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Diabetic wound shows delayed and incomplete healing processes, which in turn exposes patients to an environment with a high risk of infection. This article has summarized current developments of nanoparticles/hydrogels and nanotechnology used for promoting the wound healing process in either diabetic animal models or patients with diabetes mellitus. These nanoparticles/hydrogels promote diabetic wound healing by loading bioactive molecules (such as growth factors, genes, proteins/peptides, stem cells/exosomes, etc.) and non-bioactive substances (metal ions, oxygen, nitric oxide, etc.). Among them, smart hydrogels (a very promising method for loading many types of bioactive components) are currently favored by researchers. In addition, nanoparticles/hydrogels can be combined with some technology (including PTT, LBL self-assembly technique and 3D-printing technology) to treat diabetic wound repair. By reviewing the recent literatures, we also proposed new strategies for improving multifunctional treatment of diabetic wounds in the future.

In recent years, chemodynamic therapy (CDT) has received extensive attention as a novel means of cancer treatment. The CDT agents can exert Fenton and Fenton-like reactions in the acidic tumor microenvironment (TME), converting hydrogen peroxide ([H.sub.2][O.sub.2]) into highly toxic hydroxyl radicals (*OH). However, the pH of TME, as an essential factor in the Fenton reaction, does not catalyze the reaction effectively, hindering its efficiency, which poses a significant challenge for the future clinical application of CDT. Therefore, this paper reviews various strategies to enhance the antitumor properties of nanomaterials by modulating tumor acidity. Ultimately, the performance of CDT can be further improved by inducing strong oxidative stress to produce sufficient *OH. In this paper, the various acidification pathways and proton pumps with potential acidification functions are mainly discussed, such as catalytic enzymes, exogenous acids, CAIX, MCT, NHE, NBCn1, etc. The problems, opportunities, and challenges of CDT in the cancer field are also discussed, thereby providing new insights for the design of nanomaterials and laying the foundation for their future clinical applications. Keywords: chemodynamic therapy, Fenton/Fenton-like reactions, tumor microenvironment, reactive oxygen specie

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO 2 @GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO 2 nanoparticles were prepared first and MnO 2 @GA-Fe nanoparticles with Fe 3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO 2 @GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO 2 could deplete intracellular GSH and produce Mn 2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe 3+ to Fe 2+ . Mn 2+ and Fe 2+ catalyzed the endogenous H 2 O 2 to produce high-lever ROS to kill tumor cells. Compared with MnO 2 , MnO 2 @GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment. Graphical Abstract

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.

Diabetes-related chronic wounds are often accompanied by a poor wound-healing environment such as high glucose, recurrent infections, and inflammation, and standard wound treatments are fairly limited in their ability to heal these wounds. Metal–organic frameworks (MOFs) have been developed to improve therapeutic outcomes due to their ease of engineering, surface functionalization, and therapeutic properties. In this review, we summarize the different synthesis methods of MOFs and conduct a comprehensive review of the latest research progress of MOFs in the treatment of diabetes and its wounds. State-of-the-art in vivo oral hypoglycemic strategies and the in vitro diagnosis of diabetes are enumerated and different antimicrobial strategies (including physical contact, oxidative stress, photothermal, and related ions or ligands) and provascular strategies for the treatment of diabetic wounds are compared. It focuses on the connections and differences between different applications of MOFs as well as possible directions for improvement. Finally, the potential toxicity of MOFs is also an issue that we cannot ignore.

Lesion mimic mutants display spontaneous cell death, and thus are valuable for understanding the molecular mechanism of cell death and disease resistance. Although a lot of such mutants have been characterized in rice, the relationship between lesion formation and abscisic acid (ABA) synthesis pathway is not reported. In the present study, we identified a rice mutant, ( ), exhibiting spontaneous cell death, pre-harvest sprouting, enhanced growth, and resistance to rice bacterial and blast diseases. Cell death in the mutant was accompanied with excessive accumulation of H O . Enhanced disease resistance was associated with cell death and upregulation of defense-related genes. Map-based cloning identified a G-to-A point mutation resulting in a D-to-N substitution at the amino acid position 110 of OsABA2 (LOC_Os03g59610) in . Knock-out of through CRISPR/Cas9 led to phenotypes similar to those of . Consistent with the function of in ABA biosynthesis, ABA level in the mutant was significantly reduced. Moreover, exogenous application of ABA could rescue all the mutant phenotypes of . Taken together, our data linked ABA deficiency to cell death and provided insight into the role of ABA in rice disease resistance.

Panicle apical abortion (PAA) causes severe yield losses in rice production, but details about its development and molecular basis remain elusive. Herein, a PAA mutant, , was identified among the progeny of an elite indica maintainer rice line Yixiang 1B (YXB) mutagenized population obtained using ethyl methyl sulfonate. The abortion rate of spikelets in was observed up to 60%. Genetic mapping combined with Mutmap analysis revealed that harbored a single-bp substitution (C to T) that altered its transcript length. This gene encodes calcineurin B-like protein-interacting protein kinase 31 (OsCIPK31) localized into the cytoplasm, and is preferentially expressed in transport tissues of rice. Complementation of by transferring the open reading frame of from YXB reversed the mutant phenotype, and conversely, gene editing by knocking out of in YXB results in PAA phenotype. Our results support that plays an important role in panicle development. We found that dysregulation is caused by the disruption of function due to excessive accumulation of ROS, which ultimately leads to cell death in rice panicle. and MAPK pathway might have a synergistic effect to lead ROS accumulation in response to stresses. Meanwhile the PAA distribution is related to IAA hormone accumulation in the panicle. Our study provides an understanding of the role of OsCIPK31 in panicle development by responding to various stresses and phytohormones.

In the early stages of healing severe burn wounds, increased exudate and immune dysregulation heighten the risk of scar formation. Current dressings for severe burns present significant challenges and are inadequate in effectively managing early burn wounds. To address the above challenges, a deoxyribonucleic acid-functionalized collagen dressing with aligned channels and interconnected porous structure (DNA-Cryo-ACol) was developed. The DNA-Cryo-ACol dressing demonstrated superior exudate drainage abilities: (i) draining excess exudate at a rate 50 times faster than commercial dressings; (ii) doubling the maximum exudate absorption capacity compared to commercial dressings; and (iii) preventing exudate maceration through evident capillary action. Furthermore, DNA-Cryo-ACol dressings exhibited the immunomodulatory property to regulate immune responses mediated by CD4 + T cells. Results indicated that the interaction between DNA-Cryo-ACol dressing and CD4 + T cells stimulated the production of scar-inhibiting cytokines while reducing the expression of α-smooth muscle actin. By effectively managing exudate drainage and immune response, DNA-Cryo-ACol dressings significantly promoted tissue regeneration in healed burn wounds, resulting in a sevenfold increase in hair regrowth and recovery of collagen components to levels comparable to unwounded skin. The findings from this study laid the groundwork for the development of smart materials aimed at early burn wound management to inhibit scarring. Graphical abstract

Background Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China. Patients and Methods This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX ( n = 55, each). Results In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69–1.68]. The objective response rate was higher [50.0% (95% CI 34.6–65.4%) versus 23.9% (95% CI 11.1–36.7%)] in the sintilimab + mFFX group ( P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62–1.40), and 84.1% (72.8–95.3%) and 71.7%, (58.2–85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively. Conclusions The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%. Trial registration ClinicalTrials.Gov; NCT03977272

Background Sarcopenia, characterized by loss of muscle mass and strength, has been linked to various health outcomes, including diabetes mellitus. This study aims to investigate the association of sarcopenia index, based on serum creatinine and cystatin C levels, with incident diabetes mellitus in middle-aged and older adults in China. Methods This study extracted data from 2015 to 2020 China Health and Retirement Longitudinal Study (CHARLS), including age ≥ 45-year adults without diabetes mellitus at baseline. Sarcopenia index was calculated based on serum creatinine and cystatin C levels, and incident diabetes mellitus was assessed through follow-up surveys. Cox proportional hazards regression models were used to analyze the association between sarcopenia index and incident diabetes mellitus, adjusting for potential confounders, with hazard ratio (HR) with 95% confidence interval (95% CI) reported. Results During a mean follow-up period of 5.0 years, a total of 501 new cases of diabetes were recorded. A total of 7718 participants were included in the analysis. The median age was 60 years, and 46.2% were male. During a mean follow-up period of 5.0 years, 501 cases of incident diabetes mellitus were identified. After adjusting for covariates, Compared with participants in the lowest quartile, the corresponding diabetes HRs (95% CIs) for participants in the second, third, and fourth quartiles were 0.930 (95% CI 0.724–1.193; P  = 0.567); 0.892 (95% CI 0.685–1.162; P  = 0.398), 0.869 (95% CI 0.657–1.150; P  = 0.327). Restricted cubic spline curves revealed that incident rate decreased with increase in sarcopenia index. Conclusions This study provides national longitudinal evidence in China on the association of sarcopenia index, based on serum creatinine and cystatin C levels, with incident diabetes mellitus in middle-aged and older adults. Our findings suggest that sarcopenia index may be a useful biomarker for predicting the risk of diabetes mellitus in this population.