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Abstract Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms.

Background Under the background of new medical science, the deep integration of information technology and medical education is encouraged to train first-class medical talents to serve the construction of healthy China.Currently, empathy training in doctor-patient communication mainly consists of simulated communication and group discussion, with less reliance on artificial intelligence technology for learning. Objective To develop a system for teaching and evaluating doctor-patient communication empathy language. This system will be used in course teaching to pave the way for future doctor-patient communication empathy teaching methods. Carry out teaching applications to enhance the communication and empathy language expression skills of medical students and doctors, and gather feedback to optimize and improve the system. Methods Between September 2021 and February 2022, the research group focus on utilizing iFlytek speech recognition technology and the empathy semantic recognition algorithm. A system called the "Doctor-patient Communication Virtual Simulation Teaching and Evaluation System of empathic language" was developed using 10 typical cases of doctor-patient communication, demonstrations of empathic language, a semantic database of empathic language, empathic language skills, and an overall scoring standard.A total of 950 students from Nanjing Medical University, including 515 undergraduates, 102 medical doctoral students, and 333 clinicians participating in doctor-patient communication courses or training, were selected as the research subjects from March to May 2022. Based on this system, the Doctor-patient Communication Skills Course (2 class hours) teaching experiment was conducted at Nanjing Medical University. A self-designed questionnaire was used to gather information on the subjects' understanding of empathetic language connotations, their improved empathetic language skills, their perception of system ease of use, and their perception of how the system integrates into the rationality of teaching. NVivo software was used to analyze the subjects' feedback, comments, and suggestions. Results Following the implementation of the system, there were statistically significant differences in the mastery of empathic language connotation, the degree of enhancement of empathic language ability, the degree of convenience of the system, and the degree of integration of the system into teaching rationality among undergraduate students, clinicians, and medical doctoral students (P

Abstract Chiral organic-inorganic hybrid perovskites offer a promising platform for developing non-linear chiro-optical applications and chiral-induced spin selectivity. Here, we show that achiral hybrid perovskites that have highly ordered ferroelectric domains with orthogonal polarization exhibit planar chirality, as manifested by second harmonic generation with strong circular dichroism. Interestingly, the handedness of the second harmonic generation circular dichroism response can be alternatingly switched between orthogonally polarized domains and domain walls. To correlate the origin of planar chirality in these domains, atom-resolved atomic force microscopy is used to reveal distinct arrangements of atomic rows in these ferroelectric crystals that indicate planar symmetry breaking. Remarkably, a large SHG anisotropy factor of 0.41 is measured at the domain wall. Additionally, spatially resolved two-photon photoluminescence excitation measurement provide evidence of larger Rashba spin-splitting in these chiral ferroelectric domains compared to domain-free areas. Our discoveries of domain-dependent planar chirality and spin texture hold great promise for advancement of domain-specific chiro-optical applications.

Abstract Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficult isolation of neoantigen-specific T cells limits the clinical application of ACT. Here, we propose a method to prepare neoantigen-reactive T cells (NRT) for ACT following immunization with a tumor lysate-loaded dendritic cell (DC) vaccine. We show that the DC vaccine not only induces a neoantigen-reactive immune response in lung cancer-bearing mice in vivo, but also facilitate NRT cell preparation in vitro. Adoptive transfer of the NRTs as combinatorial therapy into DC vaccine-immunized, LL/2 tumor-bearing mice allows infiltration of the infused NRTs, as well as the enrichment of neoantigen reactive, non-ACT/NRT T cells into the tumor microenvironment with the function of these neoantigen-reactive T-cell receptors validated in vitro. In summary, we propose a method for preparing NRTs that increases ACT efficacy and paves the way to the design of personalized immunotherapies.

Abstract Objectives This study was designed to compare the clinical data of vesicoureteral reflux (VUR) in children with and without an allergic constitution. Methods The clinical data of patients hospitalized with VUR due to a urinary tract infection (UTI) between September 1, 2019, and December 31, 2020, were retrospectively analyzed. The patients were divided into two groups: an anallergic constitution group (AC group) and a non-allergic constitution (NAC group), and their UTIs and VUR were compared at baseline and during the follow-up period. Results (1) Between September 1, 2019, and December 31, 2020, a total of 284 children were hospitalized at Shengjing Hospital Affiliated to China Medical University due to a UTI. These children included 37 cases with primary VUR and 247 cases without VUR (including 59 cases of non-VUR urinary malformation). The proportion of children with an allergic constitution was significantly higher in the patients with VUR than it was in those without VUR or with other urinary malformations (72.97% vs. 48.18% vs. 50.85%, P = 0.005, 0.032). (2) At baseline, the levels of immunoglobulin and immunoglobulin E in the AC group were significantly higher than those in the NAC group (P = 0.042, 0.017). (3) During the follow-up period, the number of recurrent UTI cases in the AC group was significantly higher than that in the NAC group (0.70 ± 0.91 vs. 0.10 ± 0.32, P= 0.005). The difference between the two groups in the VUR remission rate was not statistically significant (40% vs. 50%, P = 0.563). (4) During the follow-up period, the differences in the remission rates of recurrent UTIs and VUR in the two groups were not statistically significant. Conclusions The incidence of having an allergic constitution is high in patients with VUR, and patients with an allergic constitution present with a higher frequency of recurrent UTIs.

Abstract Food‐sourced proteins have been shown to have ameliorative effects on ulcerative colitis (UC), and studies have identified potential anti‐inflammatory activity of silkworm pupa proteins. Here, we identified and screened two novel protein‐derived peptides, PDLGLF (PD‐6) and GTEGGFPF (GT‐8), from Bombyx mori using UPLC–MS/MS and bioinformatics analysis. These peptides can serve as effective experimental drugs for colitis by modulating the gut microbiota. Treatment with peptides PD‐6 and GT‐8 inhibited colitis inflammation in UC mice, improved oxidative stress levels, and maintained intestinal epithelial barrier function. Peptides PD‐6 and GT‐8 also altered the diversity and composition of the gut microbiota in UC mice and increased the concentration of short‐chain fatty acids. In conclusion, these findings reveal the potential of the naturally derived bioactive peptides PD‐6 and GT‐8 in controlling intestinal inflammation and underscore the potential of PD‐6 and GT‐8 as promising candidates for the prevention and improvement of UC‐related inflammatory diseases.

The collaborative learning approach as a universal teaching strategy is widely used in online learning. It is proven that the group leader has an important impact on group collaborative knowledge construction in online collaborative learning (OCL). However, limited research is available on how leadership styles influence a group. Universal teaching strategy is widely used in online learning. This study, the authors adopted lag sequential analysis, epistemic network analysis, and social network analysis to explore the influence of divergent and convergent leadership styles on cognitive engagement in OCL groups. Compared with convergent leadership, divergent leadership strengthened online collaborative cognitive engagement through significant organizer and manager roles, triggered high-quality cognitive behavior transformation within the group, and promoted the balanced development of learners' cognitive structure.

The underlying mechanisms between family income and mental health of children merit further investigation. Based on the family stress model and the psychological factors model, we proposed that familial factors (parental depression and parenting) and the individual factor (child self-esteem) would mediate the relationship between family income and child depression concurrently. Data were obtained from a nationally representative longitudinal survey (i.e., the China Family Panel Studies), involving 1,283 families (2,732 parents and 1,384 children). The age of the children ranged from 4 to 15 years (M[subscript age] = 8.04, SD = 1.87) at baseline. Path analysis showed that the effect of family income (in 2010, T1) on child depression (in 2014, T3) was mediated by parental depression (in 2012, T2), parental bonding (in 2012 or 2014, T2 or T3), and child self-esteem (in 2012 or 2014, T2 or T3), in a parallel rather than sequential manner. The findings indicate that health policies and psychosocial interventions that simultaneously improve parental depression, parenting techniques, and child self-esteem would be an effective approach to alleviate the impact of family income on child depression.

Abstract As analogies to magnetic skyrmions, polar skyrmions in ferroelectric superlattices and multilayers have garnered widespread attention for their non-trivial topology and novel properties like negative capacitance and nonlinear optical effect. So far, they have only been theoretically predicted to be able to assemble ordered hexagonal skyrmion lattices (SkLs) in ferroelectric thin films. Here, based on phase-field simulations, we report the critical roles of flexoelectricity playing in the stabilization and transformation of polar SkLs. Different polar SkL patterns can emerge in the ferroelectric thin films, including tetragonal-SkL, and hexagonal-SkLs with diverse orientations, as summarized by phase diagrams. These emergent SkL states are attributed to the material anisotropy modified by the flexoelectric effect. Interestingly, we further found that the hexagonal-SkLs can be rotated by applying strain gradient or in-plane electric field to the films. Moreover, a nonreciprocal bending response of tetragonal-SkL is also induced by the flexoelectric effect. Our results provide useful guidelines for the implementation of polar skyrmion lattices in experiments.

Abstract Objectives To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC’s etiology and further support the development of therapeutic strategies. Methods A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results UC patients demonstrated significantly higher native T1 (p

Abstract Ovarian function suppression (OFS) benefits young women with hormone receptor (HR)-positive breast cancer but they are at risk for ovarian function breakthrough. We assessed endocrine effects of gonadotropin-releasing hormone agonist (GnRHa) treatment in a prospective cohort of patients aged ≤ 40 years with HR-positive breast cancer. Plasma estradiol (E2), estrone, and follicule-stimulating hormone (FSH) levels were measured from blood samples drawn 1 and 4 years after diagnosis. Patient characteristics, invasive breast cancer-free survival (iBCFS), and overall survival (OS) were compared between those with and without E2 > 2.72 pg/mL during GnRHa treatment. Among eligible patients, 54.7% (46/84) and 60% (15/25) had E2 > 2.72 pg/mL at 1 and 4 years, respectively. Factors associated with E2 > 2.72 pg/mL at 1 year were no prior chemotherapy (P = 0.045) and tamoxifen use (P = 0.009). After a median follow-up of 7 years, among patients with stage I-III breast cancer (N = 74), iBCFS events were seen in 6 (8.1%) with E2 > 2.72 pg/mL and 5 (6.8%) with E2 ≤ 2.72 pg/mL (P = 0.893). Among patients with de novo metastatic breast cancer (N = 12), 6 (50%) with E2 > 2.72 pg/mL and 3 (25%) with E2 ≤ 2.72 pg/mL died during follow-up (P = 0.052). Larger studies exploring the clinical implications of incomplete E2 suppression by GnRHa are needed to ensure optimal OFS treatment strategies are being employed for this population.

Abstract Objectives Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is extensively employed for the identification of filamentous fungi on MALDI Biotyper (Bruker Daltonics) and Vitek MS (biomerieux), but the performance of fungi identification on new EXS2600 (Zybio) is still unknow. Our study aims to evaluate the new EXS2600 system's (Zybio) ability to rapidly identify filamentous fungi and determine its effect on turnaround time (TAT) in our laboratory. Methods We tested 117 filamentous fungi using two pretreatment methods: the formic acid sandwich (FA-sandwich) and a commercial mold extraction kit (MEK, Zybio). All isolates were confirmed via sequence analysis. Laboratory data were extracted from our laboratory information system over two 9-month periods: pre-EXS (April to December 2022) and post-EXS (April to December 2023), respectively. Results The total correct identification (at the species, genus, or complex/group level) rate of fungi was high, FA-sandwich (95.73%, 112/117), followed by MEK (94.02%, 110/117). Excluding 6 isolates not in the database, species-level identification accuracy was 92.79% (103/111) for FA-sandwich and 91.89% (102/111) for MEK; genus-level accuracy was 97.29% (108/111) and 96.39% (107/111), respectively. Both methods attained a 100% correct identification rate for Aspergillus, Lichtheimia, Rhizopus Mucor and Talaromyces species, and were able to differentiate between Fusarium verticillioides and Fusarium proliferatum within the Fusarium fujikuroi species complex. Notably, high confidence was observed in the species-level identification of uncommon fungi such as Trichothecium roseum and Geotrichum candidum. The TAT for all positive cultures decreased from pre EXS2600 to post (108.379 VS 102.438, P

Objective: This study aimed to analyze the factors influencing artificial intelligence (AI) diagnostic system detection of pulmonary nodules on computed tomography (CT) scans, using a chest simulation phantom experiment with simulated lung nodules. Methods: A Toshiba (Canon) 64-slice spiral CT scanner was used. The phantom was scanned and images were reconstructed under varying scanning parameters (dose, reconstruction algorithm, and layer thickness) and non-scanning parameters (nodule size, density, and chest location). Subsequently, the AI diagnostic system performed pulmonary nodule detection on the images. Results: (1) No statistically significant difference was observed in the true positive rate of pulmonary nodules detected at different scanning doses. However, the low-dose mode produced a higher number of false positives. (2) Comparisons across the three iterative reconstruction algorithms revealed no statistically significant difference in the true positive rate of detected pulmonary nodules. However, the Strong group exhibited a higher true positive rate and a higher number of false positives. (3) The true positive rate of lung nodules detected in thin images was significantly higher than in thick images. (4) The true positive rate of pulmonary nodules located in the paramediastinum was significantly higher in the subpleural and lung parenchyma. (5) The true positive rate of nodules ≥8 mm was significantly higher than that of nodules ≤5 mm. (6) No statistically significant difference was observed in the true positive rate when detecting nodules with differing densities. Conclusion: Both CT scanning parameters (dose, reconstruction algorithm, and layer thickness) and non-scanning parameters (nodule size, density, and chest location) can influence the detection of pulmonary nodules by AI systems.

Background: Anhedonia is a deficit of dynamic reward process, and a large proportion of schizophrenia patients continue to experience anhedonia even during the stable phase. However, few studies have examined the multiple aspects of performance in reward processing in patients with stable schizophrenia and evidence suggests that physical and cognitive effort may involve different neural mechanisms. Methods: Parallel measures of effort-based expenditure for reward tasks (EEfRT) and self-report questionnaires of pleasure were applied in 61 patients with stable schizophrenia (SSZ) and 46 healthy controls (HCs), and percentages of hard task choices (HTC%) were used to assess motivation in reward processing. Negative symptoms, neurocognitive and social function were evaluated in SSZ patients, and associations with performance in reward tasks were explored. Results: SSZ patients reported more severe consummatory and anticipatory anhedonia and social anhedonia. HTC% in reward tasks of SSZ patients were significantly lower than that of HCs, especially in cognitive-effort tasks. HTC% in cognitive tasks were correlated with motivation and pleasure dimension of negative symptoms, whereas HTC% in physical tasks were associated with expression dimension. Anticipatory anhedonia and negative symptoms were correlated with Personal and Social Performance Scale (PSP) scores. Conclusion: Patients with stable schizophrenia have social anhedonia, physically consummatory and anticipatory anhedonia and reduced reward motivation. They are less willing to make cognitive effort than physical effort for reward. The different associations of physical and cognitive effort with negative symptoms indicate physical and cognitive effort may represent disparate neuropsychological processes. Anticipatory anhedonia is closely related to social functioning.

IntroductionThe composition and subsets of skin cells continuously change in a dynamic manner. However, the specific microcosmic alterations of human photoaged skin, independent of chronologic aging, remain unclear and have been infrequently analyzed. This study aimed to evaluate the biological processes and mechanisms underlying cell-subgroup alterations in skin photoaging.MethodsWe utilized single-cell sequencing and biological analysis from a single case to investigate the effects of photoaging. Skin punch biopsies were taken from sun-exposed forearm skin and unexposed buttock skin from the same individual for comparative analysis.ResultsOur analysis identified 25 cell clusters and 12 skin cell types, revealing significant changes in unique gene expressions between the sun-exposed and unexposed skin samples. A comparison of cell numbers within each cluster revealed 9 dominant cell clusters in sun-exposed skin and 16 dominant cell clusters in unexposed skin. Enrichment analysis indicated that PD-L1 expression and the PD-1 checkpoint pathway were more prominent in sun-exposed skin, while MAPK, TNF-alpha, TGF-beta, and apoptosis pathways were more enriched in hair follicle cells of sun-exposed skin.DiscussionThis study reveals changes in cell components in photoaged skin from a single case and provides novel insights into cellular subpopulations and pathology during repeated UVA-induced skin damage. These findings enhance our understanding of the complex interplay between different cells in photoaged skin and offer potential targets for preventing human skin photoaging and UV-induced skin cancers.

ObjectiveThe objective of this study was to investigate the prevalence of overactive bladder (OAB) and its risk factors related to allergies among children in Northeastern China.MethodsA community survey on OAB was conducted in Northeast China from 1 April 2022 to 30 April 2022. The survey targeted children aged 5–14 years and utilized questionnaires. A total of 1,394 children were enrolled, and their parents were requested to fill out a questionnaire to provide basic information about the children. This encompassed details regarding the presence or absence of urgent urination unrelated to urinary tract infection, urinary tract infection, allergic rhinitis, asthma or cough variant asthma, atopic dermatitis, anaphylactic conjunctivitis, urticaria, constipation, and attention deficit hyperactivity disorder (ADHD). The prevalence of OAB was calculated. The chi-squared test was used to analyze OAB-related factors, which were subsequently included in the logistic regression model for multi-factor analysis.ResultsThe overall OAB prevalence was 10.7% (120 of 1,121), including 47 mild cases (39.2%), 71 moderate cases (59.1%), and 2 severe cases (1.7%). OAB prevalence decreased with age (p

Abstract Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.

Abstract Objectives To explore the value of radiomic features derived from pericoronary adipose tissue (PCAT) obtained by coronary computed tomography angiography for prediction of coronary rapid plaque progression (RPP). Methods A total of 1233 patients from two centers were included in this multicenter retrospective study. The participants were divided into training, internal validation, and external validation cohorts. Conventional plaque characteristics and radiomic features of PCAT were extracted and analyzed. Random Forest was used to construct five models. Model 1: clinical model. Model 2: plaque characteristics model. Model 3: PCAT radiomics model. Model 4: clinical + radiomics model. Model 5: plaque characteristics + radiomics model. The evaluation of the models encompassed identification accuracy, calibration precision, and clinical applicability. Delong’ test was employed to compare the area under the curve (AUC) of different models. Results Seven radiomic features, including two shape features, three first-order features, and two textural features, were selected to build the PCAT radiomics model. In contrast to the clinical model and plaque characteristics model, the PCAT radiomics model (AUC 0.85 for training, 0.84 for internal validation, and 0.81 for external validation; p 0.05). Conclusion Radiomic feature analysis derived from PCAT significantly improves the prediction of RPP as compared to clinical and plaque characteristics. Radiomic analysis of PCAT may improve monitoring RPP over time. Critical relevance statement Our findings demonstrate PCAT radiomics model exhibited good performance in the prediction of RPP, with potential clinical value. Key Points Rapid plaque progression may be predictable with radiomics from pericoronary adipose tissue. Fibrous plaque volume, diameter stenosis, and fat attenuation index were identified as risk factors for predicting rapid plaque progression. Radiomics features of pericoronary adipose tissue can improve the predictive ability of rapid plaque progression. Graphical Abstract

With the impact of global climate change and the urbanization process, the risk of urban flooding has increased rapidly, especially in developing countries. Real-time monitoring and prediction of flooding extent and drainage system are the foundation of effective urban flood emergency management. Therefore, this paper presents a rapid nowcasting prediction method of urban flooding based on data-driven and real-time monitoring. The proposed method firstly adopts a small number of monitoring points to deduce the urban global real-time water level based on a machine learning algorithm. Then, a data-driven method is developed to achieve dynamic urban flooding nowcasting prediction with real-time monitoring data and high-accuracy precipitation prediction. The results show that the average MAE and RMSE of the urban flooding and conduit system in the deduction method for water level are 0.101 and 0.144, 0.124 and 0.162, respectively, while the flooding depth deduction is more stable compared to the conduit system by probabilistic statistical analysis. Moreover, the urban flooding nowcasting method can accurately predict the flooding depth, and the R2 are as high as 0.973 and 0.962 of testing. The urban flooding nowcasting prediction method provides technical support for emergency flood risk management. HIGHLIGHTS A rapid nowcasting prediction method of urban flood based on data-driven and real-time monitoring.; The deduction model accurately estimates the global water depth.; The proposed urban flooding nowcasting model was observed to outperform the traditional machine learning model to predict.;

Abstract Our preliminary investigation has identified the potential of serum fucosylated extracellular vesicles (EVs) miR-4732-5p in the early diagnosis of lung adenocarcinoma (LUAD) by a fucose-captured strategy utilizing lentil lectin (LCA)-magnetic beads and subsequent screening of high throughput sequencing and validation of real-time quantitative polymerase chain reaction (RT-qPCR). Considering the relatively complicated procedure, expensive equipment, and stringent laboratory condition, we have constructed an electrochemical biosensor assay for the detection of miR-4732-5p. miR-4732-5p is extremely low in serum, down to the fM level, so it needs to be detected by highly sensitive electrochemical methods based on the Mg2+-dependent DNAzyme splitting nucleic acid lock (NAL) cycle and hybridization chain reaction (HCR) signal amplification. In this study, signal amplification is achieved through the dual amplification reactions using NAL cycle in combination with HCR. In addition, hybridized DNA strands bind to a large number of methylene blue (MB) molecules to enhance signaling. Based on the above strategy, we further enhance our signal amplification strategies to improve detection sensitivity and accuracy. The implementation of this assay proceeded as follows: initially, miR-4732-5p was combined with NAL, and then Mg2+-dependent DNAzyme splitted NAL to release auxiliary DNA (S1) strands, which were subsequently captured by the immobilized capture probe DNA (C1) strands on the electrode surface. Following this, abundant quantities of DNA1 (H1) and DNA2 (H2) tandems were generated by HCR, and S1 strands then hybridized with the H1 and H2 tandems through base complementary pairing. Finally, MB was bonded to the H1 and H2 tandems through π–π stacking interaction, leading to the generation of a signal current upon the detection of a potential capable of inducing a redox change of MB by the electrode. Furthermore, we evaluated the performance of our developed electrochemical biosensor assay. The results demonstrated that our assay is a reliable approach, characterized by its high sensitivity (with a detection limit of 2.6 × 10−17 M), excellent specificity, good accuracy, reproducibility, and stability. Additionally, it is cost-effective, requires simple operation, and is portable, making it suitable for the detection of serum fucosylated extracellular vesicles miR-4732-5p. Ultimately, this development has the potential to enhance the diagnostic efficiency for patients with early-stage LUAD.

Abstract The emergence of magnetic transition metal dichalcogenides has significantly advanced the development of valleytronics due to the spontaneous breaking of time-reversal symmetry and space-inversion symmetry. However, the lack of regulation methods has prevented researchers from exploring their potential applications. Herein, we propose to use strain engineering to control the spin-valley coupling in the sliding ferroelectric bilayer 2H-VX2 (X = S, Se, Te). Four multiferroic states are constructed by combining the sliding ferroelectricity and antiferromagnetism in the R-stacking bilayer VX2, where the spin and valley polarizations are coupled together from the layer-dependent spin-polarized band structures. By applying a small external strain or pressure on the out-of-plane van der Waals direction, we predicted that there is an antiferromagnetic to magnetic transition in the bilayer VX2, leading to the interesting spin-polarized and chiral circularly polarized radiation at K+ and K- valleys, similar to those found in the magnetic monolayer. To comprehend the coupling between various degrees of freedom in these multiferroic systems, we have developed an effective k·p model. This model unveils a linear relationship between the electric polarization generated by interlayer sliding and the energy difference of the valence band maximum at K+ and K- valleys. Thus, providing an alternate method to measure the electric polarization in the sliding ferroelectrics. Based on the strong coupling between the strain, spin-valley, and electric polarization, it is likely to use the strain to control the interesting emerging properties of 2H-VX2 such as the anomalous valley Hall effect.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). Methods We analyzed data from 4,198 participants in the 2017–2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. Results Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. Conclusions Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.

Abstract Background Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. Methods A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. Results We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. Conclusions NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.

Abstract Background Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality. Methods The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis. Results Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI −5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI −3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p

Abstract The chemical transformations of methane (CH4) and carbon dioxide (CO2) greenhouse gases typically have high energy barriers. Here we present an approach of strategic coupling of CH4 oxidation and CO2 reduction in a switched microbial process governed by redox cycling of iron minerals under temperate conditions. The presence of iron minerals leads to an obvious enhancement of carbon fixation, with the minerals acting as the electron acceptor for CH4 oxidation and the electron donor for CO2 reduction, facilitated by changes in the mineral structure. The electron flow between the two functionally active microbial consortia is tracked through electrochemistry, and the energy metabolism in these consortia is predicted at the genetic level. This study offers a promising strategy for the removal of CH4 and CO2 in the natural environment and proposes an engineering technique for the utilization of major greenhouse gases.

Abstract Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

Humor, a higher-order social cognitive process unique to humans, is commonly impaired in patients with chronic schizophrenia. However, humor processing and its association with the clinical characteristics in the early stage of the illness remain unknown. In this study, we investigated humor processing and its relationship with clinical features in patients with first-episode schizophrenia (FES). We recruited 45 patients with FES and 44 healthy controls matched for age, sex, and education level. The participants completed the Picture Humor Processing Task (HPT-p) and Video Humor Processing Task (HPT-v), which evaluated humor comprehension and appreciation, and a questionnaire assessing their humor styles. Clinical participants also completed clinical and social functioning measurements. Signal detection theory analysis was used to calculate the d' and β values, which represent the detection of humor signals in the comprehension phase and inner criteria of the humor appreciation phase, respectively. In the HPT-p, patients with FES showed a higher false alarm rate (p = 0.048) than healthy controls, whereas the hitting rate, signal recognition ability (d' value), and intrinsic evaluation criterion (β value) were comparable between the two participants groups. In the HPT-v, patients with FES showed lower within-group coherence in the funniness rating (p = 0.023) than healthy controls. In addition, the false alarm rate in the HPT-p and negative symptoms effectively predicted social functioning in patients with FES (R2 = 0.681, p

The essence of fluid phase transition is the jump of physical properties distinctly induced by shock waves in the hard-sphere model. Due to the strong impact of the wave, the internal freedoms of molecules are stimulated, releasing tremendous energy that commonly triggers the phase transition. Conversely, typical thermal and dynamic jumps can be described by the Rankine–Hugoniot conditions based on the Euler equation. In the theoretical simulation, the initial density and rotational freedoms of molecules are directly regarded as the primary factors to affect processes of phase transition. However, the influence of vibrational freedom in molecules has not been discussed yet. As the increasing temperature can gradually excite the affection of vibrational freedom, it is unwise to assume that the temperature element is constant in the theory. What would be a suitable model that accurately reflects the relationship between temperature and affection from vibrational freedom? The non-limited model has been courageously attempted with the temperature range from T0 to 6T0 (T0 is unperturbed temperature). We have found that the vibrational freedom can have a great effect on properties during phase transition processes.

Abstract Two‐dimensional (2D) materials with free of dangling bonds have the potential to serve as ideal channel materials for the next generation of field‐effect transistors (FETs) due to their atomic‐thin and excellent electronic properties. However, the performance of 2D materials‐based FETs is still dictated by the interface between electrodes/dielectrics and 2D materials. Several technical challenges such as improving device stability, reducing contact resistance, and advancing mobility need to be overcome. Herein, we focus on the effects of atomic‐scale interface engineering on the contact resistance and dielectric layer for 2D FETs. Universal strategies we consider to achieve ohmic contact and develop high‐quality, defect‐free dielectric layers are provided. Furthermore, advancing the performance of 2D materials‐based FETs and binding to silicon substrates are briefly analyzed.

BackgroundLEOPARD syndrome (LS) is a rare genetic disorder presenting various clinical manifestations from childhood, complicating its diagnosis. In this study, we aim to refine the imaging presentation of LS and emphasize the importance of multimodality imaging in enhancing diagnostic accuracy and preventing serious cardiovascular events.CaseA 41-year-old woman was admitted to hospital with a suspected apical tumor detected by a transthoracic echocardiogram (TTE), which was later identified as apical myocardial hypertrophy through cardiac magnetic resonance imaging (CMR). She had abnormal electrocardiograms from the age of 2 years and freckles around the age of 4 years. In recent years, she has been experiencing exertional dyspnea. Supplemental coronary computer tomography angiography (CCTA) revealed diffuse coronary dilatation. Both multimodality imaging and clinical manifestations led to a suspicion of LS, which was confirmed by subsequent genetic testing. The patient declined further treatment. A 3-month follow-up CMR showed no significant change in the lesion.ConclusionThis report elucidates the diagnostic transition from an initial suspicion of an apical tumor by TTE to a definitive diagnosis of left ventricular apical hypertrophy by CMR in a 41-year-old woman with LS. It underscores the value of multimodality imaging (TTE, CCTA, CMR) in unraveling unusual cardiac manifestations in rare genetic disorders such as LS.

With the popularization of electronic products, visual fatigue is inevitably frequent. The causes of visual fatigue are varied, but from the perspective of physiological mechanisms, it is mainly closely related to retinal function or structural damage, especially the light source from various mobile devices and office equipments nowadays, which induces oxidative stress damage in the retina and exacerbates the degree of visual fatigue, resulting in the inability to use the eyes for a long period of time, pain in the eyes and periorbital area, blurred vision, dry eyes, tearing, and other discomforts. Food ingredients derived from natural plants have greater application in relieving visual fatigue. Therefore, this paper presents a detailed compilation of six plants that are widely used for their visual fatigue-relieving function, in the hope of providing more raw material choices for the development of products with visual fatigue-relieving functions in the future.

Abstract Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions.

Abstract Background Both sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis. Methods The data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis. Results 2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS’s overall 30-day attributable mortality was 11.9% (95% CI 7.5–16.3%, p

Abstract Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.

Abstract Background Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features, and PCOS is associated with infertility. PH domain Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) has been shown to regulate AKT. The aim of present study is to investigate the role of PHLPP1 in PCOS. Methods The expression levels of PHLPP1 in dihydrotestosterone (DHT)-treated human ovarian granular KGN cells were determined by qRT-PCR and Western blot. PHLPP1 was silenced or overexpressed using lentivirus. Cell proliferation was detected by CCK-8. Apoptosis and ROS generation were analyzed by flow cytometry. Glycolysis was analyzed by measuring extracellular acidification rate (ECAR). Results DHT treatment suppressed proliferation, promoted apoptosis, enhanced ROS, and inhibited glycolysis in KGN cells. PHLPP1 silencing alleviated the DHT-induced suppression of proliferation and glycolysis, and promotion of apoptosis and ROS in KGN cells. PHLPP1 regulated cell proliferation and glycolysis in human KGN cells via the AKT signaling pathway. Conclusions Our results showed that PHLPP1 mediates the proliferation and aerobic glycolysis activity of human ovarian granular cells through regulating AKT signaling.

Thermal errors affect machining accuracy in high-speed precision machining. The variability of machine tool operating conditions poses a challenge to the modeling of thermal errors. In this paper, a thermal error model based on transfer temperature feature fusion is proposed. Firstly, the temperature information fusion features are built as inputs to the model, which is based on a self-attention mechanism to assign weights to the temperature information and fuse the features. Secondly, an improved direct normalization-based adaptive matrix approach is proposed, updating the background matrix using an autoencoder and reconstructing the adaptive matrix to realize domain self-adaptation. In addition, for the improved adaptive matrix, a criterion for determining whether the working conditions are transferrable to each other is proposed. The proposed method shows high prediction accuracy while ensuring training efficiency. Finally, thermal error experiments are performed on a VCM850 CNC machine tool.

The purpose of this experiment was to investigate the effects of Hot Water Extract of Juncao-substrate Ganoderma lucidum Residue (HWE-JGLR) on the immune function and intestinal health of yellow-feather broilers. In an animal feeding experiment, 288 male yellow-feather broilers (1 day old) were randomly allocated to four treatment groups with six replicates of 12 birds each. The control (CON) group was fed a basal diet. HJ-1, HJ-2, and HJ-3 were fed a basal diet supplemented with 0.25%, 0.50%, and 1.00% HWE-JGLR, respectively. The feeding trial lasted for 63 d. The results showed increased ADFI (p = 0.033) and ADG (p = 0.045) of broilers in HJ-3, compared with the CON group. Moreover, higher contents of serum IL-4 and IL-10 and gene expression of IL-4 and IL-10 in jejunum mucosa and lower contents of serum IL-1β and gene expression of IL-1β in jejunum mucosa in HJ-3 were observed (p < 0.05). Additionally, the jejunal mucosal gene expression of Claudin-1 and ZO-1 in HJ-2 and HJ-3 was higher than that in the CON group (p < 0.05). As for the microbial community, compared with the CON group, the ACE index, Shannon index, and Shannoneven index of cecal microorganisms in HJ-2 and HJ-3 were elevated (p < 0.05). PCoA analysis showed that the cecal microbial structure of broilers in HJ-2 and HJ-3 was different from the CON group (p < 0.05). In contrast with the CON group, the broilers in HJ-2 and HJ-3 possessed more abundant Desulfobacterota at the phylum level and unclassified Lachnospiraceae, norank Clostridia vadinBB60 group and Blautia spp. at the genus level, while Turicibacter spp. and Romboutsia spp. were less (p < 0.05). In conclusion, dietary supplementation with HWE-JGLR can improve growth performance, enhance body immunity and intestinal development, and maintain the cecum microflora balance of yellow-feather broilers.