Advancing stroke therapy: A deep dive into early phase of ischemic stroke and recanalization.

Ischemic stroke, accounting for the majority of stroke events, significantly contributes to global morbidity and mortality. Vascular recanalization therapies, namely intravenous thrombolysis and mechanical thrombectomy, have emerged as critical interventions, yet their success hinges on timely application and patient-specific factors. This review focuses on the early phase pathophysiological mechanisms of ischemic stroke and the nuances of recanalization. It highlights the dual role of neutrophils in tissue damage and repair, and the critical involvement of the blood-brain barrier (BBB) in stroke outcomes. Special emphasis is placed on ischemia-reperfusion injury, characterized by oxidative stress, inflammation, and endothelial dysfunction, which paradoxically exacerbates cerebral damage post-revascularization. The review also explores the potential of targeting molecular pathways involved in BBB integrity and inflammation to enhance the efficacy of recanalization therapies. By synthesizing current research, this paper aims to provide insights into optimizing treatment protocols and developing adjuvant neuroprotective strategies, thereby advancing stroke therapy and improving patient outcomes.

Integrated transcriptomic and proteomic profiling reveals the key molecular signatures of brain endothelial reperfusion injury.

BACKGROUND: Reperfusion therapy after ischemic stroke often causes brain microvascular injury. However, the underlying mechanisms are unclear. METHODS: Transcriptomic and proteomic analyses were performed on human cerebral microvascular endothelial cells following oxygen-glucose deprivation (OGD) or OGD plus recovery (OGD/R) to identify molecules and signaling pathways dysregulated by reperfusion. Major findings were further validated in a mouse model of cerebral ischemia and reperfusion. RESULTS: Transcriptomic analysis identified 390 differentially expressed genes (DEGs) between the OGD/R and OGD group. Pathway analysis indicated that these genes were mostly associated with inflammation, including the TNF signaling pathway, TGF-ß signaling pathway, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and NF-κB signaling pathway. Proteomic analysis identified 201 differentially expressed proteins (DEPs), which were primarily associated with extracellular matrix destruction and remodeling, impairment of endothelial transport function, and inflammatory responses. Six genes (DUSP1, JUNB, NFKBIA, NR4A1, SERPINE1, and THBS1) were upregulated by OGD/R at both the mRNA and protein levels. In mice with cerebral ischemia and reperfusion, brain TNF signaling pathway was activated by reperfusion, and inhibiting TNF-α with adalimumab significantly attenuated reperfusion-induced brain endothelial inflammation. In addition, the protein level of THBS1 was substantially upregulated upon reperfusion in brain endothelial cells and the peri-endothelial area in mice receiving cerebral ischemia. CONCLUSION: Our study reveals the key molecular signatures of brain endothelial reperfusion injury and provides potential therapeutic targets for the treatment of brain microvascular injury after reperfusion therapy in ischemic stroke.

Pressure does not affect fibrotic function of dermal fibroblast through an in vitro 3D hydrogel culture model.

Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long-lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA-seq identified 437 differentially regulated genes after an 8-h compression intervention compared with control cells, among which 256 genes were up-regulated and 181 genes were down-regulated. Further q-PCR analysis confirmed that early growth response 1(EGR1) and c-fos were down-regulated after an 8-h compression intervention. However, the down-regulation of EGR1 and c-fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20-h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor ß1(TGF-ß1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α-SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear. Here, a rodent model of thromboembolic stroke followed by rtPA thrombolysis at different time points was performed with or without RIC. Brain infarction, neurological outcomes, BBB permeability, and intracerebral hemorrhage were assessed. The platelet-derived growth factor CC (PDGF-CC)/PDGFRα pathway in the brain tissue, PDGF-CC levels in the skeletal muscle and peripheral blood were also measured. Furthermore, impact of RIC on serum PDGF-CC levels were measured in healthy subjects and AIS patients. Our results showed that RIC substantially reduced BBB injury, intracerebral hemorrhage, cerebral infarction, and neurological deficits after stroke, even when rtPA was administrated in a delayed therapeutic time window. Mechanistically, RIC significantly decreased PDGFRα activation in ischemic brain tissue and reduced blood PDGF-CC levels, which partially resulted from PDGF-CC reduction in the skeletal muscle of RIC-applied hindlimbs and platelets. Intravenous or intraventricular recombinant PDGF-CC supplementation abolished RIC protective effects on BBB integrity. Moreover, similar changes of PDGF-CC in serum by RIC were also observed in healthy humans and acute ischemic stroke patients. Together, our study demonstrates that RIC can attenuate rtPA-aggravated BBB disruption after ischemic stroke via reducing the PDGF-CC/PDGFRα pathway and thus supports RIC as a potential approach for BBB disruption prevention or treatment following thrombolysis.

In situ scarless skin healing of a severe human burn wound induced by a hCTLA4Ig gene-transferred porcine skin graft.

Preventing fibrosis or hypertrophic scar formation following tissue damage is still a big challenge despite the numerous approaches clinicians currently use. Hitherto, no written account was available of a successful case of scarless skin healing after a severe burn injury. Here, we report the first case of the "perfect regenerative healing" of a severe burn wound with no hypertrophic scar formation in which a postage stamp skin autograft was covered with human cytotoxic-T-lymphocyte associated antigen4-immunoglobulin (hCTLA4Ig) gene-transferred pig skin. We also discuss the mechanisms involved in the scarless healing of human burn wounds.

Type 2 Diabetic Mellitus Inhibits Skin Renewal through Inhibiting WNT-Dependent Lgr5+ Hair Follicle Stem Cell Activation in C57BL/6 Mice.

Background: Hair follicles are important accessory organs of the skin, and it is important for skin renewal and performs variety of important functions. Diabetes can cause several dermatoses; however, its effect on hair follicles is unclear. The purpose of this study was to investigate the effect of type II diabetes (T2DM) on the hair follicles of mice. Methods: Seven-week-old male C57BL/6 littermate mice were divided into two groups. The treatment group was injected with streptozotocin (STZ) to induce T2DM, and the control group was parallelly injected with the same dose of buffer. Seven days after injection, the back is depilated to observe the hair follicle regeneration. Hair follicle regeneration was observed by naked eyes and HE staining. The proliferation of the skin cells was observed by PCNA and K14 staining. The altered genes were screened by RNA sequencing and verified by qRT-PCR. In addition, Lgr5 + GFP/mTmG transgenic mice were used to observe the effect of T2DM on Lgr5 hair follicle stem cells (HFSC). And the expression of WNT4 and WNT8A were measured by Western Blot. Results: T2DM inhibited hair follicle regeneration. Compared to control mice, T2DM mice had smaller hair follicles, reduced skin thickness, and less expression of PCNA and K14. RNA sequencing showed that the two groups had significant differences in cell cycle and proliferation-related pathways. Compared with the control mice, the mRNA expression of Lgr4, Lgr5, Wnt4, and Wnt8a was decreased in the T2DM group. Moreover, T2DM inhibited the activation of Lgr5 HFSC and the expression of WNT4 and WNT8A. Conclusions: T2DM inhibited hair follicle regeneration and skin cells proliferation by inhibiting WNT-dependent Lgr5 HFSC activation. This may be an important reason for the reduction of skin renewal ability and the formation of chronic wounds caused by diabetes. It is important for the treatment of chronic diabetic wounds and the development of tissue engineering.

The clinical effectiveness and safety of using epidermal growth factor, fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing: a systematic review and meta-analysis.

Background: Promoting wound healing is crucial to restore the vital barrier function of injured skin. Growth factor products including epidermal growth factor (EGF), fibroblast growth factor (FGF) and granulocyte-macrophage colony stimulating factor (GM-CSF) have been used for decades although no systematic evaluation exists regarding their effectiveness and safety issues in treating acute skin wounds. This has resulted in a lack of guidelines and standards for proper application regimes. Therefore, this systematic review and meta-analysis was performed to critically evaluate the effectiveness and safety of these growth factors on skin acute wounds and provide guidelines for application regimes. Methods: We searched PubMed/Medline (1980-2020), Cochrane Library (1980-2020), Cochrane CENTRAL (from establishment to 2020), ClinicalTrials.gov (from establishment to 2020), Chinese Journal Full-text Database (CNKI, 1994-2020), China Biology Medicine disc (CBM, 1978-2019), Chinese Scientific Journal Database (VIP, 1989-2020) and Wanfang Database (WFDATA, 1980-2019). Randomized controlled trials (RCTs), quasi-RCTs and controlled clinical trials treating patients with acute skin wounds from various causes and with those available growth factors were included. Results: A total of 7573 papers were identified through database searching; 229 papers including 281 studies were kept after final screening. Administering growth factors significantly shortened the healing time of acute skin wounds, including superficial burn injuries [mean difference (MD) = -3.02; 95% confidence interval (CI):-3.31 ~ -2.74; p < 0.00001], deep burn injuries (MD = -5.63; 95% CI:-7.10 ~ -4.17; p < 0.00001), traumata and surgical wounds (MD = -4.50; 95% CI:-5.55 ~ -3.44; p < 0.00001). Growth factors increased the healing rate of acute skin wounds and decreased scar scores. The incidence of adverse reactions was lower in the growth factor treatment group than in the non-growth factor group. Conclusions: The studied growth factors not only are effective and safe for managing acute skin wounds, but also accelerate their healing with no severe adverse reactions.

Subcutaneous Low-Density Foreign Bodies Detection via Grating-Based Multimodal X-ray Imaging.

Detecting low-density foreign bodies within soft tissues still stands for a serious challenge. Grating-based multimodal X-ray imaging typically has low hardware requirements while simultaneously providing three kinds of imaging information, i.e., absorption, phase-contrast, and dark-field. We aimed to explore the capacity of grating-based multimodal X-ray imaging technology for detecting common foreign bodies within subcutaneous tissues, and to assess the advantages as well as disadvantages of the three kinds of images obtained via grating-based X-ray multimodal technology in relation to diverse kinds of foreign bodies within different tissues. In this study, metal, glass, wood, plastic, graphite, and ceramic foreign bodies were injected into chunks of the pig adipose tissue and chicken thigh muscles. Next, a grating-based multimodal X-ray imaging device developed in our laboratory was used to detect the above foreign bodies within the adipose and muscle tissues. Our results show that grating-based multimodal X-ray imaging clearly revealed the subcutaneous foreign bodies within the adipose and muscle tissues by acquiring complementary absorption, phase-contrast, and dark-field imaging data in a single shot. Grating-based multimodal X-ray imaging has an exciting potential to detect foreign bodies underneath the epidermis.

Identification of microbes in wounds using near-infrared spectroscopy.

BACKGROUND: Rapid diagnosis of microbes in the burn wound is a big challenge in the medical field. Traditional biochemical detection techniques take hours or days to identify the species of contaminating and drug-resistant microbes. Near-infrared spectroscopy (NIRS) is evaluated to address the need for a fast and sensitive method for the detection of bacterial contamination in liquids. METHODS: Herin, we developed a novel technique which by using NIRS together with supporting vector machine (SVM), to identify the microbial species and drug-resistant microbes in LB medium, and to diagnose the wound colonization and wound infection models of pigs. RESULTS: The device could recognize 100% of seven kinds of microbes and 99.47% of the multi-drug resistant Staphylococcus aureus (S. aureus), with a concentration of 109 cfu ml-1 in LB medium. The accuracy of the microbial identification in colonized and infected wounds in-situ was 100%. The detection limit of NIRS with SVM for the detection of S. aureus and Escherichia coli (E. coli) was 101 cfu ml-1 in LB medium. Identification time was less than 5 s. CONCLUSION: Our findings validate for the first time a novel technique aimed at the rapid, noncontacted, highly sensitive, and specific recognition of several microbial species including drug-resistant ones. This technique could represent a promising approach to identify diverse microbial species and a potential bedside device to rapidly diagnose infected wounds.

Dietary supplementation with N-3 polyunsaturated fatty acid-enriched fish oil promotes wound healing after ultraviolet B-induced sunburn in mice.

N-3 polyunsaturated fatty acids (n-3 PUFA) can alleviate ultraviolet B (UVB)-induced skin cancers, but their effects on sunburn and upcoming wound healing remain controversial. This study aimed to explore the impact of n-3 PUFA-enriched fish oil (n-3 PUFA-FO) on UVB-induced sunburns and subsequent healing. Sixty C57BL/6 female mice were divided into two groups. The treated group mice were fed n-3 PUFA-FO for the entire duration of the experiment. Mice in the control group were fed a standard diet. After two weeks of n-3 PUFA-FO feeding, mice were exposed to UVB for 20 min and sacrificed 20 d later. Skin photodamage and lesion area were recorded during wound healing. Epidermal lesion thickness was quantified in hematoxylin and eosin-stained skin sections. Inflammation and macrophage polarization were assessed by qRT-PCR. Oxidative stress and antioxidant enzyme activity were quantified using specific ELISA kits. N-3 PUFA-FO feeding decreased UVB photodamage and accelerated wound healing progression, both of which were coupled with less intense inflammation and increased macrophage M2 phenotype polarization. Furthermore, n-3 PUFA-FO brought about a decrease in malondialdehyde (MDA) levels but increased the activity of catalase (CAT) and glutathione peroxidase (GP), without changing superoxide dismutase (SOD) activity. N-3 PUFA-FO protects against UVB-induced skin photodamage and promotes wound healing by modulating macrophage phenotypic polarization and antioxidant enzyme activities. N-3 PUFA-FO could be a novel therapeutic approach for both the prevention and treatment of sunburns.

A novel method for objectively, rapidly and accurately evaluating burn depth via near infrared spectroscopy.

The accurate and objective evaluation of burn depth is a significant challenge in burn wound care. Herein, we used near infrared spectroscopy (NIRS) technology to measure the different depth of thermal burns in ex vivo porcine models. Based on the intensity of the spectral signals and the diffuse reflection theory, we extracted the optical parameters involved in functional (total hemoglobin and water content) and structural (tissue scattered size and scattered particles) features that reflect the changes in burn depth. Next, we applied support vector regression to construct a model including the optical property parameters and the burn depth. Finally, we histologically verified the burn depth data collected via NIRS. The results showed that our inversion model could achieve an average relative error of about 7.63%, while the NIRS technology diagnostic accuracy was in the range of 50 µm. For the first time, this novel technique provides physicians with real-time burn depth information objectively and accurately.

COVID-19 mRNA Vaccines Are Generally Safe in the Short Term: A Vaccine Vigilance Real-World Study Says.

Background: The prophylactic vaccination of COVID-19 mRNA vaccines is the first large-scale application of this kind in the human world. Over 1.8 million doses of the COVID-19 vaccine had been administered in the US until December 2020, and around 0.2% submitted AE reports to the Vaccine Adverse Event Reporting System (VAERS). This study aimed to evaluate the AEs following immunization (AEFIs) and analyze the potential associations based on the information from the VAERS database. Methods: We searched the VAERS database recorded AEFIs after COVID-19 vaccines in December 2020. After data mapping, we summarized demographic and clinical features of reported cases. Fisher exact test was used to comparing the clinical characteristics among AE groups with an anaphylactic response, concerning neurological disorders and death. Results: VAERS reported 3,908 AEFIs of COVID-19 vaccines in December 2020. Most (79.68%) were reported after the first dose of the vaccine. Among the reported cases, we found that general disorders (48.80%), nervous system disorders (46.39%), and gastrointestinal disorders (25.54%) were the most common AEFIs. The allergy history was more frequent in vaccine recipients with anaphylactic reactions than those without (64.91% vs. 49.62%, OR = 1.88, P <0.017). History of anxiety or depression was more common in subjects reporting severe neurological AEFIs than those reporting other AEFIs (18.37% vs. 7.85%, OR = 2.64, P <0.017). Cases reporting death were significantly older (79.36 ± 10.41-year-old vs. 42.64 ± 12.55-year-old, P <0.01, 95% CI 29.30-44.15) and more likely experienced hypertension (50.00% vs. 11.42%, OR = 7.76, P <0.01) and neurological disorders (50.00% vs. 5.36%, OR = 17.65, P <0.01) than other vaccine recipients. The outpatient and emergency room visit rates were 11.92 and 22.42% for AEFIs, and 2.53% of cases needed hospitalization. Conclusion: AEFIs of COVID-19 mRNA vaccines were generally non-severe local or systemic reactions. A prior allergy history is the risk factor for anaphylaxis, while a history of anxiety may link with severe neurological AEs. Such vaccine recipients need further evaluation and monitor.

Porcine Acellular Dermal Matrix Increases Fat Survival Rate after Fat Grafting in Nude Mice.

BACKGROUND: Autologous fat grafts have been widely in use for reconstruction, contour abnormalities, and cosmetic surgeries. However, the grafted fat one-year survival rate is unpredictable and always low (20%-80%). Standardizing the existing transplantation technology is difficult due to the limiting conditions. Scaffold materials or drugs are unsuitable to employ because of legal restrictions, complex production, and undetermined hazards. Therefore, a simpler and more effective approach to improve grafted fat survival rate is using commercial products as additives. Earlier studies proved that porcine acellular dermal matrix (PADM), a biomaterial clinically used for wound repair, could work as a scaffold for lipo-implantation. This study aimed at investigating the hitherto unclear effect of PADM on transplanted fat survival. METHODS: Thirty-two 8-week-old female nude mice were divided into two groups. Control mice received a 300 µl fat injection, while the PADM group mice were injected with a 300 µl PADM-fat mixture. After a 4-week treatment, fat weight and liquefaction ratio were assessed. Histological changes were quantified via hematoxylin & eosin (H&E) staining. Macrophage infiltration and vascular regeneration were revealed using an anti-CD34 antibody. Mouse and human mRNA expression levels were gauged via RNA-sequencing. On the third day post implantation, the mRNA expression levels of inflammatory genes Mcp-1 and Tnf-α were measured by qRT-PCR. RESULTS: The weight of surviving grafted fat did not differ between the control and the PADM group. However, adding PADM significantly decreased fat liquefaction. H&E-stained sections showed that PADM decreased fat necrosis, increased fat tissue regeneration, and raised CD34 levels in the regenerated tissue. RNA-sequencing showed that, compared to controls, fats from PADM-added group expressed more mouse-related mRNA but less human-related mRNA. The following GO and KEGG analysis showed that added PADM increased extracellular matrix (ECM) genes expression levels. The qRT-PCR showed that adding PADM increased Mcp-1 and Tnf-α mRNA expression levels. CONCLUSIONS: In summary, PADM addition increased fat survival rate by reducing fat liquefaction through an increased macrophage infiltration, ECM regeneration, and revascularization. Therefore, PADM addition is a workable application in autologous fat grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

In situ Fabrication of Nano ZnO/BCM Biocomposite Based on MA Modified Bacterial Cellulose Membrane for Antibacterial and Wound Healing.

BACKGROUND: Developing an ideal wound dressing that meets the multiple demands of safe and practical, good biocompatibility, superior mechanical property and excellent antibacterial activity is highly desirable for wound healing. Bacterial cellulose (BC) is one of such promising class of biopolymers since it can control wound exudates and can provide moist environment to a wound resulting in better wound healing. However, the lack of antibacterial activity has limited its application. METHODS AND RESULTS: We prepared a flexible dressing based on a bacterial cellulose membrane and then modified it by chemical crosslinking to prepare in situ synthesis of nZnO/BCM via a facile and eco-friendly approach. Scanning electron microscopy (SEM) results indicated that nZnO/BCM membranes were characterized by an ideal porous structure (pore size: 30~ 90 µm), forming a unique string-beaded morphology. The average water vapor transmission of nZnO/BCM was 2856.60 g/m2/day, which improved the moist environment of nZnO/BCM. ATR-FITR further confirmed the stepwise deposition of nano-zinc oxide. Tensile testing indicated that our nanocomposites were flexible, comfortable and resilient. Bacterial suspension assay and plate counting methods demonstrated that 5wt. % nZnO/BCM possessed excellent antibacterial activity against S.aureus and E. coli, while MTT assay demonstrated that they had no measurable cytotoxicity toward mammalian cells. Moreover, skin irritation test and histocompatibility examination supported that 5wt. % nZnO/BCM had no stimulation to skin and had acceptable biocompatibility with little infiltration of the inflammatory cells. Finally, by using a bacteria-infected (S. aureus and E. coli) murine wound model, we found that nZnO/BCM could prevent in vivo bacterial infections and promote wound healing via accelerating the re-epithelialization and wound contraction, and these membranes had no obvious toxicity toward normal tissues. CONCLUSION: Therefore, the constructed nZnO/BCM has great potential for biomedical applications as an efficient antibacterial wound dressing.

Selective debridement of burn wounds using hydrosurgery system.

In recent years, hydrosurgery is a technology that has been applied more and more in debridement procedures. However, the selectivity of hydrosurgery to cutaneous necrotic tissues has not been proved. This study was designed to investigate the possible tissue selectivity of hydrosurgery in the debridement in burn wounds. Deep partial-thickness burns were produced on the back of porcine, and 48 hours later, both burn wounds and normal skin were debrided using the hydrosurgery system. Then tissue samples were taken, and histological staining was performed and observed under microscope. Burn wound resection rates and the normal skin damaged rates were measured. Our result indicated that the burn wounds were significantly more sensitive than the normal skin when the water pressure produced by the hydrosurgery system was set between 3000 and 5000 psi (pounds per square inch), that is, the necrotic tissue portions were debrided more easily than the normal skin tissue. Based on these data, we suggest that 3000 to 5000 psi of water pressure in the hydrosurgery system has a skin tissue selectivity in burn wounds.

Full-field burn depth detection based on near-infrared hyperspectral imaging and ensemble regression.

The accurate and instant diagnosis of burn severity is always the key point of optimal wound management and clinical treatment. However, the accuracy of burn depth assessment is low via visual inspection and lacks a quantitative measurement. In this work, a full-field burn depth detection system is proposed using the near-infrared hyperspectral imaging with the ensemble regression. The rotational feature subspace ensemble regression is introduced to establish a complex regression model between the hyperspectral imaging data and the burn depth. By the in vivo measurement of a porcine model, the method can get the average relative error about 7% for the burn depth measurement, which demonstrates that the proposed method can perform an accurate full-field assessment of burn depth and provide more practical references for clinicians.

CD9 regulates keratinocyte migration by negatively modulating the sheddase activity of ADAM17.

CD9 is a trans-membrane protein, and has recently been implicated in different physiological and cellular processes, such as cell migration and adhesion. According to previous study, down-regulation of CD9 contributes to keratinocyte migration, critical for wound re-epithelialization. Nevertheless, it is widely believed that tetraspanin CD9 does not have ligands or function as the cell surface receptor, rather it is thought to associate with other transmembrane molecules, thereby mediate keratinocyte migration. Little is known about how CD9 associates with transmembrane molecules in migratory keratinocytes. Here, using confocal microscopy, we observed that tetraspanin CD9 and ADAM17 co-localized on the surface of keratinocytes in the course of wound repair in vivo and in vitro. Co-immunoprecipitation experiments demonstrated a direct association between CD9 and ADAM17 in HaCaT cells and C57-MKs. Functional studies revealed that down-regulation or over-expression of CD9 exerted negative regulatory effects on ADAM17 sheddase activity. This activity is involved in CD9-regulated cell motility and migration. Further studies found that ADAM17 inhibitor-TAPI-2 or siADAM17 significantly abolished the enhanced effect of keratinocyte migration induced by CD9 down-regulation. Meanwhile, the sheddase activity of ADAM17 was inhibited by TAPI-2, which decreased this release of AREG and HB-EGF in CD9-silenced HaCat cells and C57-MKs. Importantly, neutralizing antibody against HB-EGF significant weakened keratinocyte migration and motility in CD9-silenced keratinocytes, and the inhibition of CD9-regulated keratinocyte migration by siADAM17 was rescued by addition of recombinant HB-EGF, activating EGFR/ERK pathway. Collectively, our results suggest that ADAM17 sheddase activity is activated by down-regulation of CD9, thereby mediating shedding of HB-EGF and activation of EGFR/ERK signaling, which crucially affects the keratinocyte migration and wound healing.

Epidemiologic and clinical characteristics of severe burn patients: results of a retrospective multicenter study in China, 2011-2015.

BACKGROUND: Severe burns injury is a serious pathology, leading to teratogenicity and significant mortality, and it also has a long-term social impact. The aim of this article is to describe the hospitalized population with severe burns injuries in eight burn centers in China between 2011 and 2015 and to suggest future preventive strategies. METHODS: This 5-year retrospective review included all patients with severe burns in a database at eight institutions. The data collected included gender, age, month distribution, etiology, location, presence of inhalation injury, total burn surface area, depth of the burn, the length of hospitalization, and mortality. SPSS 19.0 software was used to analyze the data. RESULTS: A total of 1126 patients were included: 803 (71.3%) male patients and 323 (28.7%) female patients. Scalds were the most common cause of burns (476, 42.27%), followed by fire (457, 40.59%). The extremities were the most frequently affected areas, followed by the trunk. The median length of hospitalization was 30 (15, 52) days. The overall mortality rate was 14.21%. CONCLUSIONS: Although medical centers have devoted intensive resources to improving the survival rates of burn patients, expenditures for prevention and education programs are minimal. Our findings suggest that more attention should be paid to the importance of prevention and the reduction of injury severity. This study may contribute to the establishment of a nationwide burn database and the elaboration of strategies to prevent severe burns injury.

A burn depth detection system based on near infrared spectroscopy and ensemble learning.

Near infrared (NIR) spectroscopy can effectively detect the changes in the burned tissue. However, due to the complex relationship between the spectral signals and the burn depth, simple methods of data analysis are difficult to solve this problem effectively. Therefore, in this paper, a machine learning method is introduced into the NIR spectral signal analysis, which is used to establish the relationship between NIR spectral signals and burn depth. First, based on the intensity of the spectral signal and the diffuse reflection theory, the optical properties that can reflect the change of burned tissue are extracted. And then the chained-agent genetic algorithm (CAGA) optimized support vector regression (SVR) is applied to establish a regression model between the optical property parameters and burn depth. Finally, the porcine model was used for verification. The experimental results demonstrate that the proposed CAGA-SVR integrated inversion model with optical properties can perform accurate inversion of burn depth and provide a reference for doctors.

Photochemical reaction, acidichromism, and supramolecular nanoarchitectures in the Langmuir-Blodgett films of an amphiphilic styrylquinoxaline derivative.

An amphiphilic styrylquinoxaline derivative, 3-(4-(hexadecyloxy)styryl)quinoxalin-2(1H)-one (SQC16), was newly synthesized to investigate their photochemical and gas responsive properties in organized molecular films. It was observed that SQC16 can spread as a monolayer on the subphases with various pH values and be subsequently transferred onto solid substrates. While SQC16 showed predominantly reversible trans-cis photoisomerization in methanol solution, it showed both photoisomerization and photodimerization in Langmuir-Blodgett (LB) films. Photodimerization was only observed in the LB film due to the face-to-face arrangement of the functional headgroup in the LB film, and the process was irreversible. In addition, the LB film showed acidichromism, i.e., when the film was exposed to HCl gas its color changed from yellow to red, and the color could be recovered after exposure to NH(3) gas. The process was reversible and could be repeated many times. An interesting surface morphology of the SQC16 LB film was revealed. It was observed that SQC16 can form nanowire architecture in the transferred one-layer LB film. This morphology can be changed upon photoirradiation or in gas reactions. Through the atomic force microscopy measurements it was suggested that the photodimerization predominantly occurred from the nanowire structures, while during the acidichromism the reaction occurred preferentially in the flat region. X-ray diffraction studies revealed that while layer distance showed a slight change for the LB film during acidichromism and photoreaction, the layer structure of SQC16 LB film was retained.