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Abstract This study aimed to explore the role of the three-dimension (3D) printed models in orthopedic resident training of tibial plateau fractures. A total of 41 residents from our institution were divided into two groups. The intervention group, consisting of 20 residents, had access to 3D-printed models illustrating thirteen tibial plateau fractures. In contrast, the control group, comprising 21 residents, received digital images of thirteen identical tibial plateau fractures. Evaluation of learning outcomes included the accurate identification of tibial plateau fracture patterns, deduction of traumatic mechanisms, preoperative plan, assessment time, and subjective questionnaire responses. The participants with 3D printed models scored significantly higher in both the Schatzker classification and Luo three-column classification compared to those without 3D printed models. Residents in the intervention group performed better in accuracy in deducing traumatic mechanisms compared to the control group. In addition, the sum score of preoperative plan in the intervention group was significantly higher than that in the control group. Specifically, participants with 3D printed models scored higher in surgical approach choice and implants placement than these in the control group. Residents exposed to 3D printed models also spent less time to complete the assessment than those with access only to digital imaging. Subjective assessments indicated that 3D-printed models boosted confidence in fracture identification, improved preoperative plan for fracture management and enhanced the understanding in injury mechanism of tibial plateau fractures. Furthermore, residents agreed that the use of 3D-printed models heightened their interest in learning tibial plateau fractures. Therefore, the addition of 3D printed models significantly contributed to a comprehensive understanding of tibial plateau fractures, the improvement in fracture identification, inferring injury mechanisms and preoperative plan.

Abstract Background Although associations have been reported linking pretreatment thrombocytosis to cancer survival outcomes, the validity and strength of existing observational evidence have been contested. This study aimed to conduct an umbrella review to comprehensively appraise the strength, validity and credibility of these reported associations. Methods We searched Medline, Embase and Cochrane Database of Systematic Reviews from inception to 8 April 2023 to retrieve meta-analyses of observational studies. Meta-analyses were re-performed using a random-effect model and the strength of evidence was graded as convincing, highly suggestive, suggestive and weak according to seven pre-defined quantitative criteria reflecting statistical significance, amount of data, heterogeneity, and evidence of bias. The quality of review was appraised using the AMSTAR2 checklist. The umbrella review was reported adhering to the PRISMA guideline and was registered on PROSPERO (CRD42023455391). Results A total of 21 unique meta-analyses investigating ten cancer subtypes were included. All meta-analyses reported inferior survival outcome in cancer patients with pretreatment thrombocytosis, and 18 of them (85.7%) yielded statistically significant results (P 300 or 400 × 109 /L) to define thrombocytosis. Although evidence appraisal did not identify convincing evidence (Class I), the associations of thrombocytosis with inferior overall survival of lung, gastric, colorectal cancer and malignant mesothelioma were classified as highly suggestive evidence (Class II). According to AMSTAR2 ratings, no meta-analysis was identified with high or moderate quality. Conclusions Our findings consolidated the association between pretreatment thrombocytosis and poor survival outcomes in various cancers. Nonetheless, the absence of convincing associations indicates a need for further large-scale, high-quality evidence to confirm whether platelets can serve as a prognostic predictor or a therapeutic target.

Abstract Background Concurrent chemoradiotherapy (CCRT) is a crucial treatment for non-small cell lung carcinoma (NSCLC). However, the use of deep learning (DL) models for predicting the response to CCRT in NSCLC remains unexplored. Therefore, we constructed a DL model for estimating the response to CCRT in NSCLC and explored the associated biological signaling pathways. Methods Overall, 229 patients with NSCLC were recruited from six hospitals. Based on contrast-enhanced computed tomography (CT) images, a three-dimensional ResNet50 algorithm was used to develop a model and validate the performance in predicting response and prognosis. An associated analysis was conducted on CT image visualization, RNA sequencing, and single-cell sequencing. Results The DL model exhibited favorable predictive performance, with an area under the curve of 0.86 (95% confidence interval [CI] 0.79–0·92) in the training cohort and 0.84 (95% CI 0.75–0.94) in the validation cohort. The DL model (low score vs. high score) was an independent predictive factor; it was significantly associated with progression-free survival and overall survival in both the training (hazard ratio [HR] = 0.54 [0.36−0.80], P = 0.002; 0.44 [0.28−0.68], P

The pipe curtain structure method (PSM) is a novel construction method to control ground deformation strictly. Compared with the traditional pipe-roofing and pipe jacking method, the connection between pipes in large spacings using PSM is widely acknowledged as a unique construction procedure. Further study on this connection procedure is needed to resolve similar cases in that the pipes are inevitably constructed on both sides of existing piles. Cutting the steel plate during the connection procedure is the first step, which is crucial to control the safety and stability of the surrounding environment and existing structures. The deformation mechanism and limit support pressure of the cutting steel plate during the connection between pipes in large spacings are studied in this paper, relying on the undercrossing Yifeng gate tower project of Jianning West Road River Crossing Channel in Nanjing, China. A modified 3D wedge-prism failure model is proposed using the 3D discrete element method. Combined with Terzaghi loose earth pressure theory and the limit equilibrium theory, the analytical solutions for the limit support pressure of the excavation face of the cutting steel plate are derived. The modified 3D wedge-prism failure model and corresponding analytical solutions are categorised into two cases: (a) unilateral cutting scheme, and (b) bilateral cutting scheme. The analytical solutions for the two cases are verified from the numerical simulation and in-situ data and compared with the previous solutions. The comparative analysis between the unilateral and bilateral cutting schemes indicates that the bilateral cutting scheme can be adopted as a priority. The bilateral cutting scheme saves more time and induces less ground deformation than the unilateral one due to the resistance generated from the superimposed wedge. In addition, the parametric sensitivity analysis is carried out using an orthogonal experimental design. The main influencing factors arranged from high to low are the pipe spacing, the cutting size, and the pipe burial depth. The ground deformation increases with the increased cutting size and pipe spacing. The pipe burial depth slightly affects the ground deformation if the other two factors are minor. Cutting steel plates in small sizes, excavating soil under low disturbance, and supporting pipes for high frequency can effectively reduce the ground surface subsidence.

Abstract Background Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. Methods A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. Results High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. Conclusions Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. Trial registration Not applicable.

Abstract Background Thyroid eye disease (TED) is a vision-threatening autoimmune disorder. Orbital tissue fibrosis leading to intractable complications remains a troublesome issue in TED management. Exploration of novel therapeutic targets and agents to ameliorate tissue fibrosis is crucial for TED. Recent work suggests that Ca2+ signaling participates in tissue fibrosis. However, whether an alteration of Ca2+ signaling has a role in fibrogenesis during TED remains unclear. In this study, we aimed to investigate the role of Ca2+ signaling in the fibrogenesis process during TED and the potential therapeutic effects of a highly selective inhibitor of the L-type calcium channel (LTCC), nimodipine, through a TGF-β1 induced in vitro TED model. Methods Primary culture of orbital fibroblasts (OFs) were established from orbital adipose connective tissues of patients with TED and healthy control donors. Real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing were used to assess the genes expression associated with LTCC in OFs. Flow cytometry, RT-qPCR, 5-ethynyl-2′-deoxyuridine (EdU) proliferation assay, wound healing assay and Western blot (WB) were used to assess the intracellular Ca2+ response on TGF-β1 stimulation, and to evaluate the potential therapeutic effects of nimodipine in the TGF-β1 induced in vitro TED model. The roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 1 (STAT1) in fibrogenesis during TED were determined by immunohistochemistry, WB, flow cytometry and co-immunoprecipitation assay. Selective inhibitors were used to explore the downstream signaling pathways. Results LTCC inhibitor nimodipine blocked the TGF-β1 induced intracellular Ca2+ response and further reduced the expression of alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 (Col1A1) and collagen type I alpha 2 (Col1A2) in OFs. Besides, nimodipine inhibited cell proliferation and migration of OFs. Moreover, our results provided evidence that activation of the CaMKII/STAT1 signaling pathway was involved in fibrogenesis during TED, and nimodipine inhibited the pro-fibrotic functions of OFs by down-regulating the CaMKII/STAT1 signaling pathway. Conclusions TGF-β1 induces an LTCC-mediated Ca2+ response, followed by activation of CaMKII/STAT1 signaling pathway, which promotes the pro-fibrotic functions of OFs and participates in fibrogenesis during TED. Nimodipine exerts potent anti-fibrotic benefits in vitro by suppressing the CaMKII/STAT1 signaling pathway. Our work deepens our understanding of the fibrogenesis process during TED and provides potential therapeutic targets and alternative candidate for TED.

Hyperspectral datasets captured by airborne are one of the important data sources in the field of hyperspectral image fusion. However, the limited number of data samples often hinders the optimal performance of deep learning-based methods on these datasets. Domain adaptation is expected to alleviate the issue of data scarcity. However, there are two issues that need to be addressed in applying domain adaptation to hyperspectral image fusion, which are the heterogeneity and spatial degradation diversity of hyperspectral data. In this paper, we propose a domain adaptation hyperspectral image fusion network based on spatial-spectral domain separation. The model, constructed with three-dimensional convolutional layers, effectively addresses the challenge of hyperspectral data heterogeneity. Compared with 2D convolution, 3D convolution is able to consider both spatial and spectral dimensions and extract spatial-spectral features efficiently. Based on this, we design a domain-separation architecture to extract domain-invariant and domain-private features in the spatial-spectral domain. The architecture achieves domain adaptation by extracting domain-invariant features from both datasets to obtain the prior knowledge in the source dataset and apply it to the target dataset. Additionally, the spatial degradation of different datasets varies due to distinct shooting conditions during the acquisition. Therefore, the fusion algorithms should be robust to various degradation scenarios. To tackle this challenge, we design the Observation Module to predict degradation information and the Degradation Information Modulation Module to apply it to the input, thereby enhancing the network’s robustness. Experiments on various datasets demonstrate that our method is qualitatively and quantitatively superior to state-of-the-art methods.

Abstract Background Colon cancer is one of the most prevalent tumors in the digestive tract, and its stemness feature significantly contribute to chemoresistance, promote the epithelial-mesenchymal transition (EMT) process, and ultimately lead to tumor metastasis. Therefore, it is imperative for researchers to elucidate the molecular mechanisms underlying the enhancement of stemness feature, chemoresistance, and EMT in colon cancer. Methods Sphere-formation and western blotting assays were conducted to assess the stemness feature. Edu, flow cytometry, and cell viability assays were employed to evaluate the chemoresistance. Immunofluorescence and western blotting assays were utilized to detect EMT. Immunoprecipitation, ubiquitination, agarose gel electrophoresis, chromatin immunoprecipitation followed by quantitative PCR (chip-qPCR), and dual luciferase reporter gene assays were employed for mechanistic investigations. Results We demonstrated a markedly higher expression level of OTUB2 in colon cancer tissues compared to adjacent tissues. Furthermore, elevated OTUB2 expression was closely associated with poor prognosis and distant tumor metastasis. Functional experiments revealed that knockdown of OTUB2 attenuated stemness feature of colon cancer, enhanced its sensitivity to oxaliplatin, inhibited its EMT process, ultimately reduced the ability of tumor metastasis. Conversely, overexpression of OTUB2 exerted opposite effects. Mechanistically, we identified OTUB2 as a deubiquitinase for SP1 protein which bound specifically to SP1 protein, thereby inhibiting K48 ubiquitination of SP1 protein. The SP1 protein functioned as a transcription factor for the GINS1, exerting its regulatory effect by binding to the 1822–1830 region of the GINS1 promoter and enhancing its transcriptional activity. Ultimately, alterations in GINS1 expression directly regulated stemness feature, chemosensitivity, and EMT progression in colon cancer. Conclusion Collectively, the OTUB2/SP1/GINS1 axis played a pivotal role in driving stemness feature, chemoresistance, and EMT in colon cancer. These results shed new light on understanding chemoresistance and metastasis mechanisms involved in colon cancer.

Accurate estimation of turbulence field is of great importance in aerospace, and existing means of obtaining turbulence field is inadequate in terms of resolution or accuracy. Experimental measurements are accurate but often have a limited number of observation points, and numerical computations can obtain full-field data but the accuracy is difficult to guarantee. The data assimilation method integrates experimental observation and numerical simulation, which is an effective tool for flow field reconstruction. This paper explored the effectiveness of data assimilation method based on ensemble transform Kalman filter(ETKF) in spatial flow field reconstruction, and also discussed the reconstruction accuracy and computational efficiency of different iterative updates, namely ETKF-M and ETKF-D, which update state variables based on turbulence model and flow field data respectively. Using the ONERA M6 airfoil as a numerical example, the algorithm was experimented by combining the pressure measurement data from 271 pressure holes on the airfoil surface from the wind tunnel test. The results show that different iterative updates of ETKF method can effectively modify the prediction of the turbulence model, and the ETKF-D improves the computational efficiency by 83% compared with the ETKF-M. In addition, two groups of 1/4 experimental observation points at different locations were selected for assimilation experiments, and results with different accuracies were obtained. It indicates that the accuracy of reconstruction is closely related to the location and number of assimilated observation points.

Abstract Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.

Abstract Background Colorectal cancer (CRC) has the third highest incidence and second mortality rate of malignant tumors globally, highlighting the urgency to explore the mechanisms underlying CRC progression for refined treatment of this patient population. Methods R Studio was used for data sorting and analysis. Cell apoptosis and cell cycle detection were performed by flow cytometry. Quantitative real-time PCR (qRT-PCR) was used to explore mRNA expression levels. Western blotting was used to explore protein expression levels. CCK8, EdU, and colony formation assays were performed to explore the proliferation capacity of CRC cells. Transwell invasion and migration assays, along with the wound healing assay, were used to explore the invasive and migratory abilities of CRC cells. Subcutaneous Xenograft Assay was utilized to evaluate the tumorigenic capacity of CRC cells in vivo. Results SULF1 was highly expressed in CRC samples and cell lines. The knockdown of SULF1 inhibited the proliferation, invasion, and migration of CRC and increased the rate of cell apoptosis. Meanwhile, we demonstrated that SULF1 could negatively regulate ARSH through the FAK/PI3K/AKT/mTOR pathway. Conclusion We demonstrated that SULF1 could promote CRC progression by regulating ARSH. The SULF1/ARSH/FAK/PI3K/AKT/mTOR signaling pathway represents a promising target for the treatment of this patient population. Simple summary Colorectal cancer (CRC) has the third highest incidence and second mortality rate of malignant tumors globally. Sulfatase 1 (SULF1) belongs to the sulfatase family, The function of SULF1 in CRC remains elusive. Our study demonstrated that the knockdown of SULF1 could inhibit the proliferation, invasion, and migration of CRC. Meanwhile, our findings indicated that SULF1 could interact with Arylsulfatase Family Member H (ARSH) to regulate the proliferation, invasion, and migration of CRC via the FAK/PI3K/AKT/mTOR signaling pathway. Taken together, our findings suggest that SULF1 might be a new therapeutic target in CRC.

IntroductionMathematical word problems refer to word problems where the information that is presented needs to be integrated, typically into a mathematical formula, to arrive at a solution to the problem. When solving mathematics word problems, elementary school students often have difficulties improving their performance due to a lack of self-regulated learning (SRL). However, SRL can be developed by adopting an appropriate teaching approach which offers quantitative feedback or learning prompts. With the sophistication of interactive and data-driven feedback technology, it is possible to provide timely and personalized strategies for promoting students’ SRL.MethodsIn this study, an interactive e-book editing platform was used to design self-regulation-level-based feedback(SRLF) and task-level-based feedback(TLF) teaching models, which were respectively conducted in two similar fifth-grade classes for the mathematics word problem solving lessons.ResultsUsing ANCOVA and repeated ANOVA, this study found that (1) the SRLF had a remarkably greater impact on elementary school students’ mathematics word problem-solving performance than the TLF, with a partial η2-value of .107; (2) In the short period of time, there was no significant difference between the two kinds of feedback on the learners’ SRL. The TLF was slightly superior to the SRLF, especially in terms of total self-regulated learning scores and cognitive strategies; (3) The TLF had a significant interaction effect on self-regulated learning and cognitive strategies, respectively with a partial η2-value of .059 and .056.

This study examined the impact of varying salt concentrations on microbiota, physicochemical properties, and metabolites in a secondary fortified fermentation process using multi-omics techniques. It aimed to determine the influence of salt stress on microbiota shifts and metabolic activities. The findings demonstrated that moderate salt reduction (MS) was found to enhance moromi's flavor and quality, while mitigating the negative effects of excessive low salt (LS). MS samples had 1.22, 1.13, and 2.92 times more amino acid nitrogen (AAN), non-volatiles, and volatiles, respectively, than high salt (HS) samples. In contrast, lactic acid and biogenic amines in LS samples were 1.56 g/100 g and 4115.11 mg/kg, respectively, decreasing to 0.15 g/100 g and 176.76 mg/kg in MS samples. Additionally, the contents of ethanol and small peptides increased in MS due to the growth of specific functional microorganisms such as Staphylococcus gallinarum, Weissella confusa, and Zygosaccharomyces rouxii, while food-borne pathogens were inhibited. Network analysis revealed that the core microbial interactions were enhanced in MS samples, promoting a balanced fermentation environment. Redundancy analysis (RDA) and correlation analyses underscored that the physicochemical properties significantly impacted bacterial community structure and the correlations between key microbes and flavor compounds. These findings provided a theoretical foundation for developing innovative reduced-salt fermentation techniques, contributing to the sustainable production of high-quality soy sauce.

The synaptic and neuronal circuit mechanisms underlying reward-based learning remain to be fully determined. In the mammalian brain, dopamine release in nucleus accumbens is thought to contribute importantly to reward signals for learning and promoting synaptic plasticity. Here, through longitudinal fiber photometry of a genetically-encoded fluorescent sensor, we investigated dopamine signals in the nucleus accumbens of thirsty head-restrained mice as they learned to lick a liquid reward spout in response to single deflections of the C2 whisker across varying reward contingencies. Reward delivery triggered by well-timed licking drove fast transient dopamine increases in nucleus accumbens. On the other hand, unrewarded licking was overall associated with reduced dopamine sensor fluorescence, especially in trials where reward was unexpectedly omitted. The dopamine reward signal upon liquid delivery decreased within individual sessions as mice became sated. As mice learned to lick the reward spout in response to whisker deflection, a fast transient sensory-evoked dopamine signal developed, correlating with the learning of the whisker detection task across consecutive training days, as well as within single learning sessions. The well-defined behavioral paradigm involving a unitary stimulus of a single whisker as a reward-predicting cue along with precisely quantified licking allows untangling of sensory, motor and reward-related dopamine signals and how they evolve across the learning of whisker-dependent goal-directed sensorimotor transformations. Our longitudinal measurements of dopamine dynamics across reward-based learning are overall consistent with the hypothesis that dopamine could play an important role as a reward signal for reinforcement learning.

Deep learning has significantly advanced hyperspectral image (HSI) classification, primarily due to its robust nonlinear feature extraction capabilities. The vision transformer has achieved notable performance but is limited by the quadratic computational burden of its self-attention mechanism. Recently, a network based on state space model named Mamba, has attracted considerable attention for its linear complexity and commendable performance. Nevertheless, Mamba was originally designed for one-dimensional causal sequence modeling, and its effectiveness in inherent non-causal HSI classification remains to be fully validated. To address this issue, we propose a novel Local Enhanced Mamba (LE-Mamba) network for hyperspectral image classification, which mainly comprises a Local Enhanced Spatial SSM (LES-S6), a Central Region Spectral SSM (CRS-S6), and a Multi-Scale Convolutional Gated Unit (MSCGU). The LES-S6 improves non-causal local feature extraction by incorporating a multi-directional local spatial scanning mechanism. Additionally, the CRS-S6 employs a bidirectional scanning mechanism in the spectral dimension to capture fine spectral details and integrate them with spatial information. The MSCGU utilizes a convolutional gating mechanism to aggregate features from diverse scanning routes and extract high-level semantic information. The overall accuracies of LE-Mamba on Indian Pines, WHU-Hi-HanChuan, WHU-Hi-LongKou, and Pavia University datasets are 99.16 %, 98.16 %, 99.57 %, and 99.63 %, respectively. Extensive experimental results on these four public datasets demonstrate that the LE-Mamba outperforms eight mainstream deep learning models in classification performance.

Software vulnerability detection aims to proactively reduce the risk to software security and reliability. Despite advancements in deep-learning-based detection, a semantic gap still remains between learned features and human-understandable vulnerability semantics. In this paper, we present an XAI-based framework to assess program code in a graph context as feature representations and their effect on code vulnerability classification into multiple Common Weakness Enumeration (CWE) types. Our XAI framework is deep-learning-model-agnostic and programming-language-neutral. We rank the feature importance of 40 syntactic constructs for each of the top 20 distributed CWE types from three datasets in Java and C++. By means of four metrics of information retrieval, we measure the similarity of human-understandable CWE types using each CWE type’s feature contribution ranking learned from XAI methods. We observe that the subtle semantic difference between CWE types occurs after the variation in neighboring features’ contribution rankings. Our study shows that the XAI explanation results have approximately 78% Top-1 to 89% Top-5 similarity hit rates and a mean average precision of 0.70 compared with the baseline of CWE similarity identified by the open community experts. Our framework allows for code vulnerability patterns to be learned and contributing factors to be assessed at the same stage.

BackgroundOzone (O3) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O3 concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O3 risk assessment and related policy making. ObjectiveTo quantitatively evaluate the effects of O3 exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. MethodsData of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O3 concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P25) and the 75th percentile (P75) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m−3 increase in daily maximum 8 h concentration of O3 (O3-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O3. ResultsThe associations between O3 and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P

Abstract Background The association between the triglyceride–glucose (TyG) index and subclinical left ventricular (LV) systolic dysfunction in obese patients remains unclear. This study aimed to investigate the relationship between the TyG index and LV global longitudinal strain (GLS) in obese patients. Methods A total of 1028 obese patients from January 2019 to January 2024 were included in the present study. Clinical parameters and biochemical and echocardiographic data were obtained from the participants. LV GLS was obtained from the GE EchoPAC workstation for evaluating subclinical LV function. The TyG index was calculated as Ln (fasting TG [mg/dL] × fasting glucose [mg/dL]/2). LV GLS was compared between obese patients with a high TyG index and those with a low TyG index. Results Obese patients with a high TyG index had greater incidences of hypertension, diabetes mellitus and hyperlipidaemia. The LV GLS was significantly lower in the high TyG index group than in the low TyG index group (P = 0.01). After adjusting for sex, age, body mass index, heart rate, hypertension, diabetes mellitus, dyslipidaemia, blood urea nitrogen, serum creatinine, LV mass and LV hypertrophy, the TyG index remained an independent risk indicator related to an LV GLS

The geographical origin was one of the important factors affecting the quality of hawthorn. To discriminate the geographical origin of hawthorn rapidly and nondestructively, hawthorns from five different provincial production areas were used as samples, and visible-shortwave infrared (410~2500 nm) band hyperspectral data were obtained for the pedicel face (G), side (C), and bottom (D) of each sample by using a near-infrared hyperspectral imaging system. Partial least squares discriminant analysis (PLS-DA), support vector machine (SVM), and random forests (RF) classification models were built by multivariate scattering correction (MSC), first derivative (D1), SG smoothing (Savitzky-Golay, SG), and standard normal transform (SNV) four preprocessing methods. The results showed that the D-D1-SVM model discriminated optimally, with 100% accuracy in both the training and prediction sets. To simplify the model, successive projections algorithm (SPA) and competitive adaptive reweighted sampling algorithm (CARS) were applied to select feature wavelength. The multivariate data analysis revealed that the D-SPA-SVM model had the best performance, with an accuracy of 95.2% and 93% for the training and prediction sets, respectively. This study could provide technical support for rapid and non-destructive identification of hawthorn origin.

Abstract Objective To evaluate the antibacterial effectiveness of a combination of ε-poly-L-lysine (ε-PL), funme peptide (FP) as well as domiphen against oral pathogens, and assess the efficacy of a BOP® mouthwash supplemented with this combination in reducing halitosis and supragingival plaque in a clinical trial. Materials and methods The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the compound against Fusobacterium nucleatum, Porphyromonas gingivalis, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were determined by the gradient dilution method. Subsequently, the CCK-8 assay was used to detect the toxicity of mouthwash on human gingival fibroblastst, and the effectiveness in reducing halitosis and supragingival plaque of the mouthwash supplemented with the combination was analyzed by a randomized, double-blind, parallel-controlled clinical trial. Results The combination exhibited significant inhibitory effects on tested oral pathogens with the MIC

Abstract Proper pericarp thickness protects the maize kernel against pests and diseases, moreover, thinner pericarp improves the eating quality in fresh corn. In this study, we aimed to investigate the dynamic changes in maize pericarp during kernel development and identified the major quantitative trait loci (QTLs) for maize pericarp thickness. It was observed that maize pericarp thickness first increased and then decreased. During the growth and formation stages, the pericarp thickness gradually increased and reached the maximum, after which it gradually decreased and reached the minimum during maturity. To identify the QTLs for pericarp thickness, a BC4F4 population was constructed using maize inbred lines B73 (recurrent parent with thick pericarp) and Baimaya (donor parent with thin pericarp). In addition, a high-density genetic map was constructed using maize 10 K SNP microarray. A total of 17 QTLs related to pericarp thickness were identified in combination with the phenotypic data. The results revealed that the heritability of the thickness of upper germinal side of pericarp (UG) was 0.63. The major QTL controlling UG was qPT1-1, which was located on chromosome 1 (212,215,145–212,948,882). The heritability of the thickness of upper abgerminal side of pericarp (UA) was 0.70. The major QTL controlling UA was qPT2-1, which was located on chromosome 2 (2,550,197–14,732,993). In addition, a combination of functional annotation, DNA sequencing analysis and quantitative real-time PCR (qPCR) screened two candidate genes, Zm00001d001964 and Zm00001d002283, that could potentially control maize pericarp thickness. This study provides valuable insights into the improvement of maize pericarp thickness during breeding.

Abstract Esophagogastric variceal bleeding (EVB) is one of the common digestive system emergencies with poor prognosis and high rate of rebleeding after treatment. To explore the effects of endoscopic therapy and drug therapy on the prognosis and rebleeding of patients with EVB, and then select better treatment methods to effectively improve the prognosis. From January 2013 to December 2022, 965 patients with EVB who were hospitalized in gastroenterology Department of the 940 Hospital of Joint Logistic Support Forces of PLA were retrospectively analyzed. Patients were divided into endoscopic treatment group (ET, n = 586) and drug treatment group (DT, n = 379). Propensity score matching (PSM) analysis was performed in both groups, and the general information, efficacy and length of hospital stay were recorded. The patients were followed up for 3 months after bleeding control to determine whether rebleeding occurred. There were 286 cases in each group after PSM. Compared with DT group, ET had higher treatment success rate (P 0.05). Compared with drug therapy, endoscopic treatment of EVB has short-term efficacy advantages, and can effectively reduce the incidence of rebleeding and mortality within 3 months.

Abstract Unraveling the effect of spatially separated bifunctional sites on catalytic reactions is significant yet challenging. In this report, we investigate the role of spatial separation on the oxidation of methane in a series of Cu-exchanged aluminosilicate zeolites. Regulation of the bifunctional sites is done either through studying a physical mixture of Cu-exchanged zeolites and acidic zeolites or by systematically varying the Cu and acid density within a family of zeolite materials. We show that separated Cu and acid sites are beneficial for the formation of hydrocarbons while high-density Cu sites, which are closer together, facilitate the production of CO2. By contrast, a balance of the spatial separation of Cu and acid sites shows more favorable formation of methanol. This work will further guide approaches to methane oxidation to methanol and open an avenue for promoting hydrocarbon synthesis using methanol as an intermediate.

Objective: To investigate the source of infection in a patient with recurrent severe neck infections caused by Klebsiella pneumoniae and to analyze the virulence of isolates obtained from different sites of the patient. Methods: We collected preoperative neck abscess puncture fluid, intraoperative neck drainage fluid, sputum, intestinal fecal specimens, and blood samples from a patient who visited Wuxi Second People's Hospital twice between 2017 and 2018. We conducted isolation, identification, drug sensitivity tests, and string tests on the isolates. Capsule serotyping and virulence gene analysis were performed using PCR. The genetic relationship of different isolates was assessed by Multilocus Sequence Typing and virulence was evaluated using the Galleria mellonella infection model. Additionally, whole-genome sequencing was used to analyze the chromosomal and plasmid genes of one isolate. Results: Klebsiella pneumoniae was detected in the sputum and fecal specimens from both hospitalizations, as well as the preoperative ultrasound-guided puncture fluid and intraoperative drainage fluid from the first hospitalization, resulting in six isolates. These isolates were all K16 serotype, positive in the string test, and identified as ST660 by Multilocus Sequence Typing, indicating they belonged to the same clone. Virulence gene analysis showed that wcaG, iucB, iroNB, rmpA, rmpA2, Aer, kfuBC, ureA, fimH, mrkD, uge, and peg344 were positive, while allS, cf29a, and Wzy_K1 were negative. In the Galleria mellonella virulence assay, the lethality of different isolates was dose-dependent. The K16 group showed significantly higher larval mortality compared to other control groups (including K1, K2, K5, K20, and K57 groups). Genome sequencing revealed that plasmid p17388 carried numerous virulence genes and insertion sequences, particularly ISKPN74, and showed high homology with other Klebsiella plasmids. Conclusion: This study is the first to report severe cervical necrotizing fasciitis caused by the K16-ST660 Klebsiella pneumoniae Isolate. The high virulence of these isolates was confirmed by the Galleria mellonella virulence assay and the detection of numerous virulence genes. In-depth analysis of plasmid p17388 suggests that ISKPN74 may enhance stable integration of the plasmid into the bacterial chromosome through recombinases and transposases, thereby reducing the likelihood of plasmid loss and increasing bacterial virulence. Additionally, IS5 family insertion sequences may carry extra promoters or enhancers that, when inserted upstream of mucoviscosity-associated genes such as rmpA, may increase the transcription levels of downstream genes. This ISKPN74-mediated integration or insertion reveals a complex genetic mechanism that may contribute to the severity of infections caused by ST660 isolates. Our findings offer new insights into the virulence and structure of ST660-K16 Klebsiella pneumoniae, suggesting that further investigation into the specific mechanisms by which these insertion sequences enhance virulence could aid in developing novel infection management strategies.

Enhanced mortality, relapse rates, and increased prevalence of Clostridioides difficile infection (CDI) emphasize the need for better therapies and management approaches. Modulating host immune response to ameliorate CDI-associated immunopathology may provide new advantages to currently inadequate antibiotic therapies. Here, we identified progranulin (PGRN) as an important immune target upregulated in response to CDI. PGRN-deficient mice displayed dramatically higher mortality and aggravated epithelial barrier disruption compared with wild type (WT) mice after CDI despite equivalent levels of bacterial burden or toxin in the large intestine. Mechanistically, PGRN protection was mediated by IL-22 production from CD4+ T helper cells, as demonstrated by a decrease in colonic IL-22-producing CD4+ T helper cells in the intestine of PGRN-deficient mice upon CDI and a boost of IL-22-producing CD4+ T helper cells activated by PGRN ex vivo. Clinical evidence suggests that CDI patients had significantly higher serum levels of PGRN compared with healthy controls, which was significantly and positively correlated with IL-22. Our findings thus indicate a critical role for PGRN-promoted CD4+ T cell IL-22 production in shaping gut immunity and reestablishing the intestinal barrier during CDI. As an alternative to pathogen-targeted therapy, this study may provide a new host-directed therapeutic strategy to attenuate severe, refractory CDI.

The current standard of care for anal squamous cell carcinoma (ASCC) is definitive concurrent chemoradiotherapy (CRT). However, about a third of patients may experience treatment failure. Recently, immunotherapy has emerged as a novel strategy for metastatic ASCC patients. We evaluated the efficacy and safety of surgery, CRT alone, and CRT with immunotherapy (CRT-I) in 100 nonmetastatic ASCC patients, treated from April 2012 through May 2023, by determining survival outcomes and acute adverse events. The median (range) follow-up was 30.7 (7.6 to 134.9) months. The study cohort 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were 80.7 %, 62.2 %, 71.1 %, and 67.6 %, respectively. The Surgery group had significantly lower rates than the CRT and CRT-I groups for 3-year PFS (33.1% vs. 65.2% vs. 92.9 %, P < 0.001), DMFS (46.7% vs. 74.6% vs. 92.9 %, P = 0.002) and LRFS (37.0% vs. 73.3% vs. 92.9 %, P < 0.001), respectively. All patients receiving CRT-I were alive at last follow-up. Of 100 patients, 26 (26.0 %) experienced severe (≥ grade 3) acute toxicity. Of 24 patients receiving CRT-I, 8 (33.3 %) had severe acute toxicity. Using immunohistochemistry, peritumoural stromal infiltration by CD8+ T cells was significantly higher after CRT-I compared to before CRT-I and to after CRT alone. The addition of immunotherapy to CRT may be an effective first-line treatment option with favourable survival outcomes and acceptable toxicity for patients with ASCC. A prospective, randomized trial assessing the efficacy of CRT combined with a PD-1 inhibitor in patients with locally advanced ASCC is in progress.

Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 109/L) and inferior OS (HR: 1.07; 95% CI: 1.04–1.10; p

Objective: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with an unclear pathogenetic mechanism in the labial gland. This study aims to investigate the cellular and molecular mechanisms contributing to the development of this disease. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on 32,337 cells of labial glands from three pSS patients and three healthy individuals. We analyzed all cell subsets implicated in pSS pathogenesis. Results: Our research revealed diminished differentiation among epithelial cells, concomitant with an enhancement of interferons (IFNs)-mediated signaling pathways. This indicates a cellular functional shift in reaction to inflammatory triggers. Moreover, we observed an augmentation in the population of myofibroblasts and endothelial cells, likely due to the intensified IFNs signaling, suggesting a possible reconfiguration of tissue structure and vascular networks in the impacted regions. Within the immune landscape, there was an apparent increase in immunosuppressive macrophages and dendritic cells (DCs), pointing to an adaptive immune mechanism aimed at modulating inflammation and averting excessive tissue harm. Elevated activation levels of CD4+T cells, along with a rise in regulatory T (Treg) cells, were noted, indicating a nuanced immune interplay designed to manage the inflammatory response. In the CD8+T cell subsests, we detected a notable increase in cells expressing granzyme K (GZMK), signaling an intensified cytotoxic activity. Additionally, the escalated presence of T cells with high levels of heat shock proteins (HSPs) suggests a cellular stress condition, possibly associated with persistent low-grade inflammation, mirroring the chronic aspect of the condition. Conclusions: Our research identified distinct stromal and immune cell populations linked to pSS, revealing new potential targets for its management. The activation of myeloid, B, and T cells could contribute to pSS pathogenesis, providing important guidance for therapeutic approaches.

Efficient catalysis of CO2 hydrogenation holds significant promise for addressing environmental concerns and advancing sustainable energy solutions. In this study, we report the synthesis of a novel series of Ru-supported on graphitic carbon nitride (g-C3N4) catalysts, with a focus on the impact of ruthenium (Ru) loading on the thermocatalytic performance. Varying Ru concentrations were introduced, including 0.2, 0.5, 1.0, 2.0, and 5.0 wt%, resulting in different Ru particle sizes on g-C3N4 support. Through a multifaceted characterization approach, it was observed that the catalyst containing 1 wt% Ru loading displayed superior performance, with a high density of active sites, indicated by an enhanced CO2 conversion rate of 36.8 % at 450 °C and a CO yield of 25 %. This catalyst also exhibited remarkable CO selectivity of 83 % at 375 °C. Conversely, lower loadings of 0.2 and 0.5 wt % Ru were found to be less effective, yielding minimal CO2 conversion. Loadings above 1 wt% Ru, while achieving high CO2 conversion, demonstrated a preference for CH4 production over CO, indicating lower selectivity for the desired product. This study elucidates the critical role of Ru nanocluster size in the catalytic activity and selectivity, with 1 wt % Ru-supported g-C3N4 emerging as a promising candidate for selective CO generation from CO2 hydrogenation, offering a pathway for the valorization of CO2 as a raw material in the chemical industry.

Abstract Engineering high‐performance and low‐cost bifunctional catalysts for H2 (hydrogen evolution reaction [HER]) and O2 (oxygen evolution reaction [OER]) evolution under industrial electrocatalytic conditions remains challenging. Here, for the first time, we use the stronger electronegativity of a rare‐Earth yttrium ion (Y3+) to induce in situ NiCo‐layered double‐hydroxide nanosheets from NiCo foam (NCF) treated by a dielectric barrier discharge plasma NCF (PNCF), and then obtain nitrogen‐doped YNiCo phosphide (N‐YNiCoP/PNCF) after the phosphating process using radiofrequency plasma in nitrogen. The obtained N‐YNiCoP/PNCF has a large specific surface area, rich heterointerfaces, and an optimized electronic structure, inducing high electrocatalytic activity in HER (331 mV vs. 2000 mA cm−2) and OER (464 mV vs. 2000 mA cm−2) reactions in 1 M KOH electrolyte. X‐ray absorption spectroscopy and density functional theory quantum chemistry calculations reveal that the coordination number of CoNi decreased with the incorporation of Y atoms, which induce much shorter bonds of Ni and Co ions and promote long‐term stability of N‐YNiCoP in HER and OER under the simulated industrial conditions. Meanwhile, the CoN‐YP5 heterointerface formed by plasma N‐doping is the active center for overall water splitting. This work expands the applications of rare‐Earth elements in engineering bifunctional electrocatalysts and provides a new avenue for designing high‐performance transition‐metal‐based catalysts in the renewable energy field.

IntroductionNuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay.MethodsThis work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells.ResultsFinally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells.ConclusionOverall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

The Jianghan Plain is simultaneously responsible for ecological protection, food security and urbanization, and land use conflicts are prominent. Revealing the driving mechanism of land use/cover change (LUCC) and simulating the land use pattern can help to coordinate the land use conflicts in the future. Utilizing the National Land Survey Data (NLSD) of Jiangling County in Jianghan Plain (2011–2020) and the patch-generating land use simulation (PLUS) model, this paper analyzed the characteristics of land use evolution, applied the random forest classification (RFC) to analyze the driving mechanism, simulated the 2035 land use pattern under three scenarios of natural development, planning guidance and ecological protection through Markov and Cellular Automaton based on multiple random seeds (CARS) models, and proposed several countermeasures. The study found that: 1) From 2011 to 2020, town construction land increased, village construction land, agricultural land and ecological land decreased. 2) The factors driving LUCC were socio-economic factors, spatial factors, and natural factors in descending order. 3) In the three scenarios, the trend of construction land expansion, agricultural land and ecological land encroachment is inevitable by 2035. 4) It is imperative to actively advocate for large-scale mechanization and informatization of agricultural production, encourage the repurposing of idle and inefficiently used construction land, facilitate multi-purpose land utilization, and implement a policy of locally balancing occupation and compensation for cultivated and ecological land. 5) When employing the PLUS model to simulate LUCC, using continuous NLSD yielded more accurate results than remote sensing image interpretation data. This study offers a theoretical basis for the coordinated development of land use in Jianghan Plain, and presents a method to enhance the simulation accuracy of the PLUS model.

Abstract BackgroundParental health literacy is important to children’s health and development, especially in the first 3 years. However, few studies have explored effective intervention strategies to improve parental literacy. ObjectiveThis study aimed to determine the effects of a WeChat official account (WOA)–based intervention on parental health literacy of primary caregivers of children aged 0-3 years. MethodsThis cluster randomized controlled trial enrolled 1332 caregiver-child dyads from all 13 community health centers (CHCs) in Minhang District, Shanghai, China, between April 2020 and April 2021. Participants in intervention CHCs received purposefully designed videos via a WOA, which automatically recorded the times of watching for each participant, supplemented with reading materials from other trusted web-based sources. The contents of the videos were constructed in accordance with the comprehensive parental health literacy model of WHO (World Health Organization)/Europe (WHO/Europe). Participants in control CHCs received printed materials similar to the intervention group. All the participants were followed up for 9 months. Both groups could access routine child health services as usual during follow-up. The primary outcome was parental health literacy measured by a validated instrument, the Chinese Parental Health Literacy Questionnaire (CPHLQ) of children aged 0-3 years. Secondary outcomes included parenting behaviors and children’s health outcomes. We used the generalized linear mixed model (GLMM) for data analyses and performed different subgroup analyses. The β coefficient, risk ratio (RR), and their 95% CI were used to assess the intervention’s effect. ResultsAfter the 9-month intervention, 69.4% (518/746) of caregivers had watched at least 1 video. Participants in the intervention group had higher CPHLQ total scores (β=2.51, 95% CI 0.12-4.91) and higher psychological scores (β=1.63, 95% CI 0.16-3.10) than those in the control group. The intervention group also reported a higher rate of exclusive breastfeeding (EBF) at 6 months (38.9% vs 23.44%; RR 1.90, 95% CI 1.07-3.38) and a higher awareness rate of vitamin D supplementation for infants younger than 6 months (76.7% vs 70.5%; RR 1.39, 95% CI 1.06-1.82). No significant effects were detected for the physical score on the CPHLQ, breastfeeding rate, routine checkup rate, and children’s health outcomes. Furthermore, despite slight subgroup differences in the intervention’s effects on the total CPHLQ score and EBF rate, no interaction effect was observed between these subgroup factors and intervention factors. ConclusionsUsing a WHO literacy model–based health intervention through a WOA has the potential of improving parental health literacy and EBF rates at 6 months. However, innovative strategies and evidence-based content are required to engage more participants and achieve better intervention outcomes.

Viral hepatitis, caused by its etiology, hepatitis virus, is a public health problem globally. Among all infections caused by hepatitis-associated viruses, hepatitis B virus (HBV) infection remains the most serious medical concern. HBV infection particularly affects people in East Asia and Africa, the Mediterranean region, and Eastern Europe, with a prevalence rate of > 2%. Currently, approximately 1 billion people worldwide are infected with HBV, and nearly 30% of them experience chronic infection. Chronic HBV infection can lead to chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma (HCC), resulting in the related death of approximately 1 million people annually. Although preventative vaccines and antiviral therapies are currently available, there is no cure for this infection. Clinical testing is not only the gateway for diagnosis of HBV infection, but also crucial for judging the timing of medication, evaluating the effect of antiviral therapy, and predicting the risk of relapse after drug withdrawal in the whole follow-up management of hepatitis B infected persons. With advances in detection technology, it is now possible to measure various viral components in the blood to assess the clinical status of HBV infection. Serum viral products of HBV infection, such as HBV DNA, HBV RNA, hepatitis B surface antigen, hepatitis B e-antigen, and hepatitis B core-related antigen, are non-invasive indicators that are critical for the rapid diagnosis and management of related diseases. Improving the sensitivity of monitoring of these products is essential, and the development of corresponding detection technologies is pivotal in achieving this goal. This review aims to offer valuable insights into CHB infection and references for its effective treatment. We provide a comprehensive and systematic overview of classical and novel methods for detecting HBV serum viral products and discusses their clinical applications, along with the latest research progress in this field.

During the service of asphalt pavement, it is affected by natural environmental factors for a long time, and the pavement performance declined. In order to simulate the cumulative effects of multiple aging components, the indoor ''ultraviolet radiation, high temperature and water'' multi-factor cyclic coupling aging test was designed. The properties of asphalt during cyclic coupled aging were measured by conventional physical properties tests, photoelectric colorimetric tests, and Fourier Transform Infrared Spectroscopy test. Then the surface morphology of asphalt was observed by camera and optical microscope. After asphalt aged, a large number of oxidation functional groups were formed, causing asphalt to become hard and brittle, adhesion to diminish, and surface roughness to increase. Ultraviolet light and high temperatures led to the exudation and dissolution of the liquid constituents within the asphalt, which were subsequently washed away by water. The thermal stress induced the shrinkage and wrinkle of the asphalt film, resulting in the formation of cracks. Under high temperatures, a limited number of cracks could potentially self-repair during the early stages of aging. Nevertheless, as the aging process progressed, the self-healing capacity of the asphalt diminished, leading to the widening and deepening of cracks. Concurrently, water infiltrated along the cracks into the inner layers of the asphalt, exacerbating the degradation of its properties.

Abstract Background Patients with DNA mismatch repair‐proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti‐PD‐1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. Methods In this pilot study, we administered six preoperative doses of each 2‐week cycle of the anti‐PD‐1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5‐FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. Results By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow‐up was 24.7 months (IQR: 21.1–26.1). All patients underwent R0 surgical resection without treatment‐related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence‐free. Treatment‐related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10−8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non‐pCR tumors (p = 0.038 and p = 0.015, respectively). Conclusions Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non‐pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD‐1 blockade‐enhanced targeted chemotherapy require further investigation.

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal biliary epithelial cancer in the liver. Here, Laminin subunit gamma‐2 (LAMC2) with important oncogenic roles in iCCA is discovered. In a total of 231 cholangiocarcinoma patients (82% of iCCA patients) across four independent cohorts, LAMC2 is significantly more abundant in iCCA tumor tissue compared to normal bile duct and non‐tumor liver. Among 26.3% of iCCA patients, LAMC2 gene is amplified, contributing to its over‐expression. Functionally, silencing LAMC2 significantly blocks tumor formation in orthotopic iCCA mouse models. Mechanistically, it promotes EGFR protein translation via interacting with nascent unglycosylated EGFR in the endoplasmic reticulum (ER), resulting in activated EGFR signaling. LAMC2‐mediated EGFR translation also depends on its interaction with the ER chaperone BiP via their C‐terminus. Together LAMC2 and BiP generate a binding “pocket” of nascent EGFR and facilitate EGFR translation. Consistently, LAMC2‐high iCCA patients have poor prognosis in two iCCA cohorts. LAMC2‐high iCCA cells are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) treatment both in vitro and in vivo. Together, these data demonstrate LAMC2 as an oncogenic player in iCCA by promoting EGFR translation and an indicator to identify iCCA patients who may benefit from available EGFR‐targeted TKIs therapies.

Abstract Phase instability poses a serious challenge to the commercialization of formamidinium lead iodide (FAPbI3)-based solar cells and optoelectronic devices. Here, we combine density functional theory and machine learning molecular dynamics simulations, to investigate the mechanism driving the undesired α-δ phase transition of FAPbI3. Prevalent iodine vacancies and interstitials can significantly expedite the structural transition kinetics by inducing robust covalency during transition states. Extrinsically, the detrimental roles of atmospheric moisture and oxygen in degrading the FAPbI3 perovskite phase are also rationalized. Significantly, we discover the compositional design principles by categorizing that A-site engineering primarily governs thermodynamics, whereas B-site doping can effectively manipulate the kinetics of the phase transition in FAPbI3, highlighting lanthanide ions as promising B-site substitutes. A-B mixed doping emerges as an efficient strategy to synergistically stabilize α-FAPbI3, as experimentally demonstrated by substantially higher initial optoelectronic characteristics and significantly enhanced phase stability in Cs-Eu doped FAPbI3 as compared to its Cs-doped counterpart. This study provides scientific guidance for the design and optimization of long-term stable FAPbI3-based solar cells and other optoelectronic devices through defect control and synergetic composition engineering.

Abstract Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity.

The rotary motion deblurring is an inevitable procedure when the imaging seeker is mounted in the rotating missiles. Traditional rotary motion deblurring methods suffer from ringing artifacts and noise, especially for large blur extents. To solve the above problems, we propose a progressive rotary motion deblurring framework consisting of a coarse deblurring stage and a refinement stage. In the first stage, we design an adaptive blur extents factor (BE factor) to balance noise suppression and details reconstruction. And a novel deconvolution model is proposed based on BE factor. In the second stage, a triple-scale deformable module CNN(TDM-CNN) is designed to reduce the ringing artifacts, which can exploit the 2D information of an image and adaptively adjust spatial sampling locations. To establish a standard evaluation benchmark, a real-world rotary motion blur dataset is proposed and released, which includes rotary blurred images and corresponding ground truth images with different blur angles. Experimental results demonstrate that the proposed method outperforms the state-of-the-art models on synthetic and real-world rotary motion blur datasets. The code and dataset are available at https://github.com/Jinhui-Qin/RotaryDeblurring.

With the development of hyperspectral sensing technology, hyperspectral target detection technology plays an important role in remote target detection. However, existing hyperspectral target detection models are poorly adapted to complex backgrounds and mainly focus on the spectral domain, making less use of spatial structure information leading to low target detection rates. Therefore, a new target detection algorithm based on the prior spectral perception and local graph fusion is proposed. First, the prior spectrum-guided target extraction method is established. This method can take full advantage of the background and target spectral information by local inner and outer window linkage, reduce the impact of spectral variability on target acquisition performance, and improve detection stability. Second, the target enhancement strategy based on the Gabor multifeature graph is proposed. This technique makes full use of multidirectional and multiscale spatial information, which can reduce the influence of brightness, contrast and amplitude variation on detection performance due to light and angle. Finally, spatial–spectral fusion is executed to achieve target detection. It can make full use of spectral and spatial structure information to improve the target detection effect. Publicly available datasets and real collected datasets are adopted to check the validity of the proposed method. After comparison, it is found that the proposed algorithm has better detection effect than existing baseline methods. The maximum improvement in AUC values are 16.56%–88.16% across the eight datasets.

Objective To explore the feasibility of using autologous platelet-rich plasma (PRP) in the treatment of deep second-degree burns complicated with wound infection. Methods A retrospective analysis was conducted on the treatment process of a patient with deep second-degree burns and bacterial infection on the wound using autologous PRP. Clinical treatment highlights and outpatient follow-up were combined to discuss the feasibility and clinical effects of using autologous PRP in the treatment of burn wounds complicated with infection. Results The patient had a deep second-degree burn with a coagulase-negative Staphylococcus infection on the left lower limb. After one week of conventional wound dressing and antibiotic treatment, the patient's body temperature returned to normal. However, wound healing was slow and yellow secretion persisted. Subsequently, the burn wound was treated combined with topical autologous PRP. The wound pain score gradually decreased from 8 to 1. After 2 weeks, the bacterial culture of the wound secretion was negative, and the wound healed completely after 18 days. The wound scar score decreased from 5 to 2 at 1, 3 and 6 months after PRP treatment, and no obvious scar formation was observed. In the course of PRP treatment, there were no adverse reactions such as increased wound inflammation, abnormal blood routine and liver and kidney function test results. Conclusion For deep second-degree burn patients with localized wound bacterial infections who either refuse surgery or are not suitable for surgery, autologous PRP is a safer alternative that can effectively promote tissue regeneration and wound healing. The patient in this case achieved a curative effect in a short period of time.

Abstract Background Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. Methods The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3−), NK (NK1.1−CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. Results Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P

Extracting small targets from complex backgrounds is the eventual goal of single-frame infrared small target detection, which has many potential applications in defense security and marine rescue. Recently, methods utilizing deep learning have shown their superiority over traditional theoretical approaches. However, they do not consider both the global semantics and specific shape information, thereby limiting their performance. To overcome this proplem, we propose a gated-shaped TransUnet (GSTUnet), designed to fully utilize shape information while detecting small target detection. Specifically, we have proposed a multiscale encoder branch to extract global features of small targets at different scales. Then, the extracted global features are passed through a gated-shaped stream branch that focuses on the shape information of small targets through gate convolutions. Finally, we fuse their features to obtain the final result. Our GSTUnet learns both global and shape information through the aforementioned two branches, establishing global relationships between different feature scales. The GSTUnet demonstrates excellent evaluation metrics on various datasets, outperforming current state-of-the-art methods.

In this paper, Al2O3/Cr composite coatings were prepared on the surface of Inconel 718 alloy by cathodic liquid plasma electrolytic deposition (CLPED) and double-glow plasma surface alloying (DGPSA) processes. The microstructure and high-temperature oxidation behavior of Al2O3/Cr composite coating were investigated. The results showed that the Al2O3 interlayer surface was fully covered with Cr coating. The interface between the Al2O3 layer and the Cr metal layer presents a mechanical interlock effect, which can absorb the deformation caused by thermal expansion, thereby reducing the adverse effects of thermal stress. The surface roughness of the Al2O3 coatings decreased after depositing Cr coating. The oxidation weight gain of the Al2O3/Cr composite coatings were significantly lower than that of the substrate, indicating that the Al2O3/Cr composite coatings improved the high-temperature oxidation resistance of Inconel 718 alloy. The oxidation weight gain of the Al2O3/Cr composite coatings at different frequencies were similar, while the Al2O3/Cr composite coating at 400 Hz was lowest. During the high-temperature oxidation process, the Al2O3 interlayer can effectively inhibit the external diffusion of Ni, Fe and other elements in the matrix, which helps to prevent the cracking of the outer oxide film, thereby reducing the oxidation rate.