Full-Space Electric Field in Mo-Decorated Zn2In2S5 Polarization Photocatalyst for Oriented Charge Flow and Efficient Hydrogen Production.

Integration of photocatalytic hydrogen (H2) evolution with oxidative organic synthesis presents a highly attractive strategy for the simultaneous production of clean H2 fuel and high-value chemicals. However, the sluggish dynamics of photogenerated charge carriers across the photocatalysts result in low photoconversion efficiency, hindering the wide applications of such a technology. Herein, this work overcomes this limitation by inducing the full-space electric field via charge polarization engineering on a Mo cluster-decorated Zn2In2S5 (Mo-Zn2In2S5) photocatalyst. Specifically, this full-space electric field arises from a cascade of the bulk electric field (BEF) and local surface electric field (LSEF), triggering the oriented migration of photogenerated electrons from [Zn-S] regions to [In-S] regions and eventually to Mo cluster sites, ensuring efficient separation of bulk and surface charge carriers. Moreover, the surface Mo clusters induce a tip enhancement effect to optimize charge transfer behavior by augmenting electrons and proton concentration around the active sites on the basal plane of Zn2In2S5. Notably, the optimized Mo1.5-Zn2In2S5 catalyst achieves exceptional H2 and benzaldehyde production rates of 34.35 and 45.31 mmol gcat -1 h-1, respectively, outperforming pristine ZnIn2S4 by 3.83- and 4.15-fold. These findings mark a significant stride in steering charge flow for enhanced photocatalytic performance.

Efficient selective aerobic oxidation of sulfides by molecular dipole modulation in methylphosphate-substituted perylene diimide supramolecular polarization photocatalyst.

Photocatalytic aerobic oxidation is a promising sustainable strategy for the selective organic synthesis of industrially valuable chemicals. However, the poor charge separation and insufficient molecular activation restrict the overall photocatalytic efficiency. To address these issues, we have developed a novel approach involving molecular dipole modulation and polar molecular self-assembly to modulate the built-in electric field (BEF) in perylene diimide (PDI) supramolecular polarization photocatalysts by adjusting the electronegativity of terminal substituents. The optimized methylphosphate-substituted PDI (P-PDIP) supramolecular system features the strongest BEF induced by its large molecular dipole, with an intensity 3.89 times higher than that observed in methylcarboxy-substituted PDI (P-PDIC) and 5.64 times higher than that observed in P-PDI. This significant enhancement in BEF generates a powerful driving force within P-PDIP, facilitating directional charge separation toward active sites. Additionally, the incorporation of methylphosphate groups improves the activation efficiency of O2 and thioether molecules, resulting in a remarkable photocatalytic performance for selective aerobic oxidation of sulfides into sulfoxide (up to 99.9% conversion and 99.8% selectivity). This study highlights that enhancing BEF through manipulating molecular dipoles can significantly improve photocatalytic activity, offering great potential for constructing efficient organic polarization photocatalysts in green chemistry and sustainable production.

Research progress on and molecular mechanism of vacuum sealing drainage in the treatment of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are common chronic wounds and a common complication of diabetes. The foot is the main site of diabetic ulcers, which involve small and medium-sized arteries, peripheral nerves, and microcirculation, among others. DFUs are prone to coinfections and affect many diabetic patients. In recent years, interdisciplinary research combining medicine and material science has been increasing and has achieved significant clinical therapeutic effects, and the application of vacuum sealing drainage (VSD) in the treatment of DFUs is a typical representative of this progress, but the mechanism of action remains unclear. In this review, we integrated bioinformatics and literature and found that ferroptosis is an important signaling pathway through which VSD promotes the healing of DFUs and that System Xc-GSH-GPX4 and NAD(P)H-CoQ10-FSP1 are important axes in this signaling pathway, and we speculate that VSD is most likely to inhibit ferroptosis to promote DFU healing through the above axes. In addition, we found that some classical pathways, such as the TNF, NF-κB, and Wnt/ß-catenin pathways, are also involved in the VSD-mediated promotion of DFU healing. We also compiled and reviewed the progress from clinical studies on VSD, and this information provides a reference for the study of VSD in the treatment of DFUs.

[Prefabricated curvature internal fixation with Kirschner needle for forearm fracture in children].

OBJECTIVE: To explore clinical effect of precast curvature internal fixation with Kirschner needle in treating forearm fracture in children. METHODS: From October 2019 to December 2022,32 children with forearm fractures were treated with precast curvature internal fixation with Kirkler's needles,including 25 males and 7 females,aged from 3 to 15 years old with an average of (8.0±0.5) years old,18 patients on the left side and 14 on the right side,24 patients with double fractures of radial and ulna,3 patients with Monteggia fractures,and 4 patients with Galeazzi fractures,and 1 patient with radial neck fracture of crooked cap. Operation time,intraoperative blood loss,C-arm fluoroscopy,fracture healing time and complications were recorded,and disabilities of arm,shoulder and hand (DASH) scale and Grace-Eversman forearm double fracture evaluation system were used to evaluate clinical efficacy of precast curvature internal fixation with Kirschner's needle for forearm fracture in children. RESULTS: All 32 patients were followed up for 2 to 12 months with an average of (7.16±2.51) months. Intraoperative blood loss was (20.68±5.50) ml,C-arm fluoroscopy was(5.80±2.50),and operation time was (24.34±5.10) min,fracture healing time was (8.82±1.62) weeks. Two patients occurred complications,including postoperative rupture of extensor pollicis longus tendon in 1 patient and obvious displacement of fracture caused by rotation of prefabricated curvature Kirschler needle on bone marrow cavity in 1 patient. DASH scores ranged from 0 to 16 scores with an average of (8.32±1.50) scores. According to Grace-Eversman double fracture evaluation system,28 patients got excellent result,2 good and 2 fair. CONCLUSION: The treatment of forearm fracture with Kirschner's needle prefabricated curvature internal fixation has advantages of less trauma,less bleeding,good reduction,stable fixation,fast fracture healing and good functional recovery.

ABA functions in low phosphate-induced anthocyanin accumulation through the transcription factor ABI5 in Arabidopsis.

KEY MESSAGE: ABI5 functions in ABA-mediated anthocyanin accumulation in plant response to low phosphate. Low phosphate (LP)-induced anthocyanin biosynthesis and accumulation play an important role in plant adaptive response to phosphate starvation conditions. However, whether and how the stress phytohormone abscisic acid (ABA) participates in LP-induced anthocyanin accumulation remain elusive. Here, we report that ABA is required for LP-induced anthocyanin accumulation in Arabidopsis thaliana. Disrupting ABA DEFICIENT2 (ABA2), a key ABA-biosynthetic gene, or BETA-GLUCOSIDASE1 (BG1), a major gene implicated in converting conjugated ABA to active ABA, significantly impairs LP-induced anthocyanin accumulation, as LP-induced expression of the anthocyanin-biosynthetic genes Chalcone Synthase (CHS) is dampened in the aba2 and bg1 mutant. In addition, LP-induced anthocyanin accumulation is defective in the mutants of ABA signaling pathway, including ABA receptors, ABA Insensitive2, and the transcription factors ABA Insensitive5 (ABI5), suggesting a role of ABI5 in ABA-mediated upregulation of anthocyanin-biosynthetic genes in plant response to LP. Indeed, LP-induced expression of CHS is repressed in the abi5-7 mutant but further promoted in the ABI5-overexpressing plants compared to the wild-type. Moreover, ABI5 can bind to and transcriptionally activate CHS, and the defectiveness of LP-induced anthocyanin accumulation in abi5-7 can be restored by overexpressing CHS. Collectively, our findings illustrates that ABI5 functions in ABA-mediated LP-induced anthocyanin accumulation in Arabidopsis.

YAP promotes the healing of ischemic wounds by reducing ferroptosis in skin fibroblasts through inhibition of ferritinophagy.

The impaired healing of chronic wounds is often attributed to the ischemic and hypoxic microenvironment, leading to increased cell death. Ferroptosis, a novel form of cell death unveiled in recent years, could potentially be linked with the process of wound healing. In this study, we explored the significance and mechanism of ferroptosis in ischemic wounds. Using transmission electron microscopy, Western blot, flow cytometry, immunofluorescence, and glutathione (GSH) assay, we observed that the death of primary mouse skin fibroblasts induced by oxygen and glucose deprivation (OGD) was associated with ferroptosis. Specifically, we observed elevated intracellular Fe2+ and lipid peroxidation levels and decreased GSH levels in vitro, indicative of ferroptosis. Importantly, we found that ferroptosis in OGD-treated skin fibroblasts was dependent on autophagy, as the autophagy inhibitor chloroquine phosphate (CHQ) significantly reduced ferroptosis induced by OGD. Moreover, our study revealed that NCOA4-mediated ferritinophagy significantly contributed to the occurrence of ferroptosis induced by OGD in skin fibroblasts. Additionally, we identified the involvement of YAP in the regulation of ferritinophagy, with YAP suppressing NCOA4 expression in OGD-treated skin fibroblasts, thereby reducing ferroptosis. Furthermore, in ischemic wound models in mice, both inhibitors of ferroptosis and autophagy promoted wound healing, while a YAP inhibitor, verteporfin, delayed wound healing. In conclusion, these findings indicate that ferroptosis, regulated by YAP through ferritinophagy inhibition, presents a novel mechanism responsible for the delayed healing of ischemic wounds. Understanding this process could offer promising therapeutic targets to improve wound healing in ischemic conditions.

P75NTR regulates autophagy through the YAP-mTOR pathway to increase the proliferation of interfollicular epidermal cells and promote wound healing in diabetic mice.

Wound healing is delayed in diabetic patients. Increased autophagy and dysfunction of interfollicular epidermal (IFE) cells are closely associated with delayed healing of diabetic wounds. Autophagy plays an important role in all stages of wound healing, but its role in diabetic wound healing and the underlying molecular mechanisms are not clear. Here, we found that diabetic mice had delayed wound healing and increased autophagy in wounds compared with normal mice and that chloroquine, an inhibitor of autophagy, decreased the level of autophagy, improved the function of IFE cells, and accelerated wound healing in diabetic mice. Treatment of IFE cells with advanced glycosylation end products (AGEs) resulted in increased microtubule-associated protein chain (LC3) expression and decreased prostacyclin-62 (P62) expression, indicating increased autophagy in AGE-treated IFE cells. Moreover, P75NTR reduced autophagy in IFE cells in the presence of AGEs and significantly increased the proliferation of IFE cells. In addition, P75NTR participated in regulating autophagy in IFE cells and in wounds in diabetic mice through the YAP-mTOR signalling pathway, which increased the functional activity of the cells and the healing rate of wounds in diabetic mice. Thus, our study suggests that P75NTR protects IFE cells against AGEs by affecting autophagy and accelerating wound healing in diabetic mice, providing a basis for understanding the role of autophagy in diabetic wound healing.

Risk factors for venous ulceration in patients with varicose veins of lower extremities.

The aim of this case-control study was to explore the potential risk factors for venous ulceration in patients with varicose veins of lower extremities and to establish a simplified diagnostic score model. Seventy subjects with varicose veins of lower extremities and venous ulceration were compared with 1164 controls with varicose veins of lower extremities and no history of venous ulceration. Stepwise multivariate logistic regression analysis was used to identify the risk factors for venous ulceration. The steps in developing the diagnostic score model were based on the Framingham Heart study. The area under the receiver operating characteristic curve (AUC) was calculated to assess the diagnostic ability of the diagnostic score model. Multivariate analysis showed that men, overweight, obesity, longer duration varicose veins, deep venous valve insufficiency, low lymphocyte counts, and high fibrinogen content were independently associated with an increased risk of venous ulceration. The AUC for the diagnostic score model was 0.75, which indicated good discriminatory ability. Special attention should be paid to the high-risk group of patients with lower extremity varicose veins. The diagnostic score model might be a useful screening tool for clinicians, policy makers, and patients.

HbBIN2 Functions in Plant Cold Stress Resistance through Modulation of HbICE1 Transcriptional Activity and ROS Homeostasis in Hevea brasiliensis.

Cold stress poses significant limitations on the growth, latex yield, and ecological distribution of rubber trees (Hevea brasiliensis). The GSK3-like kinase plays a significant role in helping plants adapt to different biotic and abiotic stresses. However, the functions of GSK3-like kinase BR-INSENSITIVE 2 (BIN2) in Hevea brasiliensis remain elusive. Here, we identified HbBIN2s of Hevea brasiliensis and deciphered their roles in cold stress resistance. The transcript levels of HbBIN2s are upregulated by cold stress. In addition, HbBIN2s are present in both the nucleus and cytoplasm and have the ability to interact with the INDUCER OF CBF EXPRESSION1(HbICE1) transcription factor, a central component in cold signaling. HbBIN2 overexpression in Arabidopsis displays decreased tolerance to chilling stress with a lower survival rate and proline content but a higher level of electrolyte leakage (EL) and malondialdehyde (MDA) than wild type under cold stress. Meanwhile, HbBIN2 transgenic Arabidopsis treated with cold stress exhibits a significant increase in the accumulation of reactive oxygen species (ROS) and a decrease in the activity of antioxidant enzymes. Further investigation reveals that HbBIN2 inhibits the transcriptional activity of HbICE1, thereby attenuating the expression of C-REPEAT BINDING FACTOR (HbCBF1). Consistent with this, overexpression of HbBIN2 represses the expression of CBF pathway cold-regulated genes under cold stress. In conclusion, our findings indicate that HbBIN2 functions as a suppressor of cold stress resistance by modulating HbICE1 transcriptional activity and ROS homeostasis.

Multicomponent prediction of 2-year mortality and amputation in patients with diabetic foot using a random survival forest model: Uric acid, alanine transaminase, urine protein and platelet as important predictors.

The current methods for the prediction of mortality and amputation for inpatients with diabetic foot (DF) use only conventional, simple variables, which limits their performance. Here, we used a random survival forest (RSF) model and multicomponent variables to improve the prediction of mortality and amputation for these patients. We performed a retrospective cohort study of 175 inpatients with DF who were recruited between 2014 and 2021. Thirty-one predictors in six categories were considered as potential covariates. Seventy percent (n = 122) of the participants were randomly selected to constitute a training set, and 30% (n = 53) were assigned to a testing set. The RSF model was used to screen appropriate variables for their value as predictors of 2-year all-cause mortality and amputation, and a multicomponent prediction model was established. Model performance was evaluated using the area under the curve (AUC) and the Hosmer-Lemeshow test. The AUCs were compared using the Delong test. Seventeen variables were selected to predict mortality and 23 were selected to predict amputation. Uric acid and alanine transaminase were the top two most useful variables for the prediction of mortality, whereas urine protein and platelet were the top variables for the prediction of amputation. The AUCs were 0.913 and 0.851 for the prediction of mortality for the training and testing sets, respectively; and the equivalent AUCs were 0.963 and 0.893 for the prediction of amputation. There were no significant differences between the AUCs for the training and testing sets for both the mortality and amputation models. These models showed a good degree of fit. Thus, the RSF model can predict mortality and amputation in inpatients with DF. This multicomponent prediction model could help clinicians consider predictors of different dimensions to effectively prevent DF from clinical outcomes .

Simultaneous Preparation of Chitin and Flavor Protein Hydrolysates from the By-Products of Shrimp Processing by One-Step Fermentation with Lactobacillus fermuntum.

One-step fermentation, inoculated with Lactobacillus fermentum (L. fermentum) in shrimp by-products, was carried out to obtain chitin and flavor protein hydrolysates at the same time. The fermentation conditions were optimized using response surface methodology, resulting in chitin with a demineralization rate of 89.48%, a deproteinization rate of 85.11%, and a chitin yield of 16.3%. The surface of chitin after fermentation was shown to be not dense, and there were a lot of pores. According to Fourier transform infrared spectroscopy and X-ray diffraction patterns, the fermented chitin belonged to α-chitin. More than 60 volatiles were identified from the fermentation broth after chitin extraction using gas chromatography-ion transfer spectrometry analysis. L. fermentum fermentation decreased the intensities of volatile compounds related to unsaturated fatty acid oxidation or amino acid deamination. By contrast, much more pleasant flavors related to fruity and roasted aroma were all enhanced in the fermentation broth. Our results suggest an efficient one-step fermentation technique to recover chitin and to increase aroma and flavor constituents from shrimp by-products.

Morphine Withdrawal-Induced Hyperalgesia in Models of Acute and Extended Withdrawal Is Attenuated by l-Tetrahydropalmatine.

Effective pain control is an underappreciated aspect of managing opioid withdrawal, and its absence presents a significant barrier to successful opioid detoxification. Accordingly, there is an urgent need for effective non-opioid treatments to facilitate opioid detoxification. l-Tetrahydropalmatine (l-THP) possesses powerful analgesic properties and is an active ingredient in botanical formulations used in Vietnam for the treatment of opioid withdrawal syndrome. In this study, rats receiving morphine (15 mg/kg, i.p.) for 5 days per week displayed a progressive increase in pain thresholds during acute 23 h withdrawal as assessed by an automated Von Frey test. A single dose of l-THP (5 or 7.5 mg/kg, p.o.) administered during the 4th and 5th weeks of morphine treatment significantly improves pain tolerance scores. A 7-day course of l-THP treatment in animals experiencing extended withdrawal significantly attenuates hyperalgesia and reduces the number of days to recovery to baseline pain thresholds by 61% when compared to vehicle-treated controls. This indicates that the efficacy of l-THP on pain perception extends beyond its half-life. As a non-opioid treatment for reversing a significant hyperalgesic state during withdrawal, l-THP may be a valuable addition to the currently limited arsenal of opioid detoxification treatments.

Antibacterial Effect of Shrimp By-Products Hydrolysate on Specific Spoilage Organisms of Squid.

In order to further develop and utilize shrimp processing by-products, in this study, a novel antibacterial hydrolysate of shrimp by-products by pepsin hydrolysis (SPH) was prepared. The antibacterial effect of SPH on specific spoilage organisms of squid after end storage at room temperature (SE-SSOs) was investigated. SPH showed an antibacterial effect on the growth of SE-SSOs, with (23.4 ± 0.2) mm of inhibition zone diameter. The cell permeability of SE-SSOs was enhanced after SPH treatment for 12 h. Some bacteria were twisted and shrunk, while pits and pores formed and intracellular contents leaked under scanning electron microscopy observation. The flora diversity of SE-SSOs treated with SPH was determined by a 16S rDNA sequencing technique. Results showed that SE-SSOs were mainly composed of the phyla of Firmicutes and Proteobacteria, among which Paraclostridium (47.29%) and Enterobacter (38.35%) were dominant genera. SPH treatment resulted in a significant reduction in the relative abundance of the genus Paraclostridium and increased the abundance of Enterococcus. Linear discriminant analysis (LDA) of LEfSe conveyed that SPH treatment had a significant impact on altering the bacterial structure of SE-SSOs. The 16S PICRUSt of Cluster of Orthologous Group (COG) annotation revealed that SPH treatment for 12 h could significantly increase the function of transcription level [K], while SPH treatment for 24 h could downregulate post-translational modifications, protein turnover, and chaperone metabolism functions [O]. In conclusion, SPH has a proper antibacterial effect on SE-SSOs and can change the flora structure of SE-SSOs. These findings will provide a technical basis for the development of inhibitors of squid SSOs.

CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Beneficial regulation of vitamin D3-rich extract from the processing by-products of Penaeus sinensis on preosteoblastic MC3T3-E1 cells and improvement of bone health in VD-deficient mice.

Vitamin D (VD) plays an important role in preventing osteoporosis. However, knowledge of the osteogenic effect of VD3 from shrimp processing by-products is limited. In this study, a VD3-rich extract from Penaeus sinensis processing by-products was prepared by saponification and liquid-liquid extraction combined with solid phase extraction for purification. The activity of purified VD3-rich extract (PPs-VD3) on MC3T3-E1, a preosteoblastic cell line, was determined. Furthermore, the improvement effect of PPs-VD3 on bone health of VD-deficient mice was investigated. PPs-VD3 stimulated the proliferation and differentiation of MC3T3-E1 cells. Compared to the same concentration of the VD3 standard, mineralization of MC3T3-E1 cells increased after 14 d or 21 d of PPs-VD3 treatment. Western blotting showed that PPs-VD3 significantly upregulated the protein levels of bone morphogenetic protein 2 and runt-related transcription factor 2 compared to the VD3 standard. Furthermore, PPs-VD3 treatment activated the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway in MC3T3-E1 cells, especially increased OPG expression was detected at day 3 to day 14 compared to the VD3 standard treatment. More than ten medium and long chain fatty acids were detected in PPs-VD3, of which n-3 polyunsaturated fatty acids (PUFA) constituted 38.83 ± 8.61%, and the n-3/n-6 PUFA ratio in PPs-VD3 was 2.84 ± 0.23. The femoral trabeculae number and thickness of VD-deficient mice increased after 3 weeks of PPs-VD3 treatment. The changes of parameters associated with bone resorption including parathyroid hormone, bone mineral density and tartrate resistant acid phosphatase revealed the contribution of PPs-VD3 treatment in improving bone remodeling in VD-deficient mice. Our results suggest that PPs-VD3 could have potential prospects in alleviating osteoporosis or promotion of bone health.

Comparison of ability of lesion detection of two MRI sequences of T2WI HASTE and T2WI BLADE for hepatocellular carcinoma.

We investigated the diagnostic accuracy of 2 magnetic resonance imaging (MRI) sequences of T2 weighted image (T2WI) half-Fourier acquired single turbo spin-echo (HASTE) and BLADE, for hepatocellular carcinoma (HCC) detection. From November 2010 to August 2018, patients diagnosed with HCC and regularly followed up, and who underwent MRI with 2 kinds of T2WI, were included in this study. The diagnosis of HCC was established based on histopathological findings or LI-RADS 4 and 5 by image. The sensitivities and positive predictive value for the detection of HCC by T2WI HASTE and BLADE were compared for each sequence. Quantitative assessment with lesion contrast-to-noise ratio and visual rating scoring of image quality, based on factors such as artifact, margin of organs, and vessel sharpness of the 2 sequences, were compared. No significant differences in lesion detection were observed based on paired comparison of all lesions and lesions larger than 1 cm across both sequences. The sensitivity was higher in larger than 1cm group in all sequences. The HASTE sequence had less motion artifact, but the BLADE images had advantage in edge sharpness of organs and vessels. The HASTE without fat-saturation seems to have better overall image quality. The lesions contrast-to-noise ratio of the 2 image modalities were not significantly different. Compared with T2 BLADE, T2 HASTE may be a more effective protocol for detecting HCC larger than 1 cm without loss of sensitivity. The accuracy of data from 2 T2WI protocols could be applied to streamline MRI protocols of HCC screening and surveillance.

Different Regulatory Effects of Heated Products and Maillard Reaction Products of Half-Fin Anchovy Hydrolysates on Intestinal Antioxidant Defense in Healthy Animals.

The oxidative state of intestinal tracts of healthy animals were investigated after short-term intake of half-fin anchovy hydrolysates (HAHp) and their thermal or Maillard reaction products (MRPs). After one month of continuous oral gavage of HAHp, HAHp-heated products (HAHp-H), the MRPs of HAHp with 3% of glucose (HAHp-3%G MRPs), and the MRPs of HAHp with 3% of fructose (HAHp-3%F MRPs) at a dose of 1.0 g/kg of body weight per day into healthy ICR male mice, the concentrations of serum low-density and high-density lipoprotein cholesterol did not significantly change compared to the control group (CK, gavage with saline). Similar results were found for the interleukin-6 concentrations of all groups. By comparison, HAHp-H, HAHp-3%G MRPs, and HAHp-3%F MRPs administration decreased serum tumor necrosis factor-α concentration as compared to the CK group (p < 0.05). No histological damage was observed in the jejunum, ileum, and colonic tissues of all groups. However, HAHp-H treatment induced higher upregulation of Kelch-like ECH-associated protein 1, transcription factors Nrf-2, associated protective phase-II enzymes of NAD(P)H: quinine oxidoreductase-1, and hemoxygenase-1 in colon tissue, as well as higher upregulation of endogenous antioxidant enzymes, including copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase 2 than other groups (p < 0.05). Additionally, increases in Nε-carboxymethyllysine expression in the colonic tissues of all groups were consistent with their increased oligopeptide transporter 1 expressions. Our results suggest that the thermal products of HAHp might have a broad application prospect in improving antioxidant defense in vivo in healthy animals.

Integrated network pharmacology and experimental validation to explore the mechanisms underlying naringenin treatment of chronic wounds.

Naringenin is a citrus flavonoid with various biological functions and a potential therapeutic agent for skin diseases, such as UV radiation and atopic dermatitis. The present study investigates the therapeutic effect and pharmacological mechanism of naringenin on chronic wounds. Using network pharmacology, we identified 163 potential targets and 12 key targets of naringenin. Oxidative stress was confirmed to be the main biological process modulated by naringenin. The transcription factor p65 (RELA), alpha serine/threonine-protein kinase (AKT1), mitogen-activated protein kinase 1 (MAPK1) and mitogen-activated protein kinase 3 (MAPK3) were identified as common targets of multiple pathways involved in treating chronic wounds. Molecular docking verified that these four targets stably bound naringenin. Naringenin promoted wound healing in mice in vivo by inhibiting wound inflammation. Furthermore, in vitro experiments showed that a low naringenin concentration did not significantly affect normal skin cell viability and cell apoptosis; a high naringenin concentration was cytotoxic and reduced cell survival by promoting apoptosis. Meanwhile, comprehensive network pharmacology, molecular docking and in vivo and in vitro experiments revealed that naringenin could treat chronic wounds by alleviating oxidative stress and reducing the inflammatory response. The underlying mechanism of naringenin in chronic wound therapy involved modulating the RELA, AKT1 and MAPK1/3 signalling pathways to inhibit ROS production and inflammatory cytokine expression.

Single-cell RNA-Seq analysis of diabetic wound macrophages in STZ-induced mice.

The crucial role of macrophages in the healing of chronic diabetic wounds is widely known, but previous in vitro classification and marker genes of macrophages may not be fully applicable to cells in the microenvironment of chronic wounds. The heterogeneity of macrophages was studied and classified at the single-cell level in a chronic wound model. We performed single-cell sequencing of CD45 + immune cells within the wound edge and obtained 17 clusters of cells, including 4 clusters of macrophages. One of these clusters is a previously undescribed population of macrophages possessing osteoclast gene expression, for which analysis of differential genes revealed possible functions. We also analysed the differences in gene expression between groups of macrophages in the control and diabetic wound groups at different sampling times. We described the differentiation profile of mononuclear macrophages, which has provided an important reference for the study of immune-related mechanisms in diabetic chronic wounds.

Gongying-Jiedu-Xiji recipe promotes the healing of venous ulcers by inhibiting ferroptosis via the CoQ-FSP1 axis.

Objective: Gongying-Jiedu-Xiji recipe (DDL, batch number Z01080175) reduces body temperature, detoxifies, activates the blood circulation, reduces swelling, and dispels decay and pus. The aim of this study was to investigate the mechanism of action by which DDL functions in the treatment of venous ulcers (VUs). Methods: Normal tissues as well as VU tissues before and after DDL treatment were collected from nine VU patients in the hospital with ethical approval. These three tissues were subjected to Prussian blue iron staining, immunoblotting, immunohistochemistry, immunofluorescence, and quantitative real-time PCR to detect the expression of ferroptosis suppressor protein 1 (FSP1), coenzyme Q (CoQ), 4-hydroxynonenal (4-HNE), and glutathione peroxidase 4 (GPX4). After successful validation of the heme-induced human foreskin fibroblast (HFF) ferroptosis model, lyophilized DDL powder was added to the cells, and the cells were subjected to viability assays, immunoblotting, flow cytometry, glutathione (GSH) and malonaldehyde (MDA) assays, electron microscopy and qPCR assays. Results: Ferroptosis in VU tissues was stronger than that in normal tissues, and ferroptosis in VU tissues after DDL treatment was weaker than that before treatment. Inhibition of CoQ and FSP1 and transfection of FSP1 influenced the effects of DDL. Conclusion: Our results suggest that DDL may promote healing by attenuating ferroptosis in VUs and that DDL may promote VU healing by modulating the CoQ-FSP1 axis.