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This study investigated the effects and evaluation indicators of air conditioning temperature control for summer storage of wheat in large flat storage silos. In the second and third years after wheat was stored in Silo No. 19 of Luliang Jituan Pingyuan Grain Storage Depot, the air conditioning was set to 25 ℃, and the conditions were compared with those in the control Silo No. 17. The temperatures at the surface, second layer, third layer, and fourth layer of the grain bulk were reduced by 3.4 ℃, 2 ℃, 1.5 ℃, and 1.35 ℃, respectively. The moisture content, relative humidity (RH), and wet-bulb temperature were reduced by 3.85 g/kg and 1.5 g/kg, 3.55% and 3.85%, and 3.65 ℃ and 2.2 ℃ for the surface grain and the entire grain bulk, respectively. No significant differences were observed in the thermal characteristic parameters of the grain bulks in the two silos. Compared with Silo No. 17, the peak viscosity, breakdown, and final viscosity of wheat in Silo No. 19 slightly decreased, and the texture parameters, such as hardness, adhesiveness, springiness, gumminess, and chewiness, also slightly decreased. Principal component analysis identified the gelatinization end temperature and peak height measured by DSC, the gelatinization temperature and peak time measured by RVA, and texture parameters such as hardness, gumminess, and chewiness as preferred indicators for evaluating the summer storage of wheat under temperature control. In-depth scanning electron microscopy analysis revealed that the cross-sections of wheat kernels in Silo No. 19 were more compact with uniformly distributed micropores, and the longitudinal sections had fewer small starch granules between large starch granules compared to those in Silo No. 17. The results indicated that operating air conditioning in large flat storage silos during summer helped reduce the dry-bulb temperature of the grain bulk and the air characteristics in the interstitial space between kernels. It also slowed the growth and development of storage pests, and maintained the microstructure of wheat kernels, which could delay quality deterioration.

Abstract We developed an automated high-throughput Smart-seq3 (HT Smart-seq3) workflow that integrates best practices and an optimized protocol to enhance efficiency, scalability, and method reproducibility. This workflow consistently produces high-quality data with high cell capture efficiency and gene detection sensitivity. In a rigorous comparison with the 10X platform using human primary CD4 + T-cells, HT Smart-seq3 demonstrated higher cell capture efficiency, greater gene detection sensitivity, and lower dropout rates. Additionally, when sufficiently scaled, HT Smart-seq3 achieved a comparable resolution of cellular heterogeneity to 10X. Notably, through T-cell receptor (TCR) reconstruction, HT Smart-seq3 identified a greater number of productive alpha and beta chain pairs without the need for additional primer design to amplify full-length V(D)J segments, enabling more comprehensive TCR profiling across a broader range of species. Taken together, HT Smart-seq3 overcomes key technical challenges, offering distinct advantages that position it as a promising solution for the characterization of single-cell transcriptomes and immune repertoires, particularly well-suited for low-input, low-RNA content samples.

Abstract Invasion and metastasis are the main reasons for the poor prognosis of patients with cervical cancer(CC). SYK is closely related to tumor development. However, the functions of its two isoforms, SYK (L) or SYK (S), are not fully understood to date. In this study, we investigated their biologic functions and possible prognostic values in CC. qRT-PCR was performed to detect the expression of SYK and two variant isoforms in cervical cancer tissues and cells. The association of SYK(L) and SYK(S) with Clinical pathological parameters were evaluated. The migration and invasion was detected by scratch assay and transwell. Western blot was conducted to measure the changes of epithelial mesenchymal transition (EMT)-related markers and PI3K/AKT signaling pathway proteins in cervical cancer cells. LY294002 (inhibitor of PI3K/AKT pathway) and IGF-1 (activator of PI3K/AKT pathway) were applied to evaluate the contribution of PI3K/AKT signaling pathway in cervical cancer cells. The expression of SYK(S) in cervical cancer tissues was significantly higher than that of SYK(L). SYK(L) and SYK(S) were correlated with muscular infiltration, SYK(L) high expression had a better prognosis, whereas SYK(S) high expression predicted a worse disease outcome. Cox multivariate regression analysis demonstrated that SYK(L) expression was an independent prognostic factor. SYK(L) significantly inhibited the proliferation, migration and invasion, while SYK(S) showed the opposite effects. LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Abstract FAR-RED IMPAIRED RESPONSE 1 (FAR1) is a class of transposase-derived transcription factors that play a very important role in the initiation of the photosensitive pigment A (phyA) signaling pathway. Despite their importance, the understanding of the function of FAR1 genes in quinoa is still limited, especially regarding how they affect the spike sprouting response. Quinoa has gained global attention in recent years for its health benefits and potential for sustainable agriculture. In our study, the CqFAR1 gene set in quinoa was characterized using HMMER (PF03101) and BLAST analyses, and 87 genes were identified. The 87 CqFAR1 genes were systematically classified into five groups that showed a high degree of conservation in gene structure and motif composition. Tissue expression profiles of the CqFAR1 gene indicated that the CqFAR1 gene plays a key role throughout the growth and development of quinoa, especially at mid (leaf) and end (spike) stages. By RT-qPCR analysis, we observed significant differences in the expression of the CqFAR1 gene at different developmental stages. Notably, the CqFAR1 gene showed significant expression enhancement at the early stage of quinoa spike sprouting. The results are useful for understanding the role of the CqFAR1 gene in quinoa growth and development and provide theoretical support for quinoa breeding.

Abstract Objective State anxiety and trait anxiety are differentially mapped in brain function. However, the genetic and neurobiological basis of anxiety-related functional changes remain largely unknown. Methods Participants aged 18–30 from the community underwent resting-state fMRI and were assessed with the State-Trait Anxiety Inventory. Using a general linear regression model, we analyzed the effects of state and trait anxiety, as well as their sum and difference (delta), on regional homogeneity (ReHo) in cortical areas. ReHo patterns denote the spatial distribution of ReHo associated with anxiety scores. We further explored the spatial correlations between ReHo patterns and neuromaps, including gene expression, neurotransmitter receptor density, myelination, and functional connectivity gradients, to elucidate the genetic and molecular substrates of these ReHo patterns. Results Our findings demonstrated robust spatial correlations between whole-brain ReHo patterns for state and trait anxiety, with trait anxiety and the delta value exhibiting stronger network correlations, notably in the dorsal attention, salience, visual, and sensorimotor networks. Genes highly correlated with ReHo patterns exhibited unique spatiotemporal expression patterns, involvement in oxidative stress, metabolism, and response to stimuli, and were expressed in specific cell types. Furthermore, ReHo patterns significantly correlated with neuromaps of neurotransmitter receptor density, myelination, and functional connectivity gradients. Conclusions The ReHo patterns associated with anxiety may be driven by genetic and neurobiological traits. Our findings contribute to a deeper understanding of the pathogenesis of anxiety from a genetic and molecular perspective.

Abstract Background Circular RNAs (circRNAs) function as essential regulatory elements with pivotal roles in various biological processes. However, their expression profiles and functional regulation during the differentiation of goat myoblasts have not been thoroughly explored. This study conducts an analysis of circRNA expression profiles during the proliferation phase (cultured in growth medium, GM) and differentiation phase (cultured in differentiation medium, DM1/DM5) of skeletal muscle satellite cells (MuSCs) in goats. Results A total of 2,094 circRNAs were identified, among which 84 were differentially expressed as determined by pairwise comparisons across three distinct groups. Validation of the expression levels of six randomly selected circRNAs was performed using reverse transcription PCR (RT-PCR) and quantitative RT-PCR (qRT-PCR), with confirmation of their back-splicing junction sites. Enrichment analysis of the host genes associated with differentially expressed circRNAs (DEcircRNAs) indicated significant involvement in biological processes such as muscle contraction, muscle hypertrophy, and muscle tissue development. Additionally, these host genes were implicated in key signaling pathways, including Hippo, TGF-beta, and MAPK pathways. Subsequently, employing Cytoscape, we developed a circRNA-miRNA interaction network to elucidate the complex regulatory mechanisms underlying goat muscle development, encompassing 21 circRNAs and 47 miRNAs. Functional assays demonstrated that circTGFβ2 enhances myogenic differentiation in goats, potentially through a miRNA sponge mechanism. Conclusion In conclusion, we identified the genome-wide expression profiles of circRNAs in goat MuSCs during both proliferation and differentiation phases, and established that circTGFβ2 plays a role in the regulation of myogenesis. This study offers a significant resource for the advanced exploration of the biological functions and mechanisms of circRNAs in the myogenesis of goats.

Abstract Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P

Abstract The long-term health impacts of niacin are still debated, and the association between dietary niacin and mortality risk in populations hasn’t been extensively explored. This study included 26,746 US adults aged 20 years or older from the National Health and Nutrition Examination Survey 2003–2018, with a median follow-up of 9.17 years. During this period, there were 3,551 all-cause deaths, including 1,096 cardiovascular deaths. Cox models were used to compare hazard ratios (HRs) for mortality among participants grouped into different dietary niacin intake quartiles. Participants with the highest dietary niacin intake had a lower risk of all-cause mortality (HR 0.74, 95%CI 0.63–0.86) compared to those in the lowest intake quartile. For cardiovascular mortality, the HR was 0.73 (95%CI 0.57–0.95) in the highest niacin intake quartile. A dose-response relationship was revealed between dietary niacin intake and mortality by restricted cubic spline. Subgroup analysis showed a significant interaction between dietary niacin intake and diabetes concerning all-cause mortality (P = 0.046). In this population-based cohort study, higher dietary niacin intake correlates with lower risk of all-cause and cardiovascular mortality among US adults. The influence of niacin intake on all-cause mortality appears to be more significant in non-diabetic individuals compared to those with diabetes.

Abstract Background Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer. Methods This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness. Results The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit. Conclusions This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer.

Abstract Phosphorylation of Ser32 and Ser36 controls the degradation of IκBα is the conserved cascade mechanisms of immune core signaling pathway, NF-κB pathway in metazoans, but it’s response to abiotic stress and the presence of novel phosphorylation mechanisms in other species remain unclear. Herein, we reported a novel heat-induced phosphorylation site (Ser74) at oysters’ major IκBα, which independently regulated ubiquitination-proteasome degradation without the requirement of phosphorylation at S32 and S36. And this site was phosphorylated by ERK/MAPK pathway, which then promoted REL nuclear translocation to activate cell survival related genes to defend heat-stress. The MAPK-NF-κB cascade exhibited divergent thermal responses and adaptation patterns between two congeneric oyster species with differential habitat temperatures, indicating its involvement in shaping temperature adaptation. This study demonstrated that the existence of complex and unique phosphorylation-mediated signaling transduction mechanism in marine invertebrates, and expanded our understanding of the evolution and function of established classical pathway crosstalk mechanisms.

Abstract Background This study aims to explore the accuracy of Convolutional Neural Network (CNN) models in predicting malignancy in Dynamic Contrast-Enhanced Breast Magnetic Resonance Imaging (DCE-BMRI). Methods A total of 273 benign lesions (benign group) and 274 malignant lesions (malignant group) were collected and randomly divided into a training set (246 benign and 245 malignant lesions) and a testing set (28 benign and 28 malignant lesions) in a 9:1 ratio. An additional 53 lesions from 53 patients were designated as the validation set. Five models—VGG16, VGG19, DenseNet201, ResNet50, and MobileNetV2—were evaluated. Model performance was assessed using accuracy (Ac) in the training and testing sets, and precision (Pr), recall (Rc), F1 score (F1), and area under the receiver operating characteristic curve (AUC) in the validation set. Results The accuracy of VGG19 on the test set (0.96) is higher than that of VGG16 (0.91), DenseNet201 (0.91), ResNet50 (0.67), and MobileNetV2 (0.88). For the validation set, VGG19 achieved higher performance metrics (Pr 0.75, Rc 0.76, F1 0.73, AUC 0.76) compared to the other models, specifically VGG16 (Pr 0.73, Rc 0.75, F1 0.70, AUC 0.73), DenseNet201 (Pr 0.71, Rc 0.74, F1 0.69, AUC 0.71), ResNet50 (Pr 0.65, Rc 0.68, F1 0.60, AUC 0.65), and MobileNetV2 (Pr 0.73, Rc 0.75, F1 0.71, AUC 0.73). S4 model achieved higher performance metrics (Pr 0.89, Rc 0.88, F1 0.87, AUC 0.89) compared to the other four fine-tuned models, specifically S1 (Pr 0.75, Rc 0.76, F1 0.74, AUC 0.75), S2 (Pr 0.77, Rc 0.79, F1 0.75, AUC 0.77), S3 (Pr 0.76, Rc 0.76, F1 0.73, AUC 0.75), and S5 (Pr 0.77, Rc 0.79, F1 0.75, AUC 0.77). Additionally, S4 model showed the lowest loss value in the testing set. Notably, the AUC of S4 for BI-RADS 3 was 0.90 and for BI-RADS 4 was 0.86, both significantly higher than the 0.65 AUC for BI-RADS 5. Conclusions The S4 model we propose has demonstrated superior performance in predicting the likelihood of malignancy in DCE-BMRI, making it a promising candidate for clinical application in patients with breast diseases. However, further validation is essential, highlighting the need for additional data to confirm its efficacy.

Abstract Medical image registration is essential and a key step in many advanced medical image tasks. In recent years, medical image registration has been applied to many clinical diagnoses, but large deformation registration is still a challenge. Deep learning‐based methods typically have higher accuracy but do not involve spatial transformation, which ignores some desirable properties, including topology preservation and the invertibility of transformation, for medical imaging studies. On the other hand, diffeomorphic registration methods achieve a differentiable spatial transformation, which guarantees topology preservation and invertibility of transformation, but registration accuracy is low. Therefore, a diffeomorphic deformation registration with CNN is proposed, based on a symmetric architecture, simultaneously estimating forward and inverse deformation fields. CNN with Efficient Channel Attention is used to better capture the spatial relationship. Deformation fields are optimized explicitly and implicitly to enhance the invertibility of transformations. An extensive experimental evaluation is performed using two 3D datasets. The proposed method is compared with different state‐of‐the‐art methods. The experimental results show excellent registration accuracy while better guaranteeing the diffeomorphic transformation.

Abstract One of the primary challenges faced by generation companies (GenCos), which operate multiple generation units within the electricity market, is the determination of the optimal bid price for these units to maximize profit. This paper proposes a novel approach to ascertain the optimal bid price direction for GenCos by leveraging the gradient vector of the profit function within the constraints of the electricity market. First, the Jacobian matrix of unit profits is computed using the electricity market structural decomposition method. This matrix highlights how the profit of generation units is affected by market input parameters, including the bid prices of the units. Then, the gradient vector of the GenCos' profit function and the optimal bid price direction are derived from the Jacobian matrix. The methodology is applied to a 24‐bus IEEE network, with results validated against those from a simulation method to confirm the efficacy of the proposed approach. The simulation results show that the highest and lowest profit changes with a step increase of 0.1$/MWh are observed for GenCo 4 and GenCo 6 with values of 60.28 and 2.20 $/h, respectively. The proposed approach can be effective in the changes of bid direction of the units of a GenCo to achieve the highest possible profit.

Abstract Background The global population’s aging has led to an increasing demand for long-term care (LTC), especially in developing countries like China. Comprehensive assessment of LTC service demands by including the time and cost analysis is crucial to inform the planning and financing of LTC resources, yet such research is lacking in China. Our research team has developed a quantitative index system of the medical and nursing services needs of older adults (QISMNSNE) based on the framework of Time-Driven Activity-Based Costing (TDABC), providing a valuable tool for measuring LTC service needs. This study aimed to assess the LTC service needs of older adults in China and the factors associated with such needs. Methods A cross-sectional study was conducted in Changsha City, Hunan Province, China, from June 2021 to December 2022. A stratified multistage cluster sampling method was used to recruit 1,270 older adults from five nursing homes and three communities/streets in three regions of Changsha City. The LTC service needs were assessed by calculating the service time required from caregivers, nurses, and doctors and the total service time (min/d) using the QISMNSNE. Participants’ disability, activities of daily living (ADLs), mental status and social involvement (MSSI), and sensory and communication (SC) were assessed using standard scales. Generalized linear regression models were used to analyze factors associated with LTC service needs. Results The participants had an average age of 76.41 ± 8.38 years, with 43.7% being female. The median service time required from caregivers, nurses, and doctors was 53.34 min/d, 3.66 min/d, and 0.33 min/d, respectively, and the total service time was 83.31 min/d. The generalized linear regression model identified the following factors that were associated with higher total service time: aged 75–84 years, living in nursing homes, income over 5000 per month, ADLs, MSSI (9 ~ 40), SC, and having 3 ~ 4 kinds of geriatric comorbidity (P

Abstract Background No standard has been established for the clinical target volume (CTV) margins of lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) receiving chemotherapy or chemotherapy combined with immunotherapy followed by radiotherapy. This study aimed to discuss the CTV range of NSCLC after chemotherapy or chemotherapy combined with immunotherapy by observing the microscopic extent of tumor spread beyond the LN capsule. Methods We retrospectively analyzed the data of 240 patients with stage II and III NSCLC who underwent surgery without neoadjuvant therapy, with neoadjuvant chemotherapy (NAC), or with NAC combined with immunotherapy (NACI). We measured the maximal distance of extracapsular extension (ECE) using a digital microscope, analyzed the correlation between clinicopathological features and ECE distance, and determined the CTV margins of metastatic LN under different treatment methods. Results The ECE distance differed significantly among the three groups (p

Abstract Cysteine-aspartic proteases (caspases) are critical drivers of apoptosis, exhibiting expansion and domain shuffling in mollusks. However, the functions and regulatory mechanisms of these caspases remain unclear. In this study, we identified a group of Caspase-3/6/7 in Bivalvia and Gastropoda with a long inter-subunit linker (IL) that inhibits cleavage activation. Within this region, we found that conserved phosphorylation at Thr260 in oysters, mediated by the PI3K-AKT pathway, suppresses heat-induced activation. This mechanism is involved in divergent temperature adaptation between two allopatric congeneric oyster species, the relatively cold-adapted Crassostrea gigas and warm-adapted Crassostrea angulata. Our study elucidates the role of these effector caspase members and their long IL in bivalves, revealing that the PI3K-AKT pathway phosphorylates Thr260 on CgCASP3/6/7’s linker to inhibit heat-induced activation. These findings provide insights into the evolution and function of apoptotic regulatory mechanisms in bivalves.

Abstract Background Phosphorus (P) plays a vital role in plant growth. The pqqC and phoD genes serve as molecular markers for inorganic and organic P breakdown, respectively. However, the understanding of how P-mobilizing bacteria in soil respond to long-term fertilization and rhizobium application is limited. Herein, soil that had been treated with fertilizer and rhizobium for 10 years was collected to investigate the characteristics of P-mobilizing bacterial communities. Five treatments were included: no fertilization (CK), phosphorus fertilizer (P), urea + potassium fertilizer (NK), NPK, and PK + Bradyrhizobium japonicum 5821 (PK + R). Results The soybean nodule dry weight was highest in the P treatment (1.93 g), while the soybean yield peaked in the PK + R treatment (3025.33 kg ha− 1). The abundance of the pqqC gene increased in the rhizosphere soil at the flowering-podding stage and in the bulk soil at the maturity stage under the P treatment, while its abundance increased in the bulk soil at the flowering-podding stage and in the rhizosphere soil at the maturity stage under the PK + R treatment. The abundance of the phoD gene was enhanced in the bulk soil at the flowering-podding stage under the PK + R treatment. The Shannon and Ace indexes of pqqC- and phoD-harboring bacteria were higher in the rhizosphere soil at maturity under the PK + R treatment compared to other treatments. Furthermore, a comprehensive analysis of the neutral community model and co-occurrence pattern demonstrated that the application of P fertilizer alone led to an increase in the distribution and dynamic movement of pqqC-harboring bacteria, but resulted in a decrease in complexity of network structure. On the other hand, rhizobium inoculation enhanced the distribution and dynamic movement of phoD-harboring bacteria, as well as the stability and complexity of the network structure. Pseudomonas and Nitrobacter, as well as Steptomyces, Stella, and Nonomuraea, may be crucial genera regulating the composition and function of pqqC- and phoD-harboring communities, respectively. Conclusions These findings affirm the crucial role of fertilization and rhizobium inoculation in regulating pqqC- and phoD-harboring bacterial communities, and highlight the significance of long-term phosphate-only fertilization and rhizobium inoculation in enhancing dissolved inorganic phosphorus and mineralized organophosphorus, respectively.

The discovery that contracting skeletal muscle generates reactive oxygen species (ROS) was first reported over 40 years ago. The prevailing view in the 1980s was that exercise-induced ROS production promotes oxidation of proteins and lipids resulting in muscle damage. However, a paradigm shift occurred in the 1990s as growing research revealed that ROS are signaling molecules, capable of activating transcriptional activators/coactivators and promoting exercise-induced muscle adaptation. Growing evidence supports the notion that reduction-oxidation (redox) signaling pathways play an important role in the muscle remodeling that occurs in response to endurance exercise training. This review examines the specific role that redox signaling plays in this endurance exercise-induced skeletal muscle adaptation. We begin with a discussion of the primary sites of ROS production in contracting muscle fibers followed by a summary of the antioxidant enzymes involved in the regulation of ROS levels in the cell. We then discuss which redox-sensitive signaling pathways promote endurance exercise-induced muscle adaptation and debate the strength of the evidence supporting the notion that redox signaling plays an essential role in muscle adaptation to endurance exercise training. In hopes of stimulating future research, we highlight several important unanswered questions in this field.

The excellent energy storage performances of dielectric materials, a high energy density and efficiency, the stability in a wide range of temperature, frequency and cycling time, are surely desirable for the energy storage devices. A trade-off relationship between polarization and breakdown strength, however, limits the enhancement of energy storage properties of dielectric materials. To effectively boost the energy density and efficiency of dielectric capacitors, by inserting a BiFeO3 layer into the BaTiO3 film in present case, the symmetric BaTiO3/BiFeO3/BaTiO3 tri-layer film heterostructure with antiferroelectric-like characteristics was constructed based on the dual-interlayer coupling effect, what's more, its antiferroelectric-like characteristics will evolve with electric field. Such the tunable polarization behavior endows it with an enhanced maximum polarization but a reduced remnant one, a delayed saturation of polarization and a high breakdown strength, which are synergistically accountable for a large energy density (Wrec∼109 J/cm3) and a high efficiency (η∼82.6%), together with the good thermal (TR∼200 °C, ΔWrec

Abstract An acellular bovine bone matrix modified to release Magnesium ions (Mg2+) (ABBM-Mg) was prepared and evaluated for its potential in osteogenesis and mandibular defect repair. Mg2+ was incorporated into ABBM using an ion exchange method. The microstructure and mechanical properties of both ABBM and ABBM-Mg were analyzed using SEM and a biomechanical testing machine. Cytocompatibility, cell adhesion, and osteogenic differentiation were assessed using various methods including CCK-8, Live/Dead staining, SEM, ALP staining, and qPCR analysis in MC3T3-E1 cells. Additionally, a mandibular defect model in rats was established. The bone defect repair outcomes were evaluated using Micro-CT, histological HE staining, and Masson staining. The study showed that mineralization containing magnesium was redeposited on the surface of the three-dimensional porous ABBM, and the ABBM-Mg scaffold promoted cell proliferation and osteogenic differentiation compared to the ABBM scaffold. In the rat mandibular defect model, the ABBM-Mg scaffold demonstrated superior bone repair ability. This study successfully incorporated Mg2+ into ABBM without significantly affecting its microstructure and compressive strength. Furthermore, ABBM-Mg showed sustained release of Mg2+ which enhanced cell proliferation, adhesion, and osteogenic differentiation in vitro, and promoted mandibular defect healing in rats. This research opens up new possibilities for the clinical application of functionalized acellular bone matrix. Graphical Abstract

Abstract With the frequent occurrence of heatwaves, heatstroke (HS) is expected to become one of the main causes of global death. Being a multi-organized disease, HS can result in circulatory disturbance and systemic inflammatory response, with the gastrointestinal tract being one of the primary organs affected. Intestinal damage plays an initiating and promoting role in HS. Multiple pathways result in damage to the integrity of the intestinal epithelial barrier due to heat stress and hypoxia brought on by blood distribution. This usually leads to intestinal leakage as well as the infiltration and metastasis of toxins and pathogenic bacteria in the intestinal cavity, which will eventually cause inflammation in the whole body. A large number of studies have shown that intestinal damage after HS involves the body’s stress response, disruption of oxidative balance, disorder of tight junction proteins, massive cell death, and microbial imbalance. Based on these damage mechanisms, protecting the intestinal barrier and regulating the body’s inflammatory and immune responses are effective treatment strategies. To better understand the pathophysiology of this complex process, this review aims to outline the potential processes and possible therapeutic strategies for intestinal damage after HS in recent years.

Abstract Objectives The study of comprehensive satisfaction with healthcare is still limited due to nonstandard measurement tools of patient satisfaction for the Chinese population. Therefore, the present study aimed to verify the validity, reliability, and measurement invariance of the revised Patient Satisfaction Questionnaire (PSQ-R) and conducted network analysis among a sample of the Chinese population. Methods A cross-sectional study using telephone surveys was conducted from April 2022 to August 2022. A total of 1377 participants who had been hospitalized completed the survey (481 males [34.9%], mean age = 49.4 years [SD ± 19.0]). Results Four factors (‘satisfaction with medical staff’, ‘satisfaction with hospital’, ‘satisfaction with medical costs’, and ‘satisfaction with medical insurance premiums’), were verified through confirmatory factor analysis (CFA) and had good equivalence across genders. The ‘satisfaction with medical staff’ and ‘satisfaction with hospital’ factors had the strongest edge intensity in the factor-level network. Conclusions The 18-item (four-factor) PSQ-R has good validity, reliability, and measurement invariance. The four dimensions appear to describe patient satisfaction well among the Chinese population who had been hospitalized. To effectively enhance patient satisfaction, the quality of healthcare service and medical staff skills should both be improved, medical insurance premiums should be increased, and medical costs should be decreased.

Low temperatures and icing in winter are significant factors that severely affect highway safety and traffic mobility. To enhance the precision and reliability of real-time winter road surface temperature (RST) prediction, a short-term prediction model is developed that harnesses both feature selection and deep learning. Leveraging meteorological data from a mountain highway in Yunnan, China, the key environmental variables affecting road surface temperature were first extracted using a random forest (RF) model for feature selection. These features were then combined with RST data to construct multiple groups of input variable combinations for the prediction model. A short-term prediction model with a 10-minute update frequency was built using a long short-term memory neural network (LSTM), namely RF-LSTM. The best input variable combination and preset parameters for the prediction model were determined through comparative testing with prevalent machine learning models, and the transferability of the prediction model was verified. The results showed that the best input variable combination for the RF-LSTM prediction model was road surface temperature and air temperature. The model recognised that the short-term RST was affected by long and short-term memory characteristics within a two-hour timeframe. When compared to the RF model, backpropagation (BP) neural network model and the standard LSTM model, the proposed model reduces prediction errors by 59.15%, 31.10% and 20.26%, respectively, while the prediction accuracy is 99.13% within an error margin of ±0.5℃. On the verification dataset, the proposed model maintains its time transferability with an average prediction absolute error of 0.0478. In all, the proposed model not only achieves a higher level of precision in real-time RST predictions but also ensures a more consistent and reliable performance under the challenging conditions of high altitude and mountainous terrain, offering enhanced support for traffic safety and road maintenance decision-making.

Abstract Aurora-B is a kinase that regulates spindle assembly and kinetochore-microtubule (KT-MT) attachment during mitosis and meiosis. SUMOylation is involved in the oocyte meiosis regulation through promoting spindle assembly and chromosome segregation, but its substrates to support this function is still unknown. It is reported that Aurora-B is SUMOylated in somatic cells, and SUMOylated Aurora-B contributes the process of mitosis. However, whether Aurora-B is SUMOylated in oocytes and how SUMOylation of Aurora-B impacts its function in oocyte meiosis remain poorly understood. In this study, we report that Aurora-B is modified by SUMOylation in mouse oocytes. The results show that Aurora-B colocalized and interacted with SUMO-2/3 in mouse oocytes, confirming that Aurora-B is modified by SUMO-2/3 in this system. Compared with that in young mice, the protein expression of SUMO-2/3 decreased in the oocytes of aged mice, indicating that SUMOylation might be related to mouse aging. Overexpression of Aurora-B SUMOylation site mutants, Aurora-BK207R and Aurora-BK292R, inhibited Aurora-B recruitment and first polar body extrusion, disrupting localization of gamma tubulin, spindle formation and chromosome alignment in oocytes. The results show that it was related to decreased recruitment of p-HDAC6 which induces the high stability of whole spindle microtubules including the microtubules of both correct and wrong KT-MT attachments though increased acetylation of microtubules. Therefore, our results corroborate the notion that Aurora-B activity is regulated by SUMO-2/3 in oocytes, and that SUMOylated Aurora B plays an important role in spindle formation and chromosome alignment.

Abstract Background Spinal cord injury (SCI) is a severe traumatic spinal condition with a poor prognosis. In this study, a scaffold called linearly ordered collagen aggregates (LOCAS) was created and loaded with induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) from human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) to treat SCI in a rat model. Methods The rats underwent a complete transection SCI resulting in a 3-mm break at either the T9 or T10 level of the spinal cord. Results Scanning electron microscope analysis revealed a uniform pore structure on the coronal plane of the scaffold. The LOCAS had a porosity of 88.52% and a water absorption of 1161.67%. Its compressive modulus and stress were measured at 4.1 MPa and 205 kPa, respectively, with a degradation time of 10 weeks. After 12 weeks, rats in the LOCAS-iPSCs-NSCs group exhibited significantly higher BBB scores (8.6) compared to the LOCAS-iPSCs-NSCs group (5.6) and the Model group (4.2). The CatWalk analysis showed improved motion trajectory, regularity index (RI), and swing speed in the LOCAS-iPSCs-NSCs group compared to the other groups. Motor evoked potentials latency was lower and amplitude was higher in the LOCAS-iPSCs-NSCs group, indicating better neural function recovery. Histological analysis demonstrated enhanced neuronal differentiation of NSCs and nerve fiber regeneration promoted by LOCAS-iPSCs-NSCs, leading to improved motor function recovery in rats. The LOCAS scaffold facilitated ordered neurofilament extension and guided nerve regeneration. Conclusions The combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. This development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair.

Abstract Background: Neoadjuvant chemoradiotherapy combined with immunotherapy (NICRT) is a new neoadjuvant treatment approach that has raised concerns regarding potential challenges in surgery and postoperative complications. This study aimed to compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) and NICRT for the treatment of resectable locally advanced esophageal squamous cell carcinoma (ESCC). Methods: We retrospectively analyzed 291 patients with locally advanced ESCC who underwent neoadjuvant therapy and esophagectomy at three centers between January 2019 and September 2023 and added the data from PALACE-1 for the analysis, Among these patients, 248 and 61 patients received NCRT and NICRT, respectively. Propensity score matching (PSM) was used to balance the potential bias. Results: After the PSM,the rate of a pathological complete response (pCR) in the NCRT group was not significantly different from that in the NICRT group (46.90% vs 36.36%, P = 0.180). There were no significant differences in the tumor regression grade (TRG) and positive lymph node pCR rates between the two groups (P = 0.233 and P = 0.354, respectively). Treatment-related toxicities and postoperative complications were not significantly different between the NCRT group and the NICRT group (P = 0.199, P = 0.284). Conclusion: Compared with NCRT, NICRT did not lead to the better treatment efficacy. There were no significant differences was observed in the incidence of treatment-related toxicities and postoperative complications.

Abstract Vaccination plays a crucial role in preventing and controlling SARS-CoV-2 infections as well as their associated adverse outcomes. But there is a notable lack of research on the effectiveness of COVID-19 vaccination in children, particularly those young preterm-born children, who are more vulnerable to severe outcomes from SARS-CoV-2 infection. We aimed to determine the effect of vaccination with inactivated vaccines BBIBP-CorV and CoronaVac on symptomatic COVID-19 infection and related symptoms in preterm-born children aged 3–7 years after relaxation of the COVID-19 prevention and control measures in December 2022 in China. We performed a retrospective cohort study involving 242 preterm-born children aged 3–7 years and the data were collected in March 2023. Logistic regression models and modified Poisson regression models combined with entropy balancing were used to explore the associations of vaccination against SARS-CoV-2 with symptomatic COVID-19, specific symptoms, and persistent symptoms one month after recovery from COVID-19. Of the 242 recruited preterm-born children, 156 (64.5%) were vaccinated with inactivated vaccines BBIBP‐CorV and CoronaVac. After entropy balancing, the covariates were balanced between the vaccinated and the unvaccinated groups, with standardized mean difference

Abstract Group 2 innate lymphocytes (ILC2) have an important role in orchestrating sepsis-induced immune response. However, the impact of LC2 on sepsis-induced cardiac injury is still not fully understood. This study investigated the mechanisms governing ILC2 activation within the cardiac tissue after sepsis. In vivo experiments using wild-type and IL-33 deficient mice indicated that the presence of interleukin (IL)-33, which participates in expanding and activating ILC2 cells, was correlated with higher ILC2 levels (246 ± 34 vs. 66 ± 18, p

Abstract Anderson localization and non-Hermitian skin effect are two paradigmatic wave localization phenomena, resulting from wave interference and the intrinsic non-Hermitian point gap, respectively. In this study, we unveil a novel localization phenomenon associated with long-range asymmetric coupling, termed scale-tailored localization, where the number of induced localized modes and their localization lengths scale exclusively with the coupling range. We show that the long-range coupling fundamentally reshapes the energy spectra and eigenstates by creating multiple connected paths on the lattice. Furthermore, we present experimental observations of scale-tailored localization in non-Hermitian electrical circuits utilizing adjustable voltage followers and switches. The circuit admittance spectra possess separate point-shaped and loop-shaped components in the complex energy plane, corresponding respectively to skin modes and scale-tailored localized states. Our findings not only expand and deepen the understanding of peculiar effects induced by non-Hermiticity but also offer a feasible experimental platform for exploring and controlling wave localizations.

Abstract Purpose This randomized controlled study aims to compare the effects of cluster training versus traditional plyometric lower limb training on vertical and horizontal jump performance, as well as the reactive strength index, in young female artistic gymnasts. Methods: A total of 54 female artistic gymnasts (15.4 ± 1.2 years) participated voluntarily this study. Participants were assigned to one of three groups: (i) cluster training (PLYct); (ii) traditional training (PLYtr); and (iii) a control group (not exposed to plyometric training). The intervention spanned 8 weeks, with evaluations conducted before and after the intervention period for the following variables: (i) squat jump; (ii) countermovement jump; and (iii) reactive strength index in a drop jump test. Results: Significant interactions time × group were found in SJ (p

Objective: To clarify the specific mechanisms of action of raw Phellodendron chinense Schneid. (RPC) and saltwater-processed PC (SPC) in the treatment of rats with a kidney-yin deficiency pattern (KYDP). Methods: Healthy rats were administered hydrocortisone to establish a KYDP model. The rats were divided into seven groups: blank control, model, positive control (Liuwei Dihuang pills), high-dose RPC, low-dose RPC, high-dose SPC, and low-dose SPC. Enzyme-linked immunosorbent assay was used to measure the levels of cAMP, cGMP, TRH, TSH, T3, T4, IFN-γ, TNF-α, and testosterone in the serum and the levels of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in the liver. TRH mRNA expression in the rat hypothalamus was measured using RT-PCR. THRα1+2 protein expression in the hypothalamus of rats was measured using Western blot. Immunohistochemistry was performed to determine the expression levels of FAS, FasL, and TSHR. Flow cytometry was used to determine CD4+ and CD8+ T lymphocyte levels. Illumina MiSeq sequencing technology was used to evaluate the diversity of intestinal flora in KYDP rats. Results: The cAMP/cGMP ratio was significantly higher in the model group than in the blank control group (P = .048). Compared with the model group, after administration, the levels of the above-mentioned serum and liver indexes decreased, except that of testosterone. The CD4+/CD8+ ratio also decreased. Compared with the RPC group, the levels of T3, IFN-γ, FAS, FasL, and TSHR in the SPC group decreased whereas that of testosterone increased. Additionally, immune function and intestinal flora diversity improved in the SPC group. SPC proved to be more effective in improving liver energy metabolism in KYDP rats than RPC. Conclusion: SPC had a better therapeutic effect on KYDP than RPC. The underlying mechanism of action may be related to improvements in liver energy metabolism, immune function, and intestinal flora diversity.

Abstract Objective To investigate indications and surgical procedures of keratoplasty in a tertiary comprehensive hospital in northern part of China over a 20-year period. Methods All patients undergoing keratoplasty between January 1, 2002 to December 31, 2021 in a tertiary comprehensive hospital in northern part of China were retrospectively reviewed. The annual proportion of keratoplasty indications and surgical procedures was recorded and analyzed. Results A total of 8266 keratoplasty procedures were included. Leading indications were keratoleukoma (n = 2108, 25.50%), followed by regraft (n = 1453 ,17.58%), corneal endothelial dysfunction (n = 1085, 13.13%), and keratoconus (n = 922,11.15%). A decreasing trend was observed for keratoleukoma (P

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and systemic fibrosis. Research on SSc has been hindered largely by lack of relevant models to study the progressive nature of the disease and to recapitulate the cell plasticity that is observed in this disease context. Generation of models for fibrotic disease using pluripotent stem cells is important for recapitulating the heterogeneity of the fibrotic tissue and are a potential platform for screening anti-fibrotic drugs. We previously reported a novel in-vitro model for fibrosis using induced pluripotent stem cell-derived mesenchymal cells (iSCAR). Here we report the generation of a “scar-like phenotype” when iPSC derived mesenchymal cells are cultured on hydrogel that mimicks a wound healing/scarring response (iSCAR). First, we performed RNA sequencing (RNA-seq) based transcriptome profiling of iSCAR culture at 48 h and 13 days to characterize early and latestage scarring phenotypes. The next generation RNA-seq of these iSCAR culture at different timepoints detected expression 92% of early “scar associated” genes and 85% late “scar associated” genes, respectively. Comparative transcriptomic analysis of a gene level SSc compendium matrix to the iSCAR wound associated model revealed genes common in both data sets. Early scar formation genes showed biological processes of hypoxia (27.5%), vascular development (13.7%) and glycolysis (27.5), while late scar formation showed genes associated with senescence (22.6%). Next we show the effects of two different antifibrotic compounds to validate the utility of the model as a screening tool to study early and late-stagelate-stage fibrosis. An autotaxin inhibitor was used to validate the iSCAR late stage fibrotic model (iSCAR-T) and an antifibrotic tool screening compound of unknown mechanism (EX00015097) was used to study and validate both early (iSCAR-P) and late-stage (iSCAR-T) fibrosis in the iSCAR model.

Abstract Background To evaluate the effect of stoma-related factors (stoma or no stoma, stoma type, and stoma reversal time) on the occurrence of low anterior resection syndrome (LARS), a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life, which includes fecal incontinence, fecal urgency and frequent defecation. Methods Patients who underwent radical rectal cancer surgery from July 2018 to July 2022 in a tertiary hospital were included. Baseline data, tumor condition, operation condition and postoperative recovery were obtained by clinical observation. Follow-up data were collected by telephone follow-up. The chi-square and Fisher exact tests were used to analyse differences, coefficient of contingency was used to determine correlations, and independent risk factors for the occurrence of LARS (Patients with a score of 21 or more points were defined as having LARS using the LARS score) were further determined by binary logistic regression. Results A total of 480 patients met the inclusion criteria, of which 267 used a defunctioning stoma and 213 did not use a defunctioning stoma. There was a positive correlation between defunctioning stoma (P 0.05). In binary logistic regression analysis, high BMI (Exp(B) = 1.072, P = 0.039), tumor closer to dentate line (Exp(B) = 0.910, P = 0.016), and ultra-low anterior resection (Exp(B) = 2.264, P = 0.011) increased the possibility of LARS at 3 months postoperatively; high BMI, proximity of the tumor to the dentate line, and ultra-low anterior resection were not independent risk factors for LARS at 6 months postoperatively (P > 0.05). However, proximity of the tumor to the dentate line (Exp(B) = 0.880, P = 0.035) increased the likelihood of LARS at 12 months postoperatively, while high BMI and ultra-low anterior resection remained non-significant as independent risk factors for LARS at 12 months postoperatively (P > 0.05). Conclusions Defunctioning stoma was not an independent risk factor for the occurrence of LARS, whereas high BMI, tumor closer to dentate line, and ultra-low anterior resection were independent risk factors for the occurrence of LARS. Trial registration Not applicable.

Abstract Background Hyperglycemia is one of the most common comorbidities in patients with acute ischemic stroke (AIS). This study aimed to assess the impact of short-term longitudinal blood glucose level change trajectories on the 30-day mortality risk in patients with AIS. Methods Data for AIS patients were obtained from the 2001–2019 Medical Information Mart for Intensive Care (MIMIC) database. The latent growth mixture modeling (LGMM) was utilized to classify a patient’s blood glucose level trajectory within 24 h of admission. Cox regression analyses were applied to examine the relationship between blood glucose levels at admission and blood glucose level trajectories and the risk of 30-day mortality in patients with AIS. Results A total of 2,432 patients with AIS were included in this retrospective cohort study, with 30-day mortality occurring in 574 (23.60%) patients. The median glucose levels of all patients were 136.00 (110.00, 178.00) mg/dL. Four blood glucose level trajectories were identified: low level-stable trend (type 1), moderate level-stable trend (type 2), high level-decreasing-increasing trend (type 3), and moderate level-increasing-decreasing trend (type 4). Type 2 blood glucose level trajectory was associated with an increased risk of 30-day mortality compared with type 1 blood glucose level trajectory [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 1.03–1.59), but there were no significant associations between type 3 (HR = 1.16, 95%CI: 0.77–1.74) and type 4 (HR = 1.44, 95%CI: 0.84–2.45) trajectories and 30-day mortality risk. Subgroup analysis demonstrated that the association between type 2 trajectory and 30-day mortality risk was observed in patients aged ≥ 65 years (HR = 1.37, 95%CI: 1.05–1.79), female (HR = 1.42, 95%CI: 1.05–1.94), with (HR = 1.44, 95%CI: 1.02–2.02) or without (HR = 1.42, 95%CI: 1.01–1.99) diabetes, and not using insulin (HR = 2.80, 95%CI: 1.43–5.49). Conclusion AIS patients with consistently high blood glucose levels within 24 h of admission increased the risk of 30-day mortality.

Abstract. Background:. Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented. Methods:. In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs). Results:. In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years. Conclusion:. These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Abstract Ensuring the traceability of agricultural products is essential for quality control and food safety. Recent technological advances have provided new ways to enhance traceability systems. This study aims to use blockchain technology, centralized database and RFID tags to develop a secure agricultural product traceability system, retain the detailed information of agricultural products traceability, ensure that the summary information of agricultural products on the chain cannot be modified, and optimize the SM3 algorithm to effectively summarize the traceability data and improve the efficiency of the system. The aggregated data is time-stamped, recorded on the blockchain, and written into an RFID tag. The optimization of the SM3 algorithm improved the efficiency by 30% and reduced the execution time of 192-byte messages to 210µs. The system ensures accurate linking of traceability data through secure data retention and unalterable summaries on the blockchain. The integrated use of blockchain, centralized database and RFID technology, as well as the enhanced SM3 algorithm, allows the system to meet the standards for data accuracy and performance requirements in agricultural traceability applications.

Abstract Functional dyspepsia (FD) is known to be influenced by gut microbiota (GM) and circulating inflammatory proteins (CIPs), however, the causal relationship between GM, CIPs and FD haven’t been investigated. This study employed two-sample Mendelian Randomization (TSMR) to investigate their associations using data from Genome-Wide Association Studies (GWAS). In this study, Inverse-variance weighted (IVW) method was employed as the primary analysis, with supplementary approaches including weighted median, weighted mode, simple mode, and MR-Egger. Heterogeneity and pleiotropy were assessed using the Cochrane Q test, MR-Egger intercept test, and MR-PRESSO global test. Totally, 196 GM traits and 91 CIPs were analyzed, and the results uncovered the causal impact of 12 GM taxa and 5 proteins on functional dyspepsia (FD). 9 GM genera were linked to a reduced risk of FD, while 3 GM genera were associated with an increased risk of FD.Additionally, reverse analysis revealed no FD-GM causation. Furthermore, IL-12, IL-10, CXCL10, CXCL9 and VEGFA were significantly correlated with FD, with CXCL9 and VEGFA acting as mediators in the association between GM traits and FD. Taken together, our findings established a link between specific GM and CIPs in the pathogenesis of FD, offering novel insights for its diagnosis and treatment.

Abstract Background Breast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM. Methods This study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models. Results 284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and

Abstract Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes and functions of immune cells. The metabolic regulation of the immune system is important in the pathogenesis and progression of numerous diseases, such as cancers, autoimmune diseases and metabolic diseases. The concept of immunometabolism was introduced over a decade ago to elucidate the intricate interplay between metabolism and immunity. The definition of immunometabolism has expanded from chronic low-grade inflammation in metabolic diseases to metabolic reprogramming of immune cells in various diseases. With immunometabolism being proposed and developed, the metabolic regulation of the immune system can be gradually summarized and becomes more and more clearer. In the context of many diseases including cancer, autoimmune diseases, metabolic diseases, and many other disease, metabolic reprogramming occurs in immune cells inducing proinflammatory or anti-inflammatory effects. The phenotypic and functional changes of immune cells caused by metabolic regulation further affect and development of diseases. Based on experimental results, targeting cellular metabolism of immune cells becomes a promising therapy. In this review, we focus on immune cells to introduce their metabolic pathways and metabolic reprogramming, and summarize how these metabolic pathways affect immune effects in the context of diseases. We thoroughly explore targets and treatments based on immunometabolism in existing studies. The challenges of translating experimental results into clinical applications in the field of immunometabolism are also summarized. We believe that a better understanding of immune regulation in health and diseases will improve the management of most diseases.

Abstract Background Recurrence of lower grade glioma (LrGG) appeared to be unavoidable despite considerable research performed in last decades. Thus, we evaluated the postoperative recurrence within two years after the surgery in patients with LrGG by preoperative advanced diffusion magnetic resonance imaging (dMRI). Materials and methods 48 patients with lower-grade gliomas (23 recurrence, 25 nonrecurrence) were recruited into this study. Different models of dMRI were reconstructed, including apparent fiber density (AFD), white matter tract integrity (WMTI), diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), Bingham NODDI and standard model imaging (SMI). Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) was used to construct a multiparametric prediction model for the diagnosis of postoperative recurrence. Results The parameters derived from each dMRI model, including AFD, axon water fraction (AWF), mean diffusivity (MD), mean kurtosis (MK), fractional anisotropy (FA), intracellular volume fraction (ICVF), extra-axonal perpendicular diffusivity (De⊥), extra-axonal parallel diffusivity (De∥) and free water fraction (fw), showed significant differences between nonrecurrence group and recurrence group. The extra-axonal perpendicular diffusivity (De⊥) had the highest area under curve (AUC = 0.885), which was significantly higher than others. The variable importance for the projection (VIP) value of De⊥ was also the highest. The AUC value of the multiparametric prediction model merging AFD, WMTI, DTI, DKI, NODDI, Bingham NODDI and SMI was up to 0.96. Conclusion Preoperative advanced dMRI showed great efficacy in evaluating postoperative recurrence of LrGG and De⊥ of SMI might be a valuable marker.

Abstract Background Currently, most elderly chronic heart failure (CHF) patients go home for rehabilitation after certain treatment in hospitals. However, the results of their rehabilitation at home are not satisfactory. According to studies, dyadic treatments can increase the efficiency of home rehabilitation, enhance both partners' quality of life, lessen the caregiver's load of care, and alleviate the strain of medical resources. Thus, the aim of our research is to design a study protocol that included elderly CHF patients and their informal caregivers as an intervention unit and to explore the impact of the protocol on their health and physical outcomes. Methods This is a prospective randomized controlled trial conducted in a triple-A hospital. In total, 80 elderly CHF patients and informal caregivers (80 dyads) will be recruited with informed consent. Based on the randomized numbers, they are divided into a control group (40 dyads) and an intervention group (40 dyads), subjects in the control group will receive usual care, and subjects in the intervention group will receive a home-based disease management program based on the Theory of Dyadic Illness Management on the basis of the control group. The duration of the intervention is 3 months, and the follow-up is 6 months. Data is collected at enrolment, 3 months after the intervention, and 3 months after the end of the intervention. The primary outcome is patients’ quality of life and readmission. Secondary outcomes include patients’ self-management behaviors, anxiety, and depression and caregivers’ quality of life and care burden. Discussion This study focuses on whether this home-based disease management program can improve the quality of life of elderly patients with CHF, reduce the readmission rate, enhance their self-management capacity, reduce negative emotions, and reduce the burden of informal caregivers. It can provide a new perspective on home management and cardiac rehabilitation of heart failure disease in the elderly, as well as alleviate problems such as the burden of healthcare resources. Trial registration Chinese Clinical Trials Registry ChiCRT2300068026. Registered on 3 February 2023, manuscript Version: 1.0, https://www.chictr.org.cn/ .

Objective The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi‐rod constructs in the revision of thoracolumbar fractures. Methods Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi‐rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow‐up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow‐up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). Results The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow‐up period. The paired t‐test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre‐revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post‐revision and last follow‐up (p = 0.551). VAS and ODI were greatly improved at the last follow‐up. Conclusion The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi‐rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Defect ratings and analysis and processing of different devices and equipment in the power system are often affected by the subjectivity of operation and maintenance personnel, resulting in different severity ratings for the same defect text description. Differences in expertise also lead to differences in diagnostic analysis and different diagnostic efficiency. In order to improve the accuracy and efficiency of defect diagnosis, a defect text rating classification method based on graph neural network and a large model intelligent diagnosis and analysis assistant are proposed. Firstly, a professional dictionary is constructed to normalize the text description using natural language processing algorithms. Secondly, the semantic representation of defective text is optimized by statistical methods. Then, graph attention neural network and robustly optimized BERT approach (RoBERTa) are integrated to accurately rate and classify defective text. Finally, low-rank adaptation (LoRA) fine-tuning training based on the large language model Qwen1.5-14B-Chat is performed to obtain the large model Qwen-ElecDiag for power equipment diagnosis, which is combined with retrieval enhancement to generate the assistant for defect diagnosis of technology development equipment. In addition, the collation provides the instruction dataset for fine-tuning the power equipment diagnosis macromodel. Comparative experimental results show that the proposed graph neural network-based defect rating classification method improves nearly 8 percentage points in accuracy over the optimal baseline model BERT; the diagnostic assistant??s power knowledge as well as defect diagnostic capability is improved. By improving the accuracy of defect ratings and providing comprehensive specialized diagnostic suggestions, it not only improves the intelligent level of power equipment O&M, but also provides new solutions for intelligent O&M in other vertical fields.

Abstract We study the interface dynamics in immiscible binary superfluids using its holographic description, which naturally consists of an inviscid superfluid component and a viscous normal fluid component. We give the first theoretical realization of interface instability for two superfluid components moving with identical velocity, providing a quantum analog to the flapping of flags that is common in daily life. This behavior is in sharp contrast to the one from Gross-Pitaevskii equation for which no such co-flow instability develops in an isolated uniform system because of Galilean invariance. The real time evolution triggered by the dynamical instability exhibits intricate nonlinear patterns leading to quantum turbulence reminiscent of the quantum Kelvin-Helmholtz instability. Moreover, we show that such interface dynamics is essentially different from the Landau instability for which the frictionless flow becomes thermodynamically unstable above a critical superfluid velocity. Our study uncovers the rich interface dynamics of quantum fluids and the emergence of complex flow phenomena.

Abstract Background Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy. Design A retrospective search spanning 20 years (2003–2022) was conducted on our archives and identified 21 cases diagnosed as “metastatic prostate adenocarcinoma (mPCa)” in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa. Result The mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis. Conclusion mPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.

Abstract Background Pulmonary arterial hypertension (PAH) is a worldwide challenging disease characterized by progressive elevation of pulmonary artery pressure. The proliferation, migration and phenotypic transformation of pulmonary smooth muscle cells are the key steps of pulmonary vascular remodeling. Quercetin (3,3', 4', 5, 6-pentahydroxyflavone, Que) is a natural flavonol compound that has antioxidant, anti-inflammatory, anti-tumor and other biological activities. Studies have shown that Que has therapeutic effects on PAH. However, the effect of quercetin on pulmonary vascular remodeling in PAH and its mechanism remain unclear. Methods and results In vivo, PAH rats were constructed by intraperitoneal injection of monocrotaline (MCT) at 60 mg/kg. Human pulmonary artery smooth muscle cells (HPASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) 20 ng/mL to construct PAH cell model in vitro. The results showed that in vivo studies, MCT could induce right ventricular wall hyperplasia, narrow the small and medium pulmonary artery cavity, up-regulate the expression of proliferating and migration-related proteins proliferating cell nuclear antigen (PCNA) and osteopontin (OPN), and down-regulate the expression of alpha-smooth muscle actin (α-SMA). Que reversed the MCT-induced results. This process works by down-regulating the transforming growth factor-β1 (TGF-β1)/ Smad2/3 signaling pathway. In vitro studies, Que had the same effect on PDGF-BB-induced proliferation and migration cell models. Conclusions Que inhibits the proliferation, migration and phenotypic transformation of HPASMCs by down-regulating TGF-β1/Smad2/Smad3 pathway, thereby reducing right ventricular hyperplasia (RVH) and pulmonary vascular remodeling, providing potential pharmacological and molecular explanations for the treatment of PAH.

Abstract Background Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. Methods/design This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. Discussion This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. Trial registration numbers Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

Abstract Can wars truly build states and rationalize their structures? This study focuses on the administrative origin of state-building and finds historical evidence that seems contrary to the idea of "war-making states". As states acquire more territory, they become increasingly vulnerable to setbacks in subsequent military activities, even when facing state failure or demise. Drawing upon geospatial data spanning from 906 to 969 AD during Chinas Five Dynasties and utilizing a difference-in-differences method, our study reveals that (1) states did not progressively expand in size due to continuous warfare, and (2) larger territorial acquisitions were associated with decreased probabilities of state survival, as expanding net territorial areas corresponded to higher likelihoods of state failure in the following years. (3) The relationship between civilian and military systems within a state profoundly impacts the validity of the "war-making states" hypothesis. This study highlights that war makes states more susceptible to collapse if the military system dominates the civilian bureaucracy. Conversely, if the civilian system controls the military and forms a centralized regime, the "war-making states" hypothesis holds true. These findings revise the prevailing hypothesis of "war-making states" in historical sociology, showing that the "war-making states" hypothesis depends on a specific political structure and bureaucratic system.

Abstract Cutaneous squamous cell carcinoma (CSCC) is common among the elderly, typically treated with surgery. However, for surgery-ineligible patients or those with non-healing wounds progressing to malignant ulcers, non-surgical local treatments are viable. This case details an 80-year-old with recurrent back CSCC and intractable malignant ulcers post-radiotherapy and chemotherapy. Treatment involved Hematoporphyrin Derivative (HpD) Photodynamic Therapy (PDT) with low-dose cindilimab immunotherapy (intravenous and intralesional). Two cycles achieved lesion remission, altering peripheral immune cell counts. HpD-PDT combined with immunotherapy is promising for treating CSCC, particularly with malignant ulcers.