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Abstract The incidence of thyroid cancer (TC) is increasing annually worldwide, with a growing burden. This study aims to analyze temporal trends in the burden of TC by age and sex in China and globally from 1990 to 2021, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates, and to predict future trends. We obtained data on TC in China and globally from 1990 to 2021 from the Global Burden of Disease (GBD) database. Using the Joinpoint regression model, we calculated and analyzed the trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). Specifically, we estimated the annual percent change (APC), the average annual percent change (AAPC), and the corresponding 95% confidence intervals (95% CI) for each metric. Additionally, we conducted a decomposition analysis to investigate the impact of aging, population growth, and epidemiological factors on the incidence and mortality rates of TC. Furthermore, the autoregressive integrated moving average (ARIMA) model was employed to predict the burden of TC from 2022 to 2036. From 1990 to 2021, the ASIR for TC in China increased from 1.249 (95% uncertainty interval [UI]: 1.009–1.473) per 100,000 to 2.473 (95% UI: 1.993–3.088) per 100,000. Conversely, the ASMR decreased from 0.473 (95% UI: 0.403–0.550) per 100,000 to 0.387 (95% UI: 0.307–0.472) per 100,000. Both males and females demonstrated an upward trajectory in ASIR. However, while the ASMR for females decreased, that for males showed an overall increase despite a decline in the last decade. The age of peak onset for TC ranged from 30 to 79 years, whereas the age of peak mortality was between 50 and 89 years. The analysis using the AAPC indicates that the growth in the ASIR (AAPC = 2.242, 95% CI: 2.112–2.371) and ASPR (AAPC = 2.975, 95% CI: 2.833–3.117) in China exceeds the global rate. Furthermore, the reduction in ASMR (AAPC = -0.651, 95% CI: -0.824 - -0.479) and ASDR (AAPC = -0.590, 95% CI: -0.787 - -0.392) in China is also more pronounced than globally. Decomposition analysis indicates that the increasing TC burden in China is primarily driven by population aging, whereas globally, population growth plays a more significant role. Projections based on predictive models suggest that from 2021 to 2036, the ASIR for both China and the global population is expected to continue rising, while the ASMR is anticipated to decline further. The incidence rates of TC in China and globally have shown a continuous upward trend, which is expected to persist over the next 15 years. Additionally, although the number of male TC cases is relatively lower compared to females, the overall ASMR and ASDR for males have shown an upward trend, despite a slight decline in recent years. This highlights the need to enhance prevention, diagnosis, and treatment measures, and to develop differentiated screening and treatment strategies based on age and sex.

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.

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.

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.

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.

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.

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

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

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.

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

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.

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.

During the postnatal stages, skeletal muscle development undergoes a series of meticulously regulated alterations in gene expression. However, limited studies have employed chromatin accessibility to unravel the underlying molecular mechanisms governing muscle development in yak species. Therefore, we conducted an analysis of both gene expression levels and chromatin accessibility to comprehensively characterize the dynamic genome-wide chromatin accessibility during muscle growth and development in the Tianzhu white yak, thereby elucidating the features of accessible chromatin regions throughout this process. Initially, we compared the differences in chromatin accessibility between two groups and observed that calves exhibited higher levels of chromatin accessibility compared to adult cattle, particularly within ±2 kb of the transcription start site (TSS). In order to investigate the correlation between alterations in chromatin accessible regions and variations in gene expression levels, we employed a combination of ATAC-seq and RNA-seq techniques, leading to the identification of 18 central transcriptional factors (TFs) and 110 key genes with significant effects. Through further analysis, we successfully identified several TFs, including Sp1, YY1, MyoG, MEF2A and MEF2C, as well as a number of candidate genes (ANKRD2, ANKRD1, BTG2 and LMOD3) which may be closely associated with muscle growth and development. Moreover, we constructed an interactive network program encompassing hub TFs and key genes related to muscle growth and development. This innovative approach provided valuable insights into the molecular mechanism underlying skeletal muscle development in the postnatal stages of Tianzhu white yaks while also establishing a solid theoretical foundation for future research on yak muscle development.

Barrier-free metal-semiconductor interfaces are crucial to improve the performance of 2D electronic devices. Here, the authors report a strategy to induce local bonding distortion in 2D transition metal dichalcogenides via soft oxygen plasma treatments, leading to reduced contact resistance and improved transport properties.

The coal and coal-bearing measures in the Jungar Coalfield in Inner Mongolia are characterized by rare earth element (REE) enrichment. Combustion in coal-fired power plants can lead to further enrichment of REEs in coal ash, which serves as a new potential source for REE extraction and smelting. Further, investigating the content, modes of occurrence, and transformation behavior of REEs during coal combustion may help in better understanding REE differentiation during coal combustion and facilitate the development of economically feasible REE recovery technologies. Therefore, in this study, we analyzed coal ash from the Jungar Energy Gangue Power Plant in Inner Mongolia via inductively coupled plasma mass spectrometry, X-ray diffraction, and scanning electron microscopy combined with energy-dispersive spectroscopy. Our results showed that the REE content of the feed coal was 220 μg/g, slightly higher than the average for global coal. Additionally, fly ash had a higher REE content (898 μg/g) than bottom ash, and its rare earth oxide content was approximately 1152 μg/g, which meets the industrial requirements. Bottom and fly ashes contained similar minerals; however, their relative abundances were different. Specifically, mullite, quartz, calcite, and gypsum were slightly more abundant in fly ash than in bottom ash, whereas amorphous solids were slightly more abundant in bottom ash than in fly ash. Furthermore, fly ash, dominated by Si- and Al-rich minerals, was composed of irregular particles of different shapes and sizes. It also contained monazite and REE fluoro-oxides, which possibly originated from the feed coal and had mineral structures that remained unchanged during coal combustion. Thus, the REE fluoro-oxides possibly resulted from the conversion of bastnaesite in the feed coal during combustion and thereafter became attached to the edge of the Si–Al minerals in the fly ash.

Abstract Background Tibetan pigs have exhibited unique characteristics from low‐altitudes pigs and adapted well to the Qinghai‐Tibet Plateau. Objectives The current study was undertaken to investigate the hypoxic adaptation of heart in Tibetan pigs. Methods The hearts of Tibetan pigs and Landrace pigs raised at high or low altitudes were compared using 3D casting technology, scanning electron microscopy and real‐time quantitative PCR (qRT‐PCR). Results We found that the ratio of the major axis to the minor axis and the density of the heart were significantly higher in Tibetan pigs than in Landrace pigs (p

Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms of ferroptosis is intensively related to the development and treatment of multiple diseases, including musculoskeletal disorders. Moreover, in vitro and in vivo studies have shown the importance of oxidative stress in musculoskeletal conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Ferroptosis-derived clinical management of musculoskeletal diseases offers tremendous and attractive opportunities. Notably, ferroptosis agonists have been proven to enhance the sensitivity of osteosarcoma cells to conventional therapeutic strategies. In this review, we have mainly focused on the implications of ferroptosis regulation in the pathophysiology and therapeutic response of musculoskeletal disorders. Understanding roles of ferroptosis for controlling musculoskeletal diseases might provide directions for ferroptosis-driven therapies, which could be promising for the development of novel therapeutic strategies.

Schizophrenia (SCZ) and obsessive–compulsive disorder (OCD) are complex polygenic disorders with brain morphology abnormalities. The etiologies and relationship of both disorders remain elusive, and should be further investigated. Thus, induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) from an OCD patient, his mother with SCZ and his healthy father with reprograming method. All iPSCs were characterized to have normal karyotype and expression of pluripotency makers. These iPSCs will be a valuable model to elucidate the pathophysiological mechanisms and association of both diseases.

BackgroundCurrently, telomere length is known to reflect the replication potential and longevity of cells, and many studies have reported that telomere length is associated with age-related diseases and biological aging. Studies have also shown that vitamin C acts as an oxidant and free radical scavenger to protect cells from oxidative stress and telomere wear, thus achieving anti-aging effects. At present, there are few and incomplete studies on the relationship between vitamin C and telomere length, so this study aims to explore the relationship between vitamin C and telomere length.MethodsThis study used cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) database from 1999 to 2002, a total of 7,094 participants were selected from all races in the United States. Male participants accounted for 48.2% and female participants accounted for 51.8%. The correlation between vitamin C and telomere length was assessed using a multiple linear regression model, and the effect of dietary vitamin C on telomere length was obtained after adjusting for confounding factors such as age, gender, race, body mass index (BMI), and poverty income ratio (PIR).ResultsThis cross-sectional study showed that vitamin C was positively correlated with telomere length, with greater dietary vitamin C intake associated with longer telomeres (β = 0.03, 95% CI: 0.01–0.05, P = 0.003).ConclusionThis study shows that vitamin C intake is positively correlated with human telomere length, which is of guiding significance for our clinical guidance on people’s health care, but our study need to be confirmed by more in-depth and comprehensive other research results.

Abstract Background Diabetic wound healing remains a challenge because of its susceptibility to drug-resistant bacterial infection and its persistent proinflammatory state. Switching from proinflammatory M1 macrophages (Mφs) to proregenerative M2 dominant Mφs in a timely manner accelerates wound healing by coordinating inflammatory, proliferative, and angiogenic processes. Methods We propose a sequential photothermal antibacterial and subsequent M2 Mφ polarization strategy based on nanofibers (NFs) consisting of polydopamine (PDA) coating on curcumin (Cur) nanocrystals to treat Methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. Results The PDA/Cur NFs showed excellent photothermal conversion and antibacterial effects due to the PDA shell under laser irradiation, consequently resulting in the release of the inner Cur with the ability to promote cell proliferation and reinforce the M2 Mφ phenotype in vitro. In vivo studies on MRSA-infected diabetic wounds showed that PDA/Cur NFs not only inhibited MRSA infection but also accelerated the wound regeneration process. Furthermore, the NFs displayed the ability to promote the M2 Mφ phenotype with enhanced collagen deposition, angiogenesis, and cell proliferation. Conclusion Overall, the NFs displayed great potential as promising therapeutics for healing infected diabetic wounds through a sequential photothermal antibacterial and M2 Mφ polarization strategy. Graphical abstract

Abstract Background Yaks that inhabit the Tibetan Plateau exhibit striking phenotypic and physiological differences from cattle and have adapted well to the extreme conditions on the plateau. However, the mechanisms used by these animals for the regulation of gene expression at high altitude are not fully understood. Results Here, we sequenced nine lung transcriptomes of yaks at altitudes of 3400, 4200 and 5000 m, and low-altitude Zaosheng cattle, which is a closely related species, served as controls. The analysis identified 21,764 mRNAs, 1377 circRNAs and 1209 miRNAs. By comparing yaks and cattle, 4975 mRNAs, 252 circRNAs and 75 miRNAs were identified differentially expressed. By comparing yaks at different altitudes, we identified 756 mRNAs, 64 circRNAs and 83 miRNAs that were differentially expressed (fold change ≥2 and P-value

Abstract Alterations of mitogen-activated protein kinase kinase 1 (MEK1) are commonly associated with tumorigenesis, and MEK1 is thought to be a suitable targeted therapy for various cancers. However, abnormal MEK1 alterations and their relevant clinical implications are unknown. Our research comprehensively analyzed the MEK1 alteration spectrum and provided novel insight for targeted therapies. There were 7694 samples covering 32 types of cancer from The Cancer Genome Atlas (TCGA) database. They were used to conduct an integrative analysis of MEK1 expression, alterations, functional impacts and clinical significance. There was a dramatic difference in the alteration frequency and distribution and clinical implications in 32 types of cancer from the TCGA. Skin cutaneous melanoma (SKCM) has the most alterations and has therapeutic targets located in the protein kinase domain, and the growing expression of SKCM is positively related to patient prognosis. MEK1 expression in lung adenocarcinoma (LUAD), kidney renal papillary cell carcinoma (KIRP), esophageal carcinoma (ESCA) and liver hepatocellular carcinoma (LIHC) is decreased, which is associated with better prognosis, while MEK1 expression in thymoma (THYM), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), testicular germ cell tumors (TGCTs) and head and neck squamous cell carcinoma (HNSC) is increased, which is associated with better prognosis. Mesothelioma (MESO) has the second highest alterations but has no therapy targets. This study provided a great and detailed interpretation of MEK1 expression, alterations and clinical implications in 32 types of cancer and reminded us to fill the gap in MEK1 research from a new perspective.

IntroductionSerum vitamin D3 concentration is associated with the risk of insulin resistance. Zinc has also been reported to be associated with a lower risk of insulin resistance. In addition, zinc is an essential cofactor in the activation of vitamin D3. However, the effect of dietary zinc intake on the relationship between vitamin D3 and insulin resistance risk has not been fully studied. Therefore, we designed this cross-sectional study to assess the impact of changes in zinc intake on the relationship between vitamin D3 and insulin resistance risk.Study design and methodsThis study analyzed data from the national Health and Nutrition Examination Survey (NHANES) from 2005 to 2018, involving 9,545 participants. Participants were stratified by zinc intake category (low zinc intake

Alternative splicing (AS) allows the generation of multiple transcript variants from a single gene and affects biological processes by generating protein diversity in organisms. In total, 41,642 AS events corresponding to 9,924 genes were identified, and SE is the most abundant alternatively spliced type. The analysis of functional categories demonstrates that alternatively spliced differentially expressed genes (DEGs) were enriched in the MAPK signaling pathway and hypoxia-inducible factor 1 (HIF-1) signaling pathway. Proteoglycans in cancer between the normoxic (21% O2, TN and LN) and hypoxic (2% O2, TL and LL) groups, such as SLC2A1, HK1, HK2, ENO3, and PFKFB3, have the potential to rapidly proliferate alveolar type II epithelial (ATII) cells by increasing the intracellular levels of glucose and quickly divert to anabolic pathways by glycolysis intermediates under hypoxia. ACADL, EHHADH, and CPT1A undergo one or two AS types with different frequencies in ATII cells between TN and TL groups (excluding alternatively spliced DEGs shared between normoxic and hypoxic groups), and a constant supply of lipids might be obtained either from the circulation or de novo synthesis for better growth of ATII cells under hypoxia condition. MCM7 and MCM3 undergo different AS types between LN and LL groups (excluding alternatively spliced DEGs shared between normoxic and hypoxic groups), which may bind to the amino-terminal PER-SIM-ARNT domain and the carboxyl terminus of HIF-1α to maintain their stability. Overall, AS and expression levels of candidate mRNAs between Tibetan pigs and Landrace pigs revealed by RNA-seq suggest their potential involvement in the ATII cells grown under hypoxia conditions.

Understanding the signaling pathway regulatory mechanisms in type II alveolar epithelial (ATII) cells, the progenitor cells responsible for proliferating and regenerating type I alveolar epithelial (ATI) and ATII cells, in Tibetan pigs is beneficial for exploring methods of preventing and repairing cellular damage during hypoxia. We simulated a hypoxic environment (2% O2) for culture ATII cells of Tibetan pigs and Landrace pigs, with cells cultured under normoxic conditions (21% O2) as a control group, and performed integrated analysis of circular RNA (circRNA)–microRNA (miRNA)–messenger RNA (mRNA) regulatory axes by whole-transcriptome sequencing. Functional enrichment analysis indicated that the source genes of the differential expressed circRNAs (DEcircRNAs) were primarily involved in cell proliferation, cellular processes, and cell killing. A series of DEcircRNAs were derived from inhibitors of apoptosis proteins and led to a key autonomous effect as modulators of cell repair in Tibetan pigs under hypoxia. The significant higher expression of COL5A1 in TL groups may inhibited apoptosis of ATII cells in Tibetan pigs under lower oxygen concentration, and may lead their better survive in the hypoxia environment. In addition, a competing endogenous RNA (ceRNA) network of functional interactions was constructed that included novel_circ_000898-ssc-miR-199a-5p-CAV1 and novel_circ_000898-ssc-miR-378-BMP2, based on the node genes ssc-miR-199a-5p and ssc-miR-378, which may regulate multiple miRNAs and mRNAs that mediate endoplasmic reticulum (ER) stress-induced apoptosis and inflammation and attenuate hypoxia-induced injury in ATII cells under hypoxic conditions. These results broaden our knowledge of circRNAs, miRNAs, and mRNAs associated with hypoxia and provide new insights into the hypoxic response of ATII cells in Tibetan pigs.

Abstract Passivating undercoordinated ions is an effective way to reduce the defect densities at the surface and grain boundaries (GBs) of perovskite materials for enhanced photovoltaic performance and stability of perovskite solar cells (PSCs). Here, (BBF) complex is chosen as a multifunctional additive, which contains both C7H9N and BF3 groups working as Lewis base and Lewis acid, respectively, can bond with Pb2+/I− and FA+ on the surface and in the GBs in the perovskite film, affording passivation of both cation and anion defects. The synergistic effect of the C7H9N and BF3 complex slows the crystallization during the perovskite film deposition to improve the crystalline quality, which reduces the trap density and the recombination in the perovskite film to suppress nonradiative recombination loss and minimizes moisture permeation to improve the stability of the perovskite material. Meanwhile, such an additive improves the energy-level alignment between the valence band of the perovskite and the highest occupied molecular orbital of the hole-transporting material, Spiro-OMeTAD. Consequently, our work achieves power conversion efficiency of 23.24%, accompanied by enhanced stability under ambient conditions and light illumination and opens a new avenue for improving the performance of PSCs through the use of a multifunctional complex.

Chronic diabetic wounds affect the quality of life of patients, resulting in significant social and economic burdens on both individuals and the health care system. Although treatment methods for chronic diabetic wounds have been explored, there remains a lack of effective treatment strategies; therefore, alternative strategies must be explored. Recently, the abnormal expression of non-coding RNA in diabetic wounds has received widespread attention since it is an important factor in the development of diabetic wounds. This article reviews the regulatory role of three common non-coding RNAs (microRNA [miRNA], long non-coding RNA [lncRNA], and circular RNA [circRNA]) in diabetic wounds and discusses the diagnosis, treatment potential, and challenges of non-coding RNA in diabetic wounds. This article provides insights into new strategies for diabetic wound diagnosis and treatment at the genetic and molecular levels.

Lipoic acid synthetase (LIAS) has been demonstrated to play a crucial role in the progression of cancer. Exploring the underlying mechanisms and biological functions of LIAS could have potential therapeutic guidance for cancer treatment. Our study has explored the expression levels and prognostic values of LIAS in pan-cancer through several bioinformatics platforms, including TIMER2.0, Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2.0), and Human Protein Atlas (HPA). We found that a high LIAS expression was related to the good prognosis in patients with kidney renal clear cell carcinoma (KIRC), rectum adenocarcinoma (READ), breast cancer, and ovarian cancer. Inversely, a high LIAS expression showed unfavorable prognosis in lung cancer patients. In addition, the genetic alteration, methylation levels, and immune analysis of LIAS in pan-cancer have been evaluated. To elucidate the underlying molecular mechanism of LIAS, we conduct the single-cell sequencing to implicate that LIAS expression was related to hypoxia, angiogenesis, and DNA repair. Thus, these comprehensive pan-cancer analyses have conveyed that LIAS could be potentially significant in the progression of various cancers. Moreover, the LIAS expression could predict the efficacy of immunotherapy in cancer patients.

Abstract Phase patterning in polymorphic two‐dimensional (2D) materials offers diverse properties that extend beyond what their pristine structures can achieve. If precisely controllable, phase transitions can bring exciting new applications for nanometer‐scale devices and ultra‐large‐scale integrations. Here, the focused electron beam is capable of triggering the phase transition from the semiconducting T’’ phase to metallic T’ and T phases in 2D rhenium disulfide (ReS2) and rhenium diselenide (ReSe2) monolayers, rendering ultra‐precise phase patterning technique even in sub‐nanometer scale is found. Based on knock‐on effects and strain analysis, the phase transition mechanism on the created atomic vacancies and the introduced substantial in‐plane compressive strain in 2D layers are clarified. This in situ high‐resolution scanning transmission electron microscopy (STEM) and in situ electrical characterizations agree well with the density functional theory (DFT) calculation results for the atomic structures, electronic properties, and phase transition mechanisms. Grain boundary engineering and electrical contact engineering in 2D are thus developed based on this patterning technique. The patterning method exhibits great potential in ultra‐precise electron beam lithography as a scalable top‐down manufacturing method for future atomic‐scale devices.

Structural and physiochemical properties contribute to the biological adaptation of deep-sea animals to their harsh living environment but have hardly been investigated systematically. In the present study, we for the first time applied various material characterization techniques including transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier-transform infrared (FT-IR) spectroscopy to investigate the shell microstructures and chemical composition of a deep-sea limpet Eulepetopsis crystallina collected from the Tiancheng hydrothermal vent field at a depth of around 2,700 m in the Southwest Indian Ocean. Analyses of shell microstructural morphology and diffraction patterns of E. crystallina explicitly revealed the layered structures, exfoliation characteristics, and crystallographic orientation of each layer’s unit cell which was tilted at a small angle sequentially. In comparison with ordinary shallow-water limpet Cellana toreuma shells, E. crystallina shells showed a unique chemical composition and contained pure calcite of calcium carbonate polymorph and the trace of phosphate originated from regional phosphatic sediments of the Southwest Indian Ocean. The further microscopic analyses indicated that the shell of the deep-sea limpet E. crystallina features integrated and untruncated layer structures with a compressed width, possibly owning to the ultra-high hydrostatic pressure, which confirmed the effects of the living environment on the shell microstructure of deep-sea animals.

Pyroptosis is a cell death pathway that plays a significant role in lung adenocarcinoma (LUAD). Also, studies regarding the correlation between the expression of long non-coding RNAs (lncRNAs) and the mechanism of LUAD has aroused concern around the world. The purpose of this paper is to explore the underlying relationship of differentially expressed lncRNAs and pyroptosis-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression were applied to construct a prognostic risk score model from the TCGA database. A pyroptosis-related five-lncRNA signature (CRNDE, HHLA3, MIR193BHG, LINC00941, LINC01843) was considered to be correlated to the prognosis and immune response of LUAD patients. In addition, the cytological experiments revealed that aberrantly expressed HHLA3 displayed a proliferation promotion role in LUAD cells A549 and H460. Next, the forest and nomogram plots have shown this lncRNA signature could be served as an independent prognostic factor for LUAD. The ROC curves further identified the prognostic value of the five-lncRNA signature. The infiltration of immune cells, such as T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated and M0 macrophages were greatly different between the high-risk group and the low-risk group. It implicated that the signature is significantly effective in immunotherapy of LUAD patients. This study has supplied a novel pyroptosis-related lncRNA signature and provided a predictive model for prognosis and immune response of LUAD patients.

ObjectiveDepression and schizophrenia (SCH) were accompanied by an acute phase response (APR) that was implicated in the alterations in total protein (TP), albumin, and globulin levels. The aims of this study are to examine serum TP, albumin, globulin levels, depressive symptoms, and their associations in patients with SCH.MethodsWe recruited 34 patients with SCH and 136 healthy controls (HCs) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Psychiatric symptoms and biomarkers were assessed using the Chinese version of the Positive and Negative Syndrome Scale (PANSS) as well as the bromocresol green and biuret methods.ResultsSerum TP (F = 46.11, p < 0.001, η2 = 0.19), albumin (F = 31.69, p < 0.001, η2 = 0.14), and globulin (F = 12.48, p < 0.001, η2 = 0.06) levels were lower in patients than those in HCs after adjusting for covariates. Serum TP (r = −0.37, p = 0.03) and albumin (r = −0.37, p = 0.03) levels were negatively correlated with depressive score in patients. Stepwise multivariate regression analysis showed the negative associations of depressive score with serum TP (β = −0.13, t = −2.92, p = 0.007), albumin (β = −0.23, t = −2.36, p = 0.03), and globulin (β = −0.16, t = −2.40, p = 0.02) levels in patients. Serum TP, albumin, and globulin levels exhibited the accuracies of 87.1, 70.0, and 69.4% in discriminating between patients and HCs (area under the curve [AUC]: 0.78, 0.68, and 0.77; sensitivity/specificity: 52.9%/95.6%, 55.9%/73.5%, and 76.5%/67.6%).ConclusionOur data suggested that decreased serum TP, albumin, and globulin should be regarded as the SCH risk factors and were implicated in the depressive severity of SCH, which further provided the support for the hypothesis that SCH and depression were accompanied by the abnormal inflammatory cytokines with the APR.

B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.

Background: The different pharmacological effects of drugs in different people can be explained by the polymorphisms of drug metabolism-related genes. Emerging studies have realized the importance of drug metabolism-related genes in the treatment and prognosis of cancers, including ovarian cancer (OV). In this study, using comprehensive bioinformatics and western blot, we identified that the drug metabolism-related gene, ADH1B, was significantly down-regulated in OV cells and tissues. The patients with a high level of ADH1B presented a good prognosis. We also found a negative correlation between ADH1B expression and the activity of chemotherapeutic agents, such as cyclophosphamide. In addition, positive correlations were observed between ADH1B expression and multiple immune checkpoints, including LAG3 and HAVCR2. The immune infiltration analysis further indicated that aberrantly expressed ADH1B might have important roles in regulating the infiltration of macrophages and neutrophils in OV tissues. Then, the co-expression analysis was conducted and the top three enriched KEGG pathways were spliceosome, RNA transport, and DNA replication. In conclusion, the drug metabolism-related gene ADH1B and its interactive network play an essential role in the immune regulation and therapeutic response and maybe identified as promising therapeutic targets for OV patients.

Abstract Background As China’s aging trend intensifies and the proportion of empty nests increases, the health-related quality of life of the elderly is the focus of social attention. Previous studies focused on the quality of life of the elderly, rather than empty nesters, and lacked the discussion of the mechanism of influencing factors. Thus, this study aimed to explore the influencing factors of the quality of life (QOL) and interaction mechanisms among empty nesters in Shanxi Province, China, so as to provide practical reference for improving the QOL of empty nesters. Methods A total of 4901 empty nesters in Shanxi Province, China, were selected using multi-stage random cluster sampling method in this cross-sectional study. The quality of life was assessed with the Short Form 36 Health Survey (SF-36). Multiple linear regression analysis (stepwise) was performed to examine the factor associated with QOL. Structural equation model (SEM) approach was conducted to test the direct and indirect association between QOL influencing factors with QOL. Results The average QOL score of empty nesters was 63.34 (SD = 17.23). The multiple linear regression revealed that gender, age, education, monthly income, drinking status, exercise frequency, physical examination frequency, attention to daily nutritional health, relationship with a spouse and relationship with children were significant predictors of the empty nester’s QOL (P

Abstract Due to their long-term colonization of and widespread distribution in plateau environments, yaks can serve as an ideal natural animal model for the adaptive evolution of other plateau species, including humans. Some studies reported that the lung and heart are two key organs that show adaptive transcriptional changes in response to high altitudes, and most of the genes that show differential expression in lung tissue across different altitudes display nonlinear regulation. To explore the molecular mechanisms that are activated in yak lung tissue in response to hypoxia, the mRNAs, lncRNAs and miRNAs of lung tissue from 9 yaks living at three different altitudes (3400 m, 4200 m and 5000 m), with three repetitions per altitude, were sequenced. Two Zaosheng cattle from 1500 m were selected as low-altitude control. A total of 21,764 mRNAs, 14,168 lncRNAs and 1209 miRNAs (305 known and 904 novel miRNAs) were identified. In a comparison of yaks and cattle, 4975 mRNAs, 3326 lncRNAs and 75 miRNAs were differentially expressed. A total of 756 mRNAs, 346 lncRNAs and 83 miRNAs were found to be differentially expressed among yaks living at three different altitudes (fold change ≥ 2 and P-value

Abstracts Background In China, more and more older people have encountered a situation called “empty nest.” Meanwhile, the health status of empty-nest older adults is an increasing public health concern. This research aims to examine the effectiveness of Self-Mutual-Group (SMG) model in improving quality of life of the empty-nest older adults to provide a scientific evidence for improving their health. Methods A prospective intervention study was conducted among empty-nest older adults in Taiyuan, Shanxi. Multi-stage stratified random cluster sampling was employed to selected participants. A total of 396 empty nesters were enrolled as participants, of which 204 and 192 were in the intervention and control group, respectively. The intervention group received a seven-month SMG-based intervention. A participant’s quality of life was measured at the baseline and seven months after using the Short Form 36-Item Health Survey (SF-36). Results No significant difference was found between the intervention and control groups in terms of participant characteristics at baseline (P > 0.05). After the intervention, participants’ scores on Mental Component Summary (MCS), Physical Component Summary (PCS), role emotional (RE), vitality (VT), social function (SF), mental health (MH) and general health (GH) increased significantly in the intervention group. Additionally, these scores differed significantly from those in the control group (P

Inspired by the flapping wings of seagulls during flight, a new low-cost, magnet-free, bistable piezoelectric energy harvester is proposed to obtain energy from low-frequency vibration and convert it into electrical energy and reduce fatigue damage caused by stress concentration. In order to optimize the power generation efficiency of this energy harvesting, finite element analysis and experimental tests were carried out. The results of finite element analysis and experimental results are in good agreement, and the superior performance in improving stress concentration of the energy harvester compared to the previous parabolic (bow-shaped) one using bistable technology was quantitatively analyzed using finite element simulation, with a maximum stress reduction of 32.34%. The experimental results showed that under optimal operating conditions, the maximum open-circuit voltage of the harvester was 11.5 V, and the maximum output power was 73 μW. These results indicate that this is a promising strategy, which provides a reference for collecting vibrational energy in low-frequency environments.

Objective Tibetan pigs, an excellent species unique to China, face serious threats, which in turn affects the development and utilization of the outstanding advantages of plateau hypoxia adaptability and reduces their genetic diversity. Therefore, a discussion of measures to conserve this genetic resource is necessary. The method, based on genetic diversity, genetic divergence and total genetic contribution rate of population, reflects the priority conservation order and varies depending on the three different purposes of conservation. Methods We analyzed mitochondrial DNA control region (D-loop) variation in 1,201 individuals from nine Tibetan pig populations across five provinces and downloaded 564 mtDNA D-loop sequences from three indigenous pig breeds in Qinghai, Sichuan, and Yunnan Provinces distributed near the Tibetan pigs. Results We analyzed three different aspects: Changdu Tibetan pigs have the highest genetic diversity, and from the perspective of genetic diversity, the priority conservation is Changdu Tibetan pigs. Hezuo Tibetan pigs have the highest genetic contribution, so the priority conservation is Hezuo Tibetan pigs in the genetic contribution aspect. Rkaze Tibetan pigs were severely affected by indigenous pig breeds, so if considering from the perspective of introgression, the priority conservation is Rkaze Tibetan pigs. Conclusion This study evaluated genetic diversity and comprehensively assessed conservation priority from three different aspects in nine Tibetan pig populations.