Single Crystal Seed Induced Epitaxial Growth Stabilizes α-FAPbI3 in Perovskite Solar Cells.

FAPbI3 stands out as an ideal candidate for the photoabsorbing layer of perovskite solar cells (PSCs), showcasing outstanding photovoltaic properties. Nonetheless, stabilizing photoactive α-FAPbI3 remains a challenge due to the lower formation energy of the competitive photoinactive δ-phase. In this study, we employ tetraethylphosphonium lead tribromide (TEPPbBr3) single crystals as templates for the epitaxial growth of PbI2. The strategic use of TEPPbBr3 optimizes the evolution of intermediates and the crystallization kinetics of perovskites, leading to high-quality and phase-stable α-FAPbI3 films. The TEPPbBr3-modified perovskite exhibits optimized carrier dynamics, yielding a champion efficiency of 25.13% with a small voltage loss of 0.34 V. Furthermore, the target device maintains 90% of its initial PCE under maximum power point (MPP) tracking over 1000 h. This work establishes a promising pathway through single crystal seed based epitaxial growth for achieving satisfactory crystallization regulation and phase stabilization of α-FAPbI3 perovskites toward high-efficiency and stable PSCs.

GDNF facilitates the differentiation of ADSCs to Schwann cells and enhances nerve regeneration through GDNF/MTA1/Hes1 axis.

Adipose tissue-derived stem cells (ADSCs) are a kind of stem cells with multi-directional differentiation potential, which mainly restore tissue repair function and promote cell regeneration. It can be directionally differentiated into Schwann-like cells to promote the repair of peripheral nerve injury. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the repair of nerve injury, but the underlying mechanism remains unclear, which seriously limits its further application.The study aimed to identify the molecular mechanism by which overexpression of glial cell line-derived neurotrophic factor (GDNF) facilitates the differentiation of ADSCs into Schwann cells, enhancing nerve regeneration after injury. In vitro, ADSCs overexpressing GDNF for 48 h exhibited changes in their morphology, with 80% of the cells having two or more prominences. Compared with that of ADSCs, GDNF-ADSCs exhibited increased expression of the Schwann cell marker S100, nerve damage repair-related factors.ADSC cells in normal culture and ADSC cells were overexpressing GDNF(GDNF-ADSCs) were analysed using TMT-Based Proteomic Analysis and revealed a significantly higher expression of MTA1 in GDNF-ADSCs than in control ADSCs. Hes1 expression was significantly higher in GDNF-ADSCs than in ADSCs and decreased by MTA1 silencing, along with a simultaneous decrease in the expression of S100 and nerve damage repair factors. These findings indicate that GDNF promotes the differentiation of ADSCs into Schwann cells and induces factors that accelerate peripheral nerve damage repair.

Placing a New Filter before Removing Embolized Nonconical Filter: A Report of 13 Cases.

OBJECTIVES: Permanent filter placement may result in numerous complications. Filter removal is recommended if there are no risks of pulmonary embolism. This study aimed to explore the feasibility of placing a new filter when the embolized nonconical filter is removed. METHODS: This study included patients who had received a new filter between 2018 and 2019 before the nonconical filters were removed. Patient characteristics, new filter types, thrombus interception rate, filter removal rate, feasibility, and safety were analyzed retrospectively. Feasibility was defined as the successful placement of new filters and the removal of the nonconical filters. Safety was defined as the absence of symptomatic pulmonary embolism and inferior vena cava hemorrhage after removing the nonconical filters, as well as the successful removal of new filters without symptomatic pulmonary embolism. RESULTS: The average indwelling period of the nonconical filters was 29 (range, 17-30) days among the 13 patients. The removal rate of the nonconical filters was 100%. Five patients (38.5%) received new Denali filters, one (7.7%) received a new Celect filter, and 7 (53.8%) received new temporary filters. Thrombi were intercepted in 10 of the patients (76.9%). The removal rate of the replaced new filters was 100%. No rupture or shifting of the new filters occurred. No symptomatic pulmonary embolism was found after the removal of both the nonconical filters and the new filters. The patients were followed up for 3 months after the surgeries, and the inferior vena cavae of 12 (92.3%) patients were patent, and no new embolic events were found. CONCLUSIONS: Placing a new replacement filter before removal of the embolized nonconical filter may be a feasible approach to prevent pulmonary embolism. Both the nonconical filter and the new filter could be removed subsequently after the thrombi were treated.

Comparison of traditional vascular reconstruction with covered stent in the treatment of subclavian artery injury.

PURPOSE: To explore the significance of traditional vascular reconstruction and covered stent for limb salvage after subclavian artery injury. METHODS: Patients with subclavian artery injury admitted to Beijing Jishuitan Hospital from January 2010 to December 2018 were retrospectively analyzed. All the injuries have been confirmed by intraoperative exploration, computed tomography angiography or digital subtraction angiography. Complete or partial amputation injuries were excluded. Mild artery defect or partial intimal damage was treated by interventional implantation, while other patients received open surgeries, including direct suture of small defect less than 2 cm and transplantation with autologous vein or artificial blood when the defect was more than 2 cm. Patients were divided into open surgery group and stent implantation group based on the treatment they received. Patients were followed up at 2 weeks (first stage) and 6 months (second stage) after operation to investigate limb salvage. Student's t-test was used to compare the general data between two groups and Chi-square test to analyze the rate of limb salvage. RESULTS: Altogether 50 cases of subclavian artery injury were treated, including 36 cases of open surgery and 14 cases of stent implantation. Combination of nerve injury was observed in 27 cases (75.0%) in open surgery group and 12 cases (85.7%) in stent implantation group. Amputation developed in 3 cases with open surgery and 1 case with stent implantation. Consequently the rate of successful limb salvage was respectively 91.7% (33/36) and 92.9% (13/14), revealing no significant difference (p > 0.05). CONCLUSION: Rapid reconstruction of blood circulation is crucial following subclavian artery injury, no matter what kinds of treatment strategies have been adopted. Interventional stent implantation can achieve a good effect for limb salvage.

The plant sesquiterpene lactone parthenolide inhibits Wnt/ß-catenin signaling by blocking synthesis of the transcriptional regulators TCF4/LEF1.

The Wnt/ß-catenin pathway is essential for embryonic development and homeostasis, but excessive activation of this pathway is frequently observed in various human diseases, including cancer. Current therapeutic drugs targeting the Wnt pathway often lack sufficient efficacy, and new compounds targeting this pathway are therefore greatly needed. Here we report that the plant-derived natural product parthenolide (PTL), a sesquiterpene lactone, inhibits Wnt signaling. We found that PTL dose-dependently inhibits Wnt3a- and CHIR99021-induced transcriptional activity assessed with the T-cell factor (TCF)/lymphoid enhancer factor (LEF) firefly luciferase (TOPFlash) assay in HEK293 cells. Further investigations revealed that PTL decreases the levels of the transcription factors TCF4/LEF1 without affecting ß-catenin stability or subcellular distribution. Moreover, this effect of PTL on TCF4/LEF1 was related to protein synthesis rather than to proteasome-mediated degradation. Of note, siRNA-mediated knockdown of RPL10, a ribosome protein PTL binds, substantially decreased TCF4/LEF1 protein levels and also Wnt3a-induced TOPFlash activities, suggesting a potential mechanism by which PTL may repress Wnt/ß-catenin signaling. In summary, PTL binds RPL10 and thereby potently inhibits the Wnt/ß-catenin pathway.

Correlating Aggregation Ability of Polymer Donors with Film Formation Kinetics for Organic Solar Cells with Improved Efficiency and Processability.

Film formation kinetics significantly impact molecular processability and power conversion efficiency (PCE) of organic solar cells. Here, two ternary random copolymerization polymers are reported, D18─N-p and D18─N-m, to modulate the aggregation ability of D18 by introducing trifluoromethyl-substituted pyridine unit at para- and meta-positions, respectively. The introduction of pyridine unit significantly reduces material aggregation ability and adjusts the interactions with acceptor L8-BO, thereby leading to largely changed film formation kinetics with earlier phase separation and longer film formation times, which enlarge fiber sizes in blend films and improve carrier generation and transport. As a result, D18─N-p with moderate aggregation ability delivers a high PCE of 18.82% with L8-BO, which is further improved to 19.45% via interface engineering. Despite the slightly inferior small area device performances, D18─N-m shows improved solubility, which inspires to adjust the ratio of meta-trifluoromethyl pyridine carefully and obtain a polymer donor D18─N-m-10 with good solubility in nonhalogenated solvent o-xylene. High PCEs of 13.07% and 12.43% in 1 cm2 device and 43 cm2 module fabricated with slot-die coating method are achieved based on D18─N-m-10:L8-BO blends. This work emphasizes film formation kinetics optimization in device fabrication via aggregation ability modulation of polymer donors for efficient devices.

Limited debridement combined with ReCell® Techniques for deep second-degree burns.

BACKGROUND: The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep second-degree burn wounds. METHOD: A total of 20 patients suffered with deep second-degree burns less than 10% of total body surface area (TBSA) who were admitted to our department, from June 2019 to June 2021, participated in this study. These patients first underwent limited debridement with an electric/pneumatic dermatome, followed by the ReCell® technique for secondary wounds. Routine treatment was applied to prevent scarring after the wound healed. Clinical outcomes were scored using the Vancouver Scar Scale (VSS). RESULTS: All wounds of the patients healed completely. One patient developed an infection in the skin graft area and finally recovered by routine dressing changes. The average healing time was 12 days (range: 10-15 days). The new skin in the treated area was soft and matched the colour of the surrounding normal skin and the VSS score ranged from 3~5 for each patient. Of the 20 patients, 19 were very satisfied and 1 was satisfied. CONCLUSIONS: This article reports a useful treatment method that combines electric dermatome-dependent limited debridement and the ReCell® technique for the treatment of deep second-degree burn wounds. It is a feasible and effective strategy that is easy to implement and minimally invasive, and it is associated with a short healing time, mild scar formation and little damage to the donor skin area.

Exosomes from adipose-derived stem cells restore fibroblast function and accelerate diabetic wound healing.

Background: Diabetes is common yet challenging chronic disease, that affects a wide range of people around the world. Complex cellular environments around diabetic wounds tend to damage the function of effector cells, including vascular endothelial cells (VECs), fibroblasts and epithelial cells. This study aims to analyze the differences between diabetic wounds and normal skin as well as whether adipose-derived stem cell (ADSC) exosome could promote healing of diabetic wound. Methods: Human diabetic wounds and normal skin were collected and stained with HE, Masson, CD31 and 8-hydroxy-2 deoxyguanosine immunohistochemical staining. RNA-seq data were collected for further bioinformatics analysis. ADSC exosomes were isolated and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The effect of ADSC exosomes on diabetic wound healing was assessed on full thickness wounds in mice. To further verify the regulative impact of ADSCs exosomes in high glucose treated fibroblasts, we isolated fibroblasts from normal skin tissue and measured the cell viability, apoptosis rate, proliferation and migration of fibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on the function of high glucose treated fibroblasts, we detected the expression of apoptosis related molecules including BCL2, Bax, and cleaved caspase-3. Results: Histological observation indicated that perilesional skin tissues from diabetic patients showed structural disorder, less collagen disposition and increased injury compared with normal skin. Bioinformatics analysis showed that the levels of inflammatory and collagen synthesis related molecules, as well as oxidative stress and apoptosis related molecules, were significantly changed. Furthermore, we found that ADSC exosomes could not only speed up diabetic wound healing, but could also improve healing quality. ADSC exosomes restored high glucose induced damage to cell viability, migration and proliferation activity, as well as fibrosis-related molecules such as SMA, collagen 1 and collagen 3. In addition, we verified that ADSC exosomes downregulated high glucose induced increased apoptosis rate in fibroblast and the protein expression of Bax as well as cleaved caspases 3. Conclusions: This study indicated that ADSC exosomes alleviated high glucose induced damage to fibroblasts and accelerate diabetic wound healing by inhibiting Bax/caspase 3.

miR-125b-5p delivered by adipose-derived stem cell exosomes alleviates hypertrophic scarring by suppressing Smad2.

Background: Hypertrophic scarring is the most serious and unmet challenge following burn and trauma injury and often leads to pain, itching and even loss of function. However, the demand for ideal scar prevention and treatment is difficult to satisfy. We aimed to discover the effects and mechanisms of adipose-derived stem cell (ADSC) exosomes in hypertrophic scarring. Methods: ADSC exosomes were isolated from the culture supernatant of ADSCs and identified by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The effect of ADSC exosomes on wound healing and scar formation was detected by the wound model of BALB/c mice. We isolated myofibroblasts from hypertrophic scar tissue and detected the cell viability, proliferation and migration of myofibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on fibrosis in myofibroblasts, we detected the expression of Smad2 in hypertrophic scar tissue and normal skin and the regulatory mechanism of ADSC exosomes on Smad2. Injection of bleomycin was performed in male BALB/c mice to establish an in vivo fibrosis model while ADSC exosomes were administered to observe their protective effect. The tissue injury of mice was observed via hematoxylin and eosin and Masson staining and related testing. Results: In this study, we found that ADSC exosomes could not only speed up wound healing and improve healing quality but also prevent scar formation. ADSC exosomes inhibited expression of fibrosis-related molecules such as α-smooth muscle actin, collagen I (COL1) and COL3 and inhibited the transdifferentiation of myofibroblasts. In addition, we verified that Smad2 is highly expressed in both hypertrophic scar tissue and hypertrophic fibroblasts, while ADSC exosomes downregulated the expression of Smad2 in hypertrophic fibroblasts. Further regulatory mechanism analysis revealed that microRNA-125b-5p (miR-125b-5p) is highly expressed in ADSC exosomes and binds to the 3' untranslated region of Smad2, thus inhibiting its expression. In vivo experiments also revealed that ADSC exosomes could alleviate bleomycin-induced skin fibrosis and downregulate the expression of Smad2. Conclusions: We found that ADSC exosomes could alleviate hypertrophic scars via the suppression of Smad2 by the specific delivery of miR-125b-5p.

The Relationship Between Bone Metabolism and Peripheral Artery Disease in Patients on Hemodialysis: The Potential Role of Osteocalcin.

Introduction: To examine the factors associated with PAD, with a specific focus on bone metabolism factors such as osteocalcin. Methods: This cross-sectional study examined factors about demographic, clinical, and laboratory parameters including bone metabolism biomarkers in hemodialysis patients. The ankle-brachial index (ABI) was measured in all patients, with PAD diagnosed as an ABI <0.9. Results: Out of the 71 patients, PAD was found in 23 individuals. These patients had an average age of 63.5±13.0 years, with 59.2% being male. Compared to non-PAD patients, those with PAD were older, had a lower proportion of males, and had a higher prevalence of diabetes and coronary artery disease. Among the factors related to bone metabolism, only osteocalcin exhibited a significant increase in the PAD group compared to the non-PAD group. Conclusion: PAD in patients on hemodialysis was independently linked to high levels of osteocalcin in the bloodstream, indicating the presence of bone metabolism disorders.

Central Core Substitutions and Film-Formation Process Optimization Enable Approaching 19% Efficiency All-Polymer Solar Cells.

Molecular interactions and film-formation processes greatly impact the blend film morphology and device performances of all-polymer solar cells (all-PSCs). Molecular structure, such as the central cores of polymer acceptors, would significantly influence this process. Herein, the central core substitutions of polymer acceptors are adjusted and three quinoxaline (Qx)-fused-core-based materials, PQx1, PQx2, and PQx3 are synthesized. The molecular aggregation ability and intermolecular interaction are systematically regulated, which subsequently influence the film-formation process and determine the resulting blend film morphology. As a result, PQx3, with favorable aggregation ability and moderate interaction with polymer donor PM6, achieves efficient all-PSCs with a high power conversion efficiency (PCE) of 17.60%, which could be further improved to 18.06% after carefully optimizing device annealing and interface layer. This impressive PCE is one of the highest values for binary all-PSCs based on the classical polymer donor PM6. PYF-T-o is also involved in promoting light utilization, and the resulting ternary device shows an impressive PCE of 18.82%. In addition, PM6:PQx3-based devices exhibit high film-thickness tolerance, superior stability, and considerable potential for large-scale devices (16.23% in 1 cm2 device). These results highlight the importance of structure optimization of polymer acceptors and film-formation process control for obtaining efficient and stable all-PSCs.

Concretized structural evolution supported assembly-controlled film-forming kinetics in slot-die coated organic photovoltaics.

Bulk-heterojunction structured small-area organic solar cells are approaching 20% power conversion efficiency, but the blurred film-forming kinetics in the fabrication of large-area devices causes significant PCE loss and restrains the potential of commercialization. Such blurring came from insufficient knowledge of structural evolution during the film-forming process. Here, we concretize the evolution process with structures detailed to the submolecular level by comprehensive investigations of in-situ UV-vis spectroscopy, Atomic Force Microscope, Grazing Incident Wide Angle X-ray Scattering, and molecular dynamic simulation. With such hierarchical structural knowledge, assembly-controlled film-forming kinetics is proposed to explain the whole picture. Such assembly is determined by molecule configuration and can be tuned via external conditions. Understanding this kinetics will contribute to screening large-area device fabrication conditions, and the detailed structural knowledge could inspire the future design of novel photovoltaic materials that are intrinsically excellent in large-area device fabrications.

Adipose Mesenchymal Stem Cell Derived Exosomes Promote Keratinocytes and Fibroblasts Embedded in Collagen/Platelet-Rich Plasma Scaffold and Accelerate Wound Healing.

Engineered skin substitutes derived from human skin significantly reduce inflammatory reactions mediated by foreign/artificial materials and are consequently easier to use for clinical application. Type I collagen is a main component of the extracellular matrix during wound healing and has excellent biocompatibility, and platelet-rich plasma can be used as the initiator of the healing cascade. Adipose mesenchymal stem cell derived exosomes are crucial for tissue repair and play key roles in enhancing cell regeneration, promoting angiogenesis, regulating inflammation, and remodeling extracellular matrix. Herein, Type I collagen and platelet-rich plasma, which provide natural supports for keratinocyte and fibroblast adhesion, migration, and proliferation, are mixed to form a stable 3D scaffold. Adipose mesenchymal stem cell derived exosomes are added to the scaffold to improve the performance of the engineered skin. The physicochemical properties of this cellular scaffold are analyzed, and the repair effect is evaluated in a full-thickness skin defect mouse model. The cellular scaffold reduces the level of inflammation and promotes cell proliferation and angiogenesis to accelerate wound healing. Proteomic analysis shows that exosomes exhibit excellent anti-inflammatory and proangiogenic effects in collagen/platelet-rich plasma scaffolds. The proposed method provides a new therapeutic strategy and theoretical basis for tissue regeneration and wound repair.

Solution Processed Semi-Transparent Organic Solar Cells Over 50% Visible Transmittance Enabled by Silver Nanowire Electrode with Sandwich Structure.

Photovoltaic windows with easy installation for the power supply of household appliances have long been a desire of energy researchers. However, due to the lack of top electrodes that offer both high transparency and low sheet resistance, the development of high-transparency photovoltaic windows for indoor lighting scenarios has lagged significantly behind photovoltaic windows where privacy issues are involved. Addressing this issue, this work develops a solution-processable transparent top electrode using sandwich structure silver nanowires, realizing high transparency in semi-transparent organic solar cells. The wettability and conducting properties of the electrode are improved by a modified hole-transport layer named HP. The semi-transparent solar cell exhibits good see-through properties at a high average visible transmittance of 50.8%, with power conversion efficiency of 7.34%, and light utilization efficiency of 3.73%, which is the highest without optical modulations. Moreover, flexible devices based on the above-mentioned architecture also show excellent mechanical tolerance compared with Ag electrode counterparts, which retains 94.5% of their original efficiency after 1500 bending cycles. This work provides a valuable approach for fabricating solution-processed high transparency organic solar cells, which is essential in future applications in building integrated photovoltaics.

A method of constructing a dynamic chart depth model for coastal areas.

The depth is important for vessel navigation at sea. Currently, most vessels use electronic navigation charts to navigate at sea. In coastal areas, especially close to shallow water areas, the dynamic change of the water level is very important to safe navigation. Ships calculate the change of water level by using up-to-date tide tables, to obtain the dynamic water depth in the channels. However, the depth caused by the tide and non-tidal components may reach several meters in some seas, causing the dynamic depth below the safety depth, which can easily lead to grounding of vessels stranding accidents. The channel is regularly dredged to achieve navigational depth. Without regular dredging, the offshore non-channel area becomes the common area of ship grounding. The dynamic chart depth model studied in this article can provide real-time depth, which serves the ships navigation in the non-channel. The model incorporates the chart depth and the dynamic water levels on the same reference datum. The chart depth is from the electronic navigational chart depth. The dynamic water levels are constructed by the simulated tidal levels and continuous series of nontidal residual. We then designed a deviation correction method to reduce the discrepancy of the simulated tidal level with the actual water level, including datum offset correction and residual water level correction. Finally, by merging the revised dynamic water levels with the electronic navigational chart depth, we obtained the dynamic chart depth model of the study region.

In Situ Absorption Characterization Guided Slot-Die-Coated High-Performance Large-Area Flexible Organic Solar Cells and Modules.

Slot-die coating is recognized as the most compatible method for the roll-to-roll (R2R) processing of large-area flexible organic solar cells (OSCs). However, the photovoltaic performance of large-area flexible OSC lags significantly behind that of traditional spin-coating devices. In this work, two acceptors, Qx-1 and Qx-2, show quite different film-formation kinetics in the slot-die coating process. In situ absorption spectroscopy indicates that the excessive crystallinity of Qx-2 provides early phase separation and early aggregation, resulting in oversized crystal domains. Consequently, the PM6:Qx-1-based 1 cm2 flexible device exhibits an excellent power conversion efficiency (PCE) of 13.70%, which is the best performance among the slot-die-coated flexible devices; in contrast, the PM6:Qx-2 blend shows a pretty poor efficiency, which is lower than 1%. Moreover, the 30 cm2 modules based on PM6:Qx-1, containing six 5 cm2 sub-cells, exhibit a PCE of 12.20%. After being stored in a glove box for over 6000 h, the PCE remains at 103% of its initial values, indicating excellent shelf stability. Therefore, these results show a promising future strategy for the upscaling fabrication of flexible large-area OSCs.

Removal of inferior vena cava filter by open surgery after failure of endovenous retrieval.

Background: The permanent placement of inferior vena cava (IVC) filters may lead to numerous complications and their removal is recommended once the risk of pulmonary embolism is reduced. Removal of IVC filters by endovenous means is preferred. But failure of endovenous removal happens when recycling hooks penetrate the vein wall and filters are left in place for too long time. In these scenarios, open surgery may be effective for removal of IVC filters. We aimed to describe the surgical approach, outcomes, and 6-month follow-up of the removal of IVC filter by open surgery, after the failure of removal via the endovenous method. Methods: A total of 1,285 patients with retrievable IVC filters were admitted from July 2019 to June 2021, including 1,176 (91.5%) endovenous filter removals, and 24 (1.9%) open surgical IVC filter removals after the failure by endovenous method, of whom 21 (1.6%) were followed-up and eligible for analysis of the study. Patient characteristics, filter type, filter removal rate, IVC patency rate, and complications were retrospectively analyzed. Results: Twenty-one patients were left with IVC filters for 26 (10, 37) months, of which 17 (81.0%) patients had non-conical filters and 4 (19.0%) had conical filters; all 21 filters were successfully removed, with a 100% removal rate, no deaths, no serious complications, and no symptomatic pulmonary embolism. At the 3rd month follow-up after surgery and 3rd month follow-up after discontinuation of anticoagulation therapy, only 1 case (4.8%) had IVC occlusion, but without any occurrence of new lower limb deep venous thrombosis and silent pulmonary embolism. Conclusion: Open surgery can be used for the removal of IVC filters after failure of removal by endovenous method or when accompanied by complications without symptoms of pulmonary embolism. Open surgical approach can be used as an adjunctive clinical intervention for the removal of such filters.

Exosome/metformin-loaded self-healing conductive hydrogel rescues microvascular dysfunction and promotes chronic diabetic wound healing by inhibiting mitochondrial fission.

Chronic diabetic wounds remain a globally recognized clinical challenge. They occur due to high concentrations of reactive oxygen species and vascular function disorders. A promising strategy for diabetic wound healing is the delivery of exosomes, comprising bioactive dressings. Metformin activates the vascular endothelial growth factor pathway, thereby improving angiogenesis in hyperglycemic states. However, multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported, and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear. Here, we engineered dual-loaded hydrogels possessing tissue adhesive, antioxidant, self-healing and electrical conductivity properties, wherein 4-armed SH-PEG cross-links with Ag+, which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair. Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group, creating a stable three-dimensional structure for exosome and metformin loading. The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M + E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury. The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission, thereby protecting F-actin homeostasis and alleviating microvascular dysfunction. Hence, we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.

MiR-197-3p affects angiogenesis and inflammation of endothelial cells by targeting CXCR2/COX2 axis.

BACKGROUND: Decreased circulating miR-197-3p was found in patients with recurrent deep vein thrombosis (DVT), but the specific role of miR-197-3p needs further exploration. MATERIALS AND METHODS: Venous blood samples were collected from DVT patients and healthy controls, and peripheral blood mononuclear cells (PBMCs) were isolated to examine the expression patterns of miR-197-3p, CXCR2 and COX2 by qRT-PCR. Human umbilical vein endothelial cells (HUVECs) were further used as a cellular model to investigate the role of the miR-197-3p/CXCR2/COX2 axis in regulating cell viability, angiogenesis, and inflammation, which were determined by MTT assay, Matrigel-based tube formation assay, and enzyme-linked immunosorbent assay, respectively. Dual-luciferase reporter assay was used to examine the interactions between miR-198-3p and CXCR2. Expression of NF-κB p65 was examined by western blot to investigate whether the NF-κB pathway was involved in the regulatory effect of miR-197-3p on DVT. RESULTS: miR-197-3p was decreased in PBMCs of patients with DVT, while CXCR2 and COX2 were increased compared to the healthy controls. In HUVECs, overexpression of miR-197-3p reduced CXCR2 levels and inhibited cell viability, angiogenesis, and release of inflammatory cytokines including TNF-α, IL-1ß, and IL-6, which were reversed by miR-197-3p inhibition. Dual-luciferase reporter assay indicated miR-197-3p directly bound to CXCR2. CXCR2 further upregulated the expression of COX2 and activated the NF-κB pathway, promoting cell viability, angiogenesis and release of inflammatory cytokines in HUVECs. The effect of miR-197-3p inhibition on cell viability, angiogenesis and inflammation of HUVECs could be reversed by CXCR2 silencing. CONCLUSION: MiR-197-3p affected viability, angiogenesis and inflammation of endothelial cells by targeting CXCR2/COX2 axis in vitro. Our findings provided a novel theoretical basis to investigate more effective therapies for DVT.

Adiponectin ameliorates hypertrophic scar by inhibiting Yes-associated protein transcription through SIRT1-mediated deacetylation of C/EBPß and histone H3.

The clinical correlation between adiponectin (APN) signal and hypertrophic scar (HS) remains unclear. Here, we found significantly reduced expression of APN receptors (AdipoR1/2) in HS tissues and derived fibroblasts (HFs), suggesting that HS formation may be associated with APN/AdipoR1/2 decline. RNA sequencing and RT-PCR validation revealed that APN significantly elevated the expression of SIRT1. Both in vitro and in vivo experiments confirmed that SIRT1 plays important role in APN inhibiting the fibrotic phenotype transformation and proliferation of scar fibroblasts and improving skin fibrosis. Mechanistically, SIRT1 inhibited the acetylation of C/EBPß K39, histone H3K27, and H3K9, resulting in impaired transcription activity of C/EBPß and compact chromatin conformation, thus preventing C/EBPß from activating the transcription of YAP. Moreover, we found that YAP was critical for the transcriptional regulation of CTGF, CCND1, and CCNE1 by TEAD4. In conclusion, our study revealed the role of APN in antagonizing HS fibrosis by regulating the SIRT1/C/EBPß/YAP pathway.