Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Tracking Fat Grafts by Magnetic Resonance Imaging: A Comparative Study of Adolescent and Adult Patients with Stable Localized Scleroderma.

BACKGROUND: The optimal timing of reconstruction for patients with facial localized scleroderma is uncertain. The purpose of this study was to compare the outcomes of autologous fat transplantation in adolescent and adult patients with stable localized scleroderma. METHODS: Adolescent (age 10-19 years) and adult (age >19 years) patients with no previous surgery were enrolled (n = 10, each group). Preoperative magnetic resonance imaging (MRI), blood tests and dermatological assessments were used for disease activity assessment. All patients underwent autologous fat transplantation for anatomic facial fat restoration with preoperative MRI planning. Preoperative, immediate and one-year postoperative 3D Dixon MRI scans with image registration and fusion techniques were used for fat graft tracking. Patient satisfaction was assessed with a 5-point Likert scale. RESULTS: There was no significant difference in sex, body mass index, disease severity, or volume of injected fat between the two groups (p > 0.05), except for age (p < 0.05). The one-year postoperative fat graft retention rate was not significantly different, with 36.6 ± 2.4% (ranging from 25.3 to 49.3%) in the adolescent group and 32.9 ± 1.7% (ranging from 27.3 to 40.1%) in the adult group (p > 0.05). Surgical outcomes were favorable in all patients, with satisfaction scores of 3.8 ± 0.2 points in the adolescent group and 3.6 ± 0.2 points in the adult group (p > 0.05). CONCLUSION: In stable localized scleroderma, the initial autologous fat transplantation was equally effective for facial contour deformity improvement, with no significant difference in fat graft retention or satisfaction.

Dynamic Fall Recovery Control for Legged Robots via Reinforcement Learning.

Falling is inevitable for legged robots when deployed in unstructured and unpredictable real-world scenarios, such as uneven terrain in the wild. Therefore, to recover dynamically from a fall without unintended termination of locomotion, the robot must possess the complex motor skills required for recovery maneuvers. However, this is exceptionally challenging for existing methods, since it involves multiple unspecified internal and external contacts. To go beyond the limitation of existing methods, we introduced a novel deep reinforcement learning framework to train a learning-based state estimator and a proprioceptive history policy for dynamic fall recovery under external disturbances. The proposed learning-based framework applies to different fall cases indoors and outdoors. Furthermore, we show that the learned fall recovery policies are hardware-feasible and can be implemented on real robots. The performance of the proposed approach is evaluated with extensive trials using a quadruped robot, which shows good effectiveness in recovering the robot after a fall on flat surfaces and grassland.

Exploration of the mode of death and potential death mechanisms of nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is a common chronic orthopaedic disease in orthopaedics that imposes a heavy economic burden on people and society. Although it is well established that IVDD is associated with genetic susceptibility, ageing and obesity, its pathogenesis remains incompletely understood. Previously, IVDD was thought to occur because of excessive mechanical loading leading to destruction of nucleus pulposus cells (NPCs), but studies have shown that IVDD is a much more complex process associated with inflammation, metabolic factors and NPCs death and can involve all parts of the disc, characterized by causing NPCs death and extracellular matrix (ECM) degradation. The damage pattern of NPCs in IVDD is like that of some programmed cell death, suggesting that IVDD is associated with programmed cell death. Although apoptosis and pyroptosis of NPCs have been studied in IVDD, the pathogenesis of intervertebral disc degeneration can still not be fully elucidated by using only traditional cell death modalities. With increasing research, some new modes of cell death, PANoptosis, ferroptosis and senescence have been found to be closely related to intervertebral disc degeneration. Among these, PANoptosis combines essential elements of pyroptosis, apoptosis and necroptosis to form a highly coordinated and dynamically balanced programmed inflammatory cell death process. Furthermore, we believe that PANoptosis may also crosstalk with pyroptosis and senescence. Therefore, we review the progress of research on multiple deaths of NPCs in IVDD to provide guidance for clinical treatment.

Self-assembly of amphiphilic asymmetric comb-like copolymers with responsive rigid side chains.

Amphiphilic asymmetric comb-like copolymers (AACCs) exhibit distinct self-assembly behaviours due to their unique architecture. However, the synthetic difficulties of well-defined AACCs have prohibited a systematic understanding of the architecture-morphology relationship. In this work, we conducted dissipative particle dynamics simulations to investigate the self-assembly behaviours of AACCs with responsive rigid side chains in selective solvents. The effects of side chain length, number of branches, and spacers on the morphology of aggregates were investigated by mapping out morphology diagrams. Besides, the numbers and surface areas of aggregates clearly depicted the morphological transitions during the self-assembly process. Moreover, the rod-to-coil conformation transitions were simulated to explore the stimuli-responsive behaviour of the AACCs with responsive rigid side chains by adjusting the bond angle parameter of the rigid chains. The results indicated that without the support of the rigid chains, the assembly structure collapsed, leading to the tube-to-channelized micelles and one-compartment-to-multicompartment vesicle morphology transformations. The simulation results are consistent with earlier experimental results, which can provide theoretical guidance for assembly toward desired nanostructures.

Genetic prediction of the causal relationship between schizophrenia and tumors: a Mendelian randomized study.

Background: Patients with schizophrenia are at a higher risk of developing cancer. However, the causal relationship between schizophrenia and different tumor types remains unclear. Methods: Using a two-sample, two-way Mendelian randomization method, we used publicly available genome-wide association analysis (GWAS) aggregate data to study the causal relationship between schizophrenia and different cancer risk factors. These tumors included lung adenocarcinoma, lung squamous cell carcinoma, small-cell lung cancer, gastric cancer, alcohol-related hepatocellular cancer, tumors involving the lungs, breast, thyroid gland, pancreas, prostate, ovaries and cervix, endometrium, colon and colorectum, and bladder. We used the inverse variance weighting (IVW) method to determine the causal relationship between schizophrenia and different tumor risk factors. In addition, we conducted a sensitivity test to evaluate the effectiveness of the causality. Results: After adjusting for heterogeneity, evidence of a causal relationship between schizophrenia and lung cancer risk was observed (odds ratio [OR]=1.001, 95% confidence interval [CI], 1.000-1.001; P=0.0155). In the sensitivity analysis, the causal effect of schizophrenia on the risk of lung cancer was consistent in both direction and degree. However, no evidence of causality or reverse causality between schizophrenia and other tumors was found. Conclusion: This study elucidated a causal relationship between the genetic predictors of schizophrenia and the risk of lung cancer, thereby providing a basis for the prevention, pathogenesis, and treatment of schizophrenia in patients with lung cancer.

High-efficiency fourth harmonic generation and polarization smoothing based on an orthogonal cascade of DKDP crystals: publisher's note.

This publisher's note corrects an error in Appl. Opt.63, 1411 (2024)APOPAI0003-693510.1364/AO.512229.

High-efficiency fourth harmonic generation and polarization smoothing based on an orthogonal cascade of DKDP crystals.

Because of the high efficiency of frequency conversion and beam-target coupling, a fourth harmonic (4ω) laser has a splendid application prospect in a high-power laser facility. The polarization smoothing (PS) crystal is preferably after the frequency conversion crystal to flexibly obtain the best uniformity illumination of the target. However, as a high irradiance 4ω laser beam propagates through the PS crystal, the transverse stimulated Raman scattering (TSRS) effect of the PS crystal will be stronger, resulting in significant energy dissipation and crystal damage. This paper proposes a novel, to the best of our knowledge, fourth harmonic generation (FHG) scheme based on an orthogonal cascade of the DKDP crystals. This orthogonal cascaded FHG (OC-FHG) scheme employs two cascaded FHG crystals with orthogonal optical axes, and the PS crystal is in the middle. The PS crystal can rotate the polarization direction of the 2ω laser by 90°, while the polarization direction of the 4ω laser is maintained to a great extent. This OC-FHG scheme realizes the FHG by two steps, and the laser intensity at the PS crystal cuts down nearly 50%. The output intensity of the 4ω laser can be increased from 1.8G W/c m 2 to about 3.6G W/c m 2 under the condition of effectively inhibiting the TSRS effect. Meanwhile, the output 4ω laser contains two orthogonal polarized beams realizing in-beam polarization smoothing instantaneously. In addition, the novel FHG scheme can also have a high conversion efficiency and bandwidth tolerance.

Effect of Bionic Crab Shell Attitude Parameters on Lift and Drag in a Flow Field.

Underwater bionic-legged robots encounter significant challenges in attitude, velocity, and positional control due to lift and drag in water current environments, making it difficult to balance operational efficiency with motion stability. This study delves into the hydrodynamic properties of a bionic crab robot's shell, drawing inspiration from the sea crab's motion postures. It further refines the robot's underwater locomotion strategy based on these insights. Initially, the research involved collecting attitude data from crabs during underwater movement through biological observation. Subsequently, hydrodynamic simulations and experimental validations of the bionic shell were conducted, examining the impact of attitude parameters on hydrodynamic performance. The findings reveal that the transverse angle predominantly influences lift and drag. Experiments in a test pool with a crab-like robot, altering transverse angles, demonstrated that increased transverse angles enhance the robot's underwater walking efficiency, stability, and overall performance.

Deciphering Depressor Anguli Oris for Lower Face Rejuvenation: A Prospective Ultrasound-Based Investigation.

BACKGROUND: The depressor anguli oris muscle (DAO) is a pivotal treatment target in creation of harmonic jawline. However, evidence of its live morphology remains scarce. OBJECTIVES: This study aimed to reevaluate DAO by a facile ultrasound analysis and hereby guide safer and more effective botulinum toxin type A (BTX-A) injection. METHODS: A prospective ultrasound assessment was conducted in 41 patients. Morphology of DAO and its relative position with neighboring structures were appraised at the ubiquitous facial landmark, labiomandibular fold (LMF). Three-dimensional images were captured before and after receiving BTX-A injection based on sonographic evidence. RESULTS: The skin-to-muscle depths of DAO on average (measured from the medial to lateral border) were 5.26, 5.61, and 8.42 mm. DAO becomes thinner and wider from zone 1 to 3 (p < 0.001). Overlapping lengths between DAO and DLI increased from zone 1 to 3: 4.74, 9.68, 14.54 mm (p < 0.001). The medial border of DAO was located at 4.33, 6.12, 8.90 mm medial to LMF (zone 1-3), and no muscle fibers of DAO was observed at zone 1 and 2 in near one-third of patients. Mouth corner downturn angle improvement upon receiving BTX-A injection at zone 2 and 3 were 88.3%, 32.3%, and 14.7% for the neutral, maximum smile, and down-pulling mouth corner expressions. CONCLUSIONS: This work established an informative ultrasound portrait of the DAO and structures in the perioral region, which suggests LMF as a convenient landmark to locate DAO. Injections at the middle and lower thirds of LMF at a 4-5 mm depth is recommended.

Global research status of localised scleroderma reported over the period 1993-2022: A 30-year bibliometric analysis.

Localised scleroderma predominantly affects the skin with an unknown aetiology. Despite its clinical importance, no comprehensive bibliometric analysis has been conducted to assess the existing research landscape and future prospects for localised scleroderma. The articles related to localised scleroderma were retrieved from the WoSCC database and analysed by VOSviewer 1.6.10.0 (Leiden University, Netherlands), CiteSpace 6.1.R1 (Dreiser University, USA), and HistCite 2.1 (New York, United States). 2049 research papers pertaining to localised scleroderma spanning the years from 1993 to 2022 were extracted from the WoSCC database. The United States exhibited the highest productivity with 644 papers, accounting for 31.43% of the total output, followed by Germany with 206 papers (10.05%) and Italy with 200 papers (9.76%). Regarding academic institutions and journals, the University of Texas System and Dermatology published the most significant number of papers, and Professor Ihn, H emerged as the most prolific contributor among scholars. The top 10 cited references primarily concentrated on the diagnosis and treatment of localised scleroderma. "Phototherapy" and "methotrexate (MTX)" surfaced as the most recent and noteworthy keywords, representing the research hotspots in the domain of localised scleroderma. This bibliometric analysis furnishes valuable insights into the contemporary research landscape of localised scleroderma.

Real-Time Fault Diagnosis for Hydraulic System Based on Multi-Sensor Convolutional Neural Network.

This paper proposed a real-time fault diagnostic method for hydraulic systems using data collected from multiple sensors. The method is based on a proposed multi-sensor convolutional neural network (MS-CNN) that incorporates feature extraction, sensor selection, and fault diagnosis into an end-to-end model. Both the sensor selection process and fault diagnosis process are based on abstract fault-related features learned by a CNN deep learning model. Therefore, compared with the traditional sensor-and-feature selection method, the proposed MS-CNN can find the sensor channels containing higher-level fault-related features, which provides two advantages for diagnosis. First, the sensor selection can reduce the redundant information and improve the diagnostic performance of the model. Secondly, the reduced number of sensors simplifies the model, reducing communication burden and computational complexity. These two advantages make the MS-CNN suitable for real-time hydraulic system fault diagnosis, in which the multi-sensor feature extraction and the computation speed are both significant. The proposed MS-CNN approach is evaluated experimentally on an electric-hydraulic subsea control system test rig and an open-source dataset. The proposed method shows obvious superiority in terms of both diagnosis accuracy and computational speed when compared with traditional CNN models and other state-of-the-art multi-sensor diagnostic methods.

Effects of Heated Infiltration Solutions and Forced-Air Heating Blankets on Intraoperative Hypothermia During Liposuction: A Factorial Randomized Controlled Trial.

BACKGROUND: This study was conducted to compare the effects of heat preservation by two recommended methods, heated infiltration solutions and forced-air heating blankets, in patients undergoing liposuction under general anesthesia. METHODS: Forty patients were divided into four groups based on whether heated infiltration solutions or forced-air heating blankets were used. Group A received general anesthesia liposuction plastic surgery routine temperature care. Based on the care measures of group A, heated infiltration solutions were used in group B; forced-air heating blanket was used in group C; and heated infiltration solutions and forced-air heating blankets were both used in group D. The primary end point was intraoperative and perioperative temperature measured with an infrared tympanic membrane thermometer. Secondary end points included surgical outcomes, subjective experience, and adverse events. RESULTS: Compared with group A, the intraoperative body temperatures of groups B, C, and D were significantly higher, indicating that the two intervention methods were helpful on increasing the core body temperature. Pairwise comparisons of these three groups showed that there was no significant difference between group C and group D. However, using forced-air heating blankets had a marked effect compared with using heated infiltration solutions alone at three time points. The same trend could be seen in other surgical outcomes. CONCLUSIONS: Heated infiltration solutions and forced-air heating blankets could reduce the incidence of intraoperative hypothermia and improve patients' prognosis after liposuction under general anesthesia. Compared with the heated infiltration fluid, the forced-air heating blanket may have a better thermal insulation effect. LEVEL OF EVIDENCE I: 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 .

Nerve Distribution Method is Superior to the Conventional Method in BoNT-A Treatment of Trapezius Hypertrophy: A Randomized Controlled Trial.

The contour of the neck and shoulder is defined by the trapezius muscle (TM). Beyond facial procedures, botulinum toxin A (BoNT-A) injections has been increasingly adopted to create a smooth shoulder line. Several studies described the intramuscular nerve branching and the pattern of perforating branch of the accessory nerve in the trapezius muscle, providing essential information for botulinum neurotoxin injection. To this date, research groups seldom perform clinical investigations, especially randomized controlled trials, that demonstrates whether BoNT-A injections using the nerve distribution method for aesthetic purposes is more effective. Patients met the criteria for inclusion were randomized to either the Nerve Distribution group (ND group) or control group. Control group patients received injection using the conventional method while ND group patients received the nerve distribution method. Photographic and ultrasonographic evaluations were carried out at baseline, one month, three months, and six months after the procedure. Patients were also required to complete a questionnaire to evaluate their feedbacks to the injection. After screening, 30 healthy young Chinese women were included. At one-month follow-up, no statistically significant difference was observed between the two methods. At the three-month follow-up, the reduction of the TM thickness for the ND group (0.21 ± 0.09 cm) was more than that for the control group (0.27 ± 0.08 cm), with p = 0.047*. Similar differences were observed for the reduction of the shoulder area proportion (p = 0.031*) and the shoulder angle (p = 0.035*). At the six-month follow-up, the reduction in TM thickness in the ND group (0.2 ± 0.09 cm) was more than that of the control group (0.28 ± 0.06 cm), with p = 0.041*. The global aesthetic improvement scale feedbacks of the two methods showed no significant difference (3.4 ± 0.71 vs 3.8 ± 0.91, p = 0.207). The patients did not experience severe side effects. Compared to the conventional injection method, the nerve distribution method is more effective in reducing the trapezius muscle thickness, shoulder area proportion, and shoulder angle at three months, and shows longer lasting effects. The results of this study introduce unique insights into the design and tailoring of treatment protocols for shoulder-line contouring using BoNT-A.Level of Evidence I 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 .

Potential Linkage between Heavy Metal Pollution Risk Assessment and Dissolved Organic Matter Spectra in the WWTPs-River Integrated Area-Case Study from Ashi River.

Direct sewage discharge can cause severe damage to the water environment of the river. However, the impacts of dissolved organic matter (DOM) in the discharge on the original pattern of DOM and the distribution of heavy metals (HMs) in the river are little known. How to monitor such areas in a long-term and systematic manner also needs to be urgently addressed. In this paper, we characterized the DOM of the sediments in the WWTPs (wastewater treatment plants)-river integrated zone by ultraviolet-visible absorption spectroscopy (UV-vis), three-dimensional excitation-emission matrix (3D-EEM) combined with parallel factor (PARAFAC) method. The effects of WWTP on receiving waters were investigated, and the potential link between DOM and HM pollution was explored. Hg (Igeo: 3.94 ± 0.65; EF: 44.83 ± 31.11), Cd (Igeo: 1.81 ± 0.69; EF: 8.02 ± 2.97), Cu (Igeo: 1.61 ± 0.83; EF: 6.85 ± 2.37), Zn (Igeo: 1.55 ± 0.54; EF: 7.24 ± 3.58), and Ni (Igeo: 1.46 ± 0.56; EF: 6.12 ± 1.99) in rivers were the primary risk sources of HM. The combined pollution risk indicates that the WWTPs-river integrated area is in a high pollution risk state. Moreover, α(254) has a significant correlation with pollution indicators and can be used as a proxy indicator. These results help to understand better the impact of WWTPs on receiving water bodies and the potential connection between DOM and HM pollution and provide new ideas for monitoring the water environment in highly polluted areas.

Soluble immune checkpoints are elevated in patients with primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronically progressive liver disease mediated by an autoimmune response. The aetiology and pathogenesis of PBC are not fully understood and may be related to immune disorders caused by genetic factors and their interaction with environmental factors. Immune checkpoints play an important role in preventing the occurrence of autoimmunity. However, the level of immune checkpoints in PBC has not been reported. Here, we aimed to identify the serum levels of soluble checkpoints in patients with PBC. METHODS: Soluble checkpoint levels were evaluated using enzyme-linked immunosorbent assay in 60 patients with PBC and 20 healthy controls (HCs). The expression of immune checkpoints was compared in liver biopsy tissue samples using immunohistochemistry. Receiver operating characteristic (ROC) curves and area under the curve (AUCs) were used to determine the diagnostic performance of soluble checkpoints and laboratory indexes between patients with PBC and HCs and patients with mild and advanced PBC. A logistic regression was performed for advanced PBC. RESULTS: sCD134, sLAG-3, sPD-1, sPD-L1, and sTIM-3 levels were significantly increased in patients with PBC compared with those in healthy controls. Additionally, the levels of sCD134, sPD-1, sPD-L1, and sTIM-3 were positively associated with disease progression. Moreover, soluble checkpoints were correlated with immunoglobulin and liver functions. ROC analyses between patients with PBC and HCs showed that the AUCs of sOX40, sPD-1, and sPD-L1 were 0.967, 0.922, and 0.971, respectively. The optimal cut-off values of sOX40, sPD-1, and sPD-L1 for PBC diagnosis were 89.15, 213.4, and 68, respectively. ROC analyses between mild and advanced patients with PBC revealed that the AUCs of sOX40 and sTIM-3 were 0.767 and 0.765, respectively. The optimal cut-off values for predicting PBC stage ≥ III were 199.45 and 361.5, respectively. In univariate analysis, age, ALB, and sOX40 were associated with advanced PBC. Further, the expression of CD134 and TIM-3 was upregulated in the liver of patients with PBC. CONCLUSIONS: Our study results indicate that the serum titer of soluble checkpoints is increased in Chinese patients with PBC.

Prognostic value and immune infiltration of ARMC10 in pancreatic adenocarcinoma via integrated bioinformatics analyses.

Background: Armadillo repeat-containing 10 (ARMC10) is involved in the progression of multiple types of tumors. Pancreatic adenocarcinoma (PAAD) is a lethal disease with poor survival and prognosis. Methods: We acquired the data of ARMC10 in PAAD patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) datasets and compared the expression level with normal pancreatic tissues. We evaluated the relevance between ARMC10 expression and clinicopathological factors, immune infiltration degree and prognosis in PAAD. Results: High expression of ARMC10 was relevant to T stage, M stage, pathologic stage, histologic grade, residual tumor, primary therapy outcome (P < 0.05) and related to lower Overall-Survival (OS), Disease-Specific Survival (DSS), and Progression-Free Interval (PFI). Gene set enrichment analysis showed that ARMC10 was related to methylation in neural precursor cells (NPC), G alpha (i) signaling events, APC targets, energy metabolism, potassium channels and IL10 synthesis. The expression level of ARMC10 was positively related to the abundance of T helper cells and negatively to that of plasmacytoid dendritic cells (pDCs). Knocking down of ARMC10 could lead to lower proliferation, invasion, migration ability and colony formation rate of PAAD cells in vitro. Conclusions: Our research firstly discovered ARMC10 as a novel prognostic biomarker for PAAD patients and played a crucial role in immune regulation in PAAD.

Exosomes from human adipose-derived mesenchymal stem cells attenuate localized scleroderma fibrosis by the let-7a-5p/TGF-ßR1/Smad axis.

BACKGROUND: Inflammation and fibrosis of the skin are characteristics of localized scleroderma (LS). Emerging evidence has demonstrated that exosomes from human adipose tissue-derived mesenchymal stem cells (ADSC-Exo) could alleviate skin fibrosis. OBJECTIVE: The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. METHODS: ADSC-Exo was isolated and identified. The effects of ADSC-Exo on the abilities of proliferation and migration of LS-derived fibroblasts (LSFs) were assessed by CCK-8 and scratch assays, respectively. qRT-PCR, western blot, and immunofluorescence were conducted to detect LSFs stimulated with ADSC-Exo, ADSC-ExoAnti-let-7a-5p, let-7a-5p mimic/TGF-ßR1 shRNA virus, and negative controls. The impact of ADSC-Exo on C57BL/6j LS mice was evaluated by photographic morphology, hematoxylin-eosin (H&E), Masson's trichrome, and immunohistochemical staining. RESULTS: The verified ADSC-Exo limited the proliferation and migration of LSFs and reduced the expression of COL1, COL3, α-SMA, TGF-ßR1, and p-Smad2/ 3 in vitro and in vivo. TGF-ßR1 knockdown and let-7a-5p mimic in LSFs reduced the expression of COL1, COL3, α-SMA, and p-Smad2/3. However, compared with the ADSC-ExoNC group, the dermal thickness was increased, collagen arrangement was disordered, and α-SMA and TGF-ßR1 levels were increased after exposure to ADSC-ExoAnti-let-7a-5p. CONCLUSIONS: In this study, it might show that ADSC-Exo may successfully prevent LSF bioactivity, collagen deposition, and myofibroblast trans-differentiation. Additionally, we confirmed that let-7a-5p in ADSC-Exo could directly target TGF-R1 to control the Smad pathway and reduce fibrosis in LSFs. Our work offered a brand-new therapeutic approach and clarified the unique mechanism for the clinical management of LS.

Efficient exploration of compositional space for high-performance copolymers via Bayesian optimization.

The traditional approach employed in copolymer compositional design, which relies on trial-and-error, faces low-efficiency and high-cost obstacles when attempting to simultaneously improve multiple conflicting properties. For example, designing co-cured polycyanurates that exhibit both moisture and thermal resistance, along with high modulus, is a long-term challenge because of the intrinsic trade-offs between these properties. In this work, to surmount these barriers, we developed a Bayesian optimization (BO)-guided method to expedite the discovery of co-cured polycyanurates exhibiting low water uptake, coupled with higher glass transition temperature and Young's modulus. By virtue of the knowledge of molecular simulations, benchmarking studies were carried out to develop an effective BO-guided method. Propelled by the developed method, several copolymers with improved comprehensive properties were obtained experimentally in a few iterations. This work provides guidance for efficiently designing other high-performance copolymers.

Spatial Transcriptomics of Aging Rat Ovaries Reveals Unexplored Cell Subpopulations with Reduced Antioxidative Defense.

INTRODUCTION: Ovarian aging is characterized by a gradual decline in quantity and quality of oocytes and lower chance of fertility. Better understanding the genetic modulation during ovarian aging can further address available treatment options for aging-related ovarian diseases and fertility preservation. METHODS: A novel technique spatial transcriptomics (ST) was used to investigate the spatial transcriptome features of rat ovaries. Transcriptomes from ST spots in the young and aged ovaries were clustered using differentially expressed genes. These data were analyzed to determine the spatial organization of age-induced heterogeneity and potential mechanisms underlying ovarian aging. RESULTS: In this study, ST technology was applied to profile the comprehensive spatial imaging in young and aged rat ovary. Fifteen ovarian cell clusters with distinct gene-expression signatures were identified. The gene expression dynamics of granulosa cell clusters revealed three sub-types with sequential developmental stages. Aged ovary showed a significant decrease in the number of granulosa cells from the antral follicle. Besides, a remarkable rearrangement of interstitial gland cells was detected in aging ovary. Further analysis of aging-associated transcriptional changes revealed that the disturbance of oxidative pathway was a crucial factor in ovarian aging. CONCLUSIONS: This study firstly described an aging-related spatial transcriptome changes in ovary and identified the potential targets for prevention of ovarian aging. These data may provide the basis for further investigations of the diagnosis and treatment of aging-related ovarian disorders.