therapeutic methods based on microalgae, while providing insights and prospects for the future development of microalgae in the fields of biomaterials and medicine.

Chronic wound management in diabetes represents a significant global medical challenge, primarily due to the complex microenvironment of diabetic wounds. Recently, fish-skin-collagen (Co)-based hydrogels have gained attention for treating skin wounds. However, their application in diabetic wounds has been restricted by their limited antibacterial properties, mechanical strength, and thermal stability. Here, a Co-based hydrogel (CFP) is developed, cross-linked via Co and a protocatechualdehyde-iron(III) Complex chelate (PCA@Fe) formed between protocatechualdehyde (PCA) and ferric ion (Fe3+). The CFP enhances its mechanical properties and thermal stability by forming Schiff base bonds between PCA@Fe and Co, while endowing itself with self-healing ability and photothermal effect. Co promotes angiogenesis and collagen remodeling, while PCA inhibits ferroptosis in cells and disrupts bacterial iron homeostasis, thereby suppressing the oxidative stress and bacterial infection in diabetic wounds. Furthermore, the photothermal effect synergizing with the disruption of bacterial iron homeostasis significantly reduces bacterial infections in diabetic wounds, thereby accelerating the healing process of chronic diabetic wounds.

Intrahepatic cholangiocarcinoma (ICC) cells preferentially utilize aerobic glycolysis to support their uncontrolled proliferation. This metabolic reprogramming leads to lactate accumulation in the tumor microenvironment, which promotes the polarization of tumor-associated macrophages (TAMs) toward a pro-tumor phenotype, thereby facilitating immune escape and malignant progression. Although celastrol exhibits inhibitory effects on ICC, its underlying mechanism of action remains unclear. This study aims to elucidate whether celastrol suppresses ICC progression by targeting glycolysis and its subsequent impact on TAM polarization. The anti-tumor effect of celastrol and its influence on TAM polarization were systematically investigated using in vitro co-culture models and in vivo animal experiments. We demonstrated that celastrol significantly inhibits ICC progression and restrains the pro-tumor polarization of TAMs. Mechanistically, celastrol suppressed glycolysis in ICC cells and reduced lactate accumulation and further influenced TAMs polarization and ICC proliferation. In conclusion, our findings demonstrate that celastrol suppresses ICC progression by dually targeting glycolysis in tumor cells and lactate-mediated TAM polarization, highlighting its potential as a multi-faceted therapeutic agent against ICC.

Cerebral malaria (CM), a lethal neurological complication of Plasmodium falciparum, is characterized by blood–brain barrier (BBB) disruption. Although astrocytes constitute essential components of the BBB neurovascular unit, their immunoregulatory functions during CM pathogenesis remain elusive. Clinical evidence of altered copper homeostasis in patients with CM, coupled with known associations between copper dysregulation and astrocyte reactivity, prompted investigation of cuproptosis—a copper-dependent programmed cell death pathway—in the disease progression of CM. Using a P. berghei ANKA (PbA)-induced experimental CM (ECM) model in C57BL/6 mice, we evaluated pharmacological modulation with copper ionophore disulfiram (DSF) versus copper chelator tetrathiomolybdate (TTM). Parallel in vitro experiments assessed astrocytes stimulated by PbA-infected red blood cells (iRBCs)/blood-stage soluble antigen (PbAg) under DSF-CuCl2 or TTM-CuCl2 treatment. ECM mice demonstrated significant cerebral copper accumulation with concomitant upregulation of cuproptosis markers (SLC31A1, FDX1, DLAT, and DLST) and downregulation of ATP7A copper transporter. DSF administration exacerbated ECM progression through amplified parasitemia, aggravated BBB permeability, cerebral edema, and neuroinflammatory responses, whereas TTM treatment counteracted these pathological manifestations. Immunohistochemical analysis revealed DSF-induced astrocyte reactivity (GFAP+/Serping1+) with colocalization of cuproptosis markers (GFAP+-SLC31A1+/FDX1+/DLAT+/DLST+), contrasting with TTM-mediated suppression. In vitro, DSF-CuCl2 treatment augmented iRBC-stimulated astrocyte expression of reactivity markers (GFAP and Serping1), cuproptosis regulators (SLC31A1, FDX1, DLAT, and DLST), and proinflammatory mediators (CXCL10, tumor necrosis factor (TNF)-ɑ, interleukin (IL)-1β, and IL-6), but conversely reduced PbAg-stimulated cell viability. These effects were reversed by TTM-CuCl2 treatment. These findings establish that cuproptosis exacerbates ECM pathogenesis by promoting astrocyte reactivity, highlighting copper homeostasis modulation as a potential therapeutic strategy for CM.

Food as medicine shows promise for disease intervention or treatment. Here, we found phytate, an active ingredient of plant-based diets, exhibits properties in mitigating radiotherapy-related complications. Oral gavage of phytate restored hematogenic organ atrophy, elevated peripheral blood neutrophils and white blood cells, reduced inflammation, and improved gastrointestinal (GI) integrity in irradiated mice. Phytate intake modulated the gut microbiota, facilitating the colonization of symbiotic Parasutterella in GI tract, thus combating intestinal radiation toxicity. In vitro assays and untargeted metabolomics identified 3-phenyllactic acid (PLA) and N-acetyl-L-leucine (NL) as functional metabolites produced by Parasutterella. In vitro, ex vivo, and in vivo models showed that PLA induces M2-like polarization in macrophages, while NL reduced oxidative stress, both counteracting radiation toxicity and working synergistically. Our findings offer mechanistic insights into phytate for alleviating radiation-associated complications and suggest that Parasutterella and its metabolites might be employed as promising probiotics or postbiotics for cancer patients undergoing radiotherapy.

Recently, polysaccharide-based film materials have attracting widespread attentions due to their safety, biodegradability, and film-forming properties. However, the limited UV resistance, antibacterial and mechanical properties of polysaccharides severely restrict their applications in food packaging. This work developed a biocomposite film (PGF@Ag) consited of a natural β-glucan from Poria Cocos (PCPA), in-situ synthesized AgNPs and glycerol, showing good antibacterial and antioxidant properties as well as biocompatibility and mechanical properties. Poria Cocos is an edible traditional Chinese medicine, and its residue is rich in polysaccharide. In this system, the large amont of hydrogen groups on PCPA help fast reduce Ag+ to Ag0 in alkalescent solution and the triple-helix conformation of PCPA hinder the aggregation of AgNPs, leading to the ultra small size with 9.0-12.3 nm as well as better ABTS radical scavenging rates of 93.30 ± 0.13 %. Additionally, the hydrogen bonding interactions between glycerol and polysaccharides significantly enhance the mechanical properties of the PGF@Ag films. The tensile strength is measured at 5.94 ± 0.5 MPa, while the elongation at break reaches 128.77 ± 12.45 %, and the Young's modulus is recorded at 15.75 ± 1.91 MPa. Finally, the resulting films exhibited excellent preservation effects on grapes, as reduced weight loss reduction of 14 %, and hardness reduction of approximately 5.2 % over 12 days. This work provides a new strategy of the sustainable construction of antibacterial films, showing great potentials in food preservation and packaging applications.

An inulin-type fructan (CPS0.2B) from an edible traditional Chinese medicine (TCM) named Codonopsis pilosula was found to exhibit immunological enhancement both in vitro and in vivo. However, the commercial inulin, which has an almost identical molecular weight and monosaccharide composition as CPS0.2B, exhibited almost no biological activity in vitro. We found that this difference was attributed to the smaller particle size of CPS0.2B, facilitating enhanced cellular uptake through endocytosis. Further investigation into the corresponding immune-enhancing effect using THP-1 macrophage cells indicated that CPS0.2B can effectively activate the MAPK and NF-κB signaling pathways by stimulating the p65 protein both inside and outside the cell membrane. Additionally, in vivo strudy further confirmed CPS0.2B had an immune-enhancing effect on CTX-induced immune suppression model in mice. This study confirmed the immune-enhancing activity and related mechanisms of the inulin-type fructan CPS0.2B and, more importantly, demonstrated the significant role of the advanced structure of the polysaccharides in immunomodulatory effects.

BACKGROUND:Photoaging is a significant contributor to accelerated skin aging, primarily driven by ultraviolet B (UVB) radiation exposure, which induces damage to skin tissues. Tannic acid (TA), a high-molecular-weight, water-soluble polyphenolic compound abundant in Galla chinensis and other plant sources, exhibits remarkable antioxidant properties. This study aimed to investigate the effects of TA on UVB-induced skin photoaging and to elucidate the molecular mechanisms underlying. METHODS:In vitro, TA was applied to UVB-irradiated human skin fibroblast (HSF) cells. we measured cell viability, reactive oxygen species (ROS), markers of cellular senescence, and the activity of antioxidant enzymes. The potential mechanism of TA was explored using RNA sequencing and further verified by Western blotting and administration of ferroptosis inducers. In vivo, we employed a UVB-induced Balb/C mouse model of photoaging to assess epidermal thickness and collagen fiber density. Tissue levels of antioxidant enzymes were also examined, and the expression of mitogen-activated protein kinase (MAPK) and ferroptosis-related protein levels were detected by Western blotting. RESULTS:TA demonstrated efficacy in mitigating UVB-induced photoaging in fibroblasts. It attenuates oxidative stress damage, inhibited the onset of ferroptosis by modulating MAPK signaling, reduces Fe2+ accumulation, and activated the NRF2/SLC7A11/GPX4 signaling cascade, thereby alleviating photoaging. Furthermore, TA ameliorated UVB-induced epidermal thickening and collagen disruption in mice. CONCLUSION:This study underscores the protective effects of TA against UVB-induced photoaging in HSF cells and skin tissue. These findings provide a robust theoretical foundation for the development of TA-based natural products intended for anti-photoaging applications.

Background:Composite inflammatory markers, such as the systemic inflammatory response index (SIRI), are associated with the severity and progression of several cardiovascular diseases. However, the relationship between SIRI and chronic thromboembolic pulmonary hypertension (CTEPH) remains unclear. We hypothesized that elevated SIRI levels would correlate with disease severity and independently predict adverse clinical outcomes in patients with CTEPH. This study aimed to clarify the predictive value of SIRI in patients with CTEPH. Methods:This retrospective cohort study included 383 patients with CTEPH treated at Fuwai Hospital between June 2013 and June 2021. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic performance of SIRI to other inflammatory indices and identify the optimal cutoff value. Kaplan-Meier analysis and Cox proportional hazard models were used to examine the relationship between SIRI and clinical worsening. Results:During a mean follow-up period of 30.6 months, 79 participants experienced clinical worsening. The SIRI was significantly correlated with established markers of CTEPH severity, including the 6-minute walk distance, N-terminal pro-brain natriuretic peptide, and hemodynamic parameters. Kaplan-Meier curve revealed that individuals with a SIRI ≥ 0.80 exhibited significantly poorer survival rates and a shorter time to clinical worsening compared to those with a SIRI < 0.80 (P < 0.01). Adjusted Cox proportional hazards analysis revealed that SIRI remained an independent predictor of clinical worsening (hazard ratio (HR) 2.033; 95% confidence interval (CI) 1.227-3.370). ROC analysis revealed that SIRI exhibited the highest area under the curve value of 0.730 (95% CI 0.659-0.810). Incorporating SIRI into The COMPERA 2.0, the risk score improved its predictive value for adverse outcomes in patients with CTEPH. Conclusion:SIRI is a valuable prognostic marker for CTEPH, correlating with established markers of disease severity and independently predicting clinical worsening. SIRI provides additional prognostic predictive value when used in conjunction with the risk score of COMPERA 2.0.