Morroniside promotes skin wound re-epithelialization by facilitating epidermal stem cell proliferation through GLP-1R-mediated upregulation of ß-catenin expression.

Epidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10‒50 µg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of ß-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signaling pathways, resulting in an increase in cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expressions of ß-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing ß-catenin expression and subsequently upregulating c-Myc, cyclin D1, and cyclin E1 expressions through GLP-1R signaling pathways. Morroniside has clinical potential for treating skin wounds.

Distribution of pathogens and risk factors for post-replantation wound infection in patients with traumatic major limb mutilation.

PURPOSE: Even though replantation of limb mutilation is increasing, postoperative wound infection can result in increasing the financial and psychological burden of patients. Here, we sought to explore the distribution of pathogens and identify risk factors for postoperative wound infection to help early identification and managements of high-risk patients. METHODS: Adult inpatients with severed traumatic major limb mutilation who underwent replantation from Suzhou Ruixing Medical Group between November 09, 2014, and September 6, 2022 were included in this retrospective study. Demographic, and clinical characteristics, treatments, and outcomes were collected. Data were used to analyze risk factors for postoperative wound infection. RESULTS: Among the 249 patients, 185 (74.3%) were males, the median age was 47.0 years old. Postoperative wound infection in 74 (29.7%) patients, of whom 51 (20.5%) had infection with multi-drug resistant bacteria. Ischemia time (OR 1.31, 95% CI 1.13-1.53, P = 0.001), wound contamination (OR 6.01, 95% CI 2.38-15.19, P <0.001), and stress hyperglycemia (OR 23.37, 95% CI 2.30-236.93, P = 0.008) were independent risk factors, while the albumin level after surgery (OR 0.94, 95% CI 0.89-0.99, P = 0.031) was significant associated with the decrease of postoperative wound infection. Ischemia time (OR 1.21, 95% CI 1.05-1.40, P = 0.010), wound contamination (OR 8.63, 95% CI 2.91-25.57, P <0.001), and MESS (OR 1.32, 95% CI 1.02-1.71, P = 0.037 were independent risk factors for multi-drug resistant bacteria infection. CONCLUSIONS: Post-replantation wound infection was common in patients with severe traumatic major limb mutilation, and most were multi-drug resistant bacteria. Ischemia time and wound contamination were associated with the increase of postoperative wound infection, including caused by multi-drug resistant. Positive correction of hypoproteinemia and control of stress hyperglycemia may be beneficial.

Biomimetic nanoparticles for effective Celastrol delivery to targeted treatment of rheumatoid arthritis through the ROS-NF-κB inflammasome axis.

Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA. LEUKO were synthesized using membrane proteins purified from activated J774 macrophage. LEUKO and Cel-loaded LEUKO (Cel@LEUKO) were characterized using dynamic light scattering and transmission electron microscopy. Our results demonstrated that Cel@LEUKO can inhibit the inflammatory response of lipopolysaccharide (LPS) induced mouse monocyte macrophage leukemia cells (RAW264.7 cells) and human rheumatoid arthritis synovial fibroblasts (MH7A) cells through the inhibition of reactive oxygen species (ROS)-NF-κB pathway. In addition, research has shown that LEUKO effectively targets and transports Cel to the inflammatory site of RA, increased drug concentration in affected areas, reduced systemic toxicity of Cel, and reduced clinical symptoms, inflammatory infiltration, bone erosion, and serum inflammatory factors in collagen-induced arthritis (CIA) rats.

Experimental analysis of femoral head intraosseous vascular anastomosis in the treatment of porcine subcapital femoral neck fractures.

Introduction: Femoral neck fractures are challenging injuries associated with a compromised blood supply to the femoral head, leading to a high risk of avascular necrosis and poor clinical outcomes. This study aimed to investigate the efficacy of femoral head intraosseous vascular anastomosis in the treatment of porcine sub-capital femoral neck fractures. Methods: Ten Landrace pigs were used as experimental animal models. The femoral head was completely removed after femoral neck sub-cephalic fracture. It was fixed on the medial side of the knee joint, and the blood supply to the femoral head was reconstructed by anastomosing the femoral head vessels. One week later, blood flow in the femoral head was observed by borehole, digital subtraction angiography examination, and hematoxylin and eosin staining. Further, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling tests were performed to detect pathological changes in the femoral head. Results: After one-week, digital subtraction angiography of the femoral head revealed a blood circulation rate of 70 %, and the blood seepage rate of the borehole was 80 %. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling test results showed that necrosis of bone marrow cells in the experimental group was significantly improved compared to that in the control group. Discussion: This study highlights the potential benefits of femoral head intraosseous vascular anastomosis in the treatment of porcine sub-capital femoral neck fractures. Further research and clinical trials are warranted to validate these findings and to explore the translational potential of this technique in human patients.

Method for reconstructing femoral head blood supply by anastomosing the intraosseous artery.

Background: The reconstruction of femoral head blood supply is crucial in the management of avascular necrosis and related conditions. This study presents a method for reconstructing the femoral head blood supply by anastomosing the intraosseous artery. Methods: The femoral heads of six male Landrace swine were surgically exposed, and subcranial fractures of the femoral neck were intentionally created. Under microscopic guidance, the trophoblastic foramen of the posterior supporting artery was identified. Subsequently, a triangular bone window was carefully crafted to expose the intraosseous artery. Following the fixation of the femoral head, an anastomosis was performed between the intraosseous artery and the posterior inferior supporting artery located at the distal end of the fracture. The assessment of femoral head blood supply was conducted using Kirschner's pinhole and angiography techniques. Results: The anastomotic intraosseous artery exhibited a vibrant red color, indicating adequate blood perfusion, and demonstrated pulsatile flow. Observation through pinholes in the surface of the femoral head revealed continuous blood flow. Angiography further confirmed the successful circulation, as the contrast agent entered the inferior retinacular artery branch originating from the deep femoral artery. The contrast agent then proceeded to enter the femoral head through the retinacular artery, reaching the anastomosis site of the intraosseous artery. Notably, the angiography also revealed the presence of visible internal branches, highlighting the establishment of a functional vascular network. Discussion: The method of reconstructing the blood supply to the femoral head through anastomosis of the intraosseous artery enables utilization of the existing blood supply system within the femoral head. This study is just a preliminary study of this innovative technique that has the potential to prevent and/or treat femoral head necrosis following a femoral neck fracture. By restoring adequate blood flow to the affected area, this approach holds promise in preserving the viability and functionality of the femoral head, ultimately improving patient outcomes.

Microbially mediated mechanisms underlie soil carbon accrual by conservation agriculture under decade-long warming.

Increasing soil organic carbon (SOC) in croplands by switching from conventional to conservation management may be hampered by stimulated microbial decomposition under warming. Here, we test the interactive effects of agricultural management and warming on SOC persistence and underlying microbial mechanisms in a decade-long controlled experiment on a wheat-maize cropping system. Warming increased SOC content and accelerated fungal community temporal turnover under conservation agriculture (no tillage, chopped crop residue), but not under conventional agriculture (annual tillage, crop residue removed). Microbial carbon use efficiency (CUE) and growth increased linearly over time, with stronger positive warming effects after 5 years under conservation agriculture. According to structural equation models, these increases arose from greater carbon inputs from the crops, which indirectly controlled microbial CUE via changes in fungal communities. As a result, fungal necromass increased from 28 to 53%, emerging as the strongest predictor of SOC content. Collectively, our results demonstrate how management and climatic factors can interact to alter microbial community composition, physiology and functions and, in turn, SOC formation and accrual in croplands.

Recent advances on 3D-bioprinted gelatin methacrylate hydrogels for tissue engineering in wound healing: A review of current applications and future prospects.

Advancements in 3D bioprinting, particularly the use of gelatin methacrylate (GelMA) hydrogels, are ushering in a transformative era in regenerative medicine and tissue engineering. This review highlights the pivotal role of GelMA hydrogels in wound healing and skin regeneration. Its biocompatibility, tunable mechanical properties and support for cellular proliferation make it a promising candidate for bioactive dressings and scaffolds. Challenges remain in optimizing GelMA hydrogels for clinical use, including scalability of 3D bioprinting techniques, durability under physiological conditions and the development of advanced bioinks. The review covers GelMA's applications from enhancing wound dressings, promoting angiogenesis and facilitating tissue regeneration to addressing microbial infections and diabetic wound healing. Preclinical studies underscore GelMA's potential in tissue healing and the need for further research for real-world applications. The future of GelMA hydrogels lies in overcoming these challenges through multidisciplinary collaboration, advancing manufacturing techniques and embracing personalized medicine paradigms.

Bioprinted dermis with human adipose tissue-derived microvascular fragments promotes wound healing.

Tissue-engineered skin is an effective material for treating large skin defects in a clinical setting. However, its use is limited owing to vascular complications. Human adipose tissue-derived microvascular fragments (HaMVFs) are vascularized units that form vascular networks by rapid reassembly. In this study, we designed a vascularized bionic skin tissue using a three-dimensional (3D) bioprinter of HaMVFs and human fibroblasts encapsulated in a hybrid hydrogel composed of GelMA, HAMA, and fibrinogen. Tissues incorporating HaMVFs showed good in vitro vascularization and mechanical properties after UV crosslinking and thrombin exposure. Thus, the tissue could be sutured appropriately to the wound. In vivo, the vascularized 3D bioprinted skin promoted epidermal regeneration, collagen maturation in the dermal tissue, and vascularization of the skin tissue to accelerate wound healing. Overall, vascularized 3D bioprinted skin with HaMVFs is an effective material for treating skin defects and may be clinically applicable to reduce the necrosis rate of skin grafts.

Methods of Immobilization after Achilles Tendon Rupture Repair: A Comparative Study in Rat Model.

OBJECTIVE: The Achilles tendon (AT) is the most frequently ruptured in the human body. Literature describing different immobilization methods' impact on tendon healing after AT repair is lacking. We compare plaster cast, splint, and K-wire to determine which is the most stable and has the fewest complications. METHODS: Sixty rats aged 5-6 months were selected to establish Achilles tendon injury in two hind legs model. After suturing the ends of the AT together with a modified "Kessler" method (Prolene 5-0). The skin incision was interrupted and sutured with 1-0 thread. Rats were divided into three immobilization methods (plaster cast group, splint group, and K-wire group). In plaster cast group, the hind leg was cast with plaster in the extended position of the hip and knee joints, and the ankle joint was at 150°. Splint and K-wire group used splints and 0.8-mm K-wires, separately. The fixed period was 4 weeks. The incidence of stability and complications (death, necrosis of the legs, necrosis of the skin, and incisional infection) were recorded. Differences were detected using the chi-square test. RESULTS: Within 4 weeks observation, K-wires showed better stability (90%) compared with the other two ways (40% in plaster cast group, 65% in splint group; p < 0.05). Rats immobilized with K-wires (10%) suffered significantly lower complications compared with plaster cast and splint group (15%; p < 0.05). CONCLUSION: K-wire has better stability, lower complication rate than other methods. Immobilization with K-wire may be a promising tool in future clinical Achilles tendon rupture applications.

Engineered dermis loaded with confining forces promotes full-thickness wound healing by enhancing vascularisation and epithelialisation.

Tissue-engineered skin is ideal for clinical wound repair. Restoration of skin tissue defects using tissue-engineered skin remains a challenge owing to insufficient vascularisation. In our previous study, we developed a 3D bioprinted model with confined force loading and demonstrated that the confined force can affect vascular branching, which is regulated by the YAP signalling pathway. The mechanical properties of the model must be optimised to suture the wound edges. In this study, we explored the ability of a GelMA-HAMA-fibrin scaffold to support the confined forces created by 3D bioprinting and promote vascularisation and wound healing. The shape of the GelMA-HAMA-fibrin scaffold containing 3% GelMA was affected by the confined forces produced by the embedded cells. The GelMA-HAMA-fibrin scaffold was easy to print, had optimal mechanical properties, and was biocompatible. The constructs were successfully sutured together after 14 d of culture. Scaffolds seeded with cells were transplanted into skin tissue defects in nude mice, demonstrating that the cell-seeded GelMA-HAMA-fibrin scaffold, under confined force loading, promoted neovascularisation and wound restoration by enhancing blood vessel connections, creating a patterned surface, growth factors, and collagen deposition. These results provide further insights into the production of hydrogel composite materials as tissue-engineered scaffolds under an internal mechanical load that can enhance vascularisation and offer new treatment methods for wound healing. STATEMENT OF SIGNIFICANCE: Tissue-engineered skin is ideal for use in clinical wound repair. However, treatment of tissue defects using synthetic scaffolds remains challenging, mainly due to slow and insufficient vascularization. Our previous study developed a 3D bioprinted model with confined force loading, and demonstrated that confined force can affect vascular branching regulated by the YAP signal pathway. The mechanical properties of the construct need to be optimized for suturing to the edges of wounds. Here, we investigated the ability of a GelMA-HAMA-fibrin scaffold to support the confined forces created by 3D bioprinting and promote vascularization in vitro and wound healing in vivo. Our findings provide new insight into the development of degradable macroporous composite materials with mechanical stimulation as tissue-engineered scaffolds with enhanced vascularization, and also provide new treatment options for wound healing.

Angiopoietin-like 4 promotes epidermal stem cell proliferation and migration and contributes to cutaneous wound re-epithelialization.

Proliferation and migration of epidermal stem cells (EpSCs) are essential for epithelialization during skin wound healing. Angiopoietin-like 4 (ANGPTL4) has been reported to play an important role in wound healing, but the mechanisms involved are not fully understood. Here, we investigate the contribution of ANGPTL4 to full-thickness wound re-epithelialization and the underlying mechanisms using Angptl4-knockout mice. Immunohistochemical staining reveals that ANGPTL4 is significantly upregulated in the basal layer cells of the epidermis around the wound during cutaneous wound healing. ANGPTL4 deficiency impairs wound healing. H&E staining shows that ANGPTL4 deficiency significantly reduces the thickness, length and area of the regenerated epidermis postwounding. Immunohistochemical staining for markers of EpSCs (α6 integrin and ß1 integrin) and cell proliferation (PCNA) shows that the number and proliferation of EpSCs in the basal layer of the epidermis are reduced in ANGPTL4-deficient mice. In vitro studies show that ANGPTL4 deficiency impedes EpSC proliferation, causes cell cycle arrest at the G1 phase and reduces the expressions of cyclins D1 and A2, which can be reversed by ANGPTL4 overexpression. ANGPTL4 deletion suppresses EpSC migration, which is also rescued by ANGPTL4 overexpression. Overexpression of ANGPTL4 in EpSCs accelerates cell proliferation and migration. Collectively, our results indicate that ANGPTL4 promotes EpSC proliferation by upregulating cyclins D1 and A2 expressions and accelerating the cell cycle transition from G1 to S phase and that ANGPTL4 promotes skin wound re-epithelialization by stimulating EpSC proliferation and migration. Our study reveals a novel mechanism underlying EpSC activation and re-epithelialization during cutaneous wound healing.

Anatomical characterization of the intraosseous arteries of the porcine tibia.

Introduction: Tibial fractures have a high rate of post-fracture complications. Blood supply is recognized as a positive factor in tibial fracture healing. However, it's difficult to assess blood supply damage after tibial fracture because of the lack of understanding of the tibial intraosseous arteries. This study aimed to delineate and anatomically characterize porcine tibial intraosseous arteries, as a model for the human system. Methods: Twenty right calf specimens with popliteal vessels were prepared from ordinary Landrace pigs. Epoxy resin was perfused into the vasculature from the popliteal artery. After 24 h, casts of the intraosseous arteries of the tibia were exposed through acid and alkali corrosion. The distribution and anatomy of the exposed intraosseous arteries were observed and measured under a microscope, and the data were statistically analyzed. Results: Sixteen complete specimens were obtained. The medullary artery bifurcated into the main ascending and descending branches, which each split into two upward primary branches that further divided into 1-3 secondary branches. Among all specimens, 56 ascending and 42 descending secondary branches, which were all ≥0.3 mm in diameter. Furthermore, the horizontal plane was divided into three zones-safety, buffer, and danger zones-according to the probability of the presence of intraosseous artery. Discussion: The cast perfusion and corrosion approach was successfully applied for anatomical characterization of the intraosseous arteries of the porcine tibia. These observations provide a theoretical basis for understanding the tibial vasculature in humans and will facilitate the establishment of novel "safe corridor" in the tibia for the protection of the blood supply during surgery.

Age is Not the Most Important Factor in the Prognosis of Femoral Neck Fracture: An Analysis of Long-Term Clinical Follow-Up.

Objective: The prognosis of femoral neck fractures is affected by factors including age and type of fracture. This study aimed to explore the associations among postsurgical outcomes of internal fixation for femoral neck fracture (healing rate, necrosis rate, and joint function score) and age and type of fracture. Methods: We retrospectively analyzed 297 cases of femoral neck fracture treated with internal fixation between February 2008 and October 2018. The postoperative femoral neck nonunion rate (a measure of healing) and femoral head necrosis rate were determined by x-ray and computed tomography. The Harris hip score (a measure of joint function and pain) was calculated. The effects of age and fracture type on these factors were analyzed. Results: There was no significant difference in the rate of femoral head necrosis and postoperative joint function scores among the different age groups. There was a significant difference in the postoperative rate of femoral head necrosis by Garden (P = .001) and Pauwels (P = .01) fracture types. No significant differences were noted for the Harris hip score for fractures characterized by the Pauwels classification (P = .09). However, the Harris hip scores differed significantly among groups for fractures categorized by the Garden classification (P = .001). Conclusions: Fracture type but not age is closely related to femoral head necrosis and Harris hip score after internal fixation of femoral neck fractures.

Combined light-cured and sacrificial hydrogels for fabrication of small-diameter bionic vessels by 3D bioprinting.

BACKGROUND: Bionic grafts can replace autologous tissue through tissue engineering in cases of cardiovascular disease. However, small-diameter vessel grafts remain challenging to precellularize. OBJECTIVE: Bionic small-diameter vessels with endothelial and smooth muscle cells (SMCs) manufactured with a novel approach. METHODS: A 1-mm-diameter bionic blood vessel was constructed by combining light-cured hydrogel gelatin-methacryloyl (GelMA) with sacrificial hydrogel Pluronic F127. Mechanical properties of GelMA (Young's modulus and tensile stress) were tested. Cell viability and proliferation were detected using Live/dead staining and CCK-8 assays, respectively. The histology and function of the vessels were observed using hematoxylin and eosin and immunofluorescence staining. RESULTS: GelMA and Pluronic were printed together using extrusion. The temporary Pluronic support was removed by cooling during GelMA crosslinking, yielding a hollow tubular construct. A bionic bilayer vascular structure was fabricated by loading SMCs into the GelMA bioink, followed by perfusion with endothelial cells. In the structure, both cell types maintained good cell viability. The vessel showed good histological morphology and function. CONCLUSION: Using light-cured and sacrificial hydrogels, we formed a small ca bionic vessel with a small caliber containing SMCs and endothelial cells, demonstrating an innovative approach for construction of bionic vascular tissues.

Morphological study of branches of lateral femoral circumflex artery based on digital subtraction angiography.

In this study, the digital subtraction angiography (DSA) data were used to describe the number, course, and distribution of the branches of the lateral circumflex femoral artery (LCFA), in order to provide an imaging basis for the application of the anterolateral thigh flap pedicled with each branch of the LCFA. The number, location, direction, and distribution of the branches of the LCFA were analyzed by selective DSA angiography in 113 patients who needed an anterolateral thigh flap to repair the wound. LCFA usually originates from the deep femoral artery or femoral artery and routinely sends out four main branches: ascending branch, transverse branch, oblique branch, and descending branch. The ascending branch is about 45 °outward and upward with the horizontal axis of the body; the transverse branch is roughly parallel to the horizontal axis of the body to the outside of the thigh or slightly upward or downward; the oblique branch is about 45 °outward and downward to the body's long axis or horizontal axis and gradually turns parallel to the body's long axis; the 5∼10 cm at the beginning of the descending branch is parallel to the long axis of the body, and the internal and external branches are separated near the midpoint of the line between the anterior superior iliac spine and the lateral edge of the patella. It is of high reference value to use DSA technology to analyze the morphological characteristics of LCFA.

Transplantation of Ultra-Long Cross-Donor Conjoined Perforator Flaps with Multiple Blood Supply Sources for Wound Repair.

OBJECTIVE: There are reports about the surgical method and clinical efficacy of using ultra-long cross-donor perforator skin flap transplantation with multiple blood supply sources to repair wounds. METHOD: Between January 2013 and March 2019, 29 wounds were repaired using ultra-long skin flaps from the donor site of the chest, abdomen and anterolateral thigh. All patients were followed up on a regular basis with a view to the following: appearance of skin flap, function of recipient area and healing of donor area. RESULT: After the operation, all 28 skin flaps were fine. On the fifth day after the operation, one case of a 47-cm anterolateral thigh flap had dark skin color in the distal-most area measuring about 5 cm×4 cm, and the incision showed slow bleeding. In 11 cases, linear scars with soft edges and no obvious contractures were left in the donor area of the chest and abdomen. Eighteen cases with lateral femoral donor sites healed successfully, with linear scars forming without contracture. Three cases with lateral femoral donor sites had wide linear scars that were slightly above skin level and exhibited no contracture. CONCLUSION: Transplantation of ultra-long conjoined cross-donor perforator flaps with multiple blood supply is beneficial to wound repair and worthy of clinical promotion.

Bioprinting a skin patch with dual-crosslinked gelatin (GelMA) and silk fibroin (SilMA): An approach to accelerating cutaneous wound healing.

Clinical settings often face significant obstacles in treating large acute wounds. The alternative of therapeutic approach is needed urgently. Hydrogels derived from natural or synthetic materials may be designed to perform a variety of functions for promoting wound healing. Herein, a 3D bioprinted hydrogel patch is designed for accelerating acute wound healing, which is fabricated with methacryloyl-substituted gelatin (GelMA) and silk fibroin (SilMA) dual-cross-linked by ultraviolet (UV) light. The GelMA with added silk fibroin (GelSilMA) shows improved biodegradation and mechanical properties. Furthermore, SilMA hydrogel can maintain a moisturized healing environment in wound area persistently with adequate degradation capacity. In vivo, GelSilMA (G-S) hydrogel can help to speed wound closure by the improved microenvironment for epidermal tissue regeneration and endogenous collagen generation accordingly. In summary, the G-S hydrogel patch can accelerate acute wound healing efficiently in a relatively simple and inexpensive manner.

Repair of Compound Dorsal Defects of the Digits Using a Free Antegrade Palmaris Longus Tendocutaneous Venous Flap.

PURPOSE: To investigate the clinical effect of repairing small dorsal digit compound tissue defects using a free palmaris longus tendocutaneous flap nourished by venous blood. METHODS: In a retrospective analysis of patients treated between March 2010 and October 2017, 18 patients were identified as having small compound tissue defects, which were repaired using a free palmaris longus tendocutaneous flap nourished by venous blood. The average age of the patients, including 15 male and 3 female patients, was 34 years (range, 22-55 years). The mean wound size was 6 cm2 (range, 2.0 × 1.5 to 3.5 × 2.0 cm2). All the patients had dorsal defects. The average length of extensor tendon defect was 2.0 cm (range, 1.0-3.0 cm). The mean area of the flap was 7 cm2 (range, 2.5 × 2.0 to 4.0 × 3.5 cm2). The donor sites were primarily closed. RESULTS: All 18 flaps survived. A vascular crisis due to a venospasm occurred within 48 hours in 3 flaps, but ultimately, all the flaps survived. The patients were followed-up for a mean period of 10 months (range, 3-15 months). All the patients returned to their previous work after 10-12 weeks. No pain or scar contracture was reported in either the recipient or donor site. CONCLUSIONS: The free antegrade palmaris longus tendocutaneous venous flap enabled the repair of compound tissue defects of the dorsal digit, resulting in acceptable aesthetics, repaired tendon defects, and wound coverage. This surgical method is an option for the reconstruction of small compound defects of digits with extensor defects. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Dimethyl phthalate inhibits the growth of Escherichia coli K-12 by regulating sugar transport and energy metabolism.

Dimethyl phthalate (DMP) is one of the most widely used plasticizers, and it is easily released into the environment, posing a threat to microbes. In this study, the impact of DMP on the uptake and metabolism of sugars in E. coli K-12 was assessed using proteomics, computational simulation analysis, transcriptome analysis, and sugar utilization experiments. DMP contamination inhibited the growth of E. coli K-12 and downregulated the expression of proteins in ATP-binding cassette (ABC) transporters and the phosphotransferase (PTS) system of E. coli K-12, which are primarily involved in the transmembrane transport of sugars. DMP formed a stable complex with sugar transporters and changed the rigidity and stability of the proteins. Furthermore, DMP treatment decreased the utilization of L-arabinose, glucose, D-xylose, and maltose. Moreover, carbon metabolism and oxidative phosphorylation were also downregulated by DMP. Our study shows that DMP reduces the uptake of sugars and ATP production and subsequently inhibits the growth of E. coli K-12.

miR-100-5p Promotes Epidermal Stem Cell Proliferation through Targeting MTMR3 to Activate PIP3/AKT and ERK Signaling Pathways.

Skin epidermal stem cells (EpSCs) play a critical role in wound healing and are ideal seed cells for skin tissue engineering. Exosomes from human adipose-derived stem cells (ADSC-Exos) promote human EpSC proliferation, but the underlying mechanism remains unclear. Here, we investigated the effect of miR-100-5p, one of the most abundant miRNAs in ADSC-Exos, on the proliferation of human EpSCs and explored the mechanisms involved. MTT and BrdU incorporation assays showed that miR-100-5p mimic transfection promoted EpSC proliferation in a time-dependent manner. Cell cycle analysis showed that miR-100-5p mimic transfection significantly decreased the percentage of cells in the G1 phase and increased the percentage of cells in the G2/M phase. Myotubularin-related protein 3 (MTMR3), a lipid phosphatase, was identified as a direct target of miR-100-5p. Knockdown of MTMR3 in EpSCs by RNA interference significantly enhanced cell proliferation, decreased the percentage of cells in the G1 phase and increased the percentage of cells in the S phase. Overexpression of MTMR3 reversed the proproliferative effect of miR-100-5p on EpSCs, indicating that miR-100-5p promoted EpSC proliferation by downregulating MTMR3. Mechanistic studies showed that transfection of EpSCs with miR-100-5p mimics elevated the intracellular PIP3 level, induced AKT and ERK phosphorylation, and upregulated cyclin D1, E1, and A2 expression, which could be attenuated by MTMR3 overexpression. Consistently, intradermal injection of ADSC-Exos or miR-100-5p-enriched ADSC-Exos into cultured human skin tissues significantly reduced MTMR3 expression and increased the thickness of the epidermis and the number of EpSCs in the basal layer of the epidermis. The aforementioned effect of miR-100-5p-enriched ADSC-Exos was stronger than that of ADSC-Exos and was reversed by MTMR3 overexpression. Collectively, our findings indicate that miR-100-5p promotes EpSC proliferation through MTMR3-mediated elevation of PIP3 and activation of AKT and ERK. miR-100-5p-enriched ADSC-Exos can be used to treat skin wound and expand EpSCs for generating epidermal autografts and engineered skin equivalents.