Single-cell profiling and functional screening reveal crucial roles for lncRNAs in the epidermal re-epithelialization of human acute wounds.

Objectives: Re-epithelialization is an important physiological process for repairing skin barrier function during wound healing. It is primarily mediated by coordinated migration, proliferation, and differentiation of keratinocytes. Long noncoding RNAs (lncRNAs) are essential components of the noncoding genome and participate in various biological processes; however, their expression profiles and function in re-epithelialization during wound healing have not been established. Methods: We investigated the distribution of lncRNAs during wound re-epithelialization by comparing the genomic profiles of uninjured skin and acute wound (AW) from healthy donors. We performed functional screening of differentially expressed lncRNAs to identify the important lncRNAs for re-epithelialization. Results: The expression of multiple lncRNAs is changed during human wound re-epithelialization process. We identified VIM-AS1, SMAD5-AS1, and LINC02581 as critical regulators involved in keratinocyte migration, proliferation, and differentiation, respectively. Conclusion: LncRNAs play crucial regulatory roles in wound re-epithelialization. We established lncRNA expression profile in human acute wounds compared with intact skin, offering valuable insights into the physiological mechanisms underlying wound healing and potential therapeutic targets.

The research landscape of oxidative stress in osteoarthritis from 1998 to 2021: a systematic bibliometric analysis.

OBJECTIVE: A substantial body of literature pertaining to oxidative stress in osteoarthritis (OA) has been published over the past few decades. However, a comprehensive systematic analysis in this field is currently lacking. The objective of this study was to perform a bibliometric analysis to visualize the current research hotspots and evolving trends associated with oxidative stress in OA, in order to contribute to a more comprehensive understanding of this field. METHODS: The raw data pertaining to oxidative stress in OA, published between 1998 and 2021, were obtained from the Web of Science Core Collection database (WoSCC). In order to provide comprehensive results across multiple dimensions, various bibliometric software tools were employed to quantify and analyze the research focuses and trends regarding oxidative stress in OA. RESULTS: A total of 1178 original articles and reviews on oxidative stress in OA were included, with China and the USA emerging as the primary driving forces in this research field. Notably, Wenzhou Medical University stood out as the most prolific institution in terms of publication volume. Blanco FJ was the most prolific author, and the journal with the most publications was Osteoarthritis and Cartilage. The analysis of keyword burst detection revealed that the investigation of chondrocyte senescence induced by oxidative stress was the most frequent. CONCLUSION: The burgeoning body of literature pertaining to oxidative stress in OA has experienced a consistent growth over the past few decades, and this field will garner widespread attention and in-depth investigation. The frontier of chondrocyte senescence, as revealed by bibliometric analyses, represents a special focus of this field, with potential as a vital therapeutic target for OA.

Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.

Therapeutic targets and potential delivery systems of melatonin in osteoarthritis.

Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

The sonic hedgehog pathway suppresses oxidative stress and senescence in nucleus pulposus cells to alleviate intervertebral disc degeneration via GPX4.

Disruption of intervertebral disc (IVD) homeostasis caused by oxidative stress and nucleus pulposus cell (NPC) senescence is a main cause of intervertebral disc degeneration (IDD). The sonic hedgehog (Shh) pathway plays an important role in IVD development, but its roles in IDD are unknown. This study aimed to investigate the effects of the Shh pathway on the alleviation of IDD and the related mechanisms. In vivo, the effect of the Shh pathway on IVD homeostasis was studied by intraperitoneal injection of recombinant Shh (rShh) and GANT61 based on puncture-induced IDD. GANT61, lentivirus-coated sh-Gli1 and rShh were used to investigate the role and mechanism of the Shh pathway in NPCs based on senescence induced by Braco19 and oxidative stress induced by TBHP. Shh pathway expression decreased, and senescence and oxidative stress increased with age. Intraperitoneal injection of rShh activated the Shh pathway to suppress oxidative stress and NPC senescence and consequently alleviated needle puncture-induced IDD. In vitro, the Shh pathway upregulated glutathione peroxidase 4 (GPX4) expression to suppress oxidative stress and senescence in NPCs. Moreover, GPX4 suppression in NPCs by si-GPX4 significantly reduced the protective effect of the Shh pathway on oxidative stress and senescence in NPCs. Our results demonstrate for the first time that the Shh pathway plays a key role in the alleviation of IDD by suppressing oxidative stress and cell senescence in NP tissues. This study provides a new potential target for the prevention and reversal of IDD.

Transformation of NSCLC to SCLC harboring EML4-ALK fusion with V1180L mutation after alectinib resistance and response to lorlatinib: A case report and literature review.

BACKGROUND: Histological transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) with anaplastic lymphoma kinase (ALK) positivity is extremely uncommon in ALK-positive NSCLC. To date, there have been limited reports regarding cases of SCLC transformation, and the optimal therapeutic strategies and prognosis for such patients remain unclear. This case is the first to describe the effectiveness of lorlatinib in treating a patient with SCLC that transformed from NSCLC harboring the ALK fusion V1180L mutation following acquired resistance to alectinib therapy. CASE DESCRIPTION: We present a case of alectinib-induced transformation from ALK-positive NSCLC to SCLC with an ALK V1180L mutation after acquiring alectinib resistance. The patient achieved disease remission with lorlatinib treatment following ineffective chemotherapy. In April 2022, a 53-year-old male was diagnosed with ALK-positive advanced poorly differentiated adenocarcinoma with neuroendocrine differentiation in the left lower lobe of the lung. The diagnosis was accompanied by multiple bone metastases and brain metastases, categorizing the stage as cT3N2M1. Following 8 months of alectinib treatment, chest computed tomography (CT) and cranial magnetic resonance imaging (MRI) revealed disease progression. Pathological and genetic analyses indicated the transformation to pulmonary small cell carcinoma accompanied by ALK fusion V1180L mutation. After the administration of two cycles of EP chemotherapy with unsatisfactory response, oral lorlatinib therapy was initiated. A subsequent month of treatment resulted in notable reduction of the left lung lesion according to chest CT, as well as a significant decrease in intracranial lesions based on cranial MRI. After taking lorlatinib for 5 months, the lesions continue to shrink, and there is a noticeable improvement in the patient's quality of life. Currently, the patient remains in a state of sustained improvement. CONCLUSION: This study affirms the efficacy of lorlatinib in patients with ALK-positive SCLC transformation harboring the V1180L mutation. Furthermore, it underscores the imperative of conducting genetic testing in patients who transition to SCLC following ALK-TKI resistance, as targeted therapies may remain efficacious if a genetic driver is identified.

Identification of EGFR as an essential regulator in chondrocytes ferroptosis of osteoarthritis using bioinformatics, in vivo, and in vitro study.

Objective: The mechanisms of chondrocytes ferroptosis in osteoarthritis (OA) have not yet been fully elucidated. This study aimed to identify key ferroptosis related genes (FRGs) involved in chondrocytes ferroptosis. Methods: LASSO, SVM-RFE, and receiver operating characteristic curve (ROC) were performed to screen key differentially expressed FRGs (DEFRGs). Functional analyses were conducted using GO, and KEGG analyses. Unsupervised clustering analysis was used to identify ferroptosis related patterns. The CeRNA network was constructed to predict the upstream miRNAs and lncRNAs. Finally, we validated the role of EGFR in chondrocytes ferroptosis using in vivo and in vitro experiments. Results: A total of 42 DEFRGs were identified between OA and normal cartilages. GO and KEGG analyses indicated that these DEFRGs were significantly engaged in ferroptosis related biological processes and pathways, such as cellular response to oxidative stress, positive regulation of programmed cell death, MAPK and PI3K-Akt signaling pathways. Moreover, four key DEFRGs, including ACSF2, AURKA, EGFR, and KLHL24, were considered as potential biomarkers of OA. Moreover, two distinct ferroptosis related patterns were determined, and a total of 882 differentially expressed genes were identified which might participate in extracellular matrix degradation and inflammatory response. In addition, the CeRNA network showed that EGFR could be competitively regulated by 3 lncRNAs and 4 miRNAs. Significantly, the expression of EGFR was downregulated in human OA cartilages, OA mouse model, and erastin induced chondrocytes. EGFR inhibition could induce the occurrence of chondrocytes ferroptosis and ECM degradation which could be reversed by the addition of Ferrostatin-1. Conclusion: Our study has identified ACSF2, AURKA, EGFR, and KLHL24 as ferroptosis-related biomarkers in OA. Furthermore, we have conducted a preliminary investigation into the role of EGFR in regulating chondrocytes ferroptosis. These findings offer novel insights into the molecular mechanisms underlying OA.

Study of the Immediately Detection of Mild Traumatic Brain Injury by Feature Engineering on Electroencephalography.

The electroencephalographic (EEG) diagnosis of mild traumatic brain injury (mTBI) is not usually timely, and the detection is often performed several hours or days after the trauma, leading to a decrease in the accuracy of its detection. In this study, EEG signals are recorded immediately after mTBI by connecting a bipolar single lead to injured animals. And three types of EEG features, namely time domain, frequency domain, and nonlinear dynamics, are screened for optimal feature subset in mTBI detection. First, EEG signals of animals are recorded before and after establishing the animal model of mTBI. Second, signal preprocessing, feature extraction, and feature preprocessing are performed to obtain the full-feature dataset, and 1442 feature subsets are obtained by 15 feature reduction algorithms extracted from combinations of 47 features. Ultimately, the support vector machines and K-nearest neighbor algorithms are trained and tested respectively, and their performance is comprehensively compared to determine the optimal feature subset for mTBI detection. In the EEG dataset collected in this study, a total of eight feature subsets extracted from combinations of original 47 features and classification models with 100% accuracy are obtained. This study shows the perspective of immediately detecting mTBI based on a bipolar single-lead EEG.

A Roadmap for a Consensus Human Skin Cell Atlas and Single-Cell Data Standardization.

Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.

Worldwide survey on implantation of and outcomes for conduction system pacing with His bundle and left bundle branch area pacing leads.

BACKGROUND: Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. METHODS: We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. RESULTS: The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [IQR]: 1.5 V [1.3-2.0 V] vs 0.8 V [0.6-1.0 V], p = 0.0008) and lower ventricular sensing (median [IQR]: 4.0 mV [3.0-5.0 mV] vs. 10.0 mV [7.0-12.0 mV], p < 0.0001). CONCLUSION: In conclusion, CSP lead implantation has been broadly adopted but has yet to become the default approach at most surveyed institutions. As the indications and data for CSP continue to evolve, strategies to educate and promote CSP lead implantation at institutions without CSP lead implantation experience would be necessary.

Spatio-temporal distribution of emerging snail-infested sites in different environmental types in Yunnan Province / 中华地方病学杂志

Objective:To explore the spatial and temporal distribution patterns of emerging snail-infested sites in different environmental types in Yunnan Province.Methods:The data of snail-infested sites in Yunnan Province from 1950 to 2014 (from Yunnan Institute for Endemic Diseases Control and Prevention), were collected and sorted out, a spatial and temporal database on the distribution of emerging snail-infested sites were established, and the changes in the spatial and temporal distribution of emerging snail-infested sites in different environments types (ditches, tangerines, paddy fields, dry land, beaches and other environments) were studied by using spatial autocorrelation analysis and scanning statistics analysis.Results:From 1950 to 2014, the annual number of emerging snail-infested sites in Yunnan Province reached a peak (1 730) in 1955 and then showed a fluctuating downward trend. From 1993 to 2014, the number of emerging snail-infested sites remained below 100, and increased to 160 and 131, respectively, in 2004 and 2013. The longest mean duration of 43.85 years was recorded for the beaches environment for emerging snail-infested sites, followed by the paddy fields environment with a mean duration of 37.01 years, and the shortest mean duration of 20.44 years for the tangerines environment. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the duration of emerging snail-infested sites of different environmental types (global Moran's I ranged from 0.43 to 0.64, P < 0.05). Scanning statistics analysis showed that emerging snail-infested sites of different environmental types had spatial and temporal aggregation ( P < 0.001), with 3- 6 clusters of statistically significant aggregation detected respectively. Conclusion:The emerging snail-infested sites in different environments types in Yunnan Province have spatial and temporal aggregation, and it is necessary to strengthen monitoring and prevention and control of the aggregation areas of different environment types to prevent further spread of the snail.

Neurotoxicity mechanism of aconitine in HT22 cells studied by microfluidic chip-mass spectrometry / 药物分析学报

Aconitine,a common and main toxic component of Aconitum,is toxic to the central nervous system.However,the mechanism of aconitine neurotoxicity is not yet clear.In this work,we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine.HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system.Meanwhile,to confirm the metabolic mechanism of aconitine toxicity on HT22 cells,the levels of lactate dehydrogenase,intracellular Ca2+,reactive oxygen species,glutathione and superoxide dismutase,and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology.Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid,which was followed by the accumulation of lactic acid and reduction of glucose.The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+overload and oxidative stress,and eventually result in cell apoptosis.In general,we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Optimization of the medium and fermentation condition for the Penicillium aurantiocandidum Z12 strain with molluscicidal actions against Oncomelania hupensis / 中国血吸虫病防治杂志

Objective To optimize the culture and fermentation conditions of the Penicillium aurantiocandidum Z12 strain, a fungal strain with molluscicidal actions against Oncomelania hupensis, so as to provide the basis for the research and development of molluscicidal active substances from the P. aurantiocandidum Z12 strain and its fermentation broth and large-scale fermentation. Methods The carbon source, nitrogen source and mineral salts were identified in the optimal culture medium for the P. aurantiocandidum Z12 strain with a single-factor experiment to determine the best fermentation condition for the P. aurantiocandidum Z12 strain. Factors that significantly affected the growth of the P. aurantiocandidum Z12 strain were identified using the Plackett-Burman design, and the best range of each factor was determined using the steepest climb test. Response surface analyses of temperature, pH value, seeding amount and liquid-filling quantity were performed using the Box-Behnken design to create a regression model for fermentation of the P. aurantiocandidum Z12 strain to identify the optimal culture medium. Results Single-factor experiment preliminarily identified the best culture medium and conditions for the P. aurantiocandidum Z12 strain as follows: sucrose as the carbon source at approximately 20 g/L, tryptone as the nitrogen source at approximately 5 g/L, K2HPO4 as the mineral salt at approximately 5 g/L, initial pH at approximately 8, temperature at approximately 28 °C, seeding amount at approximately 6%, and liquid-filling quantity at approximately 50 mL/100 mL. Plackett-Burman design showed that factors that significantly affected the growth of the P. aurantiocandidum Z12 strain included temperature (t = −5.28, P < 0.05), seeding amount (t = 5.22, P < 0.05), pH (t = −4.30, P < 0.05) and liquid-filling quantity (t = −4.39, P < 0.05). Steepest climb test showed the highest mycelial growth at pH of 7.5, seeding amount of 8%, and liquid-filling quantity of 40 mL/100 mL, and this condition was selected as the central point of response surface analysis for the subsequent optimization of fermentation conditions. Response surface analyses using the Box-Behnken design showed that the optimal conditions for fermentation of the P. aurantiocandidum Z12 strain included sucrose at 15 g/L, tryptone at 5 g/L, K2HPO4 at 5 g/L, temperature at 28.2 °C, pH at 7.5, seeding amount at 10%, and liquid-filling quantity at 35.8 mL/100.0 mL, resulting in 0.132 g yield of the P. aurantiocandidum Z12 strain. Conclusion The optimal culture condition for the P. aurantiocandidum Z12 strain has been identified, and the optimized culture medium and fermentation condition may effectively improve the fermentation yield of the P. aurantiocandidum Z12 strain.

Spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020 / 中国血吸虫病防治杂志

Objective To investigate the spatial distribution characteristics of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody, and to examine the correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, so as to provide insights into advanced schistosomiais control in the province. Methods The epidemiological data of schistosomiasis in Hunan Province in 2020 were collected, including number of permanent residents in survey villages, number of advanced schistosomiasis patients, number of residents receiving serological tests and number of residents seropositive for anti-Schistosoma antibody, and the prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were descriptively analyzed. Village-based spatial distribution characteristics of prevalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody were identified in Hunan Province in 2020, and the correlation between the revalence advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody was examined using Spearman correlation analysis. Results The prevalence of advanced schistosomiasis was 0 to 2.72% and the seroprevalence of anti-Schistosoma antibody was 0 to 20.25% in 1 153 schistosomiasis-endemic villages in Hunan Province in 2020. Spatial clusters were identified in both the prevalence of advanced schistosomiasis (global Moran’s I = 0.416, P < 0.01) and the seroprevalence of anti-Schistosoma antibody (global Moran’s I = 0.711, P < 0.01) in Hunan Province. Local spatial autocorrelation analysis identified 98 schistosomiasis-endemic villages with high-high clusters of the prevalence of advanced schistosomiasis, 134 endemic villages with high-high clusters of the seroprevalence of anti-Schistosoma antibody and 36 endemic villages with high-high clusters of both the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province. In addition, spearman correlation analysis showed a positive correlation between the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody (rs = 0.235, P < 0.05). Conclusions There were spatial clusters of the prevalence of advanced schistosomiasis and seroprevalence of anti-Schistosoma antibody in Hunan Province in 2020, which were predominantly located in areas neighboring the Dongting Lake. These clusters should be given a high priority in the schistosomiasis control programs.

Cool and hot chitosan/platelet-derived growth factor nanofibers for outdoors burns.

Burns and scalds are thermal injuries caused by a large amount of heat accumulation in local tissues. The first cooling emergency is a key step. However, it is hard that in outdoors to find clean water to cool the scald tissue sites. Moreover, most dressings are concentrated on the treatment process today, neglecting the emergency treatment of temperature reduction. In this study, we imported refrigeration in the electrospinning process while using dirty water, rainwater and even urine of outdoors, so that the cooled sterile fibers were directly deposited on the burn and scald wounds, and the cooling emergency was achieved through the dual cooling mechanism. Since this fiber which is made up of cheap fish gelatin contains CuS adopting the green method, it can generate heat and effectively kill bacteria under the irradiation of an illumination lamp at the front end of a spinning device. As a result of the direct deposition, there is an excellent fit between the fibrous membrane and the skin, which reduces the air gap to achieve a better and quick cooling and heating effects. On the same Chitosan/Platelet-derived Growth Factor fiber membrane, this method of cooling first and heating second can shorten the recovery time from 30 days to 21 days. Thus, this treatment strategy has a great potential application prospect in the field of outdoor burn treatment.

Interleukin-17 governs hypoxic adaptation of injured epithelium.

Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient to trigger HIF1α in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that retinoic acid-related orphan receptor γt+ (RORγt+) γδ T cell-derived interleukin-17A (IL-17A) is necessary and sufficient to activate HIF1α. Protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling proximal of IL-17 receptor C (IL-17RC) activates mammalian target of rapamycin (mTOR) and consequently HIF1α. The IL-17A-HIF1α axis drives glycolysis in wound front epithelia. Epithelial-specific loss of IL-17RC, HIF1α, or blockade of glycolysis derails repair. Our findings underscore the coupling of inflammatory, metabolic, and migratory programs to expedite epithelial healing and illuminate the immune cell-derived inputs in cellular adaptation to hypoxic stress during repair.

Observation of Magnetism-Induced Topological Edge State in Antiferromagnetic Topological Insulator MnBi4Te7.

Breaking time reversal symmetry in a topological insulator may lead to quantum anomalous Hall effect and axion insulator phase. MnBi4Te7 is a recently discovered antiferromagnetic topological insulator with TN ∼ 12.5 K, which is composed of an alternatively stacked magnetic layer (MnBi2Te4) and nonmagnetic layer (Bi2Te3). By means of scanning tunneling spectroscopy, we clearly observe the electronic state present at a step edge of a magnetic MnBi2Te4 layer but absent at nonmagnetic Bi2Te3 layers at 4.5 K. Furthermore, we find that as the temperature rises above TN the edge state vanishes, while the point defect induced state persists upon an increase in temperature. These results confirm the observation of magnetism-induced edge states. Our analysis based on an axion insulator theory reveals that the nontrivial topological nature of the observed edge state.

Circular RNA Signatures of Human Healing and Nonhealing Wounds.

Venous ulcers (VUs) have complex and obscure pathogenicity, and effective VU therapies are still lacking. Circular RNAs (circRNAs) have emerged as powerful gene regulators with important roles in health and disease. In this study, we used paired total RNA and small RNA sequencing to profile circRNAs, protein-coding mRNAs, and microRNAs expression in a unique collection of clinical samples: healthy skin and acute wounds at inflammatory and proliferative phases and wound-edge VU biopsies. We unravel a dynamically changed expression pattern of circRNAs during human skin repair and their abnormal expression signature in VU, which are presented as a searchable web resource (www.xulandenlab.com/humanwounds-circrna). We analyzed the coexpression relationship between the circRNAs and mRNAs with weighted correlation network analysis and constructed circRNA‒mRNA‒microRNA networks. This allowed us to expose the regulatory networks specific to the inflammatory and proliferative phases of wound repair and VU, the biological processes the circRNAs may regulate, and the circRNAs that could sponge microRNAs in human wounds. Importantly, we found that hsa-CHST15_0003 and hsa-TNFRSF21_0001, two circRNAs upregulated in VU, hampered epidermal keratinocyte migration while promoting proliferation by modulating gene networks underpinning these cellular processes. This study paves the way to decipher the functional significance of circRNAs in tissue repair.

Beyond the Code: Noncoding RNAs in Skin Wound Healing.

An increasing number of noncoding RNAs (ncRNAs) have been found to regulate gene expression and protein functions, playing important roles in diverse biological processes and diseases. Their crucial functions have been reported in almost every cell type and all stages of skin wound healing. Evidence of their pathogenetic roles in common wound complications, such as chronic nonhealing wounds and excessive scarring, is also accumulating. Given their unique expression and functional properties, ncRNAs are promising therapeutic and diagnostic entities. In this review, we discuss current knowledge about the functional roles of noncoding elements, such as microRNAs, long ncRNAs, and circular RNAs, in skin wound healing, focusing on in vivo evidence from studies of human wound samples and animal wound models. Finally, we provide a perspective on the outlook of ncRNA-based therapeutics in wound care.

A nanofiber hydrogel derived entirely from ocean biomass for wound healing.

Crustaceans and fish scales in the marine food industry are basically thrown away as waste. This not only wastes resources but also causes environmental pollution. While reducing pollution and waste, biological activity and storage of materials are urgent issues to be solved. In this study, by first preparing dry fibers and then making hydrogels, we prepared a fish scale/sodium alginate/chitosan nanofiber hydrogel (FS-P) by cross-linking the nanofibers in situ. From fish and other organisms, fish gelatin (FG), collagen and CaCO3 were extracted. Fish scale (FS)/sodium alginate/chitosan nanofibers were cross-linked with copper sulfide nanoparticles prepared by a one-step green method to obtain FS-P nanofiber hydrogels under mild conditions without catalyst and additional procedures. These fiber hydrogels not only have good tissue adhesion and tensile properties, but also have the antibacterial effect of natural antibacterial and CuS photothermal synergism, which can achieve 51.32% and 49.96% of the antibacterial effect against Staphylococcus aureus and Escherichia coli respectively, avoiding the generation of superbacteria. The nanofiber hydrogels have 87.56% voidage and 52.68% degradability after 14 days. The combined strategy of using marine bio-based fibers to prepare gels promoted angiogenesis and tissue repair.