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Drawing on the survey data from 259 students enrolled at American universities, the study explores how recent tensions between China and the U.S. and issues of public safety would affect Chinese students' perceptions and aspirations for American education. The findings of the research identify significant correlations between the effects of U.S. policies regarding Chinese students, concerns about U.S. public safety, and the impact of U.S. foreign policy toward China on Chinese students at American universities. Students' responses reveal how the pursuit of an American college education remains deeply intertwined with broader societal dynamics and geopolitical realities, which challenge the aspirations of Chinese students for education abroad in an increasingly deglobalizing world.

Science teachers play a crucial role in the science education system, significantly influencing the development of students. However, existing research highlights issues such as a wide age span and uneven quality among science teachers, which undermines the effectiveness of science education. In addition, the role of science teachers can be ambiguously defined, leading to confusion about their responsibilities. To better understand the current situation and future development trend of research on the role of science teachers in China and overseas, this study compares and analyses a total of 30 documents on the role of science teachers in Chinese or English. The documents were from Web of science or CNKI databases. Content analysis was applied on time of publication, volume of papers, research topic, and similarities and differences of the role development of science teachers in China or overseas. Results show that: (1) At present, the development trend of research on the role of science teachers published in English and Chinese is relatively slow and has not received due attention. Most mainstream research paradigms are still in the stage of theoretical exploration; (2) the research theme of the role of science teachers mainly includes five aspects: Role expectation, role orientation, role identification, role transformation, and role; (3) the "should be" research published in Chinese and the "real" research published in English should be combined and form a positive interaction. This study is helpful to systematically analyze the current situation of research on the role of science teachers, with a view to providing a basis for subsequent research on the role of science teachers.

Academic burnout seriously affects the academic performance and mental health of college students. This study developed a multi-mediation model to investigate the relationship between academic self-efficacy and academic burnout. A total of 1431 undergraduate students (51.85% female) were recruited to participate in this study. And we used SPSS PROCESS developed by Hayes to examine the mediating role of academic self-efficacy and academic burnout. The results indicated that academic self-efficacy can negatively predict academic burnout. Moreover, intrinsic motivation and learning engagement have a significant mediating effect between academic self-efficacy and academic burnout. Finally, we constructed a model comprising four variables and found that it explained 47.62% of the variance in academic burnout. These findings can be conducive to a suitable intervention path to reduce academic burnout of Chinese college students, so as to develop effective instructional strategies to improve their learning performance.

Abstract Background The detection of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) by multimeric protein complexes, known as inflammasomes, triggers an inflammatory response, which is a critical component of the innate immune system. This inflammatory response plays a pivotal role in host resistance against parasitic infections, presenting a significant global health challenge. Methods We systematically searched for relevant articles from the Pubmed and the Web of Science database to summarize current insights into how inflammasomes function in preventing infections caused by the apicomplexan parasites Toxoplasma and Plasmodium. Results In vivo and in vitro studies have extensively explored inflammasomes such as the absent in melanoma 2 (AIM2), NLR family pyrin-containing protein 1 (NLRP1), NLRP3, and NLRP12 inflammasomes, alongside noncanonical inflammasomes, with particular emphasis on the NLRP1 and the NLRP3 inflammasome during Toxoplasma gondii infection or the AIM2 and the NLRP3 inflammasome at various stages of Plasmodium infection. Toxoplasma gondii interacts with inflammasomes to activate or inhibit immune responses. Conclusions Inflammasomes control parasite burden and parasite-induced cell death, contribute to immune recognition and inflammatory responses and thus influence apicomplexan parasite-associated pathogenesis and the severity of clinical outcomes. Hence, inflammasomes play crucial roles in the progression and outcomes of toxoplasmosis and malaria. A comprehensive understanding of how parasitic infections modulate inflammasome activity enhances insight into host immune responses against parasites. Graphical Abstract

Abstract X-ray imaging with a large field of view (FOV) and high resolution is extremely important for Rayleigh–Taylor instability measurement with a small amplitude and high spatial frequency in laser inertial confinement fusion. We developed an advanced Kirkpatrick–Baez (AKB) microscope based on the quadratic-aberration theory to realize a large FOV and high resolution. This microscope was assembled and tested in a laboratory, and it was then successfully applied for imaging the hydrodynamic instability of a perturbation target in implosion experiments at the Shenguang-III prototype laser facility. Imaging results demonstrate that the AKB microscope can achieve an optimal resolution of ~ 0.53 μm and ~ 0.40 μm and a spatial resolution of

Abstract Objectives This study aimed to develop and validate a deep-learning radiomics model using CT, T2, and DWI images for predicting pathological complete response (pCR) in patients with esophageal squamous cell carcinoma (ESCC) undergoing neoadjuvant chemoradiotherapy (nCRT). Materials and methods Patients with ESCC undergoing nCRT followed by surgery were retrospectively enrolled from three institutions and divided into training and testing cohorts. Both traditional and deep-learning radiomics features were extracted from pre-treatment CT, T2, and DWI. Multiple radiomics models were developed, both single modality and integrated, using machine learning algorithms. The models’ performance was assessed using receiver operating characteristic curve analysis, with the area under the curve (AUC) as a primary metric, alongside sensitivity and specificity from the cut-off analysis. Results The study involved 151 patients, among whom 63 achieved pCR. The training cohort consisted of 89 patients from Institution 1 (median age 62, 73 males) and the testing cohort included 52 patients from Institution 2 (median age 62, 41 males), and 10 in a clinical trial from Institution 3 (median age 69, 9 males). The integrated model, combining traditional and deep learning radiomics features from CT, T2, and DWI, demonstrated the best performance with an AUC of 0.868 (95% CI: 0.766–0.959), sensitivity of 88% (95% CI: 73.9–100), and specificity of 78.4% (95% CI: 63.6–90.2) in the testing cohort. This model outperformed single-modality models and the clinical model. Conclusion A multimodality deep learning radiomics model, utilizing CT, T2, and DWI images, was developed and validated for accurately predicting pCR of ESCC following nCRT. Critical relevance statement Our research demonstrates the satisfactory predictive value of multimodality deep learning radiomics for the response of nCRT in ESCC and provides a potentially helpful tool for personalized treatment including organ preservation strategy. Key Points After neoadjuvant chemoradiotherapy, patients with ESCC have pCR rates of about 40%. The multimodality deep learning radiomics model, could predict pCR after nCRT with high accuracy. The multimodality radiomics can be helpful in personalized treatment of esophageal cancer. Graphical Abstract

Abstract Though several anti-PD-1/PD-L1 antibodies approved for monotherapy in microsatellite instability-high or mismatch repair-deficient unresectable/metastatic solid tumors, novel immunotherapy with better anti-tumor activity is needed in clinic. In this single-arm, multicenter, pivotal, phase II study, patients received iparomlimab (a novel humanized anti-PD-1 mAb, 200 mg or 3 mg/kg for patients with body weight

Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with an unmet clinical need, but its epigenetic regulation remains largely undefined. By performing multiomic profiling, we recently revealed distinct super-enhancer (SE) patterns in different subtypes of breast cancer and identified a number of TNBC-specific SEs that drive oncogene expression. One of these SEs, TCOF1 SE, was discovered to play an important oncogenic role in TNBC. However, the molecular mechanisms by which TCOF1 SE promotes the expression of the TCOF1 gene remain to be elucidated. Here, by using combinatorial approaches of DNA pull-down assay, bioinformatics analysis and functional studies, we identified FOSL1 as a key transcription factor that binds to TCOF1 SE and drives its overexpression. shRNA-mediated depletion of FOSL1 results in significant downregulation of TCOF1 mRNA and protein levels. Using a dual-luciferase reporter assay and ChIP-qPCR, we showed that binding of FOSL1 to TCOF1 SE promotes the transcription of TCOF1 in TNBC cells. Importantly, our data demonstrated that overexpression of FOSL1 drives the activation of TCOF1 SE. Lastly, depletion of FOSL1 inhibits tumor spheroid growth and stemness properties of TNBC cells. Taken together, these findings uncover the key epigenetic role of FOSL1 and highlight the potential of targeting the FOSL1-TCOF1 axis for TNBC treatment.

Abstract Introduction This study aims to compare sagittal condylar inclination (SCI) measurements derived from three workflows: intraoral scan (IOS) aligned with cone-beam computed tomography (CBCT), IOS aligned with facial scan (FS), and a jaw motion analyzer (JMA) system, in a cohort of young individuals with established normal occlusion. Additionally, the study aims to identify sources contributing to variance in these measurement approaches. Methods Twenty-four healthy individuals exhibiting normal occlusion were enrolled in this clinical trial. The SCI was delineated using a virtual articulator (VA) by aligning IOS with both CBCT and FS, creating two distinct workflows labeled CBCT-IOS and FS-IOS, respectively. Concurrently, SCI measurements were also acquired using a JMA. The normality of data distribution for the difference in bilateral SCI measurements within each workflow was tested using the Shapiro-Wilk test. Depending on the outcomes of this test, we utilized either a paired-sample T-test or Wilcoxon test for bilateral SCI comparisons. The inter-workflow differences were assessed using the Kruskal-Wallis H test. Bland-Altman plots were assess the interchangeability and consistency across each pair of digital methods and to evaluate the aggregate consistency among the trio of digital approaches. Results The analysis revealed that the CBCT-IOS workflow yielded the lowest average SCI measurements, whereas the JMA workflow produced the highest values. No significant differences were found in the SCI measurements between the left and right sides obtained by CBCT-IOS and JMA (P > .05), with the exception of the FS-IOS workflow (P = .002). Additionally, inter-flow comparisons revealed no significant differences in SCI measurements (P > .05), except when contrasting the SCI as measured by CBCT-IOS and JMA (P = .0131). The Bland-Altman plots demonstrated a high degree of consistency and 95% limits of agreement across the three digital workflows. Conclusion SCI measurements obtained from the three digital workflows exhibit a high degree of consistency and are interchangeable, affirming their clinical applicability for precise SCI assessment in young individuals with normal occlusion.

Abstract The role of collagen and its receptor, discoidin domain receptor 1 (DDR1) in immune response of colorectal cancer (CRC) remains unclear. We identified DDR1 as a promising target of immunotherapy resistance using a pooled in vivo CRISPR/sgRNA screening in microsatellite stable (MSS) CRC mouse models. Our findings demonstrated that knockdown or inhibition of DDR1 could enhance infiltration of CD8+ T cells and sensitize MSS CRC to PD-1 blockade. Furthermore, DDR1 was found to facilitate kinase domain phosphorylation, upregulate EZH2, consequently elevating H3K27me3 levels at the CXCL10 promotor, which led to the suppression of CXCL10 transcription once bound to collagen in ECM. Lastly, DDR1 was found positively correlated with collagen I expression in MSS CRC specimens. These findings indicated that targeting DDR1 or its inhibitor 7rh might be potential strategy for overcoming immunotherapy resistance in MSS CRC.

Abstract Background Stereotactic body radiation therapy (SBRT) has been widely used for pancreatic cancer. However, there is still a lack of studies comparing the latest SBRT techniques in terms of clinical efficacy and safety. Objectives: This study aims to evaluate three latest SBRT delivery platforms: CyberKnife (CK), Tomography Radixact (TOMO), and Halcyon volume rotation intensity modulation therapy (VMAT) for the treatment of pancreatic cancer. Methods Sixteen patients with pancreatic cancer treated with CK were retrospectively analyzed. SBRT plans were designed using Precision and Eclipse software. CK plans were optimized in two forms: fixed collimator (CK-Fixed) and multi-leaf grating collimator (CK-MLC). TOMO plans were designed with 2.5 cm Fixed Jaw, pitch 0.123–0.43 and 4.0 modulation factors in precision system. In Eclipse 15.6 system, photon optimizer (OP) algorithm was used to design the coplanar two-arc Halcyon VMAT. The median radiation dose was 40 Gy (35–45 Gy) in 5 fractions. The effectiveness of clinical treatment was evaluated by comparing the homogeneity index (HI), conformity index (CI), coverage of the planning target volume (PTV) and dose distribution parameters of organs at risk (OAR). Results All plans met the limits of clinical target dose and OAR. CK-MLC plans had the lowest maximum dose of 2 cm normal tissue from PTV margin (D2cm), indicating a low risk of peripheral radiation damage. Additionally, the CK-MLC plans had the lowest dose parameters and provided the best protection for the kidney, spinal cord, small intestine, and duodenum, with a paired t-test p

Abstract Electrocatalysts are extensively employed to suppress the shuttling effect in lithium-sulfur (Li-S) batteries. However, it remains challenging to probe the sulfur redox reactions and mechanism at the electrocatalyst/LiPS interface after the active sites are covered by the solid discharge products Li2S/Li2S2. Here, we demonstrate the intrinsic autocatalytic activity of the Li2S (100) plane towards lithium polysulfides on single-atom nickel (SANi) electrocatalysts. Guided by theoretical models and experimental data, it is concluded that LiPS dissociates into Li2S2 and short-chain LiPS on the Li2S (100) plane. Subsequently, Li2S2 undergoes further lithiation to Li2S on the Li2S (100) surface, generating a new Li2S (100) layer, thus enabling the autocatalytic formation of a new Li2S (100) surface. Benefiting from the autocatalytic growth of Li2S, the concentration of LiPS in the electrolyte remains at a lower level, enabling Li-S batteries under high loading and low electrolyte conditions to exhibit superior electrochemical performance.

Abstract Cyclodehydrogenation is an important ring-formation reaction that can directly produce planar-conjugated carbon-based nanomaterials from nonplanar molecules. However, inherently high C–H bond energy necessitates a high temperature during dehydrogenation, and the ubiquity of C − H bonds in molecules and small differences in their bond energies hinder the selectivity of dehydrogenation. Here, we report a room-temperature cyclodehydrogenation reaction on Au(111) via radical addition of open-shell resonance structures and demonstrate that radical addition significantly decreases cyclodehydrogenation temperature and further improves the chemoselectivity of dehydrogenation. Using scanning tunneling microscopy and non-contact atomic force microscopy, we visualize the cascade reaction process involved in cyclodehydrogenation and determine atomic structures and molecular orbitals of the planar acetylene-linked oxa-nanographene products. The nonplanar intermediates observed during progression annealing, combined with density functional theory calculations, suggest that room-temperature cyclodehydrogenation involves the formation of transient radicals, intramolecular radical addition, and hydrogen elimination; and that the high chemoselectivity of cyclodehydrogenation arises from the reversibility and different thermodynamics of radical addition step.

Abstract Multi-modal image analysis using deep learning (DL) lays the foundation for neoadjuvant treatment (NAT) response monitoring. However, existing methods prioritize extracting multi-modal features to enhance predictive performance, with limited consideration on real-world clinical applicability, particularly in longitudinal NAT scenarios with multi-modal data. Here, we propose the Multi-modal Response Prediction (MRP) system, designed to mimic real-world physician assessments of NAT responses in breast cancer. To enhance feasibility, MRP integrates cross-modal knowledge mining and temporal information embedding strategy to handle missing modalities and remain less affected by different NAT settings. We validated MRP through multi-center studies and multinational reader studies. MRP exhibited comparable robustness to breast radiologists, outperforming humans in predicting pathological complete response in the Pre-NAT phase (ΔAUROC 14% and 10% on in-house and external datasets, respectively). Furthermore, we assessed MRP’s clinical utility impact on treatment decision-making. MRP may have profound implications for enrolment into NAT trials and determining surgery extensiveness.

Abstract The trade-off between rapid growth and other important physiological traits (e.g., survival and adaptability) poses a fundamental challenge for microbes to achieve fitness maximization. Studies on Bacillus subtilis biology often use strains derived after a process of lab ‘domestication’ from an ancestral strain known as Marburg strain. The domestication process led to loss of a large plasmid (pBS32) encoding a phosphatase (RapP) that dephosphorylates the Spo0F protein and thus regulates biofilm formation and sporulation. Here, we show that plasmid pBS32, and more specifically rapP, enhance growth rates by preventing premature expression of the Spo0F-Spo0A-mediated adaptive response during exponential phase. This results in reallocation of proteome resources towards biosynthetic, growth-promoting pathways without compromising long-term fitness during stationary phase. Thus, RapP helps B. subtilis to constrain physiological trade-offs and economize cellular resources for fitness improvement.

Abstract Background Whether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods. Methods Our sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods. Results 420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p

Abstract The strength of natural clay can be improved with epoxy resins. However, nanoscale curing mechanisms remain poorly understood, which is essential for enhancing stability. In this study, molecular dynamics simulation was employed to calculate the quantity of interface hydrogen bonds, adsorption energy, radius of gyration, and mechanical properties of clay cured by diglycidyl ether of bisphenol-A epoxy resin (DGEBA), diglycidyl ether 4,4’-dihydroxy diphenyl sulfone (DGEDDS), and Aliphatic epoxidation of olefin resin (AEOR). Adsorption behavior and mechanical properties of the clay cured by three epoxy resins were investigated: (1) The chain structure of AEOR led to 18.2% more hydrogen bonds than DGEBA and 59.1% more than DGEDDS. (2) The simulated adsorption energies for DGEBA, DGEDDS, and AEOR with kaolinite were 92.59, 98.25, and 116.87 kcal·mol−1, respectively. (3) The bulk and shear modulus of kaolinite increased by 4.93% and 4.80% when using AEOR. The interface stability and mechanical properties of kaolinite were also improved through strong hydrogen bonds and high adsorption energy. (4) The improvement in Young’s modulus of kaolinite was most significant with AEOR, followed by DGEDDS. AEOR excelled in the Z direction, while DGEDDS excelled in the X and Y directions. This research provided a theoretical foundation to effectively improve the properties of clay using epoxy resins.

Infected wounds pose a significant clinical challenge due to bacterial resistance, recurrent infections, and impaired healing. Reactive oxygen species (ROS)-based strategies have shown promise in eradicating bacterial infections. However, the excess ROS in the infection site after treatments may cause irreversible damage to healthy tissues. To address this issue, we developed bovine serum albumin-iridium oxide nanoclusters (BSA-IrOx NCs) which enable photo-regulated ROS generation and scavenging using near infrared (NIR) laser. Upon NIR laser irradiation, BSA-IrOx NCs exhibit enhanced photodynamic therapy, destroying biofilms and killing bacteria. When the NIR laser is off, the nanoclusters' antioxidant enzyme-like activities prevent inflammation and repair damaged tissue through ROS clearance. Transcriptomic and metabolomic analyses revealed that BSA-IrOx NCs inhibit bacterial nitric oxide synthase, blocking bacterial growth and biofilm formation. Furthermore, the nanoclusters repair impaired skin by strengthening cell junctions and reducing mitochondrial damage in a fibroblast model. In vivo studies using rat infected wound models confirmed the efficacy of BSA-IrOx NCs. This study presents a promising strategy for treating biofilm-induced infected wounds by regulating the ROS microenvironment, addressing the challenges associated with current ROS-based antibacterial approaches.

Abstract Objective Ulcerative colitis (UC) and Hashimoto’s thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. Methods We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran’s Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Results Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36–69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Conclusion Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells.

Abstract Hydrogen-bonded assembly of multiple components into well-defined icosahedral capsules akin to virus capsids has been elusive. In parallel, constructing robust zeolitic-like cluster-based supramolecular frameworks (CSFs) without any coordination covalent bonding linkages remains challenging. Herein, we report a cluster-based pseudoicosahedral H-bonded capsule Cu60, which is buckled by the self-organization of judiciously designed constituent copper clusters and anions. The spontaneous formation of the icosahedron in the solid state takes advantage of 48 charge-assisted CH···F hydrogen bonds between cationic clusters and anions (PF6 -), and is highly sensitive to the surface protective ligands on the clusters with minor structural modification inhibiting its formation. Most excitingly, an extended three-periodic robust zeolitic-like CSF, is constructed by edge-sharing the resultant icosahedrons. The perpendicular channels of the CSF feature unusual 3D orthogonal double-helical patterns. The CSF material not only keeps its single-crystal character in the desolvated phase, but also exhibits excellent chemical and thermal stabilities as well as long-lived phosphorescence emission.

Objective To explore the approach to establish a temporal lobe epilepsy model via intraperitoneal pilocarpine injection in C57BL/6J mice, and to summarize behavioral indicators predicting successful modeling during the acute phase of epileptic seizures after pilocarpine administration, aiming to offer a practical mice model for future epilepsy research.MethodsThirty C57BL/6J substrain mice (primary subjects) and forty C57BL/6N substrain mice (control subjects) were selected to establish a temporal lobe epilepsy model by inducing seizures through a single intraperitoneal injection of pilocarpine. The mice from the two substrains were each divided into 3 groups, and were injected intraperitoneally with 300 mg/kg, 330 mg/kg, or 360 mg/kg of pilocarpine, respectively. Motor seizure behaviors were observed and compared between the two substrains of C57BL/6 mice post pilocarpine injection, and the spontaneous recurrent seizures (SRS) were continuously monitored from the 7th day after injection. On the 28th day post-injection, the mice were euthanized and the histopathological changes in their hippocampi were examined. ResultsAfter pilocarpine administration, C57BL/6N mice displayed characteristic motor seizures followed by the onset of status epilepticus (SE). Conversely, C57BL/6J mice showed fewer instances of typical motor seizure behavior and the subsequent SE. Instead, they more often exhibited systemic tremors lasting several seconds to tens of seconds following limb twitching. This behavior is classified as “severe seizure (SS)” in current study. Following intraperitoneal injection of 330 mg/kg and 360 mg/kg pilocarpine, C57BL/6J mice displaying SS during the acute phase of seizure might exhibit SRS after a latency period. The percentage of spontaneous seizures observed in C57BL/6J mice post-modeling (70%) was comparable to that seen in C57BL/6N mice (75%) which developed SRS subsequent to SE. C57BL/6J mice displayed characteristic pathological alterations associated with temporal lobe epilepsy in the hippocampi after 28 d following pilocarpine injection, including increased mossy fiber sprouting and neuronal death. ConclusionsWhen inducing an epilepsy model via intraperitoneal pilocarpine injection in C57BL/6J mice, the behavioral criteria to predict the successful establishment of the model could be either the occurrence of SE or the manifestation of SS.

Abstract Prostate cancer is one of the most common cancers in men and poses a significant threat to global male health. Traditional prostate cancer assessment methods have certain limitations, necessitating the identification of new prognostic factors and treatment targets. Our study revealed that low expression of the cornichon family AMPA receptor auxiliary protein 2 (CNIH2) gene was associated with a better progression-free survival rate in prostate cancer patients. The area under the receiver operating characteristic (ROC) curve (AUC) showed that the prognostic ability of the CNIH2 gene was high at 1, 3, and 5 years. The gene was an independent prognostic factor according to multivariate analysis. Functional verification experiments showed that knocking down the CNIH2 gene could inhibit the proliferation, migration and invasion of prostate cancer cells and could also inhibit tumor growth in nude mice. Our study is the first to reveal the important role of the CNIH2 gene in prostate cancer. This discovery provides a new research direction for individualized treatment and prognostic evaluation of prostate cancer.

Abstract Background In mouse models of atherosclerosis, knockout of the PLA2G2A gene has been shown to reduce the volume of atherosclerotic plaques. Clinical trials have demonstrated the potential of using the sPLA2 inhibitor Varespladib in combination with statins to reduce lipid levels. However, this approach has not yielded the expected results in reducing the risk of cardiovascular events. Therefore, it is necessary to further investigate the mechanisms of PLA2G2A. Methods Single-cell transcriptome data from two sets of carotid plaques, combined with clinical patient information. were used to describe the expression characteristics of PLA2G2A in carotid plaques at different stages. In order to explore the mechanisms of PLA2G2A, we conducted enrichment analysis, cell–cell communication analysis and single-cell regulatory network inference and clustering analyses. We validated the above findings at the cellular level. Results Our findings indicate that PLA2G2A is primarily expressed in vascular fibroblasts and shows significant cell interactions with macrophages in the early-stage, especially in complement and inflammation-related pathways. We also found that serum sPLA2 levels have stronger diagnostic value in patients with mild carotid artery stenosis. Subsequent comparisons of single-cell transcriptomic data from early and late-stage carotid artery plaques corroborated these findings and predicted transcription factors that might regulate the progression of early carotid atherosclerosis (CA) and the expression of PLA2G2A. Conclusions Our study discovered and validated that PLA2G2A is highly expressed by vascular fibroblasts and promotes plaque progression through the activation of macrophage complement and coagulation cascade pathways in the early-stage of CA.

Abstract Background Cashmere, named as “soft gold”, derives from the secondary hair follicles (SHFs) of cashmere goat which is vital to Northwest China’s economy. The cytodifferentiation stage (E120), mirroring the complete hair follicle (HF) structure of adult goats and marking a critical phase in SHF development. Therefore, this study aims to enhance the understanding of SHF development and its impact on fiber quality, informing breeding strategies. Results From the scRNA-seq data analysis, the intricate processes and transcriptional dynamics of inner layer cell differentiation of HFs were unveiled in this study. we identified nine cell populations during cytodifferentiation and key structures such as the hair shaft and inner root sheath. And we discovered three main inner layer lineages and seven subpopulations, clarifying their roles in specialization and signaling. Pseudotime mapping analysis showed cell evolution from early stage to mature stages marked by unique gene expressions, and the intermediate stage on the differentiation of each lineage was revealed. The identification and spatial localization of specific transcription factors, such as GATA3, LEF1 and PRDM1, as well as keratin genes highlight regulatory pathways involved in HF development, which was further validated by immunofluorescence. These findings suggested the potential strategies to improve fiber quality, and the discovery of diverse cell types and their developmental molecular mechanisms, particularly in this species-specific context, offered a nuanced view of the regulatory mechanisms driving HF development in cashmere goats. Conclusion Overall, these findings provide a systematic molecular atlas of skin, defining three major branches and cell states of inner layer cells of HF, and determining how the branch-specific transcription factors, keratins, and signals coordinate HF morphogenesis during cytodifferentiation stage. This research not only advances skin tissue research in goats but also holds broader implications for the understanding of HF regeneration and development across various species.

Abstract Cell-derived extracellular vesicles (EVs), which carry diverse biomolecules such as nucleic acids, proteins, metabolites, and lipids reflecting their cell of origin, are released under both physiological and pathological conditions. EVs have been demonstrated to mediate cell-to-cell communication and serve as biomarkers. EV-associated DNA (EV-DNA) comprises genomic and mitochondrial DNA (i.e., gDNA and mtDNA) fragments. Some studies have revealed that EV-DNA can represent the full nuclear genome and mitochondrial genome of parental cells. Furthermore, DNA fragments loaded into EVs are stable and can be transferred to recipient cells to regulate their biological functions. In this review, we summarized and discussed EV-DNA research advances with an emphasis on EV-DNA detection at the population-EV and single-EV levels, gene transfer-associated biological functions, and clinical applications as biomarkers for disease liquid biopsy. We hope that this review will provide potential directions or guidance for future EV-DNA investigations.

Abstract Background Adequate sleep and rest are essential for patient recovery; however, lack of sleep has become a common problem faced by Chinese patients during hospital stays. Reduced sleep is often associated with a higher risk of disease progression and is strongly associated with increased hospital stay. However, there is no specific tool in China to assess short-term insomnia caused by hospitalization. This study aimed to translate the Hospital-acquired Insomnia Scale (HAIS) into Chinese, test its applicability to Chinese inpatients through reliability and validity indicators, and investigate the potential influencing factors of hospital-acquired insomnia. Methods Psychometric analysis from a sample of 679 hospitalized patients to whom the HAIS questionnaire was applied. The structural validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), and the content validity of the scale was assessed using the content validity index. Cronbach’s alpha coefficient, split-half reliability and test–retest reliability were calculated to evaluate the internal consistency of the scale. Multiple stepwise linear regression analysis was conducted to determine the potential correlates of hospital-acquired insomnia. Results EFA supported a four-factor structure with factor loadings for all dimensions greater than 0.40. CFA showed good indicators of model fit. The content validity index of the scale was 0.94. the Cronbach’s alpha of the scale was 0.915, the split-half reliability coefficient was 0.819, and the retest reliability was 0.844. Gender, age, total hours of sleep during the night, medical insurance, length of hospital stay, perceived stress level, and perceptions about sleep explained 46.2% of the variance in hospital-acquired insomnia. Conclusion The Chinese version of HAIS has good psychometric characteristics and is an effective instrument for evaluating hospital-acquired insomnia. In addition, hospital-acquired insomnia is more common in women, of younger age, less than 5 h of sleep a night, without medical insurance, stressed, and patients with more misconceptions about sleep.

Abstract Background Tumor cells develop multiple mechanisms to facilitate their immune evasion. Identifying tumor-intrinsic factors that support immune evasion may provide new strategies for cancer immunotherapy. We aimed to explore the function and the mechanism of the tumor-intrinsic factor NPM1, a multifunctional nucleolar phosphoprotein, in cancer immune evasion and progression. Methods The roles of NPM1 in tumor progression and tumor microenvironment (TME) reprogramming were examined by subcutaneous inoculation of Npm1-deficient tumor cells into syngeneic mice, and then explored by CyTOF, flow cytometry, immunohistochemistry staining, and RNA-seq. The in-vitro T-cell killing of OVA-presenting tumor cells by OT-1 transgenic T cells was observed. The interaction of NPM1 and IRF1 was verified by Co-IP. The regulation of NPM1 in IRF1 DNA binding to Nlrc5, Ciita promoter was determined by dual-luciferase reporter assay and ChIP-qPCR. Results High levels of NPM1 expression predict low survival rates in various human tumors. Loss of NPM1 inhibited tumor progression and enhanced the survival of tumor-bearing mice. Npm1-deficient tumors showed increased CD8+ T cell infiltration and activation alongside the reduced presence of immunosuppressive cells. Npm1 deficiency increased MHC-I and MHC-II molecules and specific T-cell killing. Mechanistically, NPM1 associates with the transcription factor IRF1 and then sequesters IRF1 from binding to the Nlrc5 and Ciita promoters to suppress IRF1-mediated expression of MHC-I and MHC-II molecules in tumor cells. Conclusions Tumor-intrinsic NPM1 promotes tumor immune evasion via suppressing IRF1-mediated antigen presentation to impair tumor immunogenicity and reprogram the immunosuppressive TME. Our study identifies NPM1 as a potential target for improving cancer immunotherapy.

Abstract Background To estimate and compare the association between metabolically healthy overweight/obesity (MHO) and the risk of type 2 diabetes (T2DM) among different ethnic groups in southwest China, while also exploring possible ethnic differences. Methods This is a prospective cohort study of 6,820 participants in Southwest China. MHO was defined as body mass index (BMI) ≥ 24 kg/m2 and the presence of ≤ 1 component of metabolic syndrome. Cox proportional risk models were utilized to analyze the association between MHO and the risk of T2DM. Results The median follow-up time was 6.58 years, during which 708 new cases of T2DM were diagnosed. In the total population, after adjusting for confounding factors, MHO was found to increase the risk of T2DM compared to metabolically healthy normal weight (MHNW) individuals (HR = 1.49, 95% CI: 1.15–1.93). Subgroup analysis by ethnicity revealed that, MHO increased the risk of T2DM in the Han population (HR = 1.64, 95% CI: 1.21–2.23), however, the difference was not statistically significant in the ethnic minority population.The results of sensitivity analysis further supported the robustness of these findings. Meanwhile, stratified by sex, age, and urban/rural, it was found that ethnic differences in the association between MHO and T2DM still existed, however, it is important to note that the association between MHO and T2DM was not statistically significant in the Han population subgroup aged ≥ 45 years (p > 0.05). Conclusion MHO was associated with an increased risk of T2DM compared to MHNW, and there are ethnic differences. Future interventions need to be strengthened for Han Chinese key populations to reduce the risk of T2DM.

Abstract Background Transfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors. Methods Adult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion. Results The analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion. Conclusion High WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Abstract Background Although the Stress-Coping Model (SCM) has been widely used to explain the coping process of individuals facing stressful situations, its applicability to caregivers of elderly people with dementia (PwD) in China needs to be further investigated. Furthermore, the role of external resources in caregivers stress coping is not yet clear. Therefore, our study aimed to investigated the mediating and moderating mechanisms between family burden and psychological distress in PwD caregivers based on the SCM. Methods A cross-sectional study, with 193 pairs of PwD and caregivers completed the self-designed questionnaire, Family Burden Scale of Disease, Kessler Psychological Distress Scale, General Self-Efficacy Scale, Simplified Coping Style Question, The Family Adaptation and Cohesion Evaluation Scales II-CV and Social Support Rating Scale. Partial least squares-structural equation modeling (PLS-SEM) analyzed the mediating and moderating effects. Results Family burden positively correlated with psychological distress; the chain mediation effects of self-efficacy and positive coping between family burden and psychological distress was significant; the interaction term (family function_positive coping) did not but (social support_positive coping) had a significant positive impact on psychological distress. Conclusions The findings provides a practical basis for the use of SCM in informal caregivers of elderly PwD, assists understanding the mechanism of the relationship between family burden and psychological distress. And it supplies new perspectives for reducing the negative psychological health status and a theoretical basis for designing interventions for caregivers.

Abstract Elaborating and understanding disparities in the burden of cardiovascular disease attributable to high fasting plasma glucose is important to improve diabetes prevention and promote cardiovascular health. In this study, we pool data on 791,373 people aged 25 years and older from three population-based surveys, and estimate the burden of cardiovascular disease attributable to high fasting plasma glucose between 2010 and 2018 in China by age, sex, region and socio-demographic index. In 2018, an estimated total of 498.61 thousand (95% uncertainty interval 463.93 to 534.12) cardiovascular disease-related deaths are attributable to high fasting plasma glucose in China. High fasting plasma glucose accounts for 1076.09 years of life lost per 100,000 people (95% uncertainty interval 1026.88–1129.04) due to cardiovascular disease in 2018, with substantial variation across provinces. In 2018, the higher age-standardised cardiovascular disease mortality rate attributable to high fasting plasma glucose is observed in the high-middle socio-demographic index region and the middle socio-demographic index region. Nationally, compared to 2010, exposure to high fasting plasma glucose and population aging in 2018 are the primary drivers of increased fasting plasma glucose-related deaths due to cardiovascular disease. Findings of this study emphasize the importance of developing population-specific tailored measures in China and other regions with similar condition.

Abstract Oats (Avena sativa L.) are rich in nutrients and bioactive compounds, serving as a roughage source for ruminants. This study investigated the impact of lactic acid bacteria (LAB), cellulase (M), and their combinations (LM) on the fermentation quality and metabolic compounds of oat silage. Results demonstrated that all additive treatments significantly increased lactic acid content compared to the control group (P

Abstract Background Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. Methods This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. Discussion This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. Trial registration Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

Abstract Background Quantifying the professional ethical challenges that nurses encounter is crucial for both theoretical insights and practical outcomes. The objective of this research is to assess the psychometric properties of the Chinese adaptation of the Moral Distress Scale for Healthcare Professionals (MD-APPS). Methods In 2024, a survey approach was utilized to engage with several tertiary-level healthcare institutions throughout China. A cohort of 448 nursing professionals who satisfied the specified selection benchmarks was consequently incorporated into the study. To evaluate the scale's reliability and validity, methods including the Content Validity Index (CVI), Factor Analysis—both Exploratory (EFA) and Confirmatory (CFA)—alongside assessments of internal consistency and test-retest reliability were employed. Results Expert evaluations yielded an I-CVI of 0.90, suggesting good content validity for the MD-APPS's Chinese adaptation. Exploratory Factor Analysis (EFA) revealed a bi-dimensional framework with 7 components, explaining 56.34% of the cumulative variance. Confirmatory Factor Analysis (CFA) outcomes displayed a χ-square/df ratio of 1.542. The estimate for Robust RMSEA was 0.054, and the SRMR was ascertained to be 0.041. Indices for both Robust TLI and Robust CFI surpassed the 0.9 threshold, indicating an acceptable fit; this aspect was supported by a P-value (Chi-square) of 0.094. The internal consistency, measured by Cronbach's α, was found to be 0.74, while the test-retest reliability over a two-week period reached 0.964. These findings provide initial evidence for the psychometric properties of the Chinese MD-APPS. Conclusion The Chinese adaptation of the MD-APPS demonstrates promising initial psychometric properties, suggesting its potential suitability for exploring nurses' professional ethical challenges within the Chinese cultural context. This scale may facilitate the identification of diverse elements influencing nurses' professional ethics and the assessment of the ethical climate in nursing practices. However, further validation studies are needed to fully establish its psychometric robustness across various healthcare settings in China.

Abstract Background The use of forced-air warming (FAW) blankets is widely recognized for preventing shivering and hypothermia in patients under general anesthesia. Various types of products are currently available for hospitals, and we have conducted a preliminary evaluation of insulation equipment based on expert opinions and initial parameters. However, we lack real-world experiments and accurate clinical data to validate these parameters and the accuracy of our decision-making results. This study aims to confirm the effectiveness of different FAW systems by assessing the thermal protection and operational characteristics of the equipment in both experimental and clinical settings, thereby enhancing our evaluation database. Methods In the manikin test, we conducted six tests including heat distribution and heating rate, heater outlet temperature stability, etc. In the clinical study, patients were randomly assigned to four groups [Group A (Bair Hugger Therapy, 3 M, St. Paul, MN, USA; 63500); Group B (EQUATOR® level I, Smith Medical ASD, MN, USA; Snuggle Warm, SW-2013); Group C (Jiang Men Da Cheng Medical Devices Co., Ltd, China; IOB-006); and Group D (Shang Hai Nest Tech Medical Materials Co., Ltd, China; BH-017)], with each group comprising 30 individuals. At the start of anesthesia induction, the FAW blanket was activated and set to 43 °C until the completion of surgery. The primary endpoint was the average core body temperature during surgery. Secondary endpoints included hemodynamic and surgical variables, adverse events, and recovery metrics. Results In the manikin test, the observed results of the experimental parameters (heat distribution, air pressure difference, and hole observation test) for Group A are superior to those of the other groups. In the clinical study, although the mean perioperative core body temperature remained above 36 °C across all groups [Group A: 36.31 ± 0.04; Group B: 36.26 ± 0.06; Group C: 36.17 ± 0.03; Group D: 36.25 ± 0.05], patients in Group A maintained higher temperatures compared to the other groups (p

AIM: To examine the disparities in macular retinal vascular density between individuals with connective tissue disease-related interstitial lung disease (CTD-ILD) and healthy controls (HCs) by optical coherence tomography angiography (OCTA) and to investigate the changes in microvascular density in abnormal eyes. METHODS: For a retrospective case-control study, a total of 16 patients (32 eyes) diagnosed with CTD-ILD were selected as the ILD group. The 16 healthy volunteers with 32 eyes, matched in terms of age and sex with the patients, were recruited as control group. The macular retina's superficial retinal layer (SRL) and deep retinal layer (DRL) were examined and scanned using OCTA in each individual eye. The densities of retinal microvascular (MIR), macrovascular (MAR), and total microvascular (TMI) were calculated and compared. Changes in retinal vascular density in the macular region were analyzed using three different segmentation methods: central annuli segmentation method (C1-C6), hemispheric segmentation method [uperior right (SR), superior left (SL), inferior left (IL), and inferior right (IR)], and Early Treatment Diabetic Retinopathy Study (ETDRS) methods [superior (S), inferior (I), left (L), and right (R)]. The data were analyzed using Version 9.0 of GraphPad prism and Pearson analysis. RESULTS: The OCTA data demonstrated a statistically significant difference (P

Background With the changing disease spectrum of the population and the advancement of the national tiered diagnosis and treatment system, general practitioners play a vital role in disease diagnosis and treatment. At the same time, the continuous updating of medical knowledge and the ongoing changes in the health service demands of the residents necessitate the ongoing participation of general practitioners in continuing education and training. This ensures they can make the best diagnostic and treatment decisions and manage diseases effectively for their patients. Objective To analyze the current developments, training quality and research quality of continuing education research of general practice in China in the past ten years (2013-2022) . Methods In January 2023, eight Chinese and English databases including PubMed, Cochrane Library, Embase, CINAHL, ERIC, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and China Biology Medicine Literature Service System were used as data sources to obtain research on the training of continuing education for general practitioners in China. The literature was read, analyzed, organized, and summarized, with the search period ranging from January 2013 to December 2022. The Medical Education Research Study Quality Instrument (MERSQI) was utilized to comprehensively evaluate the quality of the literature. Results This review included a total of 49 articles, of which 11 were in English and 38 in Chinese. The themes of continuing education training focused on cardiovascular and cerebrovascular diseases (22.4%), emergency-related content (6.1%), and mental health (6.1%). The training formats were relatively singular, mainly based on traditional expert lectures (69.3%), with only 6.1% adopting the form of skill training, and 4.0% of the studies using problem-based learning (PBL) or team-based learning (TBL) training formats. There was usually a lack of rigorous evaluation: 31 studies (63.2%) used questionnaires to assess the effectiveness of the training, of which 19 had not undergone validity and reliability testing. In the study design, the largest proportion was single-group pre-post comparison (53.1%), followed by randomized controlled trials with pre-post measurements (26.5%), and the smallest proportion was controlled pre-post comparison (4.1%). Only 9 studies (18.3%) explicitly mentioned ethical approval, while the majority of studies (81.7%) did not undergo ethical review. The evaluations focused on the enhancement of knowledge and skills of general practitioners before and after trainin (85.7%), with less coverage of actual behavioral changes (14.2%) and benefits to patients and healthcare facilities (22.4%) . Conclusion In the past decade, the attention to general practice continuing education research has been insufficient, but there is significant room for development. In the future, it is necessary to expand training themes and adopt diverse training methods based on actual needs. Utilizing assessment tools with good validity and reliability, and focusing on the actual behavioral changes brought about by training, will benefit patients and enhance the quality of continuing education for general practitioners in multiple dimensions.

The extant research evidence indicates that sensible exercise has a beneficial impact on the prevention and treatment of cancer. This paper presents a comprehensive literature review of the field of sports oncology. Its objective is to synthesize and analyze the impact of exercise training on cancer, as well as to elucidate the mechanisms through which exercise affects cancer progression. Additionally, it offers valuable insights for advancing fundamental and clinical research in sports oncology. Firstly, this paper provides a summary of the relationship between exercise and various aspects of tumor progression, including tumor size, weight, metastasis, tumor vascularity, myokine production, immune response, and the efficacy of cancer chemotherapy. Secondly, due to the diversity of tumor properties, we also explore the fact that the specificity of exercise prescription should be tailored to the different tumor types and patient profiles. Furthermore, we discuss the importance of considering individual differences when determining the type of exercise, intensity, intervention, and duration of exercise. Finally, this paper emphasizes the necessity of evaluating the interaction between exercise and conventional or novel immunotherapies and pharmacodynamics in future preclinical studies.

Sensing signals of many real-world network systems, such as traffic network or microgrid, could be sparse and irregular in both spatial and temporal domains due to reasons such as cost reduction, noise corruption, or device malfunction. It is a fundamental but challenging problem to model the continuous dynamics of a system from the sporadic observations on the network of nodes, which is generally represented as a graph. In this paper, we propose a deep learning model called Evolved Differential Model (EDM) to model the continuous-time stochastic process from partial observations on graph. Our model incorporates diffusion convolutional network to parameterize continuous-time system dynamics by graph Ordinary Differential Equation (ODE) and graph Stochastic Differential Equation (SDE). The graph ODE is applied to accurately capture the spatial-temporal relation and extract hidden features from the data. The graph SDE can efficiently capture the underlying uncertainty of the network systems. With the recurrent ODE-SDE scheme, EDM can serve as an accurate online predictive model that is effective for either monitoring or analyzing the real-world networked objects. Through extensive experiments on several datasets, we demonstrate that EDM outperforms existing methods in online prediction tasks.

Abstract Introduction Post-keratoplasty glaucoma (PKG) is a major complication following penetrating keratoplasty (PKP) for congenital corneal opacity (CCO). This study aims to assess the preoperative structural risk factors for PKG following PKP for CCO using ultrasound biomicroscopy (UBM). Methods Pediatric patients with CCO who underwent preoperative UBM and primary PKP were enrolled. Patients with anterior segment operation history or with a follow-up duration less than 12 months were excluded. The structural features of the anterior segment including central corneal thickness, anterior chamber depth, angle closure range (ACR), anterior synechia range, maximum iridocorneal adhesion length, abnormal iridocorneal synechia, and lens anomalies were identified on UBM images. The medical histories were reviewed to identify clinical features. The incidence of PKG was assessed to determine significant structural and clinical risk factors. Results Fifty-one eyes of 51 pediatric patients with CCO were included. The median age at surgery was 8.0 months, and the mean follow-up duration was 33 ± 9 months. Eleven (21.6%) eyes developed PKG. The main structural risk factors were abnormal iridocorneal synechia (P = 0.015), lens anomaly (P = 0.001), and larger ACR (P = 0.045). However, a larger range of normal anterior synechia without involvement of the angle was not a significant risk factor. Preoperative glaucoma (P

Abstract Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti‐tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co‐inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti‐tumor immune response and promote immune‐mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been firstly used in solid tumors and subsequently expanded to hematological malignancies, which are in their infancy. Currently, immune checkpoints have been investigated as promising biomarkers and therapeutic targets in hematological malignancies, and novel immune checkpoints, such as signal regulatory protein α (SIRPα) and tumor necrosis factor‐alpha‐inducible protein 8‐like 2 (TIPE2), are constantly being discovered. Numerous ICIs have received clinical approval for clinical application in the treatment of hematological malignancies, especially when used in combination with other strategies, including oncolytic viruses (OVs), neoantigen vaccines, bispecific antibodies (bsAb), bio‐nanomaterials, tumor vaccines, and cytokine‐induced killer (CIK) cells. Moreover, the proportion of individuals with hematological malignancies benefiting from ICIs remains lower than expected due to multiple mechanisms of drug resistance and immune‐related adverse events (irAEs). Close monitoring and appropriate intervention are needed to mitigate irAEs while using ICIs. This review provided a comprehensive overview of immune checkpoints on different immune cells, the latest advances of ICIs and highlighted the clinical applications of immune checkpoints in hematological malignancies, including biomarkers, targets, combination of ICIs with other therapies, mechanisms of resistance to ICIs, and irAEs, which can provide novel insight into the future exploration of ICIs in tumor treatment.

With the construction of a diversified electricity market, the factors affecting electricity prices are gradually increasing, and the market environment has undergone more drastic changes. In order to improve the accuracy of short-term electricity price prediction, an improved Transformer-particle swarm optimization (PSO) short-term electricity price prediction method considering multiple factors affecting electricity prices is proposed. First, based on the consideration of historical electricity prices and historical loads, the relevant factors of electricity price formation are further analyzed. The autocorrelation function is used to analyze the multi-cycle characteristics of electricity price and adjust input sequence, which overcomes the problem of limited prediction accuracy caused by using historical data only and adjusting the input sequence by experience. Then, by combining long short-term memory (LSTM), self-attention mechanism, multi-layer attention mechanism, and adopting a multi-input structure, an improved Transformer model is established to further enhance the ability of the LSTM model to capture long short-term dependencies between different time step information, to overcome the information utilization bottleneck of LSTM, and to adapt to complex multiple sequence inputs including historical electricity prices and various electricity price causes. In addition, the PSO intelligent algorithm is utilized to search for the optimal learning rate of the model at different learning stages, overcoming the limitations of manually adjusting the learning rate. Finally, the PJM market electricity price is used for example analysis. The results show that the proposed short-term electricity price prediction model can be applied to the market environment where electricity prices are affected by various factors and drastic changes, and effectively improve the accuracy of short-term electricity price prediction.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Dendritic cells (DCs) constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses. As a crucial component of the immune system, DCs have a pivotal role in the pathogenesis and clinical treatment of CRC. DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response. However, the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment. This review systematically elucidates the specific characteristics and functions of different DC subsets, as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment. Moreover, how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed, which will provide new perspectives and approaches for immunotherapy in patients with CRC.

Abstract Objective Premenstrual Syndrome is also known as premenstrual tension syndrome because of the pronounced premenstrual mental and emotional anomalies. This study focuses on the association between occupational stress, sleep quality and premenstrual syndrome in clinical nurses and the mediating role of sleep quality. Methods A cross-sectional study was conducted to measure occupational stress, sleep quality and premenstrual syndrome in 415 clinical nurses using the Chinese Nurses Stressor Scale, the Pittsburgh Sleep Quality Index Scale, and the Premenstrual Syndrome Scale. SPSS was used to explore the relationship between the variables, and AMOS was used to explore the mediating role between the variables. Results Nurses’ occupational stress positively predicted PMS (β = 0.176, p

Abstract Objective This study aims to evaluate the impact of virtual simulation experiment teaching model and Massive Open Online Course (MOOC) teaching model on the teaching effect in debridement teaching. Methods The study adopted a quasi-experimental design and used virtual simulation technology to construct a virtual simulation experimental teaching platform for debridement. This study was conducted at the Second Clinical College of Wuhan University. The experimental group was composed of 135 third-year clinical medicine students in the 2020 grade, who received the virtual simulation experimental teaching model; the control group was 122 third-year students in the same major in the 2019 grade, who used the MOOC teaching model. The performance of the two groups of students was evaluated through theoretical tests and animal experiment operation. In addition, the effectiveness of the experimental teaching model and student satisfaction were evaluated through questionnaire surveys. Results The theoretical test scores and animal experiment report scores of the experimental group were significantly higher than those of the control group, and the debridement animal experiment operation time of the experimental group was shorter than that of the control group, and the difference was statistically significant (P

Abstract Atomically dispersed single atom (SA) and atomic cluster (AC) metallic materials attract tremendous attentions in various fields. Expanding monometallic SA and AC to multimetallic SA/AC composites opens vast scientific and technological potentials yet exponentially increasing the synthesis difficulty. Here, we present a general energy-selective-clustering methodology to build the largest reported library of carbon supported bi-/multi-metallic SA/AC materials. The discrepancy in cohesive energy results into selective metal clustering thereby driving the symbiosis of multimetallic SA or/and AC. The library includes 23 bimetallic SA/AC composites, and expanded compositional space of 17 trimetallic, quinary-metallic, septenary-metallic SA/AC composites. We chose bimetallic M1 SAM2 AC to demonstrate the electrocatalysis utility. Unique decoupled active sites and inter-site synergy lead to 8/47 mV overpotential at 10 mA cm−2 for alkaline/acidic hydrogen evolution and over 1000 h durability in water electrolyzer. Moreover, delicate modulations towards composition and configuration yield high-performance catalysts for multiple electrocatalysis systems. Our work broadens the family of atomically dispersed materials from monometallic to multimetallic and provides a platform to explore the complex composition induced unconventional effects.

Abstract As one of the most common tumors in women, the pathogenesis and tumor heterogeneity of breast cancer have long been the focal point of research, with the emergence of tumor metastasis and drug resistance posing persistent clinical challenges. The emergence of single-cell sequencing (SCS) technology has introduced novel approaches for gaining comprehensive insights into the biological behavior of malignant tumors. SCS is a high-throughput technology that has rapidly developed in the past decade, providing high-throughput molecular insights at the individual cell level. Furthermore, the advent of multitemporal point sampling and spatial omics also greatly enhances our understanding of cellular dynamics at both temporal and spatial levels. The paper provides a comprehensive overview of the historical development of SCS, and highlights the most recent advancements in utilizing SCS and spatial omics for breast cancer research. The findings from these studies will serve as valuable references for future advancements in basic research, clinical diagnosis, and treatment of breast cancer.