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Students' problem-solving strategies and the differences among strategy groups were explored by analyzing the process data collected during student interactions with computer-based science items. Data were gathered from 1516 eleventh-grade students from 4 schools in China. Analyses of the sequences of students' response actions revealed that the students were divided into four strategy groups when designing experiments to solve scientific problems: the scientific and rigorous strategy (18.5%), scientific and less rigorous strategy (25.4%), incomplete strategy (31.5%), and chaotic strategy (24.6%). The heatmaps of response actions for each strategy and the frequencies of the most representative response sequences were further explored to understand the students' detailed trajectories. The results showed that successful problem solvers were generally inclined to explore all possibilities of experimental combinations and design experiments scientifically and rigorously based on the relevant scientific principles. Moreover, the timestamps of response actions were explored to show that the students who adopted the scientific and rigorous strategy spent more time seeking solutions, suggesting that students may need sufficient time to solve complex and authentic scientific problems. The findings enrich the literature on using process data to address theoretical issues in educational assessment and provide students with individualized instructional needs for teachers to improve students' scientific problem-solving competency.

Abstract A leaf spot disease affecting Curcuma kwangsiensis (Zingiberaceae) has been observed in Qinzhou City, Guangxi Province. Infected leaves exhibit yellow-brown spots that progressively expand and eventually lead to leaf death. Curvularia isolates were obtained from the diseased leaves with tissue isolation and single spore purification methods. To accurately identify these isolates, we analyzed their morphological characteristics and phylogenetic relationships using combinations of ITS, GAPDH, and EF-1α gene sequences. Phylogenetic analysis showed that the investigated strains formed a distinct clade separate from other recognized Curvularia species. Furthermore, the strains exhibited differences in conidiophore size and conidia shape/size. Based on phylogenetic studies, morphology, and pathogenicity tests, the pathogen was identified as a new species named Curvularia qinzhouensis. Optimal conditions for mycelial growth were observed at 30 °C and pH 8. The sensitivity of the pathogen to various phytochemicals was also examined. Honokiol, thymol, and citral demonstrated effective antifungal effects, with EC50 values of 6.72 ± 1.75, 25.74 ± 4.30, and 54.24 ± 4.69 µg/ml, respectively. The present investigation provides the first report of leaf spot disease on C. kwangsiensis caused by C. qinzhouensis, and valuable insights for the prevention and control of this disease.

Adding heterogeneous fillers with high thermal conductivity (TC) to polymer has been recognized as an effective way to increase the effective thermal conductivity (ETC) of polymer composites. Extensive researches have been conducted on the ETC of composites with heterogeneous fillers. However, the heat transfer enhancement mechanism of heterogeneous fillers remains unknown, and the combined effects of filler size, filler contact, interface thermal resistance (Rc) and other parameters on the ETC have not been explored. In this study, above combined effects are investigated. The results show that the filler contact and Rc are the key factors determining the ETC. The ETC of composite with filler contacts reaches 2.35 at filler content of 25%, which is 11.9% higher than that without filler contacts. The ETC also strongly depends on the R*c (dimensionless form of Rc) ratio (R*c1/R*c2) between two fillers, with it becoming asymmetrical when the amount of R*c(R*c1 + R*c2) is larger. The ETCs decrease with the increase of R*c1/R*c2 when the R*c1/R*c21. When R*c1 + R*c2 is a constant, the ETC increases with the competing effects of R*c. The models with filler contacts exhibit higher accuracy than other classical models in calculating the ETC across the entire range of filler content.

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 Quantum walks provide a speed-up in computational power for various quantum algorithms and serve as inspiration for the construction of complex graph representations. Many pioneering works have been dedicated to expanding the experimental state space and the complexity of graphs. However, these experiments are mostly limited to small experimental scale, which do not reach a many-body level and fail to reflect the multi-particle quantum interference effects among non-adjacent modes. Here, we present a quantum walk with three photons on a two-dimensional triangular lattice, which is mapped to a 19 × 19 × 19 high-dimensional state space and constructs a complex graph with 6859 nodes and 45,486 edges. By utilizing the statistical signatures of the output combinations and incorporating machine learning techniques, we successfully validate the nonclassical properties of the experiment. Our implementation provides a paradigm for exponentially expanding the state space and graph complexity of quantum walks, paving the way for surmounting the classical regime in large-scale quantum simulations.

Abstract Background Hypertension is a common disease, often overlooked in its early stages due to mild symptoms. And persistent elevated blood pressure can lead to adverse outcomes such as coronary heart disease, stroke, and kidney disease. There are many risk factors that lead to hypertension, including various environmental chemicals that humans are exposed to, which are believed to be modifiable risk factors for hypertension. Objective To investigate the role of environmental chemical exposures in predicting hypertension. Methods A total of 11,039 eligible participants were obtained from NHANES 2003–2016, and multiple imputation was used to process the missing data, resulting in 5 imputed datasets. 8 Machine learning algorithms were applied to the 5 imputed datasets to establish hypertension prediction models, and the average accuracy score, precision score, recall score, and F1 score were calculated. A generalized linear model was also built to predict the systolic and diastolic blood pressure levels. Results All 8 algorithms had good predictions for hypertension, with Support Vector Machine (SVM) being the best, with accuracy, precision, recall, F1 scores and area under the curve (AUC) of 0.751, 0.699, 0.717, 0.708 and 0.822, respectively. The R2 of the linear model on the training and test sets was 0.28, 0.25 for systolic and 0.06, 0.05 for diastolic blood pressure. Conclusions In this study, relatively accurate prediction of hypertension was achieved using environmental chemicals with machine learning algorithms, demonstrating the predictive value of environmental chemicals for hypertension.

Abstract We aimed to implement a fully automatic computed tomography (CT) image-detection programming algorithm as a pectus excavatum (PE) diagnostic tool, facilitating comprehensive chest wall deformity evaluation. We developed our algorithm using MATLAB, leveraging the Hounsfield unit threshold and region growing methods. The MATLAB graphical user interface enables the direct use of our program. We validated the model using CT images of anthropomorphic phantoms and one normal individual. The measurement values obtained by our algorithm demonstrated very small differences compared to the known anthropomorphic phantom model data and manual measurement. For algorithm testing, 17,214 chest CT scans obtained from 57 PE patients were processed by the algorithm and independently reviewed by a radiologist and a thoracic surgeon. The measurements of transverse, anteroposterior, and sternum-to-vertebral distance of the thoracic cavity, along with the calculated data of four indices, exhibited high positive correlations (0.94–0.99). The asymmetry index and maximum anteroposterior hemithorax distance exhibited moderate correlation (0.40–0.83). Our automatic PE diagnostic tool demonstrated high accuracy; four chest wall deformity indices were obtained simultaneously without any initial manual marking, correlating well with manual measurements.

Abstract The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.

In this study, in order to investigate the phospholipid composition characteristics and hypoglycemic activity of krill oil, we determined the content of total phospholipids in krill oil by a colorimetric method, examined the phospholipid composition by high-resolution mass spectrometry, and then applied the mass spectral fragmentation pattern and the databases Lipidmaps and Lipidblast for structural analysis. Furthermore, we evaluated the effect of krill oil on blood glucose, biochemical indexes and gene expression levels related to the regulation of blood glucose in a zebrafish model of hyperglycemia induced by the combined treatment of alloxan and sucrose, and explored the potential sites of hypoglycemic action of krill oil-specific phospholipid docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) by molecular docking. The results showed that the content of phospholipids in cold-extracted krill oil was 57.57%, and a total of 63 phospholipids were identified, of which phosphatidylcholine (PC) was the most abundant. Krill oil significantly reduced blood glucose concentration, elevated insulin and glycogen levels, inhibited the expression of FOXO1/PCK1/G6PC, and promoted the expression of GLUT4 in hyperglycemic zebrafish. Molecular docking revealed that DHA and EPA in krill oil might act at the FOXO1/PCK1/G6PC sites, suggesting close relationship between the phospholipid components and the hypoglycemic activity of krill oil. In summary, this study found that cold-extracted krill oil is rich in phospholipids and is a potential natural product with good hypoglycemic effect.

ABSTRACT Importance Digital technology is now widely available for the interventions of autism, but its validity and feasibility remain to be proved. Objective This study aimed to investigate the effectiveness of digital health interventions (DHIs) in improving core symptoms or intelligence quotient in patients with autism spectrum disorder (ASD). Methods Three databases including PubMed, Cochrane, and Scopus, were searched on November 15, 2022. Randomized clinical trials that enrolled patients with ASD who received DHIs and a control group without DHI treatment were included. Cochrane risk of bias tool (RoB 2) was applied to assess the risk of bias. Results A total of 33 studies, involving 1285 participants (658 [51.2%] in DHI groups and 627 [48.8%] in control groups), were analyzed to investigate the differences between DHI groups and control groups. Significantly greater improvements in the overall performance of ASD were observed in the DHI groups compared to the control groups (including active, waitlist, treatment‐as‐usual, and no treatment) with an effect size of 1.89 (Cohen's d 95% confidence interval [CI]: 1.26–2.52). Studies with treatment‐as‐usual, waitlist, and no treatment control demonstrated large effect sizes of Cohen's d 3.41 (95% CI: 0.84–5.97), Cohen's d 4.27 (95% CI: 1.95–6.59), and Cohen's d 4.52 (95% CI: 2.98–6.06) respectively. In contrast, studies with active control revealed insignificant effect sizes (Cohen's d 0.73, 95% CI: 0.12–1.33). Interpretation This meta‐analysis found significantly greater improvements in core symptoms or intelligence quotient in ASD patients receiving DHIs compared to those in control conditions. ASD patients may benefit from the DHIs and reduce the economic burden.

The SAF2507 duplex stainless steel with the heterogeneous structure is produced through cold rolling (ε = 90%) and subsequent 1-min normalizing at 1273 K. Compared with the corresponding initial samples, the grain sizes of ferrite and austenite phases in the 90%-1273 sample are refined by 90%, which led to an increase in the number of grain or phase boundaries between the two phases. The yield strength (YS) of the 90%-1273 sample increased to 715 MPa from 541 MPa, while the uniform elongation of 24.8% is slightly smaller than that of the coarse-grained sample. The higher YS is mainly contributed by the strengthening of grain refinement and dislocation strengthening by incorporating geometrically necessary dislocations (GNDs). During tensile deformation, the accumulation of GNDs in the heterostructured sample continuously generates hetero-deformation-induced (HDI) stress. The HDI stress plays a positive role in the 90%-1273 sample showing an ultimate tensile strength of 939 MPa. Additionally, the amount of twin boundaries in the 90%-1273 sample rose from 4.5% to 35% during tensile deformation, which indicated that the twinning induced plasticity effect was helpful in retaining the ductility of the 90%-1273 sample. This work provides strategies for optimizing the mechanical properties of duplex stainless steels and contributes to understanding the essence of a superior combination of strength and ductility of heterostructured materials.

Abstract Purpose This study aimed to compare the clinical outcomes and differences in biomechanical characteristics between the femoral neck system (FNS) and cannulated cancellous screws (CCSs) in the treatment of femoral neck fractures. Methods This study retrospectively analysed a cohort of 38 registered cases of femoral neck fractures treated surgically with either the FNS (n = 17) or CCSs (n = 21) between January 2020 and December 2023. Indicators such as fluoroscopy frequency, length of hospital stay, and fracture healing time were compared between the two groups. Functional status was evaluated via the Harris hip score (HHS) and visual analogue scale (VAS), whereas prognosis was assessed based on changes in the neck shaft angle and femoral neck shortening. Additionally, six sets of femoral neck fracture models were developed based on Pauwels angles of 30°, 40°, 50°, 60°, 70°, and 80°. Two experimental groups, FNS and CCS, were established, and a joint reaction force of 1800 N was applied to the proximal femur. The displacement, stress, and stiffness of the components of interest in the different models were tested and compared. Results The distributions of all the baseline characteristics were similar between the two groups (p > 0.05). The FNS group presented significantly shorter fluoroscopy frequency, length of hospital stay, and fracture healing time (p

The damage threshold of an Au-coated flat mirror, one of the reflective optics installed on the FEL-2 beamline of the Dalian Coherent Light Source, China, upon far-UV free-electron laser irradiation is evaluated. The surface of the coating is characterized by profilometer and optical microscope. A theoretical approach of the phenomenon is also presented, by application of conventional single-pulse damage threshold calculations, a one-dimensional thermal diffusion model, as well as finite-element analysis with ANSYS.

Red raspberries, Rubus idaeus L. 1753 are famous fruits which possess high value bioactive compounds. In this study, we report the complete chloroplast genome of R. idaeus, it displayed a typical quadripartite structure with 155687 bp in length. The genome encodes 127 genes including 79 protein coding genes, 8 rRNA genes and 40 tRNA genes, the overall GC content is 37.2%. Phylogenetic analysis revealed a close relationship between R. idaeus and R. sachalinensis in Section Malaehobatus.

Clavulina possesses important ecological and economic value and has attracted extensive attention from mycologists. Macrofungal diversity is high in China, but Clavulina species have not been thoroughly studied. In this study, based on morphological evidence and phylogenetic analyses of the nucleotide sequences of three loci (nrITS, nrLSU, and rpb2), three new species of Clavulina from North China were identified. Morphologically, Clavulina chengdeensis is characterized by its white to dirty white basidiomata with somewhat pale orange tips and somewhat wrinkled hymenium. Clavulina griseoviolacea is characterized by its gray to dark grayish violet basidiomata, with a sometimes-white stipe base, monopodial or irregularly polychotomous toward branch apices. Clavulina pallida is characterized by its white to pale cream white basidiomata with somewhat orange tips. Phylogenetically, the three new species form three independent branches with high support values in the phylogenetic tree.

Abstract Introduction This study sought to evaluate the cost-effectiveness of baloxavir marboxil compared with oseltamivir or no antiviral treatment from a US payer perspective using data from a real-world US administrative claims study. Given baloxavir’s ability to rapidly stop viral shedding, the potential health economic implications of a baloxavir-induced population-level reduction in viral transmission was also explored. Methods A decision tree cost-effectiveness model was developed for seasonal influenza (2018–2020) using a lifetime time horizon with 3.0% discounting for costs and quality-adjusted life-years (QALYs). Patients aged ≥ 12 years could receive baloxavir, oseltamivir or no antiviral treatment. Patient characteristics, complications, and costs were derived from the Merative™ MarketScan® Research Databases including US commercial claims and Medicare and Medicaid Supplemental databases. A scenario analysis explored the impact of reduced viral transmission with baloxavir. Results In the base case analysis, baloxavir was cost-effective within a willingness-to-pay threshold of US$100,000/QALY compared with oseltamivir [incremental cost-effectiveness ratio (ICER), $6813/QALY gained] or no antiviral treatment (ICER, $669/QALY gained). The net monetary benefit (NMB) of baloxavir was $1180 and $6208 compared with oseltamivir and no treatment, respectively. The NMB of baloxavir increased linearly with reductions in viral transmission, where a 5% transmission reduction yielded an NMB of $2592 versus oseltamivir and $7621 versus no treatment. Baloxavir became dominant (more effective and less costly, with ICERs

Based on the laboratory uniaxial compression test, a numerical model was established by particle flow software and the microscopic parameters were calibrated. The stress-strain curves, the number of micro-cracks, the failure process and the change of microscopic displacement field of gangue cemented backfill samples were studied under different loading rates. The results show that the peak strength and elastic modulus of the sample increase with the increase of loading rate. The number of microcracks is proportional to the loading rate; the microcrack-strain curves can be divided into three stages: no crack initiation, rapid crack growth and stable crack number; the failure process of the sample is divided into four stages: compaction, elastic deformation, plastic failure and residual deformation; the particles on both sides of the microcrack of the sample have different forms of combined failure, including tensile failure, shear failure and mixed failure of tensile and shear action.

Abstract This paper provides a study for crystallographic orientation-dependent corrosion rate of aluminum employing an ab initio model with inputs from first-principles calculations. Results showed that the sequence of corrosion rate is in the order of (111)

Abstract Locally resonant metamaterials usually have narrow bandgaps, which significantly limits their applications in realistic engineering environments. In this paper, an optimization method based on the genetic algorithm is proposed to broaden bandgaps in multi-resonant piezoelectric metamaterial through the merging of multiple separated bandgaps. Using the effective medium theory, the equivalent bending stiffness and dispersion relationship of a metamaterial plate are first obtained. Then, the criteria for determining the bandgap ranges for the two cases with and without damping are provided and analyzed. Furthermore, based on the bandgap merging phenomena, an optimization method for widening the bandgap is proposed based on the genetic algorithm. By investigating the bandgap widening effects in cases without and with damping, it is found that, when there is no damping, the bandgap can only be slightly widened; while after introducing damping into the transfer functions, the bandgap can be significantly widened by more than 200%. The bandgap widening effects are verified by comparing with finite element simulation results.

Abstract Our study presents the assembly of a high-quality Taihu goose genome at the Telomere-to-Telomere (T2T) level. By employing advanced sequencing technologies, including Pacific Biosciences HiFi reads, Oxford Nanopore long reads, Illumina short reads, and chromatin conformation capture (Hi-C), we achieved an exceptional assembly. The T2T assembly encompasses a total length of 1,197,991,206 bp, with contigs N50 reaching 33,928,929 bp and scaffold N50 attaining 81,007,908 bp. It consists of 73 scaffolds, including 38 autosomes and one pair of Z/W sex chromosomes. Importantly, 33 autosomes were assembled without any gap, resulting in a contiguous representation. Furthermore, gene annotation efforts identified 34,898 genes, including 436,162 RNA transcripts, encompassing 806,158 exons, 743,910 introns, 651,148 coding sequences (CDS), and 135,622 untranslated regions (UTR). The T2T-level chromosome-scale goose genome assembly provides a vital foundation for future genetic improvement and understanding the genetic mechanisms underlying important traits in geese.

Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.

Abstract In the process of lower coal roadway support under double gobs in close coal seams, there are problems such as the whole destruction of the lower coal seam and the intermediate strata, the thin roof of the lower coal roadway with the smaller support space, the upper rock of the lower coal roadway without anchor bearing layer, the roof falling, the anchor cable offing, and so on. On the basis of the engineering background of No. 11103 haulage roadway in Fenxi coal mine, the research methods of theoretical modeling analysis, numerical simulation analysis and field engineering test are comprehensively adopted. In this paper, the layout of the roadway with floor insertion in the lower coal seam, the distribution characteristics of surrounding rock deviatoric stress, the control principle of broken surrounding rock and the coupling support method of shed–cable–prop are systematically studied. The study shows that many measures are needed to ensure the stability of the surrounding rock in the strong mining roadway of the lower coal seam. The lower coal seam roadway section was modified from the original rectangular section to adopt an arched section to counteract the broken roof. The staggered position of the lower coal seam roadway layout was modified from the original coal roadway position to a coal–rock roadway, so as to avoid the area of high deviatoric stress in the coal pillar and the area of crushed coal body, and to leave an effective support space for the roof. The support scheme of the lower coal seam roadway was improved to use anchor cable and single prop to support the weak section of U‐type steel shed with local coupling, and realize unequal force coupling by adjusting the size of the force at different coupling points. In the field monitoring the deformation of the roadway is small, and the support effect is good.

Abstract Chemotherapy and immunotherapy have shown no significant outcome for unresectable pancreatic ductal adenocarcinoma (PDAC). Multi-drug combination therapy has become a consensus in clinical trials to explore how to arouse anti-tumor immunity and meanwhile overcome the poorly tumoricidal effect and the stroma barrier that greatly hinders drug penetration. To address this challenge, a comprehensive strategy is proposed to fully utilize both the ferroptotic vulnerability of PDAC to potently irritate anti-tumor immunity and the desmoplasia-associated focal adhesion kinase (FAK) to wholly improve the immunosuppressive microenvironment via sustained release of drugs in an injectable hydrogel for increasing drug penetration in tumor location and averting systematic toxicity. The injectable hydrogel ED-M@CS/MC is hybridized with micelles loaded with erastin that exclusively induces ferroptosis and a FAK inhibitor defactinib for inhibiting stroma formation, and achieves sustained release of the drugs for up to 12 days. With only a single intratumoral injection, the combination treatment with erastin and defactinib produces further anti-tumor performance both in xenograft and KrasG12D-engineered primary PDAC mice and synergistically promotes the infiltration of CD8+ cytotoxic T cells and the reduction of type II macrophages. The findings may provide a novel promising strategy for the clinical treatment of PDAC.

Abstract Purpose Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis. Methods A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood. Results In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments. Conclusion The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

ABSTRACT Background Anxiety disorder is one of the most common mental disorders and often accompanied with sleep disturbance which can in turn exacerbate anxiety symptoms, creating a vicious cycle. In addition to psychopharmacological therapy, the effectiveness of psychotherapy as cognitive behavioral therapy (CBT) for treating anxiety disorders and insomnia has been well documented and widely accepted, but it is labor‐intensive and costly. However, virtual reality (VR)–integrated CBT may improve this condition but needs more evidences to support its extensive application in routine clinical practice. Objectives This explorative study was aimed to conduct a retrospective analysis to evaluate the acute (2 weeks) augmented effect of VR‐integrated relaxation and mindfulness exercising in improving anxiety and insomnia symptoms for patients who were diagnosed with anxiety disorders and concurrently with prominent insomnia symptoms and admitted to the Department of Psychiatry, The Affiliated Guangdong Second Provincial General Hospital of Jinan University during January 2021 to June 2021. Methods All patients who were admitted to the department of psychiatry during January 1, 2021 to June 30, 2021 were screened with inclusion criteria and exclusion criteria, and the sociodemographic and clinical data of those included patients were collected from the electronic medical record system of the hospital using a self‐designed case report form (CRF). Subjects who were administrated with medication alone were designated as conventional group, and those receiving treatment of medication combined with VR‐integrated CBT (VR relaxation and mindfulness exercising) as VR group. The baseline and 2‐week posttreatment data were compared between the two groups. Results In total, there were 103 patients (70 female, 68%) included in the study. Among all, 68 (66.02%) were designated as the “VR group,” and 35 (33.98%) as the “conventional group.” The majority of patients (67%) were diagnosed with generalized anxiety disorder (GAD). Twenty‐three (22.3%) patients had a comorbid diagnosis with primary insomnia, and insomnia was just one of the accompanying symptoms with anxiety for the rest 80 subjects. No statistically significant differences were found between VR and conventional groups in all baseline sociodemographic and clinical characteristics except for occupation. There were statistically significant differences for the remission rates of anxiety symptoms or insomnia symptoms and reduction of Hamilton Anxiety Rating Scale or Insomnia Severity Index total scores between conventional and VR groups. Greater remission rates or score reductions were found in VR group than in conventional group either for anxiety or for insomnia. Robust differences still existed when controlled for the variable “occupation.” Conclusions Two‐week augmented VR‐integrated relaxation and mindfulness exercising is acutely beneficial for relieving both anxiety and insomnia symptoms and worth being recommended for routine clinical practice. Further prospective and randomized study compared to traditional CBT to explore its acute and long‐term effect on anxiety and insomnia is needed.

BackgroundExternalizing problem behaviors can significantly and negatively impact adolescents’ learning, daily life, and future socialization. While physical exercise is believed to inhibit adolescents’ externalizing problem behaviors, the extent of its effect and the mediating mechanisms remain unclear.MethodsThis study is based on data from the 2018 China Family Panel Studies (CFPS). The CFPS project employed the Externalizing Problem Behaviors Scale (EPBS), the Rosenberg Self-Esteem Scale (RSES), and the Self-Control Scale (SCS) to measure adolescents’ externalizing problem behaviors, self-esteem, and self-control. Additionally, physical exercise was measured by collecting data on the time and frequency of adolescents’ physical exercise. Parent-child relationships were evaluated using a composite variable that included four dimensions: frequency of quarrels, frequency of heart-to-heart talks, parental awareness of their children’s whereabouts, and children’s trust in their parents. Based on data collection and variable construction, this study employed multiple linear regression, propensity score matching, and quantile regression to analyze the impact of physical exercise on adolescents’ externalizing problem behaviors and the heterogeneity of these effects. Additionally, the Bootstrap mediation effect test was employed to explore the mediating roles of parent-child relationships, self-esteem, and self-control in this process.ResultsThe analysis demonstrates that physical exercise significantly inhibits adolescents’ externalizing problem behaviors (β = −0.095, p 0.1), individuals with poorer family economic status (β = −0.080, p

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with lung cancer, but roles and mechanisms of Cr(VI)-induced epigenetic dysregulations in carcinogenesis remain to be investigated. In this study, we identified that RNA m5C methyltransferase NSUN2 was significantly upregulated in Cr(VI)-transformed cells and lung tissues of Cr(VI)-exposed mice. Inhibition of NSUN2 reduced cell proliferation, migration, colony formation and tube formation abilities. We found NSUN2-mediated m5C modification induced metabolic reprogramming and cell cycle by promoting the mRNA stabilities of ME1, GLUT3 and CDK2. In addition, knockdown of NSUN2 attenuated tumorigenesis and angiogenesis in vivo. RNA m5C reader ALYREF was identified to be involved in NSUN2-mediated m5C modification in Cr (VI)-induced carcinogenesis. Further study showed that EP300 induced NSUN2 upregulation through transcriptional activation by inducing histone modification at H3K27ac site for regulating Cr(VI) carcinogenesis. Our findings demonstrated novel role and mechanism of NSUN2 and epigenetic changes by increasing the RNA m5C modification that are important for Cr (VI)-induced carcinogenesis through NSUN2/ALYREF pathway. NSUN2, ALYREF, ME1, GLUT3 or/and CDK2 may be used as potential new biomarkers or/and therapeutic target(s) in the future.

Epidemiological evidence indicates exposure to glyphosate-based herbicides (GBHs) increases the risk for autism spectrum disorder (ASD). The gut microbiota has been found to influence ASD behaviours through the microbiota-gut-brain axis. However, the underlying links between early life GBH exposure and ASD-like phenotypes through the microbiota-gut-brain axis remain unclear. Therefore, we exposed mice to low-dose GBH (0.10, 0.25, 0.50, and 1.00 %) and determined the effects on ASD-like behaviours. Furthermore, three kinds of omics (gut microbiomics, metabolomics, and transcriptomics) were conducted to investigate the effects of GBH exposure on gut microbiota, gut metabolites, and circular RNAs (circRNAs) in the prefrontal cortex (PFC) using a cross-generational mouse model. Behavioural analyses suggested social impairment and repetitive/stereotypic behaviours in the GBH-exposed offspring. Furthermore, maternal exposure to glyphosate significantly altered the ASD-associated gut microbiota of offspring, and ASD-associated gut metabolites were identified. Specifically, we found that alterations in the gut microenvironment may contribute to changes in gut permeability and the blood-brain barrier, which are related to changes in the levels of circRNAs in the PFC. Our results suggest a potential effect of circRNAs through the disruption of the gut-brain interaction, which is an important factor in the pathogenesis of ASD in offspring induced by maternal exposure to GBH.

Abstract The extracellular matrix (ECM) has been demonstrated to be dysregulated and crucial for malignant progression in gastric cancer (GC), but the mechanism is not well understood. Here, that discoidin domain receptor 1 (DDR1), a principal ECM receptor, is recognized as a key driver of GC progression is reported. Mechanistically, DDR1 directly interacts with the PAS domain of hypoxia‐inducible factor‐1α (HIF‐1α), suppresses its ubiquitination and subsequently strengthens its transcriptional regulation of angiogenesis. Additionally, DDR1 upregulation in GC cells promotes actin cytoskeleton reorganization by activating HIF‐1α/ Ras Homolog Family Member A (RhoA)/Rho‐associated protein kinase 1 (ROCK1) signaling, which in turn enhances the metastatic capacity. Pharmacological inhibition of DDR1 suppresses GC progression and angiogenesis in patient‐derived xenograft (PDX) and organoid models. Taken together, this work first indicates the effects of the DDR1‐HIF‐1α axis on GC progression and reveals the related mechanisms, providing experimental evidence for DDR1 as a therapeutic target for GC.

Abstract Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence‐related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3‐rich extracellular vesicles to NPCs, thereby alleviating aging‐associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane‐bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2‐TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia‐induced BMSC exosomes deliver BNIP3‐rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Abstract The contradiction of high subducting plate rate (ranging from 4 to 9 cm/yr on Earth's surface) and low slab sinking rate (about 1 and 2 cm/yr in lower mantle) calls for significant slab deformation in the middle mantle. However, mechanisms that can account for both the deformation and the rate discrepancy have not been fully explored. Here, using 2‐D numerical models that incorporate grain size evolution, we propose a new slab deformation mode, slab segmentation and stacking, to accommodate the differential slab sinking rates. Our results show that the segmented slab due to faulting and grain‐size reduction may further break off and stack over itself as it encounters the high‐viscosity lower mantle. Stacked slabs slowly sink in the lower mantle, while periodic slab tearing hinders upward stress transmission, allowing shallow plates to subduct at a higher rate. This discovered mode also provides an alternative explanation for slab thickening in the lower mantle.

This study employs panel data encompassing 31 provinces in China, spanning the period from 2010 to 2020, to investigate the distributional impact of foreign direct investment (FDI) on green innovation (GI). Employing a panel quantile regression model, the research finds the close association between FDI and GI, particularly considering the local GI foundation. Specifically, FDI plays a crucial and influential role in fostering GI within regions characterized by lower levels of GI. However, it does not have a significant impact on promoting GI in regions with higher levels of GI. Further analysis of regional heterogeneity demonstrates that in coastal areas, FDI exhibits a positive and significant impact on GI in provinces with a moderate level of GI. Conversely, in inland areas, FDI can only facilitate GI in provinces with a high level of GI. The research conclusion suggests that the government should enhance the intensity of FDI and implement tailored policies according to the specific characteristics of coastal and inland regions.