Erythrocyte Membrane Coating Alleviate Immune Response and Promoted Adipogenesis in Adipose Matrix.

Xenotransplantation of acellular adipose matrix (AAM) has come to prominence as an intriguing option for soft tissue reconstruction. However, the presence of immunogenic antigens within AAM can trigger unfavorable immune reactions, leading to inadequate in vivo regeneration outcomes. Therefore, the development of advanced technology capable of modulating immune responses is crucial for the therapeutic implementation of AAM xenografts. In this work, an innovative technique is created to bypass the immune system by covering the surface of both AAM and Arg-Gly-Asp (RGD) peptide-modified AAM xenografts with autologous red blood cell (RBC) membrane. The RBC membrane coating remained persistent and exhibited no significant decline even after 21 days. Moreover, it effectively reduced the expression of antigen major histocompatibility complex class 1 (MHC1) on the AAM surface. Following xenogeneic transplantation, the RBC-coated xenografts demonstrated increased expression of the adipogenic factor PPAR-γ, Adipoq, Fabp4, Fasn, and Plin1 and higher numbers of adipocytes. In addition, they exhibited decreased expression of immunological factors, including IL-6, IL-2, IFN-γ, and TNF-α, and fewer inflammatory cells. These findings indicate that RBC membrane coating successfully suppressed immune responses and promoted increased adipogenesis in AAM xenografts. Therefore, AAM camouflage coating with RBC has a lot of potential as a biomaterial for soft tissue reconstruction in clinical settings.

The Current Status and Trends of Research Related to Vestibular Disorders, Vertigo, and Cognitive Impairment in the Elderly Population: A Bibliometric Analysis.

Background: The vestibular system not only supports reflex function at the brainstem level, but is also associated with higher levels of cognitive function. Vertigo due to vestibular disorders may lead to or be associated with cognitive dysfunction. Patients with deficits of both vestibular as well as cognitive function may be at particularly high risk for events like falls or certain diseases, such as Alzheimer's. Objective: To analyze the current state of research and trends in the global research literature regarding the correlation between vestibular disorders, vertigo, and cognitive impairment. Methods: We utilized Bibliometrix package to search databases including PubMed, Web of Science, etc for search terms. Results: Databases were searched up to December 15, 2022, and a total of 2222 publications were retrieved. Ultimately, 53 studies were included. A total of 261 authors published in 38 journals and conferences with an overall increasing annual growth rate of 6.94%. The most-published journal was Frontiers in Neurology. The most-published country was the United States, followed by Italy and Brazil. The most-published institution was Johns Hopkins University with a total of 13 articles. On performing trend analysis, we found that the most frequent focus of research in this field include the testing of vestibular perception, activation of the brain-related cortex, and the influence of stimulus-triggered vestibular snail reflex on visual space. The potential focal points are the risk of falling and the ability to extract spatial memory information, and the focus of research in recent decades has revolved around balance, falling, and Alzheimer's disease. Conclusions: Vestibular impairment in older adults affects cognitive function, particularly immediate memory, visuospatial cognition, and attention, with spatial cognition being the most significantly affected. In the future, virtual reality-based vestibular rehabilitation techniques and caloric stimulation could be potential interventions for the treatment of cognitive impairment.

Clinical and genetic analysis of essential hypertension with mitochondrial tRNAMet 4435A>G and YARS2 mutation. / 携带线粒体tRNAMet 4435A>Gå’Œæ ¸åŸºå› YARS2çªå˜çš„åŽŸå‘æ€§é«˜è¡€åŽ‹å®¶ç³»é—ä¼ å­¦åˆ†æž.

OBJECTIVES: To investigate the role of m.4435A>G and YARS2 c.572G>T (p.G191V) mutations in the development of essential hypertension. METHODS: A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data. Clinical data were collected, and a molecular genetic study was conducted in the proband and his family members. Peripheral venous blood was collected, and immortalized lymphocyte lines constructed. The mitochondrial transfer RNA (tRNA), mitochondrial protein, adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) in the constructed lymphocyte cell lines were measured. RESULTS: Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation. The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability, which may influence the anticodon ring structure. Compared with the control group, the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis, mitochondrial protein expression, ATP production and MMP levels, as well as increased ROS levels (all P<0.05). CONCLUSIONS: The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction, indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.

Mining User Reviews From Hypertension Management Mobile Health Apps to Explore Factors Influencing User Satisfaction and Their Asymmetry: Comparative Study.

BACKGROUND: Hypertension significantly impacts the well-being and health of individuals globally. Hypertension management apps (HMAs) have been shown to assist patients in controlling blood pressure (BP), with their efficacy validated in clinical trials. However, the utilization of HMAs continues to be suboptimal. Presently, there is a dearth of real-world research based on big data and exploratory mining that compares Chinese and American HMAs. OBJECTIVE: This study aims to systematically gather HMAs and their user reviews from both China and the United States. Subsequently, using data mining techniques, the study aims to compare the user experience, satisfaction levels, influencing factors, and asymmetry between Chinese and American users of HMAs. In addition, the study seeks to assess the disparities in satisfaction and its determinants while delving into the asymmetry of these factors. METHODS: The study sourced HMAs and user reviews from 10 prominent Chinese and American app stores globally. Using the latent Dirichlet allocation (LDA) topic model, the research identified various topics within user reviews. Subsequently, the Tobit model was used to investigate the impact and distinctions of each topic on user satisfaction. The Wald test was applied to analyze differences in effects across various factors. RESULTS: We examined a total of 261 HMAs along with their associated user reviews, amounting to 116,686 reviews in total. In terms of quantity and overall satisfaction levels, Chinese HMAs (n=91) and corresponding reviews (n=16,561) were notably fewer compared with their American counterparts (n=220 HMAs and n=100,125 reviews). The overall satisfaction rate among HMA users was 75.22% (87,773/116,686), with Chinese HMAs demonstrating a higher satisfaction rate (13,866/16,561, 83.73%) compared with that for American HMAs (73,907/100,125, 73.81%). Chinese users primarily focus on reliability (2165/16,561, 13.07%) and measurement accuracy (2091/16,561, 12.63%) when considering HMAs, whereas American users prioritize BP tracking (17,285/100,125, 17.26%) and data synchronization (12,837/100,125, 12.82%). Seven factors (easy to use: P<.001; measurement accuracy: P<.001; compatibility: P<.001; cost: P<.001; heart rate detection function: P=.02; blood pressure tracking function: P<.001; and interface design: P=.01) significantly influenced the positive deviation (PD) of Chinese HMA user satisfaction, while 8 factors (easy to use: P<.001; reliability: P<.001; measurement accuracy: P<.001; compatibility: P<.001; cost: P<.001; interface design: P<.001; real-time: P<.001; and data privacy: P=.001) affected the negative deviation (ND). Notably, BP tracking had the greatest effect on PD (ß=.354, P<.001), while cost had the most significant impact on ND (ß=3.703, P<.001). All 12 factors (easy to use: P<.001; blood pressure tracking function: P<.001; data synchronization: P<.001; blood pressure management effect: P<.001; heart rate detection function: P<.001; data sharing: P<.001; reliability: P<.001; compatibility: P<.001; interface design: P<.001; advertisement distribution: P<.001; measurement accuracy: P<.001; and cost: P<.001) significantly influenced the PD and ND of American HMA user satisfaction. Notably, BP tracking had the greatest effect on PD (ß=0.312, P<.001), while data synchronization had the most significant impact on ND (ß=2.662, P<.001). In addition, the influencing factors of PD and ND in user satisfaction of HMA in China and the United States are different. CONCLUSIONS: User satisfaction factors varied significantly between different countries, showing considerable asymmetry. For Chinese HMA users, ease of use and interface design emerged as motivational factors, while factors such as cost, measurement accuracy, and compatibility primarily contributed to user dissatisfaction. For American HMA users, motivational factors were ease of use, BP tracking, BP management effect, interface design, measurement accuracy, and cost. Moreover, users expect features such as data sharing, synchronization, software reliability, compatibility, heart rate detection, and nonintrusive advertisement distribution. Tailored experience plans should be devised for different user groups in various countries to address these diverse preferences and requirements.

Deficient tRNA posttranscription modification dysregulated the mitochondrial quality controls and apoptosis.

Mitochondria are dynamic organelles in cellular metabolism and physiology. Mitochondrial DNA (mtDNA) mutations are associated with a broad spectrum of clinical abnormalities. However, mechanisms underlying mtDNA mutations regulate intracellular signaling related to the mitochondrial and cellular integrity are less explored. Here, we demonstrated that mt-tRNAMet 4435A>G mutation-induced nucleotide modification deficiency dysregulated the expression of nuclear genes involved in cytosolic proteins involved in oxidative phosphorylation system (OXPHOS) and impaired the assemble and integrity of OXPHOS complexes. These dysfunctions caused mitochondrial dynamic imbalance, thereby increasing fission and decreasing fusion. Excessive fission impaired the process of autophagy including initiation phase, formation, and maturation of autophagosome. Strikingly, the m.4435A>G mutation upregulated the PARKIN dependent mitophagy pathways but downregulated the ubiquitination-independent mitophagy. These alterations promoted intrinsic apoptotic process for the removal of damaged cells. Our findings provide new insights into mechanism underlying deficient tRNA posttranscription modification regulated intracellular signaling related to the mitochondrial and cellular integrity.

Combined Use of Autologous Sustained-Release Scaffold of Adipokines and Acellular Adipose Matrix to Construct Vascularized Adipose Tissue.

BACKGROUND: Adipose tissue engineering plays a key role in the reconstruction of soft-tissue defects. The acellular adipose matrix (AAM) is a promising biomaterial for the construction of engineered adipose tissue. However, AAM lacks sufficient adipoinduction potency because of the abundant loss of matrix-bound adipokines during decellularization. METHODS: An adipose-derived extracellular matrix collagen scaffold, "adipose collagen fragment" (ACF), was prepared using a novel mechanical method that provides sustained release of adipokines. Here, the authors used label-free proteomics methods to detect the protein components in AAM and ACF. In vivo, ACF was incorporated into AAM or acellular dermal matrix and implanted into nude mice to evaluate adipogenesis. Neoadipocytes, neovessels, and corresponding gene expression were evaluated. The effects of ACF on adipogenic differentiation of human adipose-derived stem cells and tube formation by human umbilical vein endothelial cells were tested in vitro. RESULTS: Proteomics analysis showed that ACF contains diverse adipogenic and angiogenic proteins. ACF can release diverse adipokines and induce highly vascularized, mature adipose tissue in AAM, and even in nonadipogenic acellular dermal matrix. Higher expression of adipogenic markers peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha and greater numbers of tubule structures were observed in ACF-treated groups in vitro. CONCLUSION: The combination of ACF and AAM could serve as a novel and promising strategy to construct mature, vascularized adipose tissue for soft-tissue reconstruction. CLINICAL RELEVANCE STATEMENT: The combined use of AAM and ACF has been proven to induce a highly vascularized, mature, engineered adipose tissue in the nude mouse model, which may serve as a promising strategy for soft-tissue reconstruction.

Adipose Component Transplantation: An Advanced Fat-Grafting Strategy for Facial Rejuvenation.

BACKGROUND: Autologous fat grafting is frequently used for volume augmentation and tissue regeneration. The uniform physical and biological characteristics of fat grafts, however, limit their optimal effects in various situations. Subjecting fat tissue to different mechanical processes results in adipose-derived products with distinct biological components and physical features. The present study describes a novel facial fat-grafting strategy, adipose component transplantation (ACT), that yields different adipose products that can be applied to specific injection sites. METHODS: All patients who underwent ACT were evaluated retrospectively. Fat tissue samples were fractionated into high-density fat, adipose matrix complex, stromal vascular fraction gel, and adipose collagen fragment, as described. Each of these fractions was processed and injected into indicated recipient sites. Additional SVF gel was cryopreserved and, if necessary, injected during the following 3 months. Patients were followed up after 1, 2, 3, and 6 months, and annually thereafter. RESULTS: From March of 2020 to September of 2021, 78 patients underwent whole face fat grafting using the ACT strategy. All operations and secondary injections of cryopreserved SVF gel were uneventful. There were no major complications, and final aesthetic results were satisfactory in 91% of patients. CONCLUSIONS: The ACT strategy allows specific adipose products to be applied to specific injection sites, as warranted. Adipose matrix complex is indicated for sufficient rigid support, high-density fat when large volumes are required, SVF gel for precise injection and cryopreservation, and ACF as mesotherapy for skin rejuvenation. The ACT strategy optimizes the biological functions and physical features of different adipose-derived products. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Mesenchymal stem cell-based therapy for autoimmune-related fibrotic skin diseases-systemic sclerosis and sclerodermatous graft-versus-host disease.

BACKGROUND: Systemic sclerosis (SSc) and sclerodermatous graft-versus-host disease (Scl-GVHD)-characterized by similar developmental fibrosis, vascular abnormalities, and innate and adaptive immune response, resulting in severe skin fibrosis at the late stage-are chronic autoimmune diseases of connective tissue. The significant immune system dysfunction, distinguishing autoimmune-related fibrosis from mere skin fibrosis, should be a particular focus of treating autoimmune-related fibrosis. Recent research shows that innovative mesenchymal stem cell (MSC)-based therapy, with the capacities of immune regulation, inflammation suppression, oxidation inhibition, and fibrosis restraint, shows great promise in overcoming the disease. MAIN BODY: This review of recent studies aims to summarize the therapeutic effect and theoretical mechanisms of MSC-based therapy in treating autoimmune-related fibrotic skin diseases, SSc and Scl-GVHD, providing novel insights and references for further clinical applications. It is noteworthy that the efficacy of MSCs is not reliant on their migration into the skin. Working on the immune system, MSCs can inhibit the chemotaxis and infiltration of immune cells to the skin by down-regulating the expression of skin chemokines and chemokine receptors and reducing the inflammatory and pro-fibrotic mediators. ​Furthermore, to reduce levels of oxidative stress, MSCs may improve vascular abnormalities, and enhance the antioxidant defenses through inducible nitric oxide synthase, thioredoxin 1, as well as other mediators. The oxidative stress environment does not weaken MSCs and may even strengthen certain functions. Regarding fibrosis, MSCs primarily target the transforming growth factor-ß signaling pathway to inhibit fibroblast activation. Here, miRNAs may play a critical role in ECM remodeling. Clinical studies have demonstrated the safety of these approaches, though outcomes have varied, possibly owing to the heterogeneity of MSCs, the disorders themselves, and other factors. Nevertheless, the research clearly reveals the immense potential of MSCs in treating autoimmune-related fibrotic skin diseases. CONCLUSION: The application of MSCs presents a promising approach for treating autoimmune-related fibrotic skin diseases: SSc and Scl-GVHD. Therapies involving MSCs and MSC extracellular vesicles have been found to operate through three primary mechanisms: rebalancing the immune and inflammatory disorders, resisting oxidant stress, and inhibiting overactivated fibrosis (including fibroblast activation and ECM remodeling). However, the effectiveness of these interventions requires further validation through extensive clinical investigations, particularly randomized control trials and phase III/IV clinical trials. Additionally, the hypothetical mechanism underlying these therapies could be elucidated through further research.

Hereditary Hearing Loss: A Systematic Review of Potential Treatments and Interventions.

PURPOSE: The purpose of this study was to systematically review the research literature with regards to treatments and intervention methods for hereditary hearing loss. Our goal was to provide reference guidelines for the rational use of medication and gene-targeted therapy for patients with hereditary hearing loss and discuss the future development of research in this area. METHOD: We searched two core databases, PubMed and Web of Science, for relevant literature relating to potential treatments and interventional methods for hereditary hearing loss. Then, we used Microsoft Excel to perform basic statistical analysis of the data, the R language to perform bibliometric analyses, and VOSviewer and CiteSpace to visualize data. In addition, we clustered and descriptively analyzed the data and identified the relative importance of each approach with regard to precise patient outcomes. RESULTS: In this study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standardized screening process and identified a total of 103 research articles. The average annual growth rate of publications in this area was 12.73%. The country with the highest number of publications and citations was the United States; 80 of these publications (associated with 76.92% of funding) were supported by grants from 16 countries. Potential treatments and interventions were clustered according to the stage of research and showed that 8.74% remain in the research design stage, 59.22% are in the clinical validation stage, and 32.04% are being applied in the clinic. The main research focus in this field is cochlear implants and gene therapy. CONCLUSIONS: Hereditary hearing loss is in a critical period of transition from preventive to therapeutic research. Gene-targeted interventions represent one of the most promising and effective treatments. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24309193.

Adipokines-enriched adipose extract restores skin barrier and ameliorates inflammatory dysregulation in an atopic dermatitis mouse model.

BACKGROUND: Atopic dermatitis (AD) is a chronic dermatosis with high incidence worldwide characterized by skin barrier abnormalities and immune dysregulation. Conventional therapies are usually limited by side effects and high cost. Given the anti-inflammatory and repairing properties, adipokines are increasingly considered as promising therapeutic agents for dermatoses. Adipose collagen fragments (ACF), a novel adipokine-enriched product, may alleviate AD through modulating immune microenvironment and restoring skin barrier. METHODS: ACF was extracted from adipose tissue via high-speed homogenization (10000 rpm/min, 1min) and centrifugation (3000 g, 3min). Ovalbumin-induced AD female BALB/c mice (6-week-old) were intradermally injected with 0.2ml of ACF or PBS (negative control), with normal mice being set as normal control (n=6). Dermatitis severity, inflammatory metrics (epidermal thickness, infiltrated mast cells, Th-type cytokines expression), and skin barrier-related metrics (transepidermal water loss [TEWL], skin barrier-related proteins expression) were evaluated after the AD induction period (day 50). ACF-derived bioactive components were also evaluated using proteomic analysis. RESULTS: ACF-derived adipokines contained anti-inflammatory, skin barrier- and lipid biosynthesis-related components. ACF treatment decreased dermatitis severity (6.2±1.8, p<0.0001), epidermal thickness (25.7±12.8 µm, p=0.0045), infiltrated mast cells (31.3±12.4 cells/field, p=0.0475), and Th-type cytokines expression (INF-γ, TNF-α, IL-4, IL-4R, IL-13, and IL-17A; p<0.05) in AD skins. TEWL (29.8±13.8 g/m 2.h, p=0.0306) and skin barrier-related proteins expression (filaggrin: 14258±4375, p=0.0162; loricrin: 6037±1728, p=0.0010; claudin-1: 20043±6406, p=0.0420; ZO-1: 4494±1114, p=0.0134) were also improved. CONCLUSIONS: ACF improved AD in murine model by ameliorating inflammatory dysregulation and skin barrier defects (Graphical abstract, Supplementary Digital Content 1). Further validation is needed in more advanced animal models.

Delivery of adipose-derived growth factors from heparinized adipose acellular matrix accelerates wound healing.

Dermal white adipocytes are closely associated with skin homeostasis and wound healing. However, it has not been fully investigated whether adipose-derived products improve wound healing. Here, we obtained adipose acellular matrix (AAM) and adipose-derived growth factors (ADGFs) from human adipose tissue and fabricated an ADGF-loaded AAM via surface modification with heparin. The product, HEP-ADGF-AAM, contained an adipose-derived scaffold and released ADGFs in a controlled fashion. To test its efficacy in promoting wound healing, mice with full thickness wound received three different treatments: HEP-ADGF-AAM, AAM and ADM. Control mice received no further treatments. Among these treatments, HEP-ADGF-AAM best improved wound healing. It induced adipogenesis in situ after in vivo implantation and provided an adipogenic microenvironment for wounds by releasing ADGFs. HEP-ADGF-AAM not only induced adipocyte regeneration, but also enhanced fibroblast migration, promoted vessel formation, accelerated wound closure, and enhanced wound epithelialization. Moreover, there was a close interaction between HEP-ADGF-AAM and the wound bed, and collagen was turned over in HEP-ADGF-AAM. These results show that HEP-ADGF-AAM might substantially improve re-epithelialization, angiogenesis, and skin appendage regeneration, and is thus a promising therapeutic biomaterial for skin wound healing.

Mining electronic health records using artificial intelligence: Bibliometric and content analyses for current research status and product conversion.

BACKGROUND: The use of Electronic Health Records is the most important milestone in the digitization and intelligence of the entire medical industry. AI can effectively mine the immense medical information contained in EHRs, potentially assist doctors in reducing many medical errors. OBJECTIVE: This article aims to summarize the research status and trends in using AI to mine medical information from EHRs for the past thirteen years and investigate its information application. METHODS: A systematic search was carried out in 5 databases, including Web of Science Core Collection and PubMed, to identify research using AI to mine medical information from EHRs for the past thirteen years. Furthermore, bibliometric and content analysis were used to explore the research hotspots and trends, and systematically analyze the conversion rate of research resources in this field. RESULTS: A total of 631 articles were included and analyzed. The number of published articles has increased rapidly after 2017, with an average annual growth rate of 55.73%. The US (41.68%) and China (19.65%) publish the most articles, but there is a lack of international cooperation. The extraction of disease lesions is a hot topic at present, and the research topic is gradually shifting from disease risk grading to disease risk prediction. Classification (66%), and regress (15%) are the main implemented AI tasks. For AI algorithms, deep learning (31.70%), decision tree algorithms family (26.47%), and regression algorithms family (17.43%) are used most frequently. The funding rate for publications is 69.26%, and the input-output conversion rate is 21.05%. CONCLUSIONS: Over the past decade, the use of AI to mine medical information from EHRs has been developing rapidly. However, it is necessary to strengthen international cooperation, improve EHRs data availability, focus on interpretable AI algorithms, and improve the resource conversion rate in future research.

Current Status and Trends in mHealth-Based Research for Treatment and Intervention in Tinnitus: Bibliometric and Comparative Product Analysis.

BACKGROUND: As a global medical problem, tinnitus can seriously harm human health and is difficult to alleviate, ranking among the top 3 complex diseases in the otolaryngology field. Traditional cognitive behavioral therapy and sound therapy require offline face-to-face treatment with medical staff and have limited effectiveness. Mobile health (mHealth), which, in recent decades, has been greatly applied in the field of rehabilitation health care, improving access to health care resources and the quality of services, has potential research value in the adjunctive treatment of tinnitus. OBJECTIVE: This study aimed to understand the research trends, product characteristics, problems, and research transformation of tinnitus treatment software by analyzing the research progress of mHealth for tinnitus treatment based on the literature and related marketed apps. METHODS: Bibliometric methods were used to describe the characteristics of the relevant literature in terms of the number and topics of publications, authors, and institutions. We further compared the features and limitations of the currently available tinnitus treatment software. RESULTS: Data published until February 28, 2022, were collected. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standardized screening process, 75 papers were included. The country with the highest number of publications was Germany, followed by the United Kingdom and the United States, whereas China had only a single relevant study. The most frequently found journals were the American Journal of Audiology and the Journal of the American Academy of Audiology (18/75, 24%). With regard to publication topics, cognitive behavioral therapy started to become a hot topic in 2017, and research on mHealth apps has increased. In this study, 28 tinnitus treatment apps were obtained (n=24, 86% from product data and n=4, 14% from literature data); these apps were developed mainly in the United States (10/28, 36%) or China (9/28, 32%). The main treatment methods were sound therapy (10/28, 36%) and cognitive behavioral therapy (2/28, 7%). Of the 75 publications, 7 (9%) described apps in the market stage. Of the 28 apps, 22 (79%) lacked literature studies or evidence from professional bodies. CONCLUSIONS: We found that, as a whole, the use of mHealth for treatment and intervention in tinnitus was showing a rapid development, in which good progress had been made in studies around sound therapy and cognitive behavioral therapy, although most of the studies (50/75, 67%) focused on treatment effects. However, the field is poorly accepted in top medical journals, and the majority are in the research design phase, with a lack of translation of the literature results and clinical validation of the marketed apps. Furthermore, in the future, novel artificial intelligence techniques should be used to address the issue of staged monitoring of tinnitus.

Clinical and genetic analysis of essential hypertension with CYB gene m.15024G>A mutation. / 携带CYB m.15024G>Açªå˜çš„åŽŸå‘æ€§é«˜è¡€åŽ‹å®¶ç³»é—ä¼ å­¦åˆ†æž.

OBJECTIVES: To explore the role of mitochondrial CYB 15024G>A mutation in the development of essential hypertension. METHODS: Mitochondrial genome sequences of hypertensive patients were obtained from previous studies. Clinical and genetic data of a hypertensive patient with mitochondrial CYB 15024G>A mutation and its pedigree were analyzed. Lymphocytes derived from patient and family members were transformed into immortalized lymphoblastoid cell lines, and the levels of adenosine triphosphate (ATP), mitochondrial membrane potential and intracellular reactive oxygen species (ROS) were detected. RESULTS: The penetrance of this essential hypertension family was 42.9%, and the age of onset was 46-68 years old. Mitochondrial genome sequencing results showed that all maternal members carried a highly conserved mitochondrial CYB 15024G>A mutation. This mutation could affect the free energy of mitochondrial CYB for secondary and tertiary structure and protein folding, thereby changing its structural stability and the structure of the electron transfer function area around the mutation site. Compared with the control, the cell line carrying the mitochondrial CYB 15024G>A mutation showed significantly decreased levels of mitochondrial CYB, ATP and mitochondrial membrane potential, and increased levels of ROS (P<0.01). CONCLUSIONS: Mitochondrial CYB 15024G>A mutation may affect the structure of respiratory chain subunits and mitochondrial function, leading to cell dysfunction, which suggests that the mutation may play a synergistic role in essential hypertension.

Pathological characteristics of breast nodules after large-volume fat grafting for breast augmentation.

BACKGROUND: The complications of large-volume fat grafting (LVFG) for breast augmentation remain unpredictable and include palpable breast nodules, oil cysts, and calcifications. AIMS: This study was aimed to provide an optimal treatment option for breast nodules after LVFG and evaluate their pathological characteristics. PATIENTS/METHODS: We effectively performed complete resection of breast nodules in 29 patients after LVFG using a minimal skin incision with the vacuum-assisted breast biopsy (VABB) system under ultrasound guidance. And we further carried on histologic examination of excised nodules and evaluated their pathological characteristics. RESULTS: The breast nodules were excised thoroughly with cosmetic effect satisfactorily. Interestingly, subsequent histologic examination showed that type I and VI collagens were strongly expressed in the fibrotic area and type IV collagen were positively expressed around the blood vessel. Furthermore, we found that the type VI collagen+ area appeared around mac2+ macrophages and α-SMA+ myofibroblasts. CONCLUSIONS: The VABB system may be the optimal treatment option for breast nodules after LVFG. And type VI collagens may serve as a biomarker of grafted adipose tissue fibrosis. The relationship between macrophages, fibroblasts, and collagen formation may be therapeutic targets for regulating fibrosis.

Corrigendum to 'Methoxy polyethylene glycol modification promotes adipogenesis by inducing the production of regulatory T cells in xenogeneic acellular adipose matrix' [Materials Today Bio 12 (2021) 100161].

[This corrects the article DOI: 10.1016/j.mtbio.2021.100161.].

Development of Matrix Metalloproteinases-Mediated Extracellular Matrix Remodeling in Regenerative Medicine: A Mini Review.

Extracellular matrix (ECM) components confer biomechanical properties, maintain cell phenotype and mediate tissue homeostasis. ECM remodeling is complex and plays a key role in both physiological and pathological processes. Matrix metalloproteinases (MMPs) are a group of enzymes responsible for ECM degradation and have been accepted as a key regulator in ECM remodeling. In this mini-review, we summarize MMPs categories, functions and the targeted substrates. We then discuss current understanding of the role of MMPs-mediated events, including inflammation reaction, angiogenesis, cellular activities, etc., in ECM remodeling in the context of regenerative medicine.

Understanding the research on tracking, diagnosing, and intervening in sleep disorders using mHealth apps: Bibliometric analysis and systematic reviews.

Objectives: In solving the global challenge of sleep disorders, Mobile Health app is one of the important means to monitor, diagnose, and intervene in sleep disorders. This study aims to (1) summarize the status and trends of research in this field; (2) assess the production and usage of sleep mHealth apps; (3) calculate the conversion rate of grants that the proportion of newly developed apps from being funded and developed to published on application stores. Methods: Using bibliometric and content analysis methods, based on "Research Paper-Product Output-Product Application" chain and considering the "Research Grants" of articles, we conducted a systematic review of eight databases, to identify relevant studies over the last decade. Results: Over the past decade, 1399 authors published 313 papers in 182 journals and conferences. The number of publications increased with an average annual growth of 41.6%. The current focus area is research using cognitive behavioral therapy to intervene in sleep. Sleep-staging tracking is a shortcoming of this field. A total 368 sleep mHealth apps (233 newly developed and 135 existing) were examined in 313 papers; 323 grants supported 178 articles (56.9%). Only 12 of the newly developed apps are used in the real world, resulting in a 9% grant conversion rate. Conclusions: In the last decade, the field of tracking, diagnosing, and intervening in sleep disorders using mHealth apps has shown a trend of rapid development. However, the conversion rate of products from being funded and developed for use by end-users is low.

ATG16L1 negatively regulates MAVS-mediated antiviral signaling in black carp Mylopharyngodon piceus.

Autophagy related 16 like 1 (ATG16L1) is a crucial component of autophagy that regulates the formation of the autophagosome. In mammals, ATG16L1 also performs important roles in immunity, including controlling viral replication and regulating innate immune signaling; however, investigation on the role of piscine ATG16L1 in immunity is rare. In this report, the ATG16L1 homolog of black carp Mylopharyngodon piceus (bcATG16L1) was cloned and identified, and its negative regulatory role in mitochondrial antiviral signaling protein (MAVS)-mediated antiviral signaling was described. The coding region of bcATG16L1 consists of 1830 nucleotides and encodes 609 amino acids, including one coiled-coil domain at the N-terminus, three low complexity region domains in the middle, and seven WD40 domains at the C-terminus. By immunofluorescence assay and immunoblotting, we found that bcATG16L1 is a cytosolic protein with a molecular weight of ∼74 kDa. In addition, over-expression of bcATG16L1 suppressed bcMAVS-mediated bcIFNa and DrIFNφ1 promoters transcriptional activity and inhibited bcMAVS-mediated antiviral activity. We further confirmed the co-localization of bcATG16L1 and bcMAVS by immunofluorescence assay and verified the protein interaction between bcATG16L1 and bcMAVS by immunoprecipitation assay. Our results report for the first time that black carp ATG16L1 suppresses MAVS-mediated antiviral signaling in teleost fish.

Skin-associated adipocytes in skin barrier immunity: A mini-review.

The skin contributes critically to health via its role as a barrier tissue against a multitude of external pathogens. The barrier function of the skin largely depends on the uppermost epidermal layer which is reinforced by skin barrier immunity. The integrity and effectiveness of skin barrier immunity strongly depends on the close interplay and communication between immune cells and the skin environment. Skin-associated adipocytes have been recognized to play a significant role in modulating skin immune responses and infection by secreting cytokines, adipokines, and antimicrobial peptides. This review summarizes the recent understanding of the interactions between skin-associated adipocytes and other skin cells in maintaining the integrity and effectiveness of skin barrier immunity.