Cuproptosis in microsatellite stable colon cancer cells affects the cytotoxicity of CD8+T through the WNT signaling pathway.

The microsatellite stable (MSS) colon cancer (CC) has long been considered resistant to immunotherapy. Cuproptosis, as a novel form of cell death, may interact with tumor immunity. This project focused on the impact of cuproptosis on the cytotoxicity of CD8+T in MSS CC, aiming to provide effective clues for improving the treatment strategy of MSS CC. The study developed an MSS CC cuproptosis model using 50 nM elesclomol and 1 µM CuCl2. Cuproptotic SW480 cells were directly co-cultured with CD8+ T cells. Cuproptosis levels were assessed via intracellular copper ion detection, Western blot, and confocal laser scanning microscopy. CCK-8, Hochest/PI staining, CFSE cell proliferation assay, LDH cytotoxicity detection, and ELISA were used to evaluate CD8+ T cell immune activity and cytotoxicity. Transcriptome sequencing and bioinformatics analysis identified regulated signals in cuproptotic SW480 cells. A rescue experiment utilized a WNT pathway activator (BML-284). PD-L1 expression in cells/membranes was analyzed using qRT-PCR, Western blot, and flow cytometry. NSG mice were immunoreconstituted, and the effects of cuproptosis on immune infiltration and cancer progression in MSS CC mice were assessed using ELISA and immunohistochemistry (IHC). Treatment with 50 nM elesclomol and 1 µM CuCl2 significantly increased cuproptosis in SW480 cells. Co-culture with CD8+ T cells enhanced their cytotoxicity. Sequencing revealed cuproptosis-mediated modulation of immune and inflammatory pathways, including WNT signaling. Rescue experiments showed downregulation of WNT signaling in cuproptotic SW480 cells. Indirectly, CD8+ T cell immune function was enhanced by reducing PD-L1 expression. In mice, cuproptosis resulted in increased infiltration of CD8+ T cells in tumor tissue, leading to delayed cancer progression compared to the control group. Cuproptosis in MSS CC cells enhances the cytotoxicity of CD8+ T cells, which may be achieved through downregulation of the WNT signaling pathway and decreased expression of PD-L1. In the future, drugs that can induce cuproptosis may be a promising approach to improve MSS CC immunotherapy.

Low concentrations of tetrabromobisphenol A promote the biofilm formation of methicillin-resistant Staphylococcus aureus.

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.

Asymmetric chitosan-derivative/carboxymethylcellulose layer-by-layer film combining antimicrobial and vascular regeneration for the repair of infected wounds.

Bacterially infected wounds are a serious threat to patients' lives and health, and multifunctional dressings with antimicrobial properties and healing promotion are urgently needed. Thus, we used the cationic and anionic properties of chitosan (CS)-nerol (N) derivative (CSN) and carboxymethylcellulose (CMC) to prepare asymmetric layer-by-layer self-assembled (LBL) composite films (CSN-CMC LBL films) with antibacterial and healing properties using a spin-coating method. SEM images showed that the CSN-CMC LBL films had completely different degrees of roughness at the bottom (hydrophilic layer) and at the top (hydrophobic layer), with the roughness at the top increasing as the number of layers increased. The CSN and CMC were used to prepare asymmetric LBL films via the electrostatic attraction of -COO- and NH3+. In addition, adhesion and water contact angle tests showed that the CSN-CMC LBL films had enhanced tissue adhesion and good hydrophobicity. These materials had excellent antimicrobial activity and good biocompatibility. Importantly, the animal infection model results showed that CSN-CMC-8 LBL films effectively eliminated the infection in vivo, inhibited inflammation, promoted vascular regeneration, accelerated the epithelialization process, and achieved high quality healing. Overall, the CSN-CMC LBL films in this study showed considerable potential for application in infected wound healing.

KLF5 promotes the ossification process of ligamentum flavum by transcriptionally activating CX43.

BACKGROUND: Ossification of ligamentum flavum (OLF) is a prevalent degenerative spinal disease, typically causing severe neurological dysfunction. Kruppel-like factor 5 (KLF5) plays an essential role in the regulation of skeletal development. However, the mechanism KLF5 plays in OLF remains unclear, necessitating further investigative studies. METHODS: qRT-PCR, immunofluorescent staining and western blot were used to measure the expression of KLF5. Alkaline Phosphatase (ALP) staining, Alizarin red staining (ARS), and the expression of Runt-related transcription factor 2 (RUNX2), osteopontin (OPN), and osteocalcin (OCN) were used to evaluate the osteogenic differentiation. Luciferase activity assay and ChIP-PCR were performed to investigate the molecular mechanisms. RESULTS: KLF5 was significantly upregulated in OLF fibroblasts in contrast to normal ligamentum flavum (LF) fibroblasts. Silencing KLF5 diminished osteogenic markers and mineralized nodules, while its overexpression had the opposite effect, confirming KLF5's role in promoting ossification. Moreover, KLF5 promotes the ossification of LF by activating the transcription of Connexin 43 (CX43), and overexpressing CX43 could reverse the suppressive impact of KLF5 knockdown on OLF fibroblasts' osteogenesis. CONCLUSION: KLF5 promotes the OLF by transcriptionally activating CX43. This finding contributes significantly to our understanding of OLF and may provide new therapeutic targets.

Characteristics Associated with Trial of Labor among Patients with Twin Pregnancies.

OBJECTIVE: This study aimed to identify patient and provider factors associated with undergoing trial of labor (TOL) among eligible patients with twin gestations. STUDY DESIGN: This retrospective cohort study of patients with twin gestations who received care at a large tertiary care center from 2000 to 2016 included individuals with live pregnancies greater than 23 weeks of gestation and cephalic-presenting twin. Patients with a prior uterine scar or contraindication to vaginal delivery were excluded from analyses. Maternal and clinical characteristics were compared among patients who did and did not undergo TOL. Multivariable logistic regression models included characteristics chosen a priori and those with bivariable associations with p < 0.1. Interactions between parity and other significant variables in the primary models were also investigated. RESULTS: Among 1,888 eligible patients, 80.7% (N = 1,524) underwent TOL. Those undergoing TOL were more likely to be younger, multiparous, and have a maternal-fetal medicine physician as the delivering provider (p < 0.01). Hypertensive disorders of pregnancy were less prevalent among patients undergoing TOL (20.2 vs. 27.8%, p < 0.01). In multivariable analysis, advanced maternal age (adjusted odds ratio [aOR]: 0.55, 95% confidence interval [CI]: 0.40-0.74) and nulliparity (aOR: 0.36, 95% CI: 0.25-0.52) conferred a lower odds of TOL, while having a maternal-fetal medicine provider (aOR: 2.74, 95% CI: 1.55-4.83) was associated with higher odds. Interaction analyses demonstrated no significant interaction effects between parity and other characteristics. Among those undergoing a TOL, 76.0% (1,158/1,524) had a successful vaginal delivery of both twins, with 48.1% (557/1,158) having breech extraction of the second twin. CONCLUSION: In this cohort of twin gestations with a high frequency of TOL, patient and provider characteristics are associated with attempting vaginal delivery. Variation in provider practices suggests differing skills and comfort with twin vaginal delivery may influence route of delivery decision-making in patients with twins. KEYPOINTS: · Most patients with twin pregnancies undergoing TOL had successful vaginal deliveries.. · Having an MFM delivering provider was associated with higher odds of attempting twin TOL.. · Nulliparity and advanced maternal age were associated with lower odds of twin TOL..

Prognostic Nutritional Index and the Risk of Postoperative Complications After Spine Surgery: A Meta-Analysis.

BACKGROUND: A low prognostic nutritional index (PNI) may reflect malnutrition, which has been associated with poor prognosis in patients with various clinical conditions. The aim of the systematic review and meta-analysis was to investigate the association between preoperative PNI and risk of postoperative complications in adult patients after spine surgery. METHODS: An extensive search was conducted on PubMed, Embase, and Web of Science to identify relevant cohort studies. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. RESULTS: Ten cohort studies involving 3,249 patients receiving spine surgeries were included. Pooled results showed that a low preoperative prognostic nutritional index (PNI) was associated with an increased risk of overall postoperative complications in these patients (odds ratio [OR]: 1.82, 95% confidence interval [CI]: 1.42 to 2.34, P < 0.001; I2 = 49%). Specifically, a preoperative malnutrition as evidenced by a low PNI was associated with a higher incidence of postoperative delirium (OR: 2.36, 95% CI: 1.52 to 3.66, P < 0.001; I2 = 38%) and surgical site infection (OR: 1.41, 95% CI: 1.15 to 1.73, P = 0.001; I2 = 0%). Sensitivity analyses by excluding one study at a time did not significantly change the results (P all <0.05). CONCLUSIONS: A preoperative low prognostic nutritional index (PNI) may be a risk factor of increased incidence of overall postoperative complications, postoperative delirium, and surgical site infection in adult patients after spine surgeries.

Double Network Physical Crosslinked Hydrogel for Healing Skin Wounds: New Formulation Based on Polysaccharides and Zn2.

Developing convenient, efficient, and natural wound dressings remain the foremost strategy for treating skin wounds. Thus, we innovatively combined the semi-dissolved acidified sol-gel conversion method with the internal gelation method to fabricate SA (sodium alginate)/CS (chitosan)/Zn2+ physically cross-linked double network hydrogel and named it SA/CS/Zn2+ PDH. The characterization results demonstrated that increased Zn2+ content led to hydrogels with improved physical and chemical properties, such as rheology, water retention, and swelling capacity. Moreover, the hydrogels exhibited favorable antibacterial properties and biocompatibility. Notably, the establishment of an in vitro pro-healing wound model further confirmed that the hydrogel had a superior ability to repair wounds and promote skin regeneration. In future, as a natural biomaterial with antimicrobial properties, it has the potential to promote wound healing.

Sublobar resection reduces the risk of postoperative cognitive dysfunction compared with lobectomy.

OBJECTIVES: Sublobar resection, including wedge resection and segmentectomy, is non-inferior to lobectomy in early-stage non-small cell lung cancer treatment. We aimed to compare the risk of postoperative cognitive dysfunction (POCD) between sublobar resection and lobectomy. METHODS: We conducted a prospective cohort study. Patients with sublobar resection or lobectomy were divided into the sublobar group or the lobar group, respectively. Cognition was assessed before and after surgery with Montreal Cognitive Assessment and Minimum Mental State Examination tests. POCD is defined as Z score of Montreal Cognitive Assessment change ≤-1.96. Propensity score matching (PSM) was performed to make demographics well-balanced between the 2 groups. RESULTS: A total of 335 patients were enrolled. Both the postoperative 1-day POCD rate (sublobar 5.5% vs lobar 18.2%, P < 0.001) and the postoperative 1-month POCD rate (sublobar 7.9% vs lobar 21.8%, P < 0.001) were significantly lower in the sublobar group compared with lobar group, with demographics unbalanced between the 2 groups. In the 133 demographics-matched pairs obtained by PSM, both the postoperative 1-day POCD rate (sublobar 5.3% vs lobar 17.3%, P = 0.005) and the postoperative 1-month POCD rate (sublobar 8.3% vs lobar 18.8%, P = 0.018) remained significantly lower in the sublobar group than in the lobar group. The incidences of postoperative 1-day (P = 0.109) and postoperative 1-month (P = 0.026) Minimum Mental State Examination abnormity were also lower in the sublobar group than in the lobar group but only the latter was with statistical significance after PSM. CONCLUSIONS: Sublobar resection has an advantage over lobectomy in preventing POCD. Our findings might be a reference for selecting the most suitable type of resection for non-small-cell lung cancer patients.

Marine-Derived Bioactive Peptides Self-Assembled Multifunctional Materials: Antioxidant and Wound Healing.

Peptide self-assembling materials have received significant attention from researchers in recent years, emerging as a popular field in biological, environmental, medical, and other new materials studies. In this study, we utilized controllable enzymatic hydrolysis technology (animal proteases) to obtain supramolecular peptide self-assembling materials (CAPs) from the Pacific oyster (Crassostrea gigas). We conducted physicochemical analyses to explore the pro-healing mechanisms of CAPs on skin wounds in both in vitro and in vivo experiments through a topical application. The results demonstrated that CAPs exhibit a pH-responsive behavior for self-assembly and consist of peptides ranging from 550 to 2300 Da in molecular weight, with peptide chain lengths of mainly 11-16 amino acids. In vitro experiments indicated that CAPs display a procoagulant effect, free radical scavenging activity, and promote the proliferation of HaCaTs (112.74% and 127.61%). Moreover, our in vivo experiments demonstrated that CAPs possess the ability to mitigate inflammation, boost fibroblast proliferation, and promote revascularization, which accelerates the epithelialization process. Consequently, a balanced collagen I/III ratio in the repaired tissue and the promotion of hair follicle regeneration were observed. With these remarkable findings, CAPs can be regarded as a natural and secure treatment option with high efficacy for skin wound healing. The potential of CAPs to be further developed for traceless skin wound healing is an exciting area for future research and development.

Efficient control of cyanobacterial blooms with calcium peroxide: Threshold and mechanism.

This study explored the feasibility and mechanism of cyanobacterial blooms control by calcium peroxide (CaO2). The obtained results demonstrated a strong inhibitory effect of CaO2 on cyanobacterial growth. The removal chlorophyll-a rate reached 31.4 %, while optimal/maximal quantum yield of PSII (Fv/Fm) decreased to 50 % after CaO2 treatment at a concentration of 100 mg L-1 for 96 h. Two main mechanisms were involved in the treatment of cyanobacterial bloom with CaO2, namely oxidative damage and cyanobacterial colony formation. It was found that CaO2 released reactive oxygen species (ROS), namely hydroxyl radicals (·OH), singlet oxygen (1O2), and superoxide radicals (·O2-), inhibiting the activity of antioxidant enzymes in cyanobacterial cells and resulting in intracellular oxidation imbalance. Cyanobacteria can resist oxidative damage by releasing extracellular polymeric substances (EPS). These EPS can combine with CaO2-derived Ca, forming large cyanobacterial aggregates and, consequently, accelerating cell sedimentation. In addition, CaO2 caused programmed cell death (PCD) of cyanobacteria and irreversible damage to the ultrastructure characteristic of the cyanobacterial cells. The apoptotic rate was greatly improved at 100 mg L-1 CaO2. On the other hand, the results obtained using qRT-PCR analysis confirmed the contribution of CaO2 to the down-regulation of photosynthesis-related genes (rbcL and psaB), the up-regulation of microcystins (mcyA and mcyD), the up-regulation of the oxidation system: peroxiredoxin (prx) through oxidative mechanisms. The present study proposes a novel treatment method for water-containing cyanobacterial blooms using CaO2.

A novel water-soluble chitosan grafted with nerol: Synthesis, characterization and biological activity.

In order to improve the antibacterial activity of chitosan and change its solubility, a novel water-soluble chitosan (CS)-nerol (N) derivative (CS-N) was prepared via Schiff base reaction and grafting reaction. FT-IR, NMR, XRD, TGA and SEM were used to characterize the structure and physicochemical properties, and in vitro antibacterial, antioxidant, and cellular assays were used to test for bioactivity and safety. The results revealed that the C6 hydroxyl group of CS was substituted with N, with a degree of substitution of 38 % for CS-N. Furthermore, compared to CS, CS-N demonstrated superior antibacterial activity against Escherichia coli and Staphylococcus aureus, as well as significant DPPH and ABTS free radical scavenging activity. Most importantly, CS-N did not harm HaCaT cells. In conclusion, this study provides a promising strategy for the design of chitosan derivatives with significant potential for application in pharmaceutical, food and cosmetic applications.

Relationship of anthropometric measurements and percent body fat mass to cardiovascular disease risk factors in adults with cerebral palsy.

INTRODUCTION: Adults with cerebral palsy (CP) face high morbidity from cardiovascular disease (CVD). Of concern, classic screening parameters are inconsistent in identifying CVD risk in this population. Dual-energy x-ray absorptiometry (DEXA), which provides direct measurements of fat mass (FM), may be an alternative screening method. OBJECTIVE: To evaluate whether FM measurement with DEXA is feasible in screening adults with CP and compare FM and anthropometric measures to CVD risk factors. DESIGN: Cross-sectional study. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Forty-seven adults with CP. MAIN OUTCOME MEASURES: Weight, height, waist circumference (WC), and hip circumference (HC) were measured; waist-to-hip ratio (WHR) and body mass index (BMI) were calculated. Blood pressure (BP), FM by DEXA, hemoglobin A1c (HbA1c), and lipid measurements were obtained. Logistic regression models investigated odds ratios (ORs) and 95% confidence intervals (CIs) between anthropometric measurements/FM and CVD risk factors; correlations were assessed using Pearson correlation coefficients. RESULTS: Elevated BP or hypertension diagnosis was present in 47.8%; HbA1c ≥5.7% in 22.2%; and high-density lipoprotein (HDL) level below optimal for 33.3%. DEXA FM was obtained in 29 of 47 participants, as surgical metal and positioning limited many studies. Excess FM was noted in 75.9% versus 41.3% overweight/obese by BMI. WC correlated with HbA1c (r = 0.46, p = .002), HDL (r = -0.36, p = .018), and triglyceride (TG) levels (r = 0.30, p = .045); however at-risk WC values were associated only with odds of elevated HbA1c (OR 8.53, 95% CI 1.46-50.05; p = .018). HC correlated with HbA1c levels (r = 0.38, p = .011) and systolic BPs (r = 0.35, p = .019); similarly, ORs for elevated HC were weakly associated with elevated HbA1c and BPs (OR 1.08, 95% CI 1.01-1.16; p = .024 and OR 1.07, 95% CI 1.01-1.14; p = .024, respectively). WHR correlated with TGs; however few TG levels were elevated. FM measures were not associated with at-risk lab values or BPs. CONCLUSIONS: DEXA FM measurements may not be feasible for CVD screening in many adults with CP. Although CVD risk factors are frequently present, anthropometric measurements commonly used for general population screening may not translate well to adults with CP.

Telemedicine Use Among Physiatrists During the Early Phase of the COVID-19 Pandemic and Potential for Future Use.

Introduction: With the coronavirus disease 2019 (COVID-19) pandemic causing the need for social distancing, telemedicine saw a significant increase in use to provide routine medical care. As a field, physiatry had already been implementing telemedicine prior to the pandemic. In this study, we characterized the use of telemedicine among physiatrists during the early phase of the COVID-19 pandemic to understand the barriers and facilitators to implementing telemedicine use in the field of physiatry in the future. Methods: Online survey of a cross-sectional sample of physiatrists. Analysis was conducted using logistic regression. Results: One hundred seventy one (n = 171) participants completed the survey. Before the pandemic, only 17.5% of respondents used telemedicine. In the logistic regression, physicians who used a hospital-provided platform were more likely to use telemedicine in the future compared with those who used their own secure platform, conducted a phone visit, and used a non-secure platform or other platforms. The three most popular barriers identified were "inability to complete the physical examination," "patients lack of access to technology," and "patients lack of familiarity with the technology." Discussion: Focus on education on telemedicine functional examination strategies and technology strategies for patients and providers (including addressing the digital divide and hospital-provided secure platforms) are potential targets of implementation strategies for greater telemedicine uptake for physiatrists in the future.

Race/Ethnicity and Perception of Care: Does Patient-Provider Concordance Matter?

OBJECTIVE: We determine whether racial concordance between postpartum patients and obstetric providers (dyads) impacts the perception of quality of care among people undergoing intrapartum obstetrical procedures. STUDY DESIGN: This is a prospective cohort study of postpartum people who underwent operative vaginal or cesarean deliveries in the second stage of labor. Participants were asked to identify the race of their primary provider and complete the Interpersonal Processes of Care (IPC) survey, which assesses communication, patient-centered decision-making, and interpersonal style. The association of participant-identified patient-provider racial concordance with IPC scores was determined. The primary outcome was the IPC subdomain related to discrimination, and secondary outcomes included other IPC subdomains and IPC results by participant racial identity (Black, LatinX vs. White). Sociodemographic and biomedical data were extracted from the medical record. Bivariable analyses were performed. RESULTS: Of 168 patients who were approached, 107 (63.6%) agreed to participate and 87 (81.3%) completed the survey. The majority (n=49) identified a racially discordant provider. Participants in racially concordant dyads were more likely to be older, White, use English as a primary language, complete a higher degree of education, and have a higher household income when compared with racially discordant dyads. Intrapartum outcomes were not significantly different between groups. Median IPC subtest scores were not significantly different between groups or between racial/ethnic identities. CONCLUSION: There were no significant differences in perceptions of IPC between racially concordant versus discordant dyads. However, there is an ongoing need to further clarify measures of quality of care in high-acuity obstetrical situations to remediate ongoing racial and ethnic disparities in adverse health outcomes. KEY POINTS: · Racial concordance between patient and clinician has been associated with improved quality of care.. · There are limited data on racial concordance and perceptions of operative obstetrical care (e.g., operative vaginal delivery).. · Racial concordance was not associated with differences in patient-perceived quality of care associated with operative obstetrics..

Climate change drives rapid decadal acidification in the Arctic Ocean from 1994 to 2020.

The Arctic Ocean has experienced rapid warming and sea ice loss in recent decades, becoming the first open-ocean basin to experience widespread aragonite undersaturation [saturation state of aragonite (Ωarag) < 1]. However, its trend toward long-term ocean acidification and the underlying mechanisms remain undocumented. Here, we report rapid acidification there, with rates three to four times higher than in other ocean basins, and attribute it to changing sea ice coverage on a decadal time scale. Sea ice melt exposes seawater to the atmosphere and promotes rapid uptake of atmospheric carbon dioxide, lowering its alkalinity and buffer capacity and thus leading to sharp declines in pH and Ωarag. We predict a further decrease in pH, particularly at higher latitudes where sea ice retreat is active, whereas Arctic warming may counteract decreases in Ωarag in the future.

Toxic Effects of Industrial Flocculants Addition on Bioconversion of Black Soldier Fly Larvae (Hermetia illucens L.).

Black soldier fly is a saprophagous insect that has been widely reported in recent years due to its excellent performance in bioremediation. Due to the widespread presence of flocculants in the organic waste treated by black soldier fly larvae, this study aimed to evaluate the potential impacts and risks of flocculant addition (a combination of poly aluminum chloride and polyacrylamide with the ratio of 50:1). Results showed that the growth and weight of BSFL in the high-exposure groups (≥200 mg/L) were inhibited. The bioaccumulation of aluminum (Al) in larvae was estimated, and the proportions of different Al forms in the frass from high to low were the residual state (41.38% to 67.92%), water-soluble state (16.88% to 37.03%), acid-soluble state (8.45% to 18.72%), and alkali-soluble state (3.38% to 5.14%). The relative abundance of bacterial genera related to lipid metabolism decreased with increasing flocculant concentrations while disease-related taxa increased in relative abundance. The results serve as a reference for subsequent research and application of the treatment of flocculant-contaminated waste by BSFL.

miR-126-3p-loaded small extracellular vesicles secreted by urine-derived stem cells released from a phototriggered imine crosslink hydrogel could enhance vaginal epithelization after vaginoplasty.

BACKGROUND: Due to the large area and deep width of the artificial neovagina after vaginoplasty, it takes a considerable amount of time to achieve complete epithelization of the neovagina. Currently, the clinical therapies for vaginal epithelization after vaginoplasty are still dissatisfactory. Recent studies showed that small extracellular vesicles (sEVs) derived from stem cells could accelerate wound epithelization. The sustained release of sEVs from optimized hydrogels may be a promising strategy to accelerate vaginal epithelization after vaginoplasty. METHODS: The efficacy of phototriggered imine crosslink hydrogels (piGEL) containing sEVs derived from human urine-derived stem cells (hUSC-sEVs, piGEL-sEVs) on vaginal mucosa defects in rabbits was assessed by wound closure rates, histological analysis and immunofluorescence staining analysis. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine and scratch wound assays were performed to assess the effects of hUSC-sEVs on the proliferation and migration ability of vaginal epithelial cells (VK2/E6E7). Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to test the expression of epithelial differentiation markers in VK2 cells. Moreover, a microRNA (miRNA) microarray was used to find hUSC-sEVs-specific miRNAs that potentially affected the proliferation, migration and differentiation ability of VK2 cells. RESULTS: The in vitro release profile revealed that the piGEL could ensure sustained release of hUSC-sEVs. The in vivo results showed that piGEL-sEVs effectively promoted epithelization and angiogenesis of vaginal mucosa defects in rabbits. According to miRNA microarray and qRT-PCR results, miR-126-3p might be the crucial molecule among the various miRNAs contained in hUSC-sEVs. The data showed that hUSC-sEVs promoted the migration and differentiation of VK2 cells by delivering miR-126-3p to suppress the expression of Spred1 and PIK3R2, thereby activating the ERK1/2 and ATK signaling pathways. CONCLUSION: The results indicated that piGEL-sEVs could be a novel promising approach for enhancing the epithelization of the neovagina after vaginoplasty and provided useful data for understanding the underlying mechanism of the effect of hUSC-sEVs on epithelization.

Multifunctional Gel Films of Marine Polysaccharides Cross-Linked with Poly-Metal Ions for Wound Healing.

The development of an efficient and convenient material to improve skin tissue regeneration is a major challenge in healthcare. Inspired by the theory of moist wound healing, portable chitooligosaccharide (COS)/sodium alginate (SA) dual-net gel films containing multiple metal ions were prepared by a casting and in-situ spray method, which can be used to significantly promote wound healing without the use of therapeutic drugs. A variety of divalent cations was introduced in this experiment to improve the advantages of each metal ion by forming metal ion chelates with COS. Moreover, the physicochemical properties and antioxidant properties of nIon2+-COS/SA gel films were systematically characterized and evaluated by in vitro experiments. The gel films showed good antibacterial activity against Gram-negative and Gram-positive bacteria. In addition, the gel films showed good cytocompatibility in cellular experiments, and the gel films with Zn2+ and Sr2+ addition significantly accelerated wound healing in whole skin defect model experiments. Therefore, this nIon2+-COS/SA gel film is an ideal candidate material for wound dressing.

Preparation of Ion2+-COS/SA Multifunctional Gel Films for Skin Wound Healing by an In Situ Spray Method.

The rapid preparation of safe and efficient wound dressings that meet the needs of the entire repair process remains a major challenge for effective therapeutic wound healing. Natural, sprayable Ion2+-COS/SA multifunctional dual-network gel films created by the in situ coordination of chitooligosaccharide (COS), metal ions and sodium alginate (SA) using casting and an in-situ spray method were synthesized. The gel films exhibited excellent physicochemical properties such as swelling, porosity and plasticity at a COS mass fraction of 3%. Furthermore, at this mass fraction, the addition of bimetallic ions led to the display of multifunctional properties, including significant antioxidant, antibacterial and cytocompatibility properties. In addition, experiments in a total skin defect model showed that this multifunctional gel film accelerates wound healing and promotes skin regeneration. These results suggest that the sprayable Ion2+-COS/SA multifunctional pro-healing gel film may be a promising candidate for the clinical treatment of allodermic wounds.

Oral delivery of marine shellfish supramolecule peptides for skin wound healing.

Oral administration of peptides/proteins with superior efficacy and fewer side effects is the most advantageous route of administration. In this study, we utilized controllable enzymatic (animal protease) hydrolysis technology to prepare active polypeptide self-assembling supramolecular (APs) from marine shellfish meat to explore the functional mechanism of APs in in vitro and in vivo (oral administration) experiments . In vitro experiments revealed that APs with self-assembly tendency had multifunctional activities. In vivo experiments indicated that oral administration of naturally safe APs could inhibited inflammation, promoted fibroblast proliferation and revascularization, and accelerated the epithelialization process, thus favoring a balanced repair tissue collagen I/III ratio and the promotion of hair follicle regeneration to achieve scarless healing, which was also relevant to "skin-gut" axis. These results showed that APs, as demonstrated in this study, promoted dermal wound healing in mice and may be developed and used to treat skin wounds.