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To address the cracking issues that often occur between laser cladding coatings and substrates on brake disc surfaces, methods including microhardness testing, scanning electron microscopy (SEM), and X-ray stress testing were employed. These techniques were used to study the high-temperature dry sliding friction and wear behavior of Ni60A coating on the 20CrNiMo alloy surface treated by laser shock peening (LSP) and its bonding zone. The results indicate that LSP can significantly enhance the microhardness of the coating and bonding zone, refine the microstructure, and form residual compressive stress without generating new phases. The weight loss due to wear and the average coefficient of friction for the substrate, the cladding alloy, and the LSP-treated alloy demonstrate a trend of first decreasing and then increasing with the rise in temperature. The high-temperature friction and wear performance of the LSP-treated alloy is excellent. This is particularly true at 400 °C, where its wear resistance reaches its peak. Furthermore, after strengthening by LSP, the wear mechanism of the alloy at high temperatures transitions from spalling, oxidation, and adhesive wear to primarily oxidation and abrasive wear.

The frequent occurrence of cable early faults can lead to permanent failure of cables, making the power grid damaged and unable to work normally. To avoid the cable early faults causing great damage to the power grid operation, in this paper, we propose a research method for cable early fault identification based on the fusion of Markov Transition Field (MTF)-Gramian Angular Field (GAF) and multi-head attention mechanism features to accurately identify the cable early faults. Firstly, the fault data are preprocessed by the least mean square algorithm optimized by the adaptive gradient method; then the preprocessed one-dimensional data are converted into two-dimensional (2D) images by using MTF and GAF, respectively, and then the two types of images are fused to serve as the input of the classification network; finally, a hybrid neural network for cable early fault identification composed of a deep convolutional neural network and dense convolutional network is established, the hybrid neural network is improved by using group convolution and Ghost convolution, and the output features of the hybrid neural network are fused and classified through the mechanism of multi-head attention, and the output results of the cable early fault identification are output. At the same time, the classification results of cable early faults are visualized using the t-distributed Stochastic Neighbor Embedding (t-SNE) method to visually observe the classification effect of the hybrid neural network. The experimental results show that the algorithm has a high recognition rate for cable early fault classification, and the least mean square algorithm optimized by the adaptive gradient method is more noise-resistant compared with other optimization methods.

Addressing the limitations inherent in conventional Power Quality Disturbance (PQD) identification systems, particularly regarding the restricted information obtainable from single image features and the compromised noise immunity of single-channel networks, an innovative approach, integrating Uniform Relative Position Matrix-Continuous Wavelet Transform (URPM-CWT) and multi-channel feature fusion, is presented. This method capitalizes on the principle of feature fusion to enhance microgrid PQD identification. To begin with, each PQD signal undergoes processing through the URPM and CWT, followed by horizontal splicing to yield the URPM-CWT feature image. This is followed by the parallel deployment of three refined networks—MobileNetV2, ResNet50, and ShuffleNetV2—using the Self Fusion Module (SFM) to yield a multi-channel feature fusion classification model. The final stage involves feeding the URPM-CWT feature image into the multi-channel feature fusion classification model and applying a fully connected layer for training, leading to comprehensive perturbation recognition. Constructed using the PyTorch framework, the proposed model is evaluated on an exhaustive database of 28 distinct PQD types. In a 30db white noise environment, the method demonstrates an average classification accuracy of 99.35%, surpassing the performance of standalone deep learning recognition approaches. Simulation experiments corroborate the model’s high classification accuracy, effective recognition, and robust resistance to noise when dealing with PQD signals. Thus, the model offers promising potential for practical applications in PQD identification and classification.

Ground-based tests are important for studying hypervelocity impact (HVI) damage to spacecraft pressure vessels in the orbital debris environment. We analyzed the damage to composite overwrapped pressure vessels (COPVs) in the HVI tests and classified the damage into non-catastrophic damage and catastrophic damage. We proposed a numerical simulation method to further study non-catastrophic damage and revealed the characteristics and mechanisms of non-catastrophic damage affected by impact conditions and internal pressures. The fragments of the catastrophically damaged COPVs were collected after the tests. The crack distribution and propagation process of the catastrophic ruptures of the COPVs were analyzed. Our findings contribute to understanding the damage characteristics and mechanisms of COPVs by HVIs.

Rosai-Dorfman-Destombes disease (RDD) is a rare non-Langerhans cell histiocytosis (LCH) disorder characterized by systemic extranodal lesions. Common cases include skin lesions, whereas liver lesions are rare. This study presents a case of a 66-year-old woman with a solitary extranodal liver lesion who underwent successful surgical treatment followed by glucocorticoid therapy. The patient did not experience any symptoms before surgery. The liver lesion was incidentally discovered during a routine ultrasound examination. Enhanced CT scan revealed the lesion with the characteristic of washout, similar to primary hepatic cancer (HCC). CT scans of the head, neck, chest, and abdominal pelvis revealed no lymph node or other organ lesions. After surgery, the liver lesion was diagnosed as RDD, and subsequent whole-body examinations did not reveal any skin lesions. The definitive diagnosis was solid liver RDD in adults. Although there were no typical cases of bilateral cervical lymph node lesions, ultrasound and CT examinations promptly detected liver lesions, leading to the correct diagnosis through surgical resection. The findings from this case indicate that RDD can occur in rare extrasegmental areas, and the imaging characteristics of liver lesions are not specific, indicating the importance of avoiding delayed diagnosis.

Peripheral blood mononuclear cells (PBMCs) from a 28-year-old male patient with unipolar depression were reprogrammed with reprogramming factors by electroporation. The pluripotency of transgene-free induced pluripotent stem cells (iPSCs) was verified by immunofluorescence staining for pluripotency markers, and these iPSCs were able to differentiate into the 3 germ layers in vitro. These iPSCs also showed normal karyotypes. Thus, we believe that these iPSCs could be valuable models for exploring the underlying biological mechanism of depression and the safety of antidepressants through the use of iPSCs differentiated into different kinds of neurons or brain organoids.

The hematopoietically-expressed homeobox gene (HHEX) played a critical role in regulating the immune system that the abnormality of which was involved in the psychopathology and cognitive deficits of psychiatric disorders. The aim of this study was to investigate the effect of HHEX rs1111875 polymorphism on the susceptibility and cognitive deficits of first-episode schizophrenic patients (FSP). We assessed cognitive function in 239 first-episode patients meeting DSM-IV for schizophrenia, and 368 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The HHEX rs1111875 polymorphism was genotyped. Our results showed that the allelic and genotypic frequencies of HHEX rs1111875 polymorphism didn't differ between FSP and healthy controls (both p > 0.05) after adjusting for sex and age. Cognitive test scores in FSP were significantly lower than those in healthy controls on all scales (all p 0.05) after adjusting for covariates. There was a significant genotype (p 0.05) effect on the delayed memory score after adjusting for covariates. The HHEX rs1111875 polymorphism was significantly associated with the delayed memory score in FSP (p 0.05) after adjusting for covariates. Our findings supported that the HHEX rs1111875 polymorphism did not contribute to the susceptibility to FSP. However, this polymorphism might influence the delayed memory in FSP. Moreover, FSP had poorer cognitive function than healthy controls except for the visuospatial/constructional domain.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Background: Psoriasis is a chronic, inflammatory skin disease with autoimmune characteristics. Recent research has made significant progress in the field of psoriasis metabolomics. However, there is a lack of bibliometric analysis on metabolomics of psoriasis. The objective of this study is to utilize bibliometrics to present a comprehensive understanding of the knowledge structure and research hotspots in psoriasis within the field of metabolomics. Methods: We conducted a bibliometric analysis by searching the Web of Science Core Collection database for publications on metabolomics in psoriasis from 2011 to 2024. To perform this analysis, we utilized tools such as VOSviewers, CiteSpace, and the R package ''bibliometrix''. Results: A total of 307 articles from 47 countries, with the United States and China leading the way, were included in the analysis. The publications focusing on metabolomics in psoriasis have shown a steady year-on-year growth. The Medical University of Bialystok is the main research institution. The International Journal of Molecular Sciences emerges as the prominent journal in the field, while the Journal of Investigative Dermatology stands out as the highly co-cited publication. A total of 2029 authors contributed to these publications, with Skrzydlewska Elzbieta, Baran Anna, Flisiak Iwona, Murakami Makoto being the most prolific contributors. Notably, Armstrong April W. received the highest co-citation. Investigating the mechanisms of metabolomics in the onset and progression of psoriasis, as well as exploring therapeutic strategies, represents the primary focus of this research area. Emerging research hotspots encompass inflammation, lipid metabolism, biomarker, metabolic syndrome, obesity, and arthritis. Conclusion: The results of this study indicate that metabolism-related research is thriving in psoriasis, with a focus on the investigation of metabolic targets and interventions within the metabolic processes. Metabolism is expected to be a hot topic in future psoriasis research.

AbstractContext Jiang-Zhi-Ning (JZN), a traditional Chinese medicinal formula, is used to treat hyperlipidemia in clinics.Objective To screen the hypolipidemic “bioequivalent substance system (BSS)” of JZN and elucidate the potential hypolipidemic mechanism.Materials and methods In vitro, the TG content in HepG2 cells was determined after the intervention of the combination of advantageous components (CAC) by uniform design. In vivo, hyperlipidemia models were established by Triton WR-1339 (400 mg/kg; i.p.) in male ICR mice, and corresponding treatments were administered via oral administration once. The mice were divided into 12 groups (n = 5): control, hyperlipidemic model, simvastatin (positive control, 20 mg/kg), gradient doses of JZN granules (2, 4 and 8 g/kg) and the hypolipidemic effective extraction (HEE) of JZN (120, 240 and 480 mg/kg) and CAC groups (20, 40 and 160 mg/kg). Serum TC, TG, LDL-C and HDL-C were performed after 24 h. Transcriptomics and qRT–PCR technology were used to explore the mechanism of the “BSS” of JZN.Results In vitro, the ratio of CAC was determined. CAC could reduce the TG content in HepG2 cells (77.21%). Compared with the model group, the high dose of CAC could markedly decrease the levels of TC (61.86%), TG (105.54%) and LDL-C (39.38%) and increase the level of HDL-C (232.67%). CAC was proved to be the “BSS”. Transcriptomics and qRT–PCR analysis revealed CAC regulated non-alcoholic fatty liver disease, bile secretion, PPAR and adipocytokine signalling pathway.Discussion and conclusions These findings provided new feasible ideas and methods for the elucidation of the pharmacodynamic material basis.

Pyroptosis is a regulated cell death pathway involved in numerous human diseases, especially malignant tumors. Recent studies have identified multiple pyroptosis-associated signaling molecules, like caspases, gasdermin family and inflammasomes. In addition, increasing in vitro and in vivo studies have shown the significant linkage between pyroptosis and immune regulation of cancers. Pyroptosis-associated biomarkers regulate the infiltration of tumor immune cells, such as CD4+ and CD8+ T cells, thus strengthening the sensitivity to therapeutic strategies. In this review, we explained the relationship between pyroptosis and cancer immunology and focused on the significance of pyroptosis in immune regulation. We also proposed the future application of pyroptosis-associated biomarkers in basic research and clinical practices to address malignant behaviors. Exploration of the underlying mechanisms and biological functions of pyroptosis is critical for immune response and cancer immunotherapy.

In order to investigate the infection status and genotypes of Enterocytozoon bieneusi (E. bieneusi) in sheep and goats in Jiangsu Province, a total of 786 fresh fecal samples from 18 farms across five regions in Jiangsu were collected and examined for the presence of E. bieneusi, and the genotype of E. bieneusi was examined using nested-PCR and sequencing of the ribosomal internal transcribed spacer. The results showed that E. bieneusi was detected in the fecal samples of sheep and goats in all regions, with infection rates ranging from 23.65% to 42.81%. The overall infection rate was 36.51% (287/786). The infection rate of E. bieneusi showed no significant difference between sheep and goats, as well as among different ages of animals (p > 0.05), but showed a significant difference in sheep and goats with different health conditions (p < 0.05). The positive products were amplified and cloned and subjected to sequenced analysis. Six genotypes, BEB6, CHG2, CHG3, CHC8, CHG14, and COS-I, were found. Phylogenetic analysis indicated that the six genotypes belonged to Group 2, which had previously been described as a non-zoonotic group.

Introduction: Alzheimer's disease-resemblance atrophy index (AD-RAI) is a machine-learning derived MRI-based brain atrophy biomarker that is valid in predicting cognitive decline in subjects with AD. We investigated the performance of AD-RAI in predicting long-term cognitive decline in subjects with stroke or transient ischemic attack (TIA). Methods: We recruited consecutive dementia-free stroke/TIA subjects who had brain MRI at baseline (i.e., within 3-6 months after the index event) and cognitive data at both baseline and 3 years. We defined cognitive decline as an increase in clinical dementia rating scale from 0 to 0.5 or above or from 0.5 to 1 or above at 3 years when compared with baseline. We investigated the association between AD-RAI, traditional brain atrophy biomarkers (hippocampus volume [HV], hippocampal fraction [HF], total brain volume [TBV], TBV/intracranial volume [ICV] ratio, ventricular-brain-ratio, presence of medial temporal lobe atrophy [MTLA]), and cerebral small vessel disease biomarkers (white matter hyperintensity [WMH]) volume, WMHV/ICV ratio presence of confluent WMH, presence of >/=3 lacunes) with cognitive decline. Results: Of 231 participants (mean age 66.0 ± 10.9, 124 [53.7] male), 55(23.8) had cognitive decline at 3 years. Among all the imaging biomarkers, AD-RAI and HV were associated with cognitive decline in univariate regression. Such a relationship was still significant with AD-RAI after adjusted for age, gender, and education (aOR [95%CI] 3.900 [1.221-12.458]). Among all imaging biomarkers, only AD-RAI was associated with slope of Montreal cognitive assessment (MoCA) after adjusted to age, gender, education (β(SE) −0.742[0.242], p=0.002). Discussion: AD-RAI predicted long term cognitive decline in subjects with stroke/TIA.

Introduction: The number of people living with dementia worldwide is growing. Devising and implementing preventive strategies that are globally applicable is of paramount importance. However, previous studies have largely been limited to cohorts that are geographically and culturally homogenous. It is not known whether the associations between demographics, vascular risk factors (VRFs), and cognitive changes are consistent across cohorts with cultural and geographical variations. Methods: Data were analysed retrospectively from 6 community-dwelling cohorts (> 60 years old) with cultural and geographical variations (British = 536; Hong Kong Chinese = 494; Australian = 302; Singaporean Chinese = 108; German = 102; Swedish = 94). Clinical demographics, VRFs, longitudinal cognitive changes, and MRI data (including T1, FLAIR, and diffusion images) were analysed from all 6 cohorts. First, across all cohorts, a grand canonical correlation analysis (n=1636) was used to establish common modes of covariation between demographics and VRFs on one side, and cognitive changes on the other side. Second, separately for each cohort, mediation analysis was used to investigate the mediating role of normalised total grey matter volume, microstructural integrity, white matter hyperintensity, and hippocampal structural network in the association mentioned above. Then the mediation outputs will be used in the meta- analysis to assess the indirect effect estimates and variance of each significant brain mediator. Results: We identified three modes of covariation between dementia risk and cognition across all cohorts (p< 0.01). The strongest mode linked younger age and higher levels of education with better cognition at baseline and follow-up (Figure 1). Meta-analysis showed that, across cohorts, normalised total grey matter volume (Indirect effect = 0.02, Z = 3.13, p < 0.001, I² = 0%) was a significant mediator between demographics, VRFs, and cognitive decline after Bonferroni correction (Figure 2). The hippocampal structural network did not survive Bonferroni correlation while other brain mediators were not significant in the meta-analyses. Discussion: This study investigated the complex relationship between demographics, VRFs, brain health, and cognition. Cohorts with cultural and demographic variations shared a common relationship between age, education, and cognition. However, individual cohort differences are detected in the contribution of different neuroimaging metrics.

Objective To review postoperative necrotizing enterocolitis (NEC) in patients with jejunoileal atresia (JIA) and to explore the potential risk factors related to the concurrence of NEC.Methods Patients diagnosed with JIA who received surgical treatment from January 2016 to June 2021 were enrolled. Demographics, viral infection of the fetus, transfusion within 48 hours before NEC, sepsis before JIA repair, pathological and anatomical classification of JIA, combined malformation, occurrence time of NEC after the operation, treatment, and prognosis of patients were analyzed. Patients were divided into NEC group and non-NEC group, and all patients were followed up for 3–6 months to observe for complications.Results A total of 180 patients with JIA were included, of whom 12 were diagnosed with NEC after surgery and 1 patient with NEC died during follow-up. The average age, birth weight, gestational age, proportion of premature infants, proportion of preoperative infections, and pathological classification of JIA did not significantly differ between the two groups. The probability of patients with proximal jejunal atresia (PJA) in the NEC group (58.3%) was higher than that in the non-NEC group (22.6%) (p=0.011), and patients with PJA had longer parenteral nutrition time than patients without PJA (26.64±9.21 days vs 15.11±6.58 days, p

Abstract Background Chronic refractory wounds easily relapse and seriously affect the patients’ quality of life. Previous studies have shown that stromal vascular fraction gel (SVF-gel) significantly promotes the early healing of chronic wounds; however, the mechanisms of SVF-gel function per se remain unclear, and a long-term follow-up is lacking. This study aims to explore the mechanisms of SVF-gel promoting the healing of chronic wounds and follow up the long-term efficacy of SVF-gel. Methods Autologous SVF-gel transplantation was performed in 20 patients with chronic wounds (from March 2016 to September 2019), and the size of the wound before and after SVF-gel transplantation was observed. The conditioned medium (CM) was harvested from SVF-gel under serum-free, serum-deprivation and 10% fetal bovine serum (FBS) microenvironment in vitro, respectively. The concentration of the growth factors in the two kinds of gel-CM was tested, and their effects on the proliferation and migration of human dermal fibroblasts (HDFs) were detected. Results All patients had 100% wound closure eventually, and the average time to complete closure was 28.3 ± 9.7 days. The time of follow-up ranged from 2 to 6 years, and there was no wound recurrence. Interestingly, the concentrations of epidermal growth factor and transforming growth factor β1 of the CM were higher in serum-free and serum-deprivation condition than in 10% FBS microenvironment (p

In order to test the accuracy of the weapon hitting the target, it is very important to locate and measure the spatial coordinates of the falling point target. Aiming at the needs of space coordinate positioning and measurement of targets falling into the sea/ground plane, this paper studies a positioning method of UAV camera combined with target, and uses the principle of homography transformation to calculate the space coordinates of targets. The influence of pixel error on the positioning method is simulated by Monte Carlo method, and the shooting attitude range meeting the measurement requirements is determined by simulation. The results show that the positioning method of UAV camera combined with target has high accuracy, which can meet the needs of landing target positioning and measurement.

ObjectiveThe aim of this study was to investigate the relationships and predictive value of preoperative peripheral blood inflammatory markers as a means by which to assess risk for patients with ≤ 1 cm papillary thyroid carcinomas (PTCs). In addition, a preoperative risk stratification predictive model was constructed and validated.MethodsClinical and pathologic data, as well as preoperative blood specimens, were collected from patients who underwent initial thyroid cancer surgery at the Hangzhou First People’s Hospital, from January 2014 to January 2023. Risk assessment was performed based on postoperative pathology according to the 2015 ATA guidelines for recurrence risk stratification. Using univariate analysis and multivariate logistic regression, we identified independent risk factors associated with risk stratification. A predictive model was established and its discriminative and calibration abilities were validated. An independent validation dataset was used to verify the model, and the model was deployed as an online calculator.ResultsA total of 1326 patients were included in the study, with 1047 cases (79.0%) classified as low risk and 279 cases (21.0%) classified as intermediate to high risk. The modeling group consisted of 981 cases, through univariate analysis and multivariate logistic regression analysis, preoperative blood Neutrophil/Lymphocyte Ratio (NLR), gender, tumor diameter, and multifocality were identified as independent risk factors that distinguished between low and intermediate to high risk patients with ≤ 1 cm PTCs. The clinical predictive model exhibited an AUC of 0.785, specificity of 70.6%, and sensitivity of 75.8%. For the independent validation group of 345 patients, the AUC was 0.813, specificity was 83.8%, and sensitivity was 70.4%. The calibration curve and clinical decision curve indicate that the model demonstrates excellent calibration performance.ConclusionA dynamic clinical predictive model based on preoperative blood NLR and clinical information for patients with ≤ 1 cm PTCs was established. The model is useful for preoperative risk assessment of patients with ≤ 1 cm PTCs.

Aim N6-methyladenosine (m6A) RNA methylation exerts a regulatory effect on endometrioid ovarian cancer (EOC), but the specific m6A regulator genes in EOC remain to be explored. This study investigated that sulforaphene (Sul) is implicated in EOC development by regulating methyltransferase-like 3 (METTL3). Methods The dysregulated m6A RNA methylation genes in EOC were determined by methylated RNA immunoprecipitation (MeRIP-seq) and RNA sequencing. The roles of METTL3 and/or Sul on viability, proliferative ability, cell cycle, and apoptosis of EOC cells were determined by MTT, colony formation, flow cytometry, and TUNEL staining assay, respectively. The expression of METTL3 and apoptosis-related proteins in EOC cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays. Results Five m6A RNA methylation regulators (METTL3, ELF3, IGF2BP2, FTO, and METTL14) were differentially expressed in EOC, among which METTL3 had the highest expression level. Silencing METTL3 reduced the clonal expansion and viability of EOC cells, and caused the cells to arrest in the G0/G1 phase. This also promoted apoptosis in the EOC cells and activated the FAS/FADD and mitochondrial apoptosis pathways. In contrast, overexpressing METTL3 had the opposite effect. Sul, in a dose-dependent manner, reduced the viability of EOC cells but promoted their apoptosis. Sul also increased the levels of IGF2BP2 and FAS, while decreasing the levels of KRT8 and METTL3. Furthermore, Sul was able to reverse the effects of METTL3 overexpression on EOC cells. Conclusions Sul could suppress cell proliferation and promote apoptosis of EOC cells by inhibiting the METTL3 to activate the FAS/FADD and apoptosis-associated pathways.

Introduction: Owing to the need for liposuction and its unsuitability for allogeneic transplantation, the clinical application of stromal vascular fraction gel (SVF-gel) combined with fractional CO2 laser for scar treatment is limited. Adipose tissue extract (ATE), rich in cytokines and growth factors, offers a more convenient option for clinical practice as it can be easily prepared using purely physical methods and has low immunogenicity. We aimed to evaluate the effectiveness of ATE combined with fractional CO2 laser in the treatment of hypertrophic scars.Methods: ATE was prepared using discarded liposuction fluid from patients undergoing liposuction. A rabbit ear hypertrophic scar model was established and treated with ATE, fractional CO2 laser, or a combination. PBS was used as a control. The scar appearance and histological changes were observed. The immunohistochemistry method was used to evaluate the expression of α-SMA, while perilipin was detected using immunofluorescence. Additionally, the level of adipogenic signal C/EBPα and PPARγ mRNA was studied.Results: Following treatment, the volume of hypertrophic scar decreased, resulting in a softer texture and thinner dermis. Additionally, there was a decrease in the infiltration of inflammatory cells, and the collagen arrangement became looser and more regular, and the expression of α-SMA also decreased, with the combination of ATE and fractional laser showing the most significant improvement. Moreover, the combination group was found to promote subcutaneous fat regeneration and increase the expression of adipogenic signals C/EBPα and PPARγ.Conclusion: The combination of ATE and fractional CO2 laser treatment has been shown to inhibit the development of hypertrophic scars. This effect may be attributed to the enhancement of adipogenesis and decrease in collagen deposition.

Abstract Background The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. Methods Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. Results The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p

The improvement of treatment for patients with ‘driver‐gene‐negative’ lung adenocarcinoma (LUAD) remains a critical problem to be solved. We aimed to explore the role of methylation of N6 adenosine (m6A)‐related long noncoding RNA (lncRNA) in stratifying ‘driver‐gene‐negative’ LUAD risk. Patients negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET, and ROS1 were identified as ‘driver‐gene‐negative’ cases. RNA sequencing was performed in 46 paired tumors and adjacent normal tissues from patients with ‘driver‐gene‐negative’ LUAD. Twenty‐three m6A regulators and relevant lncRNAs were identified using Pearson's correlation analysis. K‐means cluster analysis was used to stratify patients, and a prognostic nomogram was developed. The CIBERSORT and pRRophetic algorithms were employed to quantify the immune microenvironment and chemosensitivity. We identified two clusters highly consistent with the prognosis based on their unique expression profiles for 46 m6AlncRNAs. A risk model constructed from nine m6A lncRNAs could stratify patients into high‐ and low‐risk groups with promising predictive power (C‐index = 0.824), and the risk score was an independent prognostic factor. The clusters and risk models were closely related to immune characteristics and chemosensitivity. Additional pan‐cancer analysis using the nine m6AlncRNAs showed that the expression of DIO3 opposite strand upstream RNA (DIO3OS) is closely related to the immune/stromal score and tumor stemness in a variety of cancers. Our results show that m6AlncRNAs are a reliable prognostic tool and can aid treatment decision‐making in ‘driver‐gene‐negative’ LUAD. DIO3OS is associated with the development of various cancers and has potential clinical applications.

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types, including non-coding RNAs (ncRNAs). N-6-methyladenosine (m6A) is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis, and serves as a crucial regulator for multiple cancer-associated signaling pathways. The ncRNAs usually regulate the epigenetic modification, mRNA transcription and other biological processes, displaying enormous roles in human cancers. In this review, we summarized the significant implications of m6A-ncRNA interaction in various types of cancers. In particular, the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely recognized. We also discussed the relevance of m6A-ncRNA interaction in immune regulation, followed by the interference on cancer immunotherapeutic procedures. In addition, we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among ncRNAs. In summary, this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

BackgroundResults from randomized controlled trials (RCTs) and meta-analyses comparing invasive and conservative strategies in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are highly debatable. We systematically evaluate the efficacy of invasive and conservative strategies in NSTE-ACS based on time-varied outcomes.MethodsThe RCTs for the invasive versus conservative strategies were identified by searching PubMed, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials.gov. Trial data for studies with a minimum follow-up time of 30 days were included. We categorized the follow-up time into six varied periods, namely, ≤6 months, 1 year, 2 years, 3 years, 5 years, and ≥10 years. The time-varied outcomes were major adverse cardiovascular event (MACE), death, myocardial infarction (MI), rehospitalization, cardiovascular death, bleeding, in-hospital death, and in-hospital bleeding. Risk ratios (RRs) and 95% confidence intervals (Cis) were calculated. The random effects model was used.ResultsThis meta-analysis included 30 articles of 17 RCTs involving 12,331 participants. We found that the invasive strategy did not provide appreciable benefits for NSTE-ACS in terms of MACE, death, and cardiovascular death at all time points compared with the conservative strategy. Although the risk of MI was reduced within 6 months (RR 0.80, 95% CI 0.68–0.94) for the invasive strategy, no significant differences were observed in other periods. The invasive strategy reduced the rehospitalization rate within 6 months (RR 0.69, 95% CI 0.52–0.90), 1 year (RR 0.73, 95% CI 0.63–0.86), and 2 years (RR 0.77, 95% CI 0.60–1.00). Of note, an increased risk of bleeding (RR 1.80, 95% CI 1.28–2.54) and in-hospital bleeding (RR 2.17, 95% CI 1.52–3.10) was observed for the invasive strategy within 6 months. In subgroups stratified by high-risk features, the invasive strategy decreased MACE for patients aged ≥65 years within 6 months (RR 0.68, 95% CI 0.58–0.78) and 1 year (RR 0.75, 95% CI 0.62–0.91) and showed benefits for men within 6 months (RR 0.71, 95% CI 0.55–0.92). In other subgroups stratified according to diabetes, ST-segment deviation, and troponin levels, no significant differences were observed between the two strategies.ConclusionsAn invasive strategy is superior to a conservative strategy in reducing early events for MI and rehospitalizations, but the invasive strategy did not improve the prognosis in long-term outcomes for patients with NSTE-ACS.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289579, identifier PROSPERO 2021 CRD42021289579.

Asthma is a common chronic respiratory disease, which causes inflammation and airway stenosis, leading to dyspnea, wheezing and chest tightness. Using transgelin-2 as a target, we virtually screened the lead compound glycyrrhizin from the self-built database of anti-asthma compounds by molecular docking technology, and found that it had anti-inflammatory, anti-oxidative and anti-asthma pharmacological effects. Then, molecular dynamics simulations were used to confirm the stability of the glycyrrhizin-transgelin-2 complex from a dynamic perspective, and the hydrophilic domains of glycyrrhizin was found to have the effect of targeting transgelin-2. Due to the self-assembly properties of glycyrrhizin, we explored the formation process and mechanism of the self-assembly system using self-assembly simulations, and found that hydrogen bonding and hydrophobic interactions were the main driving forces. Because of the synergistic effect of glycyrrhizin and salbutamol in improving asthma, we revealed the mechanism through simulation, and believed that salbutamol adhered to the surface of the glycyrrhizin nano-drug delivery system through hydrogen bonding and hydrophobic interactions, using the targeting effect of the hydrophilic domains of glycyrrhizin to reach the pathological parts and play a synergistic anti-asthmatic role. Finally, we used network pharmacology to predict the molecular mechanisms of glycyrrhizin against asthma, which indicated the direction for its clinical transformation.

Abstract Wolfram Syndrome (WS) is a fatal human inherited disease with symptoms of diabetes, vision decreasing, and neurodegeneration caused by mutations in the endoplasmic reticulum (ER)-resident protein WFS1. WFS1 has been reported to play an important role in glucose metabolism. However, the role of WFS1 in axonal regeneration in the central nervous system has so far remained elusive. Herein, we established a model of the wfs1b globally deficient zebrafish line. wfs1b deficiency severely impeded the Mauthner-cell (M-cell) axon regeneration, which was partly dependent on the ER stress response. The administration of ER stress inhibitor 4-Phenylbutyric acid (4-PBA) promoted M-cell axon regeneration in wfs1b −/− zebrafish larvae, while the ER stress activator Tunicamycin (TM) inhibited M-cell axon regeneration in wfs1b +/+ zebrafish larvae. Moreover, complementation of wfs1b at the single-cell level stimulated M-cell axon regeneration in the wfs1b −/− zebrafish larvae. Altogether, our results revealed that wfs1b promotes M-cell axon regeneration through the ER stress signal pathway and provide new evidence for a therapeutic target for WS and axon degeneration.

Abstract Ferroptosis is a cell death process caused by metabolic dysfunction with the feature of aberrant iron accumulation. Emerging studies have identified that ferroptosis is an important biological function involving in the tumorigenesis, and targeting ferroptosis could provide promising therapeutic targets for lung cancer. However, such therapeutic strategies show limited therapeutic effect owing to drug resistance and other unknown underlying mechanisms. In this study, lysine-specific demethylase 1 (LSD1/KDM1A) was found to be significantly upregulated in lung cancer cells and tissues. The patients with KDM1A downregulation displayed the good prognosis. Using gene set enrichment analysis (GSEA), we demonstrated that KDM1A-associated genes might participate in the regulation of cell ferroptosis and Myc signaling in lung cancer. Knockdown of KDM1A inhibited the level of c-Myc and increased the concentration of malondialdehyde (MDA) and irons in human lung cancer cells H1299 and A549. Downregulation of c-Myc could facilitate KDM1A knockdown-mediated ferroptosis. Our study has elucidated the effect of KDM1A/c-Myc regulatory axis in the ferroptosis resistance of lung cancer cells.