Chronic wound healing remains challenging due to the risk of bacterial infection and the typical microenvironments characterized by oxidative stress, hypoxia, and insufficient angiogenesis. Herein, a hydrogel dressing (CLIHO) has been developed to efficiently promote the healing of methicillin-resistant Staphylococcus aureus (MRSA) infected wounds by integrating near-infrared (NIR)-controlled cascade reactions among hemin, indocyanine green (ICG), and l-arginine (l-Arg). Mild heat (approximately 45 °C) and cascade generation of reactive oxygen species (ROS), nitric oxide (NO), and ONOO− from the CLIHO hydrogel have been demonstrated under NIR irradiation. Benefiting from the O2 supplied by hemin-mediated decomposition of endogenous excess H2O2 in wounds, CLIHO hydrogel demonstrated hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial activity, enabling it to effectively inhibit MRSA, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis) proliferation, as well as eradicate the formed biofilms. The antibacterial performance of the CLIHO hydrogel was significantly superior to that of the CIO hydrogel with phototherapy alone and the CLIO hydrogel without O2 supply. Upon NIR turn-off, the CLIHO hydrogel could remodel the microenvironment of chronic wounds by scavenging excessive ROS, reducing local H2O2 levels, and alleviating hypoxia while promoting angiogenesis by releasing trace amounts of NO under endogenous nitric oxide synthase. Importantly, compared with CLIO hydrogel (without hemin), the CLIHO hydrogel significantly accelerated the high-quality healing of MRSA-infected wounds by efficiently eliminating bacterial infection, balancing inflammatory responses, and promoting angiogenesis and collagen deposition. Hence, the prepared CLIHO hydrogel integrating NIR-controlled cascade reaction provides an efficient and secure dressing for accelerating healing of MRSA-infected wounds via hypoxia-alleviation-enhanced NO/phototherapy synergistic antibacterial and microenvironment remodeling.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no effective therapies. 4,4'-Dimethoxychalcone (DMC) is a natural chalcone extracted from Angelica keiskei (Miq.) Koidz and Angelica sinensis (Oliv.) Diels, which could promote autophagy and prolong lifespan. However, the neuroprotective effects and mechanisms of DMC on AD mice have not been reported. In this study, we proved that DMC treatment significantly mitigated cognitive impairment and depressive behavior, ameliorated blood-brain barrier permeability and amyloid β pathology, and inhibited p-Tau expression in 5 × FAD mice. Also, DMC suppressed glial cell activation, enhanced neurogenesis, and decreased oxidative stress in vivo and in vitro by activating the Kelch-like ECH-associated protein1 (Keap1)/nuclear factor-erythrocyte 2-associated factor 2 (Nrf2) signaling pathway. However, Brusatol, an inhibitor of the Keap1/Nrf2 signalling, partly attenuated the neuroprotective effects of DMC on lipopolysaccharide-induced HT22 cells injury and 5 × FAD mice. In conclusion, DMC exhibited neuroprotective effects on 5 × FAD mice via the activation of Keap1/Nrf2 signalling pathway. Thus, DMC may be a promising therapeutic drug for AD.

Traumatic brain injury (TBI) presents a complex repair challenge, involving not only neural damage but also cranial defects and impaired wound healing. Dysregulated inflammation and inadequate angiogenesis are key obstacles in this process. To address these multifaceted needs, we developed CO@P, a microenvironment-responsive hydrogel loaded with platelet-rich plasma (PRP), designed for the controlled release of growth factors to synchronize neural recovery, skull regeneration, and wound healing. In vitro, CO@P demonstrated excellent stability, sustained release, and biocompatibility. It protected N2a cells from LPS-induced death, reduced M1 polarization in LPS-stimulated HMC3 cells, and enhanced the migration of BMSC and HUVEC as well as HUVEC tube formation under oxidative stress. In vivo, when applied to TBI mice, the hydrogel's microenvironment-responsive design enabled a gradient release of growth factors, preventing the burst release typical of PRP. This delivery modulated inflammation, accelerated neurogenesis and angiogenesis, and ultimately drove brain remodeling and functional recovery, evidenced by improved motor function, spatial memory, and reduced anxiety-like behaviors. Transcriptomic sequencing confirmed this reparative shift, showing upregulation of regenerative genes alongside downregulation of apoptotic and pro-inflammatory genes. Multimodal histo-immunological analyses further demonstrated that CO@P accelerated scalp wound healing by enhancing angiogenesis and suppressing inflammation. Concurrently, micro-CT and histochemistry revealed its potent osteogenic effect in cranial defects, marked by upregulated osteocalcin/osteopontin and improved structural parameters. In summary, the CO@P hydrogel, through its intelligent and microenvironment-controlled release profiles, orchestrates a multi-dimensional repair process that integrates neuroprotection with structural regeneration, offering a novel and integrated therapeutic strategy for the complex sequelae of TBI.

Efficient cryopreservation of Natural Killer (NK) cells is fundamental to manufacturing NK cell-based immunotherapy products, but it remains challenging due to irreversible cryoinjuries to cell structures (e.g., the membrane system). Herein, inspired by the damage repair mechanism of natural organisms, recombinant human MG53 (rhMG53) protein, known as a membrane repair protein, is reported as a functional additive for improving the NK cell cryopreservation efficacy. The results showed that incubating NK cells with 30 μg/mL rhMG53 protein could preserve the integrity of membranes subjected to mechanical injury, reactive oxygen species damage, and dimethyl sulfoxide (DMSO)-induced toxic injury. During the cryopreservation process, incorporating 30 μg/mL rhMG53 protein into the conventional cryopreservation solution (10% DMSO) led to a 10% increase in cell viability immediately after thawing and an 11% increase in cell viability 72 h after thawing. Besides, during the post-thaw culture process, additional supplementation of 30 μg/mL rhMG53 protein to the culture medium resulted in a 6% decrease in delayed onset cell death and promoted cell proliferation. Meanwhile, post-thawed NK cells also exhibited enhanced immune functionality compared to those cryopreserved with DMSO. Notably, RNA sequencing analysis demonstrated that post-thawed NK cells with our developed cryopreservation method showed fewer changes in transcript profiles compared to fresh cells than those in the DMSO group. This work may highlight the crucial role of membrane protection in NK cell cryopreservation and promote translation of NK cell therapy.

Bacterial infections often lead to excessive ROS production in the wound, resulting in inadequate oxygen supply and nutrient deficiencies, which trigger a severe inflammatory response and delay wound healing. In this study, a multifunctional carboxymethyl chitosan(CMCS)-3,4,5-trihydroxybenzaldehyde(THBA)@Fe (CTF) hydrogel was constructed based on the synergistic effect of the dynamic Schiff base reaction and metal coordination. The material formed a dynamic Schiff base bond with the CMCS amino group through the aldehyde group of THBA and coordinated with Fe3+ to construct a dual-network structure. Experiments have shown that CTF hydrogels exhibit excellent self-healing, on-demand removal, pH responsiveness, and antimicrobial properties. It can effectively scavenge ROS while catalyzing the decomposition of H₂O₂ to release oxygen through catalase-like activity, significantly alleviating the hypoxic state of the wound. Animal experiments demonstrated its ability to accelerate infected wound healing by promoting angiogenesis and collagen deposition, as well as modulating key genes involved in cell migration, energy metabolism, and wound repair. This antibiotic-free and multifunctional hydrogel with integrated antioxidant‑oxygenation-photothermal antimicrobial properties offers a new therapeutic strategy for wound healing.

Cholesterol depletion in tumor cells has been demonstrated as an effective strategy for cancer therapy. Previous studies have shown that cholesterol oxidase (COD) could promote cholesterol consumption. However, these tumor cells typically upregulate cholesterol synthesis as a compensatory mechanism to meet the rapid proliferation demands. To address this issue, we synthesized HM/ZIF-8@COD/IR820 nanoparticle, which simultaneously facilitates cholesterol depletion and inhibits cholesterol synthesis to enhance sonodynamic therapy against hepatocellular carcinoma (HCC). This HM/ZIF-8@COD/IR820 biomimetic nanoparticle was constructed by encapsulating cholesterol oxidase (COD) and the sonosensitizer indocyanine green (IR820) into ZIF-8 nanoparticle, followed by coating with a hybrid cell membrane from tumor cells and erythrocyte membrane. The hybrid membrane provides tumor-targeting capability, enabling HM/ZIF-8@COD/IR820 nanoparticle homes to Hepa1-6 tumor and disassembles in response to the acidic microenvironment and ultrasound stimulation. In vitro and in vivo studies confirmed significant cholesterol depletion and alleviation of hypoxia in Hepa1-6 cells. Upon ultrasound activation, a significant amount of reactive oxygen species (ROS) was generated, thereby enhancing the therapeutic effect on the inoculated tumors. Non-targeted metabolomics analysis further validated the downregulation of cholesterol metabolism-related pathways, which was consistent with the Filipin staining results observed in cellular experiments. Importantly, Hepa1-6 tumor growth was significantly suppressed and the inhibition rate reached 90%. These findings highlight HM/ZIF-8@COD/IR820 as a promising biomimetic nanoparticle orchestrates a two-pronged attack on hepatocellular carcinoma cholesterol metabolism: top-down suppression of cholesterol biosynthetic pathways, and bottom-up elimination of existing cholesterol stores, yielding outstanding therapeutic effects against HCC.

The management of infected chronic wounds is one of the urgent challenges. Herein, a hesperidin (Hes)-loaded self-assembled supramolecular hydrogel based on quaternized chitosan (CQHP) has been developed as an efficient photothermal antibacterial dressing for MRSA-infected wound healing. Specifically, CQHP hydrogels fabricated through the dynamic noncovalent interactions among CM-β-CD grafted QCS, Hes, proline and Fe3+, exhibited injectable and self-healing behaviors, along with adhesion, antioxidant, hemostatic and protein adsorption performance, satisfying the essential feature as chronic wound dressing. Of note, superior photothermal effect generated from the Hes-Fe3+ has been demonstrated, which endowed the CQHP hydrogels effectively and rapidly eliminate the E. coli, S. aureus and MRSA through photothermal therapy, thereby avoiding the use of antibiotics or photothermal conversion nanomaterials in hydrogels and substantially reducing the biological toxicity. Furtherly, sustained antibacterial performance in the absence of NIR can be achieved through the inherent antibacterial activities of Hes. Importantly, the developed CQHP hydrogels significantly promoted the closure of acute full-thickness scratch wounds, and exhibited remarkable better therapeutic effect on MRSA-infected wound than commercial 3M transparent film, by efficiency and sustained antibacterial activity, reducing inflammation, enhancing angiogenesis and collagen deposition, highlighting its promising application in the MRSA-infected wound healing with high efficiency, quality and security.

Bacterial infection of the damaged skin area hinders the wound healing process. Photothermal antibacterial therapy has attracted increasing attention. As green, safe, and possessing various bioactive properties, natural plant extracts are a good choice. However, few natural plant extracts exhibit excellent photothermal responsiveness in the near-infrared range, requiring increased concentration and radiation power to achieve satisfactory photothermal therapeutic effects. In this study, the horseradish peroxidase/hydrogen peroxide (HRP/H2O2) catalytic system was used to simultaneously oxidize anthocyanin-rich black rice extract (BRE) and hyaluronic acid-tyramine conjugate (HT), obtaining a hydrogel based on modified hyaluronic acid with enhanced photothermal ability, abbreviated as HTB. Compared to the sole HT hydrogel, the introduction and oxidation of BRE bring in the near infrared ray-responsive photothermal ability of HTB hydrogel. As a result, a lower amount of black rice extract (3 mg/mL) and reduced NIR power density (0.8 mW/cm2) are required to achieve effective photothermal therapy, further improving the hydrogel's antibacterial activity. Besides, the adhesive, coagulant, antioxidant, and anti-inflammatory properties of HTB hydrogel were also promoted. In an infected wound model in mice, the HTB hydrogel combined with photothermal treatment significantly increased CD206 expression while suppressing CD86 expression at the wound site, indicating its bactericidal and anti-inflammatory effects. Additionally, elevated levels of CD31 and alpha-SMA expression in the wound tissue suggest that the photothermal hydrogel dressing promotes angiogenesis. Therefore, this enzyme-crosslinked HTB hydrogel demonstrates strong photothermal antibacterial activity as well as good anti-inflammatory and pro-angiogenic effects and holds promising potential for application in treating infected wounds.

Cognitive disorders such as Alzheimer's disease (AD) are highly prevalent and place heavy burdens on society. Neuroinflammation is a driver of cognitive impairment, with no effective drugs. Indole 3-propionic acid (IPA) is a tryptophan metabolite mainly produced byClostridium sporogenes, which exhibits multiple functions, including antioxidant, anti-inflammatory, antiaging, and neuroprotective properties. However, the restorative effects and molecular mechanisms of IPA in cognitive impairment remain to be investigated. In this study, we found that IPA reduced LPS-induced apoptosis and oxidative damage in HT22 cells and decreased LPS-induced inflammation in BV2 cells. Besides, IPA promoted neurogenesis, inhibited glial cell activation, maintained the integrity of the BBB and intestinal barrier, and remodeled the gut microbiota, thereby alleviating memory impairment in LPS-induced cognitively impaired mice. At the mechanistic level, IPA inhibited the RAGE-JAK2-STAT3 signaling pathway and thus ameliorated neuroinflammation. Interestingly, Colivelin TFA, an activator of JAK2-STAT3 signaling, partially reversed the neurorestorative effects of IPA. In conclusion, IPA ameliorates neuroinflammation and cognitive deficits via the inhibition of the RAGE-JAK2-STAT3 signaling pathway. Thus, IPA may be a potential drug for the treatment of cognitive disorders.

BACKGROUND:Spinal cord injury (SCI) leads to motor, sensory and autonomic dysfunction with no effective therapy till now. The malignant microenvironment and glial scars at the injury site impede neural circuit remodeling and functional recovery of SCI. Urolithin B (UB), an intestinal metabolite of ellagitannin, possesses anti-inflammatory, antioxidant, antitumor and neuropharmacological activities. PURPOSE:To investigate the effects and mechanism of UB in SCI recovery both in vitro and in vivo. METHODS:At the cellular level, the study focused on the effects of UB on H2O2-induced PC12 cells damage and LPS-induced HMC3 cells polarization. At the in vivo level, the repair effect of UB gavage on SCI mice was performed by behavioral analysis, immunofluorescence, histopathology, and ELISA. Finally, network pharmacology, transcriptome sequencing, molecular docking, DARTS, and reverse validation were conducted to explore the molecular mechanism by which UB promotes SCI repair. RESULTS:UB protected PC12 cells against H2O2-induced injury and decreased LPS-induced M1-type polarization of HMC3 cells. In addition, UB promoted nerve regeneration, regulated M1/M2 polarization of microglia, and reduced the formation of glial scars, thereby facilitating the motor function recovery of SCI mice. Further studies indicated that UB inhibited the NLRP3/Caspase-1/IL-1β pathway both in vivo and in vitro to reduce neuroinflammation. In contrast, BMS-986,299 (an agonist of NLRP3 inflammasome) attenuated the restorative effects of UB in SCI mice. CONCLUSION:UB inhibits the NLRP3/Caspase-1/IL-1β signaling pathway and M1 polarization of microglia to attenuate neuroinflammation and promote the functional recovery of SCI mice. Therefore, UB may be a potential therapeutic agent for the treatment of SCI.

External pathogens and underlying diseases often complicate the wound microenvironment and hinder healing. The combination of plant polyphenols and photothermal therapy offers multiple advantages for skin wound repair and represents a promising alternative to conventional antibiotics. However, most plant polyphenols are susceptible to chemical degradation and inherently lack photothermal responsiveness. In this study, protocatechualdehyde (PA), a plant polyphenol with diverse bioactivities, was selected. Polyvinyl alcohol (PVA) was modified through acetalization with PA to obtain polyvinyl protocatechualdehyde acetal (PPA). Subsequently, the catechol groups of PA were enzymatically cross-linked using HRP/H₂O₂ to form a hydrogel. This acetal-grafting strategy not only shielded the functional groups of PA from excessive degradation, but also conferred acid-responsive properties to the hydrogel, thereby facilitating the sustained release of bioactive PA and its oligomers at the acidic microenvironment of the wound. Although native PA lacks photothermal activity, the HRP/H₂O₂-induced formation of dimeric and oligomeric PA structures endowed the hydrogel with intrinsic photothermal responsiveness, eliminating the need for additional photothermal agents. The PPA hydrogel exhibited excellent adhesion, hemostatic performance, photothermal conversion efficiency, antioxidant, antibacterial properties, and biocompatibility. When combined with photothermal therapy in a mouse infected wound model, the PPA hydrogel significantly accelerated wound closure, reduced local inflammation, promoted tissue regeneration and collagen deposition, highlighting its potential in skin wound repair.

The treatment of diabetic wounds with bacterial infection is a major challenge in the medical field. Microenvironment-responsive hydrogel dressings have shown great advantages, and photothermal antibacterial therapy is a potential antimicrobial strategy to avoid the generation of resistant bacteria. In this work, a glucose-triggered near-infrared (NIR)-responsive photothermal antibacterial hydrogel was designed and named GOGD based on a cascade reaction of glucose oxidation and polyphenol polymerization. The GOGD hydrogel was composed of gelatin and oxidized dextran (Odex), and loaded with a natural plant polyphenol gallic acid (GA) and the dual-biological enzymes (glucose oxidase GOx and horseradish peroxidase HRP). In response to the high glucose environment, GOx in the hydrogel decomposed glucose to produce hydrogen peroxide, which further catalyzed GA polymerization with HRP to produce poly-GA possessing NIR photothermal capability, thus endow GOGD hydrogel with glucose-triggered NIR responsive photothermal antibacterial property simultaneously targeting the high glucose and infection microenvironment in diabetic wounds. Furthermore, the GOGD hydrogel demonstrated good biocompatibility and a strong ability to scavenge reactive oxygen species (ROS), thereby protecting cells from oxidative damage. In a mouse model, this hydrogel not only displayed excellent hemostatic properties but also significantly enhanced the healing of Staphylococcus aureus-infected diabetic wounds by regulating inflammation and promoting angiogenesis. Therefore, the proposed GOGD hydrogel provides a novel approach to diabetic wound treatment by utilizing its unique glucose-responsive mechanism combined with integrated NIR-photothermal bacterial inhibition. This well-designed material holds great promise for significantly improving the healing of infected diabetic wounds and offers new prospects for future advancements in wound therapy.

Effective coverage and antibacterial treatment of irregular wounds remain challenging due to complex geometries, bacterial growth, and elevated levels of reactive oxygen species, which cause prolonged inflammation and impaired healing. In this study, a gelatin-gallic acid (GGA) hydrogel was enzymatically cross-linked using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). At high concentrations (10 wt % GGA and 0.04 wt % H2O2), the oxidized gallic acid moieties formed oligomeric structures with intrinsic photothermal activity, eliminating the need for exogenous photothermal agents. The hydrogel further exhibited thermosensitive behavior, maintaining an elastic state at skin temperatures but transitioning to a viscous, reflowable state above 43.6 °C. Within the photothermal therapeutic range (40-50 °C), the hydrogel undergoes reversible deformation, enabling shape readaptation and effective coverage of irregular wound surfaces under near-infrared irradiation. This system achieves synergistic photothermal antibacterial efficacy, thermal shape adaptivity, antioxidant performance, and inflammation mitigation, leading to enhanced healing outcomes.

Excessive production of reactive oxygen species(ROS)and bacterial infection are intractable obstacles for wound healing in diabetic foot ulcers.Here,we devised a novel approach using a multifunctional hydrogel to achieve self-cascade glucose depletion and ROS scavenging,thereby modifying the diabetic wound microenvironment.In this study,using polyvinyl alcohol(PVA),borax,oligomeric proanthocyanidins(OPC),and nanozymes(AuPt@PDA),a PVA/Borax/OPC/AuPt@PDA(PBON)hydrogel was prepared by a one-step process.The PBON hydrogel combined with near-infrared(NIR)treatment can match the complicated and changeable microenvironment in the diabetic high-mobility region through glucose depletion,ROS scav-enging,photothermal therapy(photothermal conversion 81.9%),and deformation adaptation,thus promoting wound healing close to the hip in diabetic mice through angiogenesis and epidermal regeneration by collagen deposition.This approach pro-vides a simple,safe,and efficient treatment for diabetic wounds in mobile regions.

Rationale: Diabetic wound treatment remains a central issue in global healthcare due to the unitary nature of clinical dressings, which lack systemic multifunctionality in terms of tissue adhesion, shape adaptation, hemostasis, antioxidant, anti-inflammatory and antimicrobial abilities and promotion of tissue repair. Methods: A hydrogel dressing loaded with active molecules of traditional Chinese medicine has been developed for the treatment of infected diabetic wounds. The naturally derived multifunctional hydrogel dressing (abbreviated as CTP) composed of Carboxymethyl chitosan (CMCS), 3,4,5-Trihydroxybenzaldehyde (THBA), and Phlorizin (PHL) was fabricated by a simple mixing process avoiding the use of any additional cross-linking agents or functional modifications. Results: The developed hydrogel demonstrated adhesiveness, shape adaptability, swelling, photothermal responsiveness, and other desirable biological functions, including hemostatic behavior and antibacterial, antioxidant and proangiogenic activities. In a diabetic wound model, compared with Hydrosorb Gel (a commercial hydrogel wound dressing), the CTP hydrogel in combination with NIR treatment accelerated diabetic wound healing by effectively preventing infection, decreasing inflammatory response, promoting re-epithelialization, enhancing both regeneration of skin attachments (e.g., hair follicles) and deposition of collagen. It also reduced scar formation and improved the overall healing process. Conclusions: As a functional wound dressing, CTP hydrogel shows great promise in diabetic wound repair.

Burns, a severe form of trauma, often cause significant skin damage due to bacterial infection and severe inflammation. Hydrogel, due to its remarkable physicochemical properties, shows great potential as a biomaterial for managing localized burn wounds. In this study, we designed a hydrogel composed of quaternized chitosan (QCS) and protocatechualdehyde (PA), cross-linked via Schiff's base reaction and horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) catalysis. This hydrogel exhibits multiple functionalities, including tissue adhesion, strong antioxidant, and antibacterial activities, as well as rapid hemostasis. HRP and H2O2 catalyze the polymerization of PA monomer and color darkening, endowing the hydrogel with near-infrared (NIR) responsiveness and a photothermal antimicrobial property. Moreover, within a murine model of full-thickness burn injury, the hydrogel assisted by NIR irradiation efficiently inhibits bacterial infection, promotes angiogenesis and collagen deposition, and mitigates inflammatory response. Our study demonstrates that the HRP/H2O2-catalyzed QCS-PA (QP) hydrogel possesses excellent antioxidant, antibacterial, and anti-inflammatory properties, offering a new therapeutic strategy for wound healing.

Lactate, a byproduct of glycolysis, was thought to be a metabolic waste until the discovery of the Warburg effect. Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions. The Astrocyte-Neuron Lactate Shuttle has clarified that lactate plays a pivotal role in the central nervous system. Moreover, protein lactylation highlights the novel role of lactate in regulating transcription, cellular functions, and disease development. This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases, thus providing optimal perspectives for future research.

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is closely associated with gut microbiota dysbiosis. The critical mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. While the significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating mucus layer and gut microbiota remains enigmatic. Current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as opposed to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation following irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice post-irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, mini-gut organoid system and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, while administration of broad-spectrum antibiotics didn't impact the alteration of goblet cell numbers and MUC2 secretion, it did effectively attenuate inflammation levels in the ileum of irradiated REGγ absent mice, aligning them with their wild-type counterparts. Collectively, these findings highlight the crucial contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.

ATP citrate lyase (ACLY), as a key enzyme in lipid metabolism, plays an important role in energy metabolism and lipid biosynthesis of a variety of tumours. Many studies have shown that ACLY is highly expressed in various tumours, and its pharmacological or gene inhibition significantly inhibits tumour growth and progression. However, the roles of ACLY in oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, our data showed that ACLY inhibitor significantly attenuated cell proliferation, migration, invasion and lipid synthesis in different ESCC cell lines, whereas the proliferation, migration, invasion and lipid synthesis of ESCC cells were enhanced after ACLY overexpression. Furthermore, ACLY inhibitor dramatically suppressed tumour growth and lipid metabolism in ESCC cells xenografted tumour model, whereas ACLY overexpression displayed the opposite effect. Mechanistically, ACLY protein harboured acetylated modification and interacted with SIRT2 protein in ESCC cells. The SIRT2 inhibitor AGK2 significantly increased the acetylation level of ACLY protein and inhibited the proliferation and migration of ESCC cells, while overexpression of ACLY partially reversed the inhibitory effect of AGK2 on ESCC cells. Overall, these results suggest that targeting the SIRT2/ACLY signalling axis may be a potential therapeutic strategy for ESCC patients.

Efficient cryopreservation of stem cells is crucial to fabricating off-the-shelf cell products for tissue engineering and regeneration medicine. However, it remains challenging due to utilization of toxic cryoprotectants for reducing ice-related cryodamages to stem cells during freeze-thaw cycle, stringent post-thaw washing process, and further integration of stem cells with scaffolds to form tissue engineering constructs for downstream applications. Herein, a novel cryopreservation platform of stem cells based on an antifreezing polyvinylpyrrolidone/gellan gum/gelatin (PGG) scaffold together is reported with an L-proline assisted cell pre-dehydration strategy. Results show that this platform is capable of inhibiting extra-/intracellular ice, thus can achieve high cryoprotection efficacy to stem cells (≈95%) without using any toxic cryoprotectants and eliminate traditional washing process. Meanwhile, the post-thawed stem cells can maintain their proliferation, differentiation, and paracrine functionalities. More importantly, due to the biocompatibility and three dimensional structure of the PGG scaffold, the post-thawed stem cell-laden PGG scaffold can be directly used as tissue engineering constructs for wound repair by mitigating inflammation and promoting collagen deposition at regenerating tissue sites. This present work demonstrates the feasibility of antifreezing scaffold-based cryopreservation platform of stem cells, which may advance the off-the-shelf stem cell-laden tissue engineering constructs for clinical translation.