Search

To improve the corrosion resistance and wide the application of Al alloy sheet in the engineering production, a corrosion potential gradient along the thickness of the Al alloy sheet was fabricated using the sprayed Zn layer. The process of arc spraying was employed to obtain the Zn coating with optimizing the parameters. Electrochemical testing was conducted on the surface of Al alloy sprayed with Zn layers at different depths. As the depth in the thickness direction increases, the content of Zn alloy elements gradually decreases and the potential gradually increases. This exhibits a gradual decrease in corrosion tendency. The results of electrochemical impedance spectra (EIS) revealed the existence of pitting corrosion on the surface of the Al alloy. This even extended to the underlying substrate material. In contrast, the Zn coating, when exposed to a corrosive environment, demonstrated the beneficial cathodic effect as a sacrificial anode and the protective function of a passivating film, thus mitigating corrosion. The gradual increase in charge transfer resistance in the impedance spectrum suggested that the corrosion resistance of the sample is increasingly improved. Therefore, it exhibited remarkable resistance to corrosion. Additionally, the SEM surface morphology and XRD pattern were utilized to further explain the corrosion mechanism of the arc-sprayed Zn coating. The Zn coating can provide sacrificial protection to the Al layer due to its higher negative potential and localized corrosion reactivity. This is attributed to the micro-galvanic couples formed between the Zn and Al layer, thus increasing the corrosion resistance of the sheets.

Abstract Background The Access, Watch, and Reserve (AWaRe) classification of antibiotics was a useful tool to support antibiotic stewardship. However, the AWaRe patterns of antibiotic consumption in Western China were unclear. We aimed to assess the antibiotic consumption patterns using the AWaRe Classification of public hospitals in Sichuan Province Western China. Methods Antibiotic consumption data of year 2020 were obtained from the Sichuan Province Drug Use Monitoring Platform. We measured the antibiotic consumption (DDDs per 1,000 inhabitants per day, DIDs), calculated the proportion of antibiotic use, the ratio of Access to Watch antibiotics and patterns of antibiotic use by using drug utilization 90%. Results This analysis included 4452 public health institutions. The antibiotic consumption rate was 10.39 DIDs (Median 8.50, IQR 7.71–12.96). The proportions of Access antibiotic use and Watch antibiotic use were 46.83% (Median 47.49, IQR 44.16–52.02) and 51.20% (Median 51.43, IQR 45.42–54.61), respectively. The Access-to-Watch index was 0.91 (Median 0.92, IQR 0.81–1.15). Amoxicillin (16.85%), cefuroxime (9.21%), cefixime (8.60%%), levofloxacin (8.11%) and metronidazole (6.16%) were the most consumed antibiotics. Conclusions The proportion of Access antibiotic consumption in Sichuan Western China has not achieved the WHO target of 60%. Overuse of antibiotic is serious in Sichuan. National and regional antibiotics management systems, stewardship programs and surveillance of antibiotic consumption based on AWaRe classification are needed to improve antibiotic consumption patterns, curb antibiotic overuse and combat antimicrobial resistance in Western China.

Abstract Relapsed/refractory (R/R) primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. We retrospectively compared the safety and efficacy of CD19/22 CAR-T-cell therapy following ASCT (ASCT + CAR-T group), CD19/22 CAR-T-cell cocktail therapy (CAR-T group) and chemoimmunotherapy (CIT group) in treating R/R CNSL patients. Analysis of the differences in clinical characteristics among the three groups revealed that the median age in the CIT group was older than that in the ASCT + CAR-T group and CAR-T group, and the median number of prior lines of therapy in the CIT group was less than that in the other groups. Patients in the two CAR-T-therapy groups exhibited comparable incidences and severities of CRS and ICANS. Grade 4–5 CRS and ICANS were not observed in either CAR-T-cell therapy group. The incidence of Grade 3/4 hematological toxicity in the ASCT + CAR-T and CAR-T groups was greater than that in the CIT group. The ORR was 82.75% in the ASCT + CAR-T group, 60.00% in the CAR-T group and 58.83% in the CIT group. As of December 31, 2022, the median follow-up after therapy was 16.73 months (range, 0.67-42.00 months). The median durations of PFS and OS were not reached in the ASCT + CAR-T group. The median PFS in the CAR-T group was 4.72 months, and OS was not reached. In the CIT group, the median PFS and OS were 6.63 months and 16.77 months, respectively. The 2-year PFS rate of patients in the ASCT + CAR-T group (65.52%) was significantly greater than that of patients in the CAR-T group (30.00%, P = 0.0321) and CIT group (23.53%, P = 0.0043). Our results support the development of CAR-T-cell therapy for R/R CNSL. With the durability of remission and low toxicity, ASCT combined with CAR-T-cell therapy appears to be a more effective and safer treatment option for primary and secondary R/R CNS lymphoma.

Abstract Background Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition. Results In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value

Abstract Background Medication Treatment Satisfaction (M-TS) from the patients’ perspective is important for comprehensively evaluating the effect of medicines. The extent to which current patient-reported outcome measures (PROMs) for M-TS are valid, reliable, responsive, and interpretable remains unclear. To assess the measurement properties of existing PROMs for M-TS and to highlight research gaps. Methods Using PubMed, Embase (Ovid), Cochrane library (Ovid), IPA (Ovid), PsycINFO, Patient-Reported Outcome and Quality of Life Questionnaires biomedical databases, and four Chinese databases, we performed a systematic search for studies addressing the development and validation of PROMs for M-TS. Based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guideline, pairs of reviewers independently assessed the measurement properties of the PROMs and rated the quality of evidence on the measurement properties of each PROM. (The Open Science Framework registration: https://doi.org/10.17605/OSF.IO/8S5ZM ). Results This review identified 69 PROMs for M-TS in 114 studies (four generic, 32 disease-specific, and 33 drug-specific) of which 60 were intended for adults. All provided limited or no information regarding interpretability. Most demonstrated appropriate construct validity including convergent validity (39/69) and discriminative or known-groups validity (40/69) (high to moderate quality of evidence). Only a few provided evidence of sufficient content validity (8/69), structural validity (13/69), and internal consistency (11/69). Of 38 PROMs reporting test–retest reliability, results in 24 provided evidence of satisfactory test–retest reliability (18 with high to moderate, 6 with low to very low quality of evidence). Few PROMs reported responsiveness (16/69). Two generic PROMs (Treatment Satisfaction Questionnaire for Medication initial Version 1.4, TSQM-1.4; Treatment Satisfaction with Medicines Questionnaire, SATMED-Q) and one drug-specific PROM (Insulin Treatment Satisfaction Questionnaire, ITSQ) demonstrated both satisfactory validity and reliability. Conclusions Most existing PROMs for M-TS require further exploration of measurement properties. Reporting guidelines are needed to enhance the reporting quality of the development and validation of PROMs for M-TS.

Abstract A single-atom catalyst with generally regarded inert Zn–N4 motifs derived from ZIF-8 is unexpectedly efficient for the activation of alcohols, enabling alcohol-mediated alkylation and transfer hydrogenation. C-alkylation of nitriles, ketones, alcohols, N-heterocycles, amides, keto acids, and esters, and N-alkylation of amines and amides all go smoothly with the developed method. Taking the α-alkylation of nitriles with alcohols as an example, the α-alkylation starts from the (1) nitrogen-doped carbon support catalyzed dehydrogenation of alcohols into aldehydes, which further condensed with nitriles to give vinyl nitriles, followed by (2) transfer hydrogenation of C=C bonds in vinyl nitriles on Zn–N4 sites. The experimental results and DFT calculations reveal that the Lewis acidic Zn-N4 sites promote step (2) by activating the alcohols. This is the first example of highly efficient single-atom catalysts for various organic transformations with biomass-derived alcohols as the alkylating reagents and hydrogen donors.

Abstract Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

Abstract The inactivation of natural enzymes by radiation poses a great challenge to their applications for radiotherapy. Single-atom nanozymes (SAzymes) with high structural stability under such extreme conditions become a promising candidate for replacing natural enzymes to shrink tumors. Here, we report a CuN3-centered SAzyme (CuN3-SAzyme) that exhibits higher peroxidase-like catalytic activity than a CuN4-centered counterpart, by locally regulating the coordination environment of single copper sites. Density functional theory calculations reveal that the CuN3 active moiety confers optimal H2O2 adsorption and dissociation properties, thus contributing to high enzymatic activity of CuN3-SAzyme. The introduction of X-ray can improve the kinetics of the decomposition of H2O2 by CuN3-SAzyme. Moreover, CuN3-SAzyme is very stable after a total radiation dose of 500 Gy, without significant changes in its geometrical structure or coordination environment, and simultaneously still retains comparable peroxidase-like activity relative to natural enzymes. Finally, this developed CuN3-SAzyme with remarkable radioresistance can be used as an external field-improved therapeutics for enhancing radio-enzymatic therapy in vitro and in vivo. Overall, this study provides a paradigm for developing SAzymes with improved enzymatic activity through local coordination manipulation and high radioresistance over natural enzymes, for example, as sensitizers for cancer therapy.

IntroductionMultifunctional nanomaterials are emerging as promising tools for treating both cancer and bacterial infections. However, integrating dual therapeutic capabilities into a single system remains challenging. This study presents multifunctional nanoparticles (ECI-NPs) based on Epigallocatechin gallate (EGCG) oligomers, Curcumin (CUR), and Indocyanine Green (ICG) for combined cancer and bacterial treatment.MethodsECI-NPs were synthesized via oxidative coupling of EGCG, CUR, and ICG. The nanoparticles were characterized for stability, size, drug loading, and release profiles. Cellular uptake, phototoxicity in melanoma cells, and antibacterial activity against Escherichia coli and Staphylococcus aureus were also evaluated.ResultsECI-NPs demonstrated optimal stability, high drug loading, and controlled release. Cellular studies showed increased uptake and greater phototoxicity in melanoma cells compared to free drugs. ECI-NPs also exhibited enhanced anticancer effects and strong antibacterial activity, outperforming the individual components.DiscussionThe polyphenol-based ECI-NPs offer synergistic therapeutic effects, overcoming the limitations of free drugs in terms of solubility and efficacy. This dual-function platform shows potential for broader biomedical applications, addressing challenges in cancer and bacterial infections. Further research will focus on in vivo studies and clinical translation.

Chimeric antigen receptor T (CAR-T) cell therapy has shown promise in treating hematological malignancies and certain solid tumors. However, its efficacy is often hindered by negative relapses resulting from antigen escape. This review firstly elucidates the mechanisms underlying antigen escape during CAR-T cell therapy, including the enrichment of pre-existing target-negative tumor clones, antigen gene mutations or alternative splicing, deficits in antigen processing, antigen redistribution, lineage switch, epitope masking, and trogocytosis-mediated antigen loss. Furthermore, we summarize various strategies to overcome antigen escape, evaluate their advantages and limitations, and propose future research directions. Thus, we aim to provide valuable insights to enhance the effectiveness of CAR-T cell therapy.

Summary: Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. We conducted an open-label, phase 2 nonrandomised, externally controlled study to evaluate the efficacy and safety of targeted agents plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) (CHOPX) for PTCL in the front-line setting. Methods: Eligible patients were ≥18 years of age and newly diagnosed PTCL. Patients in the CHOPX group received standard CHOP at Cycle 1. Specific targeted agents were added from Cycle 2, decitabine if TP53mut, azacytidine if TET2/KMT2Dmut, tucidinostat if CREBBP/EP300mut, and lenalidomide if without mutations above. Patients in the CHOP group received CHOP for 6 cycles. The primary endpoint was the complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov, NCT04480099. Findings: Between July 29, 2020, and Sep 22, 2022, 96 patients were enrolled and included for efficacy and safety analysis with 48 in each group. The study met its primary endpoint. CRR at EOT in the CHOPX group was superior to the CHOP group (64.6% vs. 33.3%, OR 0.27, 95%CI 0.12–0.64; p = 0.004). At a median follow-up of 24.3 months (IQR 12.0–26.7), improved median PFS was observed in the CHOPX group (25.5 vs. 9.0 months; HR 0.57, 95%CI 0.34–0.98; p = 0.041). The median OS was similar between two groups (not reached vs. 30.9 months; HR 0.55, 95%CI 0.28–1.10; p = 0.088). The most common grade 3–4 hematological and non-hematological adverse events in the CHOPX group were neutropenia (31, 65%) and infection (5, 10%). Interpretation: Targeted agents combined with CHOP demonstrated effective and safe as first-line treatment in PTCL. Biomarker-driven therapeutic strategy is feasible and may lead to promising efficacy specifically toward molecular features in PTCL. Funding: This study was supported by the National Key Research and Development Program (2022YFC2502600) and the General Program of the Shanghai Municipal Health Commission (202040400).

Abstract Compared with conventional soils, such as sand and clay, little knowledge on the coefficient of lateral earth pressure at-rest (K 0) has been established for loess in the current literature. This paper presents an experimental investigation on K 0 of compacted loess and the associated impacts on undrained shear behaviour. By adopting a K 0 consolidation module in the triaxial system, the K 0 stress state for loess samples was achieved through a unique feedback control. During the K 0 consolidation, the deviatoric stress (q) increases progressively with the premise that the volumetric strain (ε v) of the sample equals to the axial strain (ε a). The results show that the K 0 value of compacted loess is in a range of 0.28 to 0.53, which is dependent on the packing density and the clay content. A distinguishable decrease of K 0 was found in the course of K 0 consolidation for the loosely compacted loess sample, whereas a similar trend was not observed in the dense sample. In the undrained shear stage, all loess specimens revealed contractive response in the stress path (q-p’) diagram, which can be quantified by a modified collapsibility index (I c). The index is consistently higher for the K 0 consolidated loess samples than for the isotropic ones. The experimental results indicate a strong impact of the initial stress state on the shear behaviour of compacted loess.

Abstract The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called “challenging BC”. Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in “challenging BC” patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in “challenging BC” patients.

In naval and civilian domains, meticulous ship classification and detection are paramount. Nevertheless, predominant research has gravitated toward leveraging Convolutional Neural Network (CNN)-centered methodologies, often overlooking the diverse granularity inherent in ship samples. In our pursuit to holistically extract features from ship images across varying granularities, we present a transformative architecture: the Vision Transformer and Multi-Grain Feature Vector Feature Pyramid Network (ViT-MGFV-FPN). This model synergistically melds the merits of MGFV-FPN with an augmented Vision Transformer (ViT) for a comprehensive image feature extraction. To cater to the extraction of broader image features whilst sidestepping the innate quadratic complexity of traditional ViT, we unveil an enhanced version christened the Global Swin Transformer. Concurrently, the MGFV-FPN is orchestrated to harness the prowess of CNNs in distilling intricate ship attributes. Rigorous empirical evaluations underscore our model’s superiority in juxtaposition with extant CNN and transformer-based paradigms for nuanced ship categorization.

Abstract The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months’ median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32–0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30–0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

Remote sensing image semantic segmentation methods have become the main approach for extracting cropland information. However, in the mountainous regions of southwestern China, croplands exhibit narrow and fragmented shapes, as well as complex planting patterns, making it difficult for traditional semantic segmentation methods to accurately delineate fine-grained cropland boundaries. To address these challenges, a multiattention Transformer network named MATNet is proposed in this paper, for fine-grained extraction of cropland at the parcel level in complex scenes. MATNet built upon the fusion of CNN encoder and Transformer decoder. In the encoder, spatial and channel reconstruction units are introduced, reducing information redundancy in the convolutional layers. The Transformer decoder incorporates multiple attention mechanisms, this design feature enhances the attention window's perception of local content and improves the model's ability to extract features from fine-grained cropland parcels through optimized computationnal al location. Taking the experimental results of the Dali cropland dataset as an illustration, MATNet achieved the highest values across five evaluation metrics, including mIoU. Specifically, the Recall, F1, and mIoU scores were 94.68%, 94.69%, and 89.92%, respectively. Compared with six other advanced models, MATNet consistently performed best in terms of extracting fine-grained cropland parcels.

ABSTRACTIn the field of remote sensing, using a large amount of labeled image data to supervise the training of fully convolutional networks for the semantic segmentation of images is expensive. However, using a small amount of labeled data can lead to reduced network performance. This paper proposes an unsupervised semantic segmentation method that combines the ImSE-Net model with SLICm superpixel optimization. First, the ImSE-Net model is used to extract semantic features from the image to obtain rough semantic segmentation results. Then, the SLICm superpixel segmentation algorithm is used to segment the input image into superpixel images. Finally, an unsupervised semantic segmentation model (UGLS) is used to combine high-level abstract semantic features with detailed information on superpixels to obtain edge-optimized semantic segmentation results. Experimental results show that compared with other semantic segmentation algorithms, our method more effectively handles unbalanced areas, such as object boundaries, and achieves better segmentation results, with higher semantic consistency.

Human exposure to heavy metals, which encompasses both essential and toxic varieties, is widespread. The intestine functions as a critical organ for absorption and metabolism of heavy metals. Gut microbiota plays a crucial role in heavy metal absorption, metabolism, and related processes. Toxic heavy metals (THMs), such as arsenic (As), mercury (Hg), lead (Pb), and cadmium (Cd), can cause damage to multiple organs even at low levels of exposure, and it is crucial to emphasize their potential high toxicity. Nevertheless, certain essential trace elements, including iron (Fe), copper (Cu), and manganese (Mn), play vital roles in the biochemical and physiological functions of organisms at low concentrations but can exert toxic effects on the gut microbiota at higher levels. Some potentially essential micronutrients, such as chromium (Cr), silicon (Si), and nickel (Ni), which were considered to be intermediate in terms of their essentiality and toxicity, had different effects on the gut microbiota and their metabolites. Bidirectional relationships between heavy metals and gut microbiota have been found. Heavy metal exposure disrupts gut microbiota and influences its metabolism and physiological functions, potentially contributing to metabolic and other disorders. Furthermore, gut microbiota influences the absorption and metabolism of heavy metals by serving as a physical barrier against heavy metal absorption and modulating the pH, oxidative balance, and concentrations of detoxification enzymes or proteins involved in heavy metal metabolism. The interactions between heavy metals and gut microbiota might be positive or negative according to different valence states, concentrations, and forms of the same heavy metal. This paper reviews the metabolic interactions of 10 common heavy metals with the gut microbiota and their health implications. This collated information could provide novel insights into the disruption of the intestinal microbiota caused by heavy metals as a potential contributing factor to human diseases.

Background: Transanal total mesorectal excision has emerged as a potential solution to certain limitations associated with laparoscopic total mesorectal excision in rectal cancer patients. Differences in surgical approaches have raised questions regarding their impact on the risk of postoperative urinary retention, with limited data available from large scale randomized clinical study. Objective: To report incidence of postoperative urinary retention and evaluate the associated risk factors for transanal total mesorectal excision. Design: In this randomized controlled trial (ClinicalTrials. gov NCT06147492), we retrieved 524 patients who received total mesorectal excision (TME) for stage I–III rectal cancer between June 2019 and April 2022, and the patients were randomly assigned in a 1:1 ratio to undergo either taTME or laTME. Patients: We enrolled 524 patients who underwent total mesorectal excision for stage I–III rectal cancer between June 2019 and April 2022. Main outcome measures: The incidence of postoperative urinary retention. Results: Among the 524 enrolled patients, 261 were randomized to the laTME group, while 263 were were randomized the taTME group. The median age was 58 years, and 340 participants (64.8 %) were male. Notably, 37 individuals (7.0 %) experienced postoperative urinary retention during the follow-up period, with no significant disparity was observed between the taTME and laTME groups (6.8 % and 7.2 %, respectively, P = 0.98). Risk factors associated with PUR in patients following taTME encompassed early removal of the urinary catheter (P = 0.006), net infusion rate >4.09 ml kg−1.h−1 (P = 0.006), and an age surpassing 65 years (P = 0.0321). Limitations: The generalizability of the findings outside specialist rectal cancer centers may be limited. Conclusions: Transanal total mesorectal excision was not found to heighten the risk of postoperative urinary retention. Nonetheless, it is advisable removing postoperative catheter beyond the initial day and exercising caution in the administration of intravenous fluids in clinical practice for taTME procedures.

BackgroundOseltamivir and baloxavir marboxil are the two primary oral drugs approved by the Food and Drug Administration (FDA) for treating influenza. Limited real-world evidence exists on their adverse events in children. The purpose of this study was to explore the adverse event (AE) profiles of oseltamivir and baloxavir marboxil in children based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.MethodsFAERS reports were collected and analyzed from the first quarter of 2019 to the third quarter of 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of oseltamivir and baloxavir marboxil-related AEs.ResultsA total of 464 reports of AEs to oseltamivir as the “primary suspect (PS)” and 429 reports of AEs to baloxavir marboxil as the “PS” were retrieved in pediatric patients. A total of 100 oseltamivir-induced AE signals were detected in 17 system organ classes (SOCs), and 11 baloxavir marboxil-induced AE signals were detected in 6 SOCs after complying with the four algorithms simultaneously. Categorized and summarized by the number of reports of involvement in each SOC, the top 3 for oseltamivir were psychiatric disorders, gastrointestinal disorders, general disorders and site-of-administration conditions, respectively. The top 3 for baloxavir marboxil were injury, poisoning and surgical complications, general disorders and site of administration conditions, and psychiatric disorders, respectively.ConclusionOur study identifies potential new AE signals for oseltamivir and provides a broader understanding of the safety of oseltamivir and baloxavir marboxil in children.

Effectively utilizing the complementary characteristics between optical and SAR remote sensing images to accurately identify change information is of great practical significance. Direct pixel comparisons are challenging since they come from sensors with different imaging mechanisms. Therefore, in this paper, a novel domain transformation that incorporates channel interaction and a bridging-enhanced (CIBENet) heterogeneous change detection network is proposed, where twin-depthwise separable fused gated channel transformation is the convolutional block designed for channel information interaction. And samples without changed semantic information are used to train the deep transformation model, which effectively solves the interference of semantic information on NiceGAN. A different perspective is provided for the heterogeneous change detection task. The backend change detection network takes UNet++ with twin-depthwise separable convolution as the baseline, introduces the gated channel transformation and bridging-enhanced decoder, and models the feature relationship between channels to strengthen the channel information interaction while suppressing the expression of nonchanged information. In addition, the bridging-enhanced decoder can efficiently solve localized holes and discontinuities in binary maps by bridging identical pixels. CIBENet is supervised and experimented on three heterogeneous change detection datasets, Gloucester, Shuguang, and Italy, also compared with the classical unsupervised methods CGAN, SCCN, INLPG and advanced supervised methods DTCDN, DACDT. The network model proposed in this paper significantly improved F1 and recall, and the overall accuracies were 96.60 %, 98.23 %, and 96.29 %, respectively. The experiments validated the reliability of the proposed model.

Lithium slag (LS) is a waste residue generated during lithium extraction, posing significant environmental challenge due to its extensive accumulation. This study proposes a method of utilizing thermally activated LS as the sole precursor for geopolymer synthesis. The thermal activation mechanism of LS was investigated using XRD, FTIR, ICP, and SEM techniques, while exploring the optimal composition for LS geopolymers(LSG). The research revealed that heating at 700 °C increased the amorphous content of LS from 15.9 % to 48.1 %, altering the chemical structure of its aluminosilicates and enhancing its leaching capacity in alkaline environments, thereby boosting its reactivity. The activator modulus and alkali equivalent were found to significantly influence the strength and microstructure of LSG. As the modulus increased from 1.0 to 1.4, geopolymer strength initially rose before declining, whereas strength progressively increased with alkali equivalent from 0.10 to 0.16. The geopolymer synthesized with a modulus of 1.2 and alkali equivalent of 0.16 exhibited the highest compressive strength of 53.1 MPa after 28 days. Test results indicated that the internal structure of LSG primarily comprised unreacted particles, N(C)-A-S-H gel, and microcracks. The increased alkali equivalent facilitated the dissolution of Si4+ and Al3+ within LS, intensifying geopolymerization to produce more N(C)-A-S-H gel, thereby densifying the structure and significantly enhancing compressive strength. This study elucidates the mechanism by which high-temperature calcination enhances LS reactivity, as well as the impact of activator on compressive strength and microstructural properties of LSG, offering new insights into the engineering applications of LS in high-performance cementitious materials.

In the solidification of plasters, promptly identifying layering defects is vital to reduce later inspection and maintenance expenses. Traditional tapping methods for defect detection, while widespread, are inefficient and can damage walls. This study proposes an innovative method utilizing Infrared Thermal Imaging (IRT) for semi real-time detection of layering defects during the solidification phase. The method was applied within the first 48 h following the application of two different plasters (Cement and Gypsum, mixed on-site as needed, not pre-dosed, and applied in a single layer), systematically examining the effects of plaster composition and environmental temperature conditions. The results showed that all preset defects were successfully identified. It was observed that larger defects are more readily detectable at a given thickness, and conversely, thicker defects are more discernible at a fixed size, with the dimension of the defect having a more pronounced impact on absolute contrast than its thickness. Notably, cement plaster exhibited two distinct temporal windows for defect detection, primarily influenced by environmental temperatures. In contrast, gypsum mortar presented two detection phases, with the initial phase being predominantly governed by the heat of hydration and the latter by ambient temperature conditions. The application of IRT technology in this research demonstrates its efficacy in accurately detecting layering defects during the solidification of plasters. This method offers valuable insights and guidance for the application of plaster layers in real-world engineering scenarios, potentially reducing maintenance costs and improving construction quality.

ABSTRACT: Zinc (Zn) could alleviate the adverse effect of high temperature (HT) on intestinal integrity and barrier function of broilers, but the underlying mechanisms remain unclear. We aimed to investigate the possible protective mechanisms of Zn on primary cultured broiler jejunal epithelial cells exposed to thermal stress (TS). In Exp.1, jejunal epithelial cells were exposed to 40℃ (normal temperature, NT) and 44℃ (HT) for 1, 2, 4, 6, or 8 h. Cells incubated for 8 h had the lowest transepithelial resistance (TEER) and the highest phenol red permeability under HT. In Exp.2, the cells were preincubated with different Zn sources (Zn sulfate as iZn and Zn proteinate with the moderate chelation strength as oZn) and Zn supplemental levels (50 and 100 µmol/L) under NT for 24 h, and then continuously incubated under HT for another 8 h. TS increased phenol red permeability, lactate dehydrogenase (LDH) activity and p-PKC/PKC level, and decreased TEER, cell proliferation, mRNA levels of claudin-1, occludin, zona occludens-1 (ZO-1), PI3K, AKT and mTOR, protein levels of claudin-1, ZO-1 and junctional adhesion molecule-A (JAM-A), and the levels of p-ERK/ERK, p-PI3K/PI3K and p-AKT/AKT. Under HT, oZn was more effective than iZn in increasing TEER, occludin, ZO-1, PI3K, and AKT mRNA levels, ZO-1 protein level, and p-AKT/AKT level; supplementation with 50 μmol Zn/L was more effective than 100 μmol Zn/L in increasing cell proliferation, JAM-A, PI3K, AKT, and PKC mRNA levels, JAM-A protein level, and the levels of p-ERK/ERK and p-PI3K/PI3K; furthermore, supplementation with 50 μmol Zn/L as oZn had the lowest LDH activity, and the highest ERK, JNK-1, and mTOR mRNA levels. Therefore, supplemental Zn, especially 50 μmol Zn/L as oZn, could alleviate the TS-induced integrity and barrier function damage of broiler jejunal epithelial cells possibly by promoting cell proliferation and tight junction protein expression via the MAPK and PI3K/AKT/mTOR signaling pathways.

The multimodal properties of the grinding wheel matrix significantly impact grinding performance, while research on the interactions among these properties remains notably limited. To investigate the latent relationship between the microstructure and the bending strength of the bronze matrix, a visual quantization model based on the microstructure of the Cu-Sn alloy samples was established. The proposed model integrated a image segmentation network module, a quantitative characterization module, and a multivariate prediction module. The enhancement of the segmentation network is based on the synergistic combination of full-scale feature fusion with attention mechanism. The quantitative characterization parameters of metallographic microstructure features are proposed, and the most prominent intercorrelation between these parameters is studied from multiple dimensions. The results show that the modified image segmentation network exhibits superior performance compared to Unet, as evidenced by a 3% increase in Mean Intersection over Union (MIOU). The optimized output strategy ( $\eta Dd$ -PSO-SVR) can contribute to the model’s prediction accuracy of material bending strength (MSE = 23.558,R $^{2}=0.934$ ). Finally, this work shows that the microscopic information demonstrates great adaptability for the machine learning models in predicting bending strength.

This paper focuses on using the age of information (AoI) as a key metric for measuring the freshness of status information in a wireless fading channel. Specifically, we examine a scenario where a sensor can sample, generate, and transmit update packets at will, with the stochasticity of transmission rate intricately linked to the channel state. Moreover, our goal is to formulate a waiting policy that minimizes the time average AoI by determining the waiting time following the completion of a transmission. We first introduce a straightforward yet efficient Learning Optimal Waiting Time Threshold (LoWait) algorithm for two-state Markov channels. LoWait operates without the need for prior knowledge of the probability distributions for transmission rates and the parameters of channel alternation. In the classical ON-OFF channels, we introduce the Robbins-Monroe iteration and prove that the optimality gap of LoWait diminishes at a rate of ${\mathrm {O}}(1/\sqrt{K})$ , where K is the number of updates. Numerical results affirm that LoWait can effectively reduce the average AoI compared to other benchmarks.

Chromophoric dissolved organic matter (CDOM) is a crucial component of aquatic environments. Accurately quantifying the content of CDOM is essential for supporting lake water quality monitoring and management. In this study, we utilized quasi-analytical algorithms (QAA_v6 and QAA_CDOM) to estimate the CDOM concentration in the intricate freshwater environment of Erhai Lake. This was accomplished by utilizing in-situ hyperspectral data and water sample measurements. A quasi-analytical algorithm, named QAA_CDOM_680, was proposed to retrieve CDOM absorption coefficients from Sentinel-3 satellite images by optimizing the reference wavelength based on these two algorithms. The root mean square errors (RMSE) for QAA_V6, QAA_CDOM algorithm, and the new algorithm QAA_CDOM_680 are 0.615, 0.2235, and 0.1935, respectively. The calibration determination coefficients (R2) of the three algorithms are 0.44, 0.51, and 0.63, respectively. The new algorithm demonstrates a significant improvement in accuracy. The results of two satellite-ground synchronous inversions indicate that the calibration determination coefficients (R2) of CDOM absorption coefficients in the Erhai Lake research area are 0.42 and 0.48, respectively. This study has successfully completed the dynamic quantification monitoring of CDOM in Erhai Lake, contributing to the preservation of Erhai Lake’s water quality.

Existing deep-learning supervised change detection (CD) networks still have room for improvement, as they do not fully utilize multiscale features in their feature extraction, resulting in insufficient feature representation ability and edge blurring problems of the constructed CD networks. In this article, we proposed a very high-resolution (VHR) remote sensing image CD network (ACMFNet) with an asymmetric convolution residual block (ACRB) and multiscale fusion (MSF) to improve the feature representation ability of the CD network and alleviate the edge blurring problem. ACMFNet consists of two main subnetworks: an ACRB feature extraction encoder and an MSF decoder. The ACRB is constructed based on asymmetric convolution and focuses on extraction at the edges of the features and is more robust to rotations, flip distortions, and uneven aspect ratios of the features. In the designed MSF decoder, the fusion feature maps of each level of the decoder are generated by fusing the multiscale encoder feature maps and feature map of the next lowest level of the decoder. MSF contributes to the reconstruction of the edge change area by combining feature information at different scales. It was tested on three public VHR remote sensing image CD datasets, and the proposed method demonstrates the best recall and F1-scores, as well as near optimal precision.

Abstract Background Adenosquamous carcinoma is a rare sub-type of colorectal cancer with a poor prognosis. Little is known about its clinicopathological and molecular characteristics in Asian populations. This study aimed to investigate these features in a cohort of patients with adenosquamous carcinoma in the colorectum. Methods Tumor cases pathologically diagnosed with colorectal adenosquamous carcinoma were retrieved from the Sixth Affiliated Hospital, Sun Yat-sen University tissue archive between December 2012 and June 2020. Clinicopathological features, molecular characteristics, and oncology outcomes were analyzed. Results Among 18,139 cases of colorectal cancer, 11 were diagnosed with adenosquamous carcinoma, providing an incidence rate of 0.061%. The median overall survival (OS) was 14 months, and the expected 3-year OS rate was 29.6%. As of October 14, 2022, four cases had local recurrence and five had distant metastasis. KRAS gene mutations were found in four of seven patients (57.1%), and three out of eleven (27.3%) patients had mismatch repair-deficient (dMMR) tumors. Conclusions Adenosquamous carcinoma is associated with a poor prognosis. Compared to other sub-types of colorectal cancer, a higher proportion of patients with dMMR and KRAS mutations were observed. These findings suggested that more patients with adenosquamous carcinoma could benefit from targeted therapies, such as immunotherapy.

Abstract Background Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored. Methods The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer. Results USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination. Conclusions Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.

The effects of particles on precipitation reactions in aluminum alloy have been widely unknown. Al–Fe–Mn–Si–Mg–Cu alloy strengthened with uniformly distributed Al(Fe,Mn)Si nanoparticles was successfully produced in this study. The alloy was then characterised using high-resolution scanning transmission electron microscopy (HRTEM), to provide a fundamental insight into the interface precipitation. Interfacial precipitations of several tens of nanometers in size was formed after aging, which were found to be Al5Cu6Mg2 and Si phases. The results demonstrated that the facetted α-Al(Fe,Mn)Si particles had a significant influence on precipitation adjacent to the α-Al(Fe,Mn)Si/Al interfaces. Semi-coherent α-Al(Fe,Mn)Si/Al interfaces were revealed to have periodically spaced misfit dislocations that are generally considered to be beneficial to heterogeneous precipitation. They not only reduce nucleation energy barriers but also act as short-circuit diffusion paths to accelerate growth rates by transporting solute atoms and vacancies.

Abstract Mutant KRAS (KRASMUT) is often exploited by cancers to shape tumor immunity, but the underlying mechanisms are not fully understood. Here we report that tumor-specific cytotoxic T lymphocytes (CTLs) from KRASMUT cancers are sensitive to activation-induced cell death (AICD). circATXN7, an NF-κB-interacting circular RNA, governs T cell sensitivity to AICD by inactivating NF-κB. Mechanistically, histone lactylation derived from KRASMUT tumor cell-produced lactic acid directly activates transcription of circATXN7, which binds to NF-κB p65 subunit and masks the p65 nuclear localization signal motif, thereby sequestering it in the cytoplasm. Clinically, circATXN7 upregulation in tumor-specific CTLs correlates with adverse clinical outcomes and immunotherapeutic resistance. Genetic ablation of circAtxn7 in CD8+ T cells leads to mutant-selective tumor inhibition, while also increases anti-PD1 efficacy in multiple tumor models in female mice. Furthermore, targeting circATXN7 in adoptively transferred tumor-reactive CTLs improves their antitumor activities. These findings provide insight into how lymphocyte-expressed circRNAs contribute to T-cell fate decisions and anticancer immunotherapies.

In this work, the AZ31 Mg alloy was subjected to friction stir processing (FSP) by adding CuO and ZrO2 particles. The main aim of this study was to increase the tribological and mechanical behavior of AZ 31/(CuO + ZrO2)p surface composite in air and water. The influence of the processing media on the microstructural modification and mechanical properties of the developed composites is assessed via optical microscopy (OM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), shear punch testing (SPT) and Vickers hardness testing. It had been found that finer grains are produced in the stir zone due to the reduction in heat input for the water-cooled composite relative to the air-cooled composite. Indeed, the water-cooling system acted as a hamper and suppressed grain growth, which consequently resulted in the enhancement of the mechanical and tribological behavior of the AZ 31/(CuO + ZrO2)p surface composite.

The effect of pre-stretching on solid-liquid interaction, microstructure and brazing performance of AA4343/AA3xxx/AA4343 layered aluminum sheet during brazing at the atomic level (solid solution), nanoscale (dislocation) and micron level (grain boundary) are studied by glow discharge optical emission spectrometry (GDOES), scanning electron microscope (SEM), electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The microstructure after brazing largely depends on the forming condition. The driving force of liquid film migration (LFM) is the reduction of stored deformation energy. The interaction between the liquid clad and solid core layers changes the elemental distribution and microstructure, which in turn affects the brazing performance of the sheet. The results reveal the mechanism of solid-liquid interaction of layered aluminum sheet during brazing and clarify the driving force of LFM of layered aluminum sheet during brazing. Consequently, these results provide important insights for the design and theoretical research of functional layered aluminum sheet.

Abstract Manganese dioxide (MnO2), as a cathode material for multivalent ion (such as Mg2+ and Al3+) storage, is investigated due to its high initial capacity. However, during multivalent ion insertion/extraction, the crystal structure of MnO2 partially collapses, leading to fast capacity decay in few charge/discharge cycles. Here, through pre-intercalating potassium-ion (K+) into δ-MnO2, we synthesize a potassium ion pre-intercalated MnO2, K0.21MnO2·0.31H2O (KMO), as a reliable cathode material for multivalent ion batteries. The as-prepared KMO exhibits a high reversible capacity of 185 mAh/g at 1 A/g, with considerable rate performance and improved cycling stability in 1 mol/L MgSO4 electrolyte. In addition, we observe that aluminum-ion (Al3+) can also insert into a KMO cathode. This work provides a valid method for modification of manganese-based oxides for aqueous multivalent ion batteries. Graphical Abstract

Molecular dynamics method was used to establish composite wall/inorganic nanopores of three pore sizes, three shale oil systems, five CO2-cosolvent systems, and pure CO2 system. The process of CO2-cosolvent displacement of crude oil in shale nanopores and carbon storage was simulated and the influencing factors of displacement and storage were analyzed. It is shown that the attraction of the quartz wall to shale oil increases with the degree of hydroxylation. The higher the degree of quartz hydroxylation, the more difficult it is to extract the polar components of shale oil. Nanopore size also has a great impact on shale oil displacement efficiency. The larger the pore size, the higher the shale oil displacement efficiency. The closer the cosolvent molecules are to the polarity of the shale oil, the higher the mutual solubility of CO2 and shale oil. The more the non-polar components of shale oil, the lower the mutual solubility of CO2 and shale oil with highly polar cosolvent. Ethyl acetate is more effective in stripping relatively high polar shale oil, while dimethyl ether is more effective in stripping relatively low polar shale oil. Kerogen is highly adsorptive, especially to CO2. The CO2 inside the kerogen is not easy to diffuse and leak, thus allowing for a stable carbon storage. The highest CO2 storage rate is observed when dimethyl ether is used as a cosolvent, and the best storage stability is observed when ethyl acetate is used as a cosolvent.

Abstract Interrogation of subcellular biological dynamics occurring in a living cell often requires noninvasive imaging of the fragile cell with high spatiotemporal resolution across all three dimensions. It thereby poses big challenges to modern fluorescence microscopy implementations because the limited photon budget in a live-cell imaging task makes the achievable performance of conventional microscopy approaches compromise between their spatial resolution, volumetric imaging speed, and phototoxicity. Here, we incorporate a two-stage view-channel-depth (VCD) deep-learning reconstruction strategy with a Fourier light-field microscope based on diffractive optical element to realize fast 3D super-resolution reconstructions of intracellular dynamics from single diffraction-limited 2D light-filed measurements. This VCD-enabled Fourier light-filed imaging approach (F-VCD), achieves video-rate (50 volumes per second) 3D imaging of intracellular dynamics at a high spatiotemporal resolution of ~180 nm × 180 nm × 400 nm and strong noise-resistant capability, with which light field images with a signal-to-noise ratio (SNR) down to -1.62 dB could be well reconstructed. With this approach, we successfully demonstrate the 4D imaging of intracellular organelle dynamics, e.g., mitochondria fission and fusion, with ~5000 times of observation.

Abstract Ruthenium dioxide is the most promising alternative to the prevailing but expensive iridium-based catalysts for the oxygen evolution reaction in proton-exchange membrane water electrolyzers. However, the under-coordinated lattice oxygen of ruthenium dioxide is prone to over-oxidation, and oxygen vacancies are formed at high oxidation potentials under acidic corrosive conditions. Consequently, ruthenium atoms adjacent to oxygen vacancies are oxidized into soluble high-valence derivatives, causing the collapse of the ruthenium dioxide crystal structure and leading to its poor stability. Here, we report an oxyanion protection strategy to prevent the formation of oxygen vacancies on the ruthenium dioxide surface by forming coordination-saturated lattice oxygen. Combining density functional theory calculations, electrochemical measurements, and a suite of operando spectroscopies, we showcase that barium-anchored sulfate can greatly impede ruthenium loss and extend the lifetime of ruthenium-based catalysts during acidic oxygen evolution, while maintaining the activity. This work paves a new way for designing stable and active anode catalysts toward acidic water splitting.

The different imaging conditions of high spatial resolution remote sensing images (HSRRSIs) tend to cause large differences in the background information of bridges from the images, including problems of difficult detection of multiscale bridges, leakage of small bridges and insufficient detection accuracy for their detection. To address these problems, a YOLOv5 network with a decoupled head for the automatic detection of bridges in HSRRIs is proposed in this paper. First, the problem of inconsistent scale of information fusion of each feature in the feature pyramid network is solved using a weighted bi-directional feature pyramid network (BiFPN). Then, the convolutional block attention module (CBAM) is fused into the three effective feature layers after feature pyramid network processing. The bridge feature information is effectively extracted from the channel and spatial dimensions. Next, the decoupled head is fused in the YOLO Head to separate the classifier and regressor to speed up the network convergence and improve the network detection accuracy simultaneously. Finally, the practical effect is evaluated by calculating the average precision (AP). According to the experimental results, the AP of the proposed method is 98.1%, which is improved by 4.1%∼23.5% compared with other models.

ABSTRACTOur study investigated the role of WTAP in colon cancer. We employed experiments including m6A dot blot hybridization, methylated RNA immunoprecipitation, dual-luciferase, and RNA immunoprecipitation to investigate the regulatory mechanism of WTAP. Western blot was performed to analyze the expression of WTAP, FLNA and autophagy-related proteins in cells. Our results confirmed the up-regulation of WTAP in colon cancer and its promoting effect on proliferation and inhibiting effect on apoptosis. FLNA was the downstream gene of WTAP and WTAP-regulated m6A modification led to post-transcriptional repression of FLNA. The rescue experiments showed that WTAP/FLNA could inhibit autophagy. WTAP-mediated m6A modification was confirmed to be crucial in colon cancer development, providing new insights into colon cancer therapy.

Identifying ships is essential for maritime situational awareness. Automatic identification system (AIS) data and remote sensing (RS) images provide information on ship movement and properties from different perspectives. This study develops an efficient spatiotemporal association approach that combines AIS data and RS images for point–track association. Ship detection and feature extraction from the RS images are performed using deep learning. The detected image characteristics and neighboring AIS data are compared using a multi-dimensional feature similarity model that considers similarities in space, time, course, and attributes. An efficient spatial–temporal association analysis of ships in RS images and AIS data is achieved using the interval type-2 fuzzy system (IT2FS) method. Finally, optical images with different resolutions and AIS records near the waters of Yokosuka Port and Kure are collected to test the proposed model. The results show that compared with the multi-factor fuzzy comprehensive decision-making method, the proposed method can achieve the best performance (F1 scores of 0.7302 and 0.9189, respectively, on GF1 and GF2 images) while maintaining a specific efficiency. This work can realize ship positioning and monitoring based on multi-source data and enhance maritime situational awareness.

In the cigarette manufacturing industry, machine vision and artificial intelligence algorithms have been employed to improve production efficiency by detecting product defects. However, achieving both high accuracy and real-time defect detection for cigarettes with complex patterns remains a challenge. To address these issues, this study proposes a model based on RESNET18, combined with a feature enhancement algorithm, to improve detection accuracy. Additionally, a method is designed to deploy the model on a field-programmable gate array (FPGA) with high parallel processing capabilities to achieve high-speed detection. Experimental results demonstrate that the proposed detection model achieves a detection accuracy of 95.88% on a cigarette filter defect dataset with an end-to-end detection speed of only 9.38 ms.

Typical forms of seismic damage to laminated-rubber-bearing girder bridges in the transverse direction are falling beams, girder displacement, and bearing damage. However, the damage to piers and foundations is generally lighter. This is mainly due to slippage of the bearings. Therefore, we propose a new type of arc-shaped shear key to improve the lateral seismic performance. A 1/12-scale highway continuous-girder bridge isolated by different shear keys was tested utilizing a 4 m × 4 m shaking table with six DOFs. The seismic responses of the bridge were analyzed in terms of phenomenon, displacement, strain, and acceleration. The main girder and pier exhibited different seismic responses because the bridge had different stops. A numerical simulation based on FEM showed that the established finite element model can well reproduce the displacement time history of the main girder and the cap girder. By analyzing the finite element model, the relative displacement of the bearing under different seismic waves was obtained. A comparison between the measured and FEM responses showed that the arc-shaped shear key can well limit the displacement of the main girder and the bearing. In addition, it does not significantly amplify the seismic response of the substructure. The arc-shaped shear key dissipates more energy while limiting the displacement of the main girder, and the comprehensive seismic performance is better than that of the rubber pad shear key.

Assessing carbon emission reduction potential is vital for achieving carbon peak and neutrality in the maritime sector. In this study, we proposed a universal framework for assessing the effectiveness of different measures on carbon emission reduction from ships, including port and ship electrification (PSE), ship speed optimization (SSO), and clean fuel substitution (CFS). Firstly, the projection method of future ship traffic flows and activity levels relies on a neural network, and the ARIMA model was proposed. Then, the potential of various emission reduction measures was detailed and analyzed under different intensity scenarios. The proposed model was applied to Wuhan port, the results indicate that CFS is the most effective for long-term decarbonization, potentially achieving a carbon peak by 2025 under an aggressive scenario. For the short to medium term, PSE is favored due to technical maturity. SSO primarily delays emissions growth, making it a suitable auxiliary measure. These findings guide emission reduction strategies for ports, fostering green and sustainable shipping development.

Background Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the “real-world” use of relma-cel, especially for patients with CNS involvement.Patients and methods Retrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events.Results Among the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55–618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12–32 days).Conclusions This study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.

Background: The significance of Kirsten rat sarcoma viral oncogene (KRAS) mutation in colorectal cancer (CRC) is well established; yet, its association with KRAS expression and prognosis warrants further investigation. While high KRAS expression is commonly linked with poorer prognosis in other cancers, its role in CRC remains relatively understudied. Objective: To explore the correlation between KRAS expression, KRAS status, prognosis, and tumor-infiltrating T lymphocyte density in CRC. Design: Single-center retrospective study. Methods: Conducted between 2010 and 2020, this study utilized tumor samples to assess KRAS expression and quantify CD3+/CD8+ T lymphocytes. The Cox proportional hazards model and linear regression analysis were employed to examine the relationship between KRAS expression, prognosis, and tumor-infiltrating T lymphocytes. Results: This study included 265 CRC patients who underwent radical surgery. No significant association was observed between KRAS expression and KRAS status ( p > 0.05). High KRAS expression was associated with poorer overall survival and disease-free survival ( p 0.05). Notably, KRAS expression showed a negative correlation with the density of CD8+ T lymphocytes in tumor tissue ( p

Abstract Background Nebulized drug delivery is commonly used in pediatric clinical practice. The growing number of literatures have reported the application of nebulized ketamine in pediatric sedation in recent years. This meta-analysis of randomized controlled trials comparing the efficacy and safety of nebulized ketamine versus different pharmacological approaches was conducted to estimate the effects of this technique in pediatric sedation. Methods We searched PubMed, Embase, and Cochrane Library from inception to Feb 2023. All randomized controlled trials used nebulized ketamine as presurgical and pre-procedural sedatives in children were included. Sedative effects and various adverse events were considered as the outcomes. Results Ten studies with 727 pediatric patients were enrolled. Compared to nebulized dexmedetomidine, using of ketamine via nebulization showed similar sedation satisfaction (54.79% vs. 60.69%, RR = 0.88, with 95%CI [0.61, 1.27]), success rate of parental separation (57.27% vs. 73.64%, RR = 0.81, with 95%CI [0.61, 1.08]), and mask acceptability (37.27% vs. 52.73%, RR = 0.71, with 95%CI [0.45, 1.10]). However, the using of combination of two medications (nebulized ketamine plus nebulized dexmedetomidine) was associated with better sedative satisfaction (33.82% vs. 68.11%, RR = 0.50, with 95%CI [0.27, 0.92]) and more satisfactory mask acceptance (45.59% vs. 71.01%, RR = 0.69, with 95%CI [0.56, 0.86]). Compared with nebulized ketamine, using of nebulized dexmedetomidine was associated with less incidence of emergence agitation (18.18% vs. 3.33%, RR = 4.98, with 95%CI [1.88, 13.16]). Conclusions Based on current evidences, compared to nebulized dexmedetomidine, nebulized ketamine provides inconspicuous advantages in pediatric sedation, and it has a relatively high incidence of emergence agitation. Combination of nebulized ketamine and dexmedetomidine might be considered as one preferred option in pediatric sedation as it can provide more satisfactory sedative effects. However, there is insufficient evidence regarding nebulized ketamine versus ketamine administered through other routes and nebulized ketamine versus other sedatives. The overall low or moderate quality of evidence evaluated by the GRADE system also calls for more high-quality studies with larger sample sizes in future. Research registration The protocol of present study was registered with PROSPERO (CRD42023403226).