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Background: Paediatric acute kidney injury (AKI) is common and linked to longer hospitalisation and mortality. We investigated whether a continuous intraoperative infusion of dexmedetomidine, which increases renal blood flow, was associated with a lower risk of postoperative AKI in paediatric patients undergoing noncardiac surgery., Methods: This retrospective cohort study included paediatric patients undergoing noncardiac surgery between January 2019 and July 2021. Propensity score matching, based on the participants' baseline characteristics, was used to minimise the potential bias. The primary outcome was AKI within 7 days after surgery. The secondary outcomes included ICU admission, in-hospital mortality, length of hospitalisation, intraoperative bradycardia, and hypotension. The exposure of interest was continuous intraoperative infusion of dexmedetomidine at any dosage or duration. Multivariable logistic regression and linear regression analyses were further used to adjust for residual imbalanced intraoperative factors in the matched cohort., Results: After propensity score matching, we identified 1858/4091 paediatric patients who had received intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower risk of AKI (1.4% vs 3.2%; odds ratio 0.43, 95% confidence interval 0.27-0.66; P<0.001), postoperative ICU admission (odds ratio 0.35, 95% confidence interval 0.30-0.42; P<0.001), and shorter hospitalisation (7 [5-10] vs 9 [6-13] days; P<0.001). Intraoperative bradycardia, hypotension, and in-hospital mortality were similar between the matched groups., Conclusions: This retrospective analysis of a single-centre paediatric noncardiac surgery cohort suggests that intraoperative dexmedetomidine infusion was associated with a lower incidence of AKI within 7 days after surgery., Clinical Trial Registration: ChiCTR2300069115., Competing Interests: Declaration of interest The authors declare no conflicts of interest., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The identification of Drug-Target Interaction (DTI) is an important step in drug discovery and drug repositioning, and has high application value in multiple fields such as drug discovery, drug repositioning, and repurposing. However, the high cost of experimental validation limits its identification. In contrast, computation-based approaches are both economical and efficient. This review first synthesizes existing chemical genomic approaches, provides a comprehensive summary of prevalent databases for predicting DTIs, and categorizes the feature encodings from recent years. This is followed by an overview and brief description of the methods currently in use for predicting DTIs. The strengths and weaknesses of newly proposed prediction methods in the last five years (2020-2024), including those based on network representation learning and graph neural networks, are then discussed in detail, evaluating the performance of the different methods on a wide range of datasets. Finally, this review explores potential directions for future DTI research, emphasizing how to improve prediction accuracy and efficiency by combining big data and emerging computing technologies., Competing Interests: Declaration of competing interest Disclosure and competing interest statement: None declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Pigs have long been employed as an animal model for knee-related diseases. However, vascular anatomy around the pig knee is rare. The objective of this study was to explore the vascular anatomy around the pig knee from the perspective of comparative medicine., Materials and Methods: Fifteen fresh cadaveric hindlimbs of hybrid pigs were used in this study. The femoral artery was infused with red- or black-colored latex. The origination, course, and branches of the arteries around the pig knee were observed., Results: The femoral artery around the pig knee has the following branches: the saphenous artery, the first descending geniculate artery, the second descending geniculate artery, several muscular branches, and the caudal femoral artery. The popliteal artery gives off the following branches: the medial sural artery, lateral sural artery, and five articular branches. The caudal tibial artery was very thin, whereas the cranial tibial artery was strong and gave off a cranial recurrent tibial artery running toward the knee joint., Conclusion: With the help of two classic veterinary anatomy books, we described the vascular anatomy around the pig knee from the perspective of comparative medicine, which was useful for vessel-related studies using pig knees and was conducive to academic communication., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Noise pollution has become a significant concern for human health, yet its effects on early embryonic development remain underexplored. Specifically, data on the impact of sine wave noise on newly fertilized embryos is limited. This study aimed to address this gap by using zebrafish embryos at the 1-cell stage as a model to assess the toxicity of sine waves, following OECD Test No. 236. We exposed embryos to sound levels of 90 decibels (dB) and above, observing increased deformity rates, delayed development, and reductions in body length, heart rate and brain size. To elucidate the molecular mechanisms underlying these effects, we employed transcriptomics, metabolomics, and epigenomics (m6A-MeRIP-seq). KEGG enrichment analysis revealed significant alterations in arachidonic acid metabolism, axon guidance, and ubiquitin-mediated proteolysis. In conclusion, our findings demonstrate that high levels of sine wave noise adversely affect early embryo development. These results provide crucial insights for developing strategies to mitigate noise pollution and protect early developmental stages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options. This study aims to assess the impact of surgical intervention on overall survival (OS) in patients with MPM and to identify prognostic factors influencing survival outcomes., Methods: Data from the SEER-17 Database between 2000 and 2019 were analyzed. Patients were categorized into surgery and no-surgery groups. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) was applied to reduce biases., Results: The study included a total of 3901 MPM patients, with 1190 in the surgery group and 2711 in the no-surgery group. The median OS for the entire cohort was 10 months. The surgery group had a median OS of 15 months compared to 8 months in the no-surgery group (p < 0.001). The 1-year and 5-year OS rates for surgery patients were 56.9 % and 11.2 %, respectively, while for no-surgery patients, they were 34.9 % and 3.7 % (p < 0.001). Multivariate analysis indicated that no-surgery was an independent risk factor for worse OS (HR 1.38, 95 % CI 1.21-1.39, p < 0.001). After PSM, no-surgery remained an independent risk factor influencing OS. Subgroup analysis indicated that surgery benefited most groups except those aged ≥80 years, bilateral disease, N3 stage, and certain histological grades., Conclusion: Surgical intervention significantly improves survival in patients with MPM. However, benefits vary across subgroups, and careful consideration of patient-specific factors is essential., Competing Interests: Declaration of interest statement The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aims to develop and evaluate a novel therapeutic strategy for Alzheimer's disease (AD) by overcoming the blood-brain barrier (BBB) limitations of Neurotrophin-3 (NT-3). NT-3, a critical neurotrophic factor, plays essential roles in hippocampal neuron growth, survival, and synaptic plasticity, making it a promising candidate for AD treatment. However, its clinical application is hindered by its inability to cross the BBB. To address this, we utilized genetic engineering techniques to fuse the TAT transmembrane peptide with NT-3, producing a recombinant NT-3 (T-NT-3) with enhanced membrane-penetrating capability. Protein characterization confirmed that T-NT-3 possesses good stability and the ability to cross the BBB. In vitro experiments demonstrated that T-NT-3 inhibits oxidative stress, apoptosis, and inflammatory responses in neural cells by activating TrkC receptors and suppressing M1 microglial activation. In vivo, T-NT-3 improved cognitive and memory impairments in APP/PS1 mice and reduced AD-associated pathological changes. These findings highlight the mechanisms by which T-NT-3 alleviates hippocampal neurotoxicity, providing a foundation for its future application as a recombinant protein therapy for AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Heavy metals (HMs) exert a profound influence on soil carbon storage potential. The microbially-mediated association between HM content and carbon structure in riverine sediments remains unclear in lotic ecosystems. We investigated the spatiotemporal variations of HMs content, carbon content and microbial communities in riverine surface sediments, and further explored the chemical structure of sediment organic carbon (OC sed ), the molecular composition of dissolved organic matter (DOM), and their interactions with microorganisms. The spatial-temporal variations in the chemical structure of OC sed , excluding O-alkyl C, were minimal, whereas the molecular composition of DOM underwent substantial fluctuations with seasons and sites. Significantly positive correlations were observed between Cu, Zn, Pb, and OC sed content. However, within a certain content range, HMs can promote the mineralization risk of OC sed , as reflected in their ability to increase the proportion of unstable O-alkyl C and decrease the proportion of stable carbon fractions (aromatic C, alkyl C, and phenolic C). Additionally, appropriate contents of HMs also improved the abundance and diversity of bacteria and fungi. Bacteria consumed more stable OC under HMs enrichment, whereas fungi increased the consumption of DOM fractions (condensed aromatic hydrocarbons and amino sugars). Our findings contribute to the understanding of the molecular mechanisms of carbon storage in HM-rich riverine sediments., Competing Interests: Declaration of Competing Interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As important post-transcriptional regulators of gene expression, sRNAs play important modulatory roles in the environmental adaptation and virulence of bacteria. To investigate the regulatory role of sRNA STnc3020 in the virulence of Salmonella typhimurium (S. typhimurium). This study analyzed the impacts of STnc3020 deletion on adherence, invasion, intracellular survival, macrophage apoptosis, and pathogenicity of S. typhimurium in mice. Furthermore, potential regulatory target genes of STnc3020 were identified and its regulatory mechanism was validated. The results showed that at the cellular level, the deletion of STnc3020 significantly reduced the adhesion ability of S. typhimurium to intestinal epithelial cells (P < 0.01), as well as its proliferation and apoptosis-inducing abilities within macrophages (P < 0.01). Meanwhile, animal experiment results indicated that the deletion of STnc3020 significantly reduced the colonization rate of S. typhimurium in the liver and cecum of mice (P < 0.01), and increased the median lethal dose (4.28 × 10 5 ) in mice. Regulatory mechanism research results showed that STnc3020 can interact with the target gene prgJ of the Type III secretion system (T3SS), and the protein level of PrgJ significantly decreased after the deletion of STnc3020 (P < 0.01). These findings offer new insights into sRNA-mediated virulence control and may aid in developing new vaccines and drugs for S. typhimurium., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dipropyl phthalate (DPRP), a plasticizer commonly utilized in the plastics industry, has been identified in food and the environment and has the potential to present a hazard to human health and the environment. In this study, the first comprehensive evaluation of DPRP-induced craniofacial chondrogenic defects was conducted using a zebrafish model. Zebrafish embryos were exposed to 1, 2, and 4 mg/L DPRP from 6 to 96 h post-fertilization. At 80 hpf, it was observed that exposure to DPRP resulted in craniofacial developmental malformations, which were mainly characterized by the shortening of the mandibular pharyngeal arches and the inability of the accompanying artery to elongate forward. The resulting phenotype was similar to that of micrognathia syndrome. Transcriptome sequencing and molecular docking analyses revealed that DPRP down-regulated chondrocyte-related genes and induced activation of the FoxO signaling pathway, which in turn interfered with cell proliferation and apoptosis. In this process, DPRP induced elevated levels of oxidative stress in the craniofacial pharyngeal arch while promoting inflammatory responses. This ultimately led to craniofacial chondrogenic malformations in zebrafish. The present study demonstrates that DPRP induces developmental toxicity of zebrafish craniofacial cartilage, which may have adverse effects on other aquatic organisms and humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The microwave-assisted hydrothermal method has facilitated the straightforward and efficient production of nanoscale Ce x Zr 1-x O 2 /Ti 3 C 2 T x composites. This technique has greatly shortened the synthesis time several hours required by conventional hydrothermal method to merely 10 min. Due to the unique mechanism of microwave-hydrothermal synthesis, composites with excellent crystallinity, uniform particle size, and superior degradation capabilities can be obtained without calcination. Our investigation systematically explores the influence of various factors including mineralizer concentration, dispersant types, synthesis duration, cerium-to-zirconium ratio, as well as MXene content on the material properties. Optimal degradation of 2-chloroethyl ethyl sulfide (2-CEES), sulfur mustard simulants, is achieved using PEG1000 as the dispersant, a cerium-to-zirconium ratio of 1:2, along with 15 mL of MXene, resulting in a remarkably short half-life of only 6.5 min. Furthermore, it is confirmed that the incorporation of cerium atoms into ZrO 2 lattice, forming a solid solution that is deposited onto the interlayer and surface of Ti 3 C 2 T x nanosheets, with the composite particles measuring approximately 5.01 nm. The reduced size and increased specific surface area, coupled with the synergistic effects of oxygen vacancies and acid-base sites, ultimately contribute to the hydrolysis and elimination reactions occurring on 2-CEES. This research offers fresh perspectives on the development of novel materials for the degradation of chemical warfare agents., Competing Interests: Declaration of Competing Interest No conflict of interest exists in the submission of this manuscript. I would like to declare on behalf of my co-authors that the work described was original that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. A statement that the manuscript has been read and approved by all the authors to submit to the journal., (Copyright © 2024. Published by Elsevier B.V.)

Background: Results from the phase III KEYNOTE-177 study established pembrolizumab as a new first-line standard of care for microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Previous results from KEYNOTE-177 showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab versus chemotherapy ± bevacizumab/cetuximab in MSI-H/dMMR mCRC. Results after >5 years of follow-up are reported., Patients and Methods: Adults with untreated MSI-H/dMMR mCRC were randomly assigned 1 : 1 to receive pembrolizumab 200 mg intravenously every 3 weeks or chemotherapy. Patients assigned to chemotherapy could cross over to pembrolizumab after centrally confirmed progressive disease. Dual primary endpoints were PFS per RECIST v1.1 and overall survival (OS). Secondary endpoints included duration of response and safety., Results: At data cut-off (17 July 2023), median follow-up was 73.3 months (range, 64.9-89.2 months). Overall, 307 patients were assigned to receive pembrolizumab (n = 153) or chemotherapy (n = 154). Fifty-seven (37.0%) patients assigned to chemotherapy crossed over to pembrolizumab per protocol; 39 (25.3%) received a programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitor off protocol (effective crossover rate, 62%). Median OS was 77.5 months with pembrolizumab versus 36.7 months with chemotherapy (hazard ratio, 0.73; 95% confidence interval 0.53-0.99); 5-year OS rates were 54.8% versus 44.2%. Median PFS was 16.5 months with pembrolizumab and 8.2 months with chemotherapy (hazard ratio, 0.60; 95% confidence interval 0.45-0.79). Median duration of response was 75.4 months (range, 2.3+ to 80.1+ months) with pembrolizumab versus 10.6 months (range, 2.8 to 71.5+ months) with chemotherapy. Compared with chemotherapy, fewer patients in the pembrolizumab arm experienced adverse events (80% versus 99%; grade 3-5, 22% versus 67%)., Conclusions: With >5 years of follow-up, responses to pembrolizumab remained durable. Median OS was more than twice as long in patients treated with pembrolizumab versus chemotherapy in first line despite an effective crossover rate of 62%. Pembrolizumab remains a standard of care for MSI-H/dMMR mCRC., (Copyright © 2025 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Although bioinformatics-based methods accurately identify SEs (Super-enhancers), the results depend on feature design. It is foundational to representing biological sequences and automatically extracting their key features for improving SE identification. We propose a deep learning model MuSE (Multi-Feature Fusion for Super-Enhancer), based on multi-feature fusion. This model utilizes two encoding methods, one-hot and DNA2Vec, to signify DNA sequences. Specifically, one-hot encoding reflects single nucleotide information, while k-mer representations based on DNA2Vec capture both local sequence fragment information and global sequence characteristics. These types of feature vectors are conducted and combined by neural networks, which aim at SE prediction. To validate the effectiveness of MuSE, we design extensive experiments on human and mouse species datasets. Compared to baselines such as SENet, MuSE improves the prediction of F1 score to a maximum improvement exceeding 0.05 on mouse species. The k-mer representations based on DNA2Vec among the given features have the most important impact on predictions. This feature effectively captures context semantic knowledge and positional information of DNA sequences. However, its representation of the individuality of each species negatively affects MuSE's generalization ability. Nevertheless, the cross-species prediction results of MuSE improve again to reach an AUC of nearly 0.8, after removing this type of feature. Source codes are available at https://github.com/15831959673/MuSE., Competing Interests: Declaration of Competing Interest The authors assert that they have no conflicts of interest to this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Protein lysine crotonylation is an important post-translational modification that regulates various cellular activities. For example, histone crotonylation affects chromatin structure and promotes histone replacement. Identification and understanding of lysine crotonylation sites is crucial in the field of protein research. However, due to the increasing amount of non-histone crotonylation sites, existing classifiers based on traditional machine learning may encounter performance limitations. In order to address this problem, a novel deep learning-based model for identifying crotonylation sites is presented in this study, given the unique advantages of deep learning techniques for sequence data analysis. In this study, an MLP-Attention-based model was developed for the identification of crotonylation sites. Firstly, three feature extraction strategies, namely Amino Acid Composition, K-mer, and Distance-based residue features extraction strategy, were used to encode crotonylated and non-crotonylated sequences. Then, in order to balance the training dataset, the FCM-GRNN undersampling algorithm combining fuzzy clustering and generalized neural network approaches was introduced. Finally, to improve the effectiveness of crotonylation site identification, we explored various classification algorithms, and based on the relevant experimental performance comparisons, the multilayer perceptron (MLP) combined with the superimposed self-attention mechanism was finally selected to construct the prediction model ILYCROsite. The results obtained from independent testing and five-fold cross-validation demonstrated that the model proposed in this study, ILYCROsite, had excellent performance. Notably, on the independent test set, ILYCROsite achieves an AUC value of 87.93 %, which is significantly better than the existing state-of-the-art models. In addition, SHAP (Shapley Additive exPlanations) values were used to analyze the importance of features and their impact on model predictions. Meanwhile, in order to facilitate researchers to use the prediction model constructed in this study, we developed a prediction program to identify the crotonylation sites in a given protein sequence. The data and code for this program are available at: https://github.com/wmqskr/ILYCROsite., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Carboxymethyl cellulose (CMC) hydrogels are commonly used for heavy metal removal due to their abundant hydroxyl and carboxyl groups. However, pristine CMC hydrogels always suffer from low gel strength and limited adsorption properties in large-scale applications. In this study, to improve the gel strength and heavy metal ions removal capacity, fish gelatin and bamboo shoot particle (BSP) were introduced to CMC hydrogels, respectively. The formation of the composite hydrogel with enhanced gel strength was primarily driven by hydrogen bonding, which exhibited an increase strain resistance with a critical strain value up to 214.68 %. As expected, the composite hydrogel can effectively remove Cd 2+ , Hg 2+ , and Pb 2+ from aqueous solutions simultaneously. The physical adsorption process of heavy metals by the composite hydrogel was well described by the pseudo-second-order kinetic model, while the Langmuir model indicated maximum adsorption capacities of 147.7 mg/g for Cd 2+ , 88.62 mg/g for Hg 2+ , and 163.89 mg/g for Pb 2+ . Notably, the composite hydrogel exhibited enhanced recyclability, maintaining its efficacy for up to at least five cycles. This study underscores the potential of using naturally occurring biodegradable materials for the removal of heavy metals, and paved ways for heavy metal removal at industrial levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring., Methods: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy., Result: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (β = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (β = 0.015,95%CI: 0.007-0.024) and were frailer (β = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (β = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (β = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group., Conclusion: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

2,4,6-Trichloroanisole (2,4,6-TCA), a compound with a characteristic earthy odor, is a common source of odorous pollutants in drinking water and wine. However, research on its biological toxicity is limited. In this study, we used zebrafish as an indicator model to investigate the effects of 2,4,6-TCA exposure on morphological development, oxidative stress, apoptosis, heart rate, blood flow, and motility. We found that exposure to 2,4,6-TCA resulted in significant spinal, tail, and cardiac deformities in zebrafish larvae and promoted a pronounced oxidative stress response and extensive cell apoptosis, notably in the digestive tract, head, spine, and heart, ultimately leading to significant reductions in zebrafish heart rate, blood flow, and motility. Moreover, these effects became more pronounced with an increase in the concentration of 2,4,6-TCA to which the zebrafish were exposed. Furthermore, qPCR analysis revealed that exposure to 2,4,6-TCA promoted significant changes in the expression levels of genes associated with oxidative stress, apoptosis, cardiac development, and the nervous system, particularly key genes (p53, apaf1, casp9, and casp3) in the mitochondrial apoptotic pathway, which were significantly upregulated. Similarly, we detected significant upregulation of ache gene expression. These findings indicated that exposure to 2,4,6-TCA resulted in the accumulation of reactive oxygen species in zebrafish, induced strong oxidative stress responses, and triggered lipid peroxidation and extensive cell apoptosis. Cellular apoptosis, which mitochondrial signaling pathways may mediate, has been found to lead to malformations in zebrafish embryos, resulting in significant reductions in cardiac function and motility. To our knowledge, this is the first systematic assessment of the toxicity of 2,4,6-TCA, and our findings provide an important reference for risk assessment and early warning of 2,4,6-TCA exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gelatin (Gel) hydrogels are widely utilized in various aspects of tissue engineering, such as wound repair, due to their abundance and biocompatibility. However, their low strength and limited functionality have constrained their development and scope of application. Tannic acid (TA), a naturally occurring polyphenol found in plants and fruits, has recently garnered interest as a crosslinking, anti-inflammatory, and antioxidant agent. In this study, we fabricated novel multifunctional gelatin methacrylate/alginate-tannin (GelMA/Alg-TA) hydrogels using chemical and physical crosslinking strategies with gelatin methacrylate (GelMA), alginate (Alg), and TA as the base materials. The GelMA/Alg-TA hydrogels maintained a stable three-dimensional porous structure with appropriate water content and exhibited excellent biocompatibility. Additionally, these hydrogels demonstrated significant antioxidant and antibacterial properties and substantially promoted wound healing in a mouse model of full-thickness skin defects by modulating inflammatory responses and enhancing granulation formation. Therefore, our study offers valuable insights into the design principles of novel multifunctional GelMA/Alg-TA hydrogels, highlighting their exceptional biocompatibility, antioxidant, and antibacterial properties. GelMA/Alg-TA hydrogels are promising candidates for wound healing applications., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Dioscorea has a history spanning over 2000 years for both medicinal and edible purposes in China. It contains rich polysaccharides, which are frequently utilized as thickening and stabilizing agents in the food industry. However, there has been relatively little focus on polysaccharides from common Dioscorea species besides D. opposita, such as D. alata and D. esculenta. In this study, non-starch crude polysaccharides were isolated from D. opposita (BD), D. alata (WC), and D. esculenta (GZ). Their structures, physicochemical compositions, and functional properties were characterized and compared. The results indicated three polysaccharides all exhibited characteristic peaks of polysaccharides and possessed triple-helix structures. The Glc (36.78-83.90 %), Man (6.71-26.68 %), and GalA (8.54-10.22 %) were identified as the primary monosaccharide components. In terms of functionality, three polysaccharide solutions demonstrated non-Newtonian flow characteristics and displayed commendable thermal stability. It is worth noting that the antioxidant and emulsifying properties of polysaccharides isolated from D. opposita (BD) and D. alata (WC) were superior to those of D. esculenta (GZ), making them more suitable for use as antioxidants and stabilizers. By comparing polysaccharides derived from different Dioscorea species, this study provides valuable insights into the food, cosmetic, and pharmaceutical industries based on the unique properties of these different polysaccharides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Histone lysine demethylase (KDM), AlkB homolog (ALKBH), and Ten-Eleven Translocation (TET) proteins are members of the 2-Oxoglutarate (2OG) and ferrous iron-dependent oxygenases, each of which harbors a catalytic domain centered on a double-stranded β-helix whose topology restricts the regions directly involved in substrate binding. However, they have different catalytic functions, and the deeply structural biological reasons are not yet clear. In this review, the catalytic domain features of the three protein families are summarized from both sequence and structural perspectives. The construction of the phylogenetic tree and comparison of the structure show ten relatively conserved β-sheets and three key regions with substantial structural differences. We summarize the relationship between three key regions of remarkable differences and the substrate compatibility of the three protein families. This review facilitates research into substrate-selective inhibition and bioengineering by providing new insights into the catalytic domains of KDM, ALKBH, and TET proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coronary artery disease poses a significant threat to human health. In clinical settings, coronary angiography remains the gold standard for diagnosing coronary heart disease. A crucial aspect of this diagnosis involves detecting arterial narrowings. Categorizing these narrowings can provide insight into whether patients should receive vascular revascularization treatment. The majority of current deep learning methods for analyzing coronary angiography are mostly confined to the theoretical research domain, with limited studies offering direct practical support to clinical practitioners. This paper proposes an integrated deep-learning model for the localization and classification of narrowings in coronary angiography images. The experimentation employed 1606 coronary angiography images obtained from 132 patients, resulting in an accuracy of 88.9 %, a recall rate of 85.4 %, an F1 score of 0.871, and a MAP value of 0.875 for vascular stenosis detection. Furthermore, we developed the "Hemadostenosis" web platform (http://bioinfor.imu.edu.cn/hemadostenosis) using Django, a highly mature HTTP framework. Users are able to submit coronary angiography image data for assessment via a visual interface. Subsequently, the system sends the images to a trained convolutional neural network model to localize and categorize the narrowings. Finally, the visualized outcomes are displayed to users and are downloadable. Our proposed approach pioneers the recognition and categorization of arterial narrowings in vascular angiography, offering practical support to clinical practitioners in their learning and diagnostic processes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Benzalkonium chloride (BAC) is a broad-spectrum antibacterial agent that possesses cleaning and bactericidal properties, but impact of BAC on wellbeing of aquatic organisms remains uncertain. Consequently, in this current study, we have examined the immunotoxic potential of BAC in zebrafish embryos, thus marking it as the pioneering effort in this field. According to the findings, zebrafish embryos exposed to BAC exhibited a decline in yolk area that varied with the concentration, along with a significant decrease in the count of neutrophils, macrophages, red blood cells, and thymus T-cells. We observed significantly up-regulated expression of immune-related signaling genes such as cxcl-c1c, il-8, tir4 and inf-γ, but expression of nf-κb was downregulated. In addition, we observed a marked reduction in the number of hematopoietic stem cells in zebrafish larvae after BAC exposure, which could be the result of oxidative stress-mediated apoptosis. We found that compared with the control group, the number of red blood cells in juvenile zebrafish in BAC-exposure group was significantly down-regulated, which could be attributed to hematopoietic stem cell defect. Astaxanthin restored immune cells and hematopoietic stem cells after BAC exposure, whereas Inhibitor of Wnt Response-1(IWR-1) restored neutrophils after BAC exposure. The research findings demonstrated that exposure to BAC displayed harmful effects on the development and immune system of zebrafish embryos. These effects might be associated with alterations in reactive oxygen species(ROS) levels and activation of the Wnt signaling pathway caused by BAC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024. Published by Elsevier Inc.)

Urine cytology is a non-invasive, cost-efficient, and sensitive test to detect high-grade urothelial carcinoma. The Paris System (TPS) for Reporting Urinary Cytology is an evidence-based system that uses the risk of malignancy to guide patient management. Since its inception, TPS has standardized urine cytology reports, facilitating communication among pathologists and between pathologists and clinicians. It is imperative to correlate the urine cytology findings with the concurrent tissue sample to avoid false-negative and false-positive results when possible. Several ancillary tests and artificial intelligence algorithms are being developed to increase the accuracy of urine cytology interpretation., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming suitable for the survival and reproduction of dengue vector, consequently are becoming suitable for dengue transmission in China. Chongqing, a metropolis in southwestern China, has recently been hit by imported and local dengue fever, experiencing its first local outbreak in 2019. However, the genetic evolution dynamics of dengue viruses and the spatiotemporal patterns of imported and local dengue cases have not yet been elucidated. Hence, this study implemented phylogenetic analyses using genomic data of dengue viruses in 2019 and 2023 and a spatiotemporal analysis of dengue cases collected from 2013 to 2022. We sequenced a total of 15 nucleotide sequences of E genes. The dengue viruses formed separate clusters and were genetically related to those from Guangdong Province, China, and countries in Southeast Asia, including Laos, Thailand, Myanmar and Cambodia. Chongqing experienced a dengue outbreak in 2019 when 168 imported and 1,243 local cases were reported, mainly in September and October. Few cases were reported in 2013-2018, and only six were imported from 2020 to 2022 due to the COVID-19 lockdowns. Our findings suggest that dengue prevention in Chongqing should focus on domestic and overseas population mobility, especially in the Yubei and Wanzhou districts, where airports and railway stations are located, and the period between August and October when dengue outbreaks occur in endemic regions. Moreover, continuous vector monitoring should be implemented, especially during August-October, which would be useful for controlling the Aedes mosquitoes. This study is significant for defining Chongqing's appropriate dengue prevention and control strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Polymer-based scaffolds with different degradability have been investigated to screen the matrix whose degradation rate is more closely matched with the bone regeneration rate. However, these comparisons are inclined to be compromised by the animal individual differences. In this study, we constructed an integrated scaffold model comprising four parts with different degradability and bioactivity to achieve an in situ comparison of bone regeneration ability of different scaffolds. Slow-degradable polycaprolactone (PCL), fast-degradable poly (lactic-co-glycolic acid) (PLGA), and silica-coated PCL and PLGA scaffolds were assembled into a round sheet to form a hydroxyapatite (HA)-free integrated scaffold. HA-doped PCL, PLGA, and silica-coated PCL and PLGA scaffolds were assembled to create an HA-incorporated integrated scaffold. The in vivo experimental results demonstrated that the local acid microenvironment caused by the rapid degradation of PLGA interfered with the osteogenic process promoted by PCL-based scaffolds in defect areas implanted with HA-free integrated scaffolds. Since the incorporation of HA alleviated the acidic microenvironment to some extent, each scaffold in HA-incorporated scaffolds exhibited its expected bone regeneration capacity. Consequently, it is feasible to construct an integrated structure for comparing the osteogenic effects of various scaffolds in situ, when there is no mutual interference between the materials. The strategy presented in this study inspired the structure design of biomaterials to enable in situ comparison of bone regeneration capacity of scaffolds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abdominal aortic aneurysm (AAA) is a dangerous condition affecting the aorta. Macrophage pyroptosis, phenotypic transformation, and apoptosis of aortic smooth muscle cells (ASMCs) are pivotal mechanisms in AAA pathogenesis. This study explores how Gasdermin B (GSDMB) regulates macrophage non-canonical pyroptosis and its impact on the phenotypic transformation and apoptosis of ASMCs, thereby unveiling the role of GSDMB in AAA pathogenesis. Immunofluorescence analysis was used to assess the expression levels and localization of GSDMB, cysteinyl aspartate-specific protease-4 (Caspase-4), and N-terminal of cleaved GSDMD (N-GSDMD) in AAA tissues. A cell model that mimics macrophage non-canonical pyroptosis was established by treating THP-1 cells with lipopolysaccharide (LPS). THP-1 cells with reduced or increased GSDMB were generated using small interfering RNA (siRNA) or plasmids. Co-culture experiments involving THP-1 cells and HASMCs were conducted to explore the impact of GSDMB on HASMCs. The mitochondrial reactive oxygen species (mtROS) scavenger Mito-TEMPO lowered mtROS levels in THP-1 cells. Our findings revealed that GSDMB was significantly upregulated in AAA macrophages, which was accompanied by robust non-canonical pyroptosis. THP-1 cells showed non-canonical pyroptosis in response to LPS, which was accompanied by an increase in GSDMB. Further research demonstrated that altering GSDMB, either by knockdown or overexpression, can affect macrophage non-canonical pyroptosis as well as the phenotypic transformation and apoptosis of HASMCs. LPS-induced non-canonical pyroptosis in THP-1 cells was associated with an increase in mtROS, whereas Mito-TEMPO effectively decreased non-canonical pyroptosis and the expression of GSDMB. These findings suggest that GSDMB plays a role in AAA macrophage non-canonical pyroptosis, which influences the phenotypic transformation and apoptosis of HASMCs. The mtROS-Dynamin-Related Protein 1 (Drp1) axis is likely to regulate the GSDMB-mediated non-canonical pyroptosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Salivary gland lesions are routinely evaluated by fine-needle aspiration cytology (FNAC) preoperatively. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has standardized salivary gland FNAC reporting. Its application in major salivary glands (MSGs) has been well-established; however, its utility in minor salivary glands (MiSGs) is not well-known. We studied the utility of MSRSGC in MiSG FNAC., Materials and Methods: A retrospective search of MiSG FNACs from 2 academic institutions (2006-2023) was performed. FNACs were classified using the MSRSGC. Histologic data were reviewed and recorded. The risk of malignancy (ROM), risk of neoplasia (RON), diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated., Results: The series included 43 MiSG FNAC (24 males and 18 females), with a mean age of 55 years (range 10-92). Aspirated sites included the following: palate, buccal space, floor of mouth, lip, tongue, and maxillary sinus. FNACs were classified as nondiagnostic (1), nonneoplastic (3), atypia of undetermined significance (6), benign neoplasm (9), salivary gland neoplasm of uncertain malignant potential (15), suspicious for malignancy, (2) and malignant (7). The risk of neoplasia and risk of malignancy were 87% and 39%. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 100%, respectively., Conclusions: Milan System for Reporting Salivary Gland Cytopathology offers valuable information for stratifying MiSG lesions. However, the distribution and the range of diagnostic entities encountered differ somewhat from those in MSGs. For instance, mucinous cyst contents may warrant unique consideration in MiSG; while an atypical classification is recommended in MSGs, the high prevalence of mucoceles in MiSG may tilt this group toward benignity., (Copyright © 2024 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

To remove iodine ion (I - ) from wastewater, a novel hydrogel, the fluorescent cellulose nanofibrils-based hydrogel (FCNH), was synthesized to enable both detection and adsorption of I - . The FCNH comprised cellulose nanofibrils (CNs), silver nanoclusters (AgNCs), and MIL-125-NH 2 . It exhibited an excellent adsorption capacity for I - , with a maximum adsorption capacity of 373.7 mg/g, fitting both the Langmuir and pseudo-second-order models. Additionally, FCNH displayed excellent regeneration properties, retaining 88.0 % of its initial adsorption capacity after six adsorption-desorption cycles. Functioning as a fluorescent sensor, the synthesized FCNH enabled the detection of I - through dynamic quenching, with linear ranges of 5 to 200 mg/L and 0.2 to 1.0 μg/L, and a determination limit of 0.11 μg/L. Analysis of the adsorption and detection mechanisms revealed that FCNH's outstanding performance arose from its 3D porous structure comprising CNs, AgNCs, and MIL-125-NH 2 . Economic analysis indicated that FCNH was inexpensive compared to commercially available activated carbon. Thus, FCNH demonstrated significant potential as an economical and reusable adsorbent for iodine ion removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Keratoconus (KC) is a degenerative condition affecting the cornea, characterized by progressive thinning and bulging, which can ultimately result in serious visual impairment. The onset and progression of KC are closely tied to the gradual weakening of the cornea's biomechanical properties. KC progression can be prevented with corneal cross-linking (CXL), but this treatment has shortcomings, and evaluating its tissue stiffening effect is important for determining its efficacy. In this field, the shortage of human corneas has made it necessary for most previous studies to rely on animal corneas, which have different microstructure and may be affected differently from human corneas. In this research, we have used the lenticules obtained through small incision lenticule extraction (SMILE) surgeries as a source of human tissue to assess CXL. And to further improve the results' reliability, we used inflation testing, personalized finite element modeling, numerical optimization and histology microstructure analysis. These methods enabled determining the biomechanical and histological effects of CXL protocols involving different irradiation intensities of 3, 9, 18, and 30 mW/cm 2 , all delivering the same total energy dose of 5.4 J/cm 2 . The results showed that the CXL effect did not vary significantly with protocols using 3-18 mW/cm 2 irradiance, but there was a significant efficacy drop with 30 mW/cm 2 irradiance. This study validated the updated algorithm and provided guidance for corneal lenticule reuse and the effects of different CXL protocols on the biomechanical properties of the human corneal stroma., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Accurately predicting RNA-protein binding sites is essential to gain a deeper comprehension of the protein-RNA interactions and their regulatory mechanisms, which are fundamental in gene expression and regulation. However, conventional biological approaches to detect these sites are often costly and time-consuming. In contrast, computational methods for predicting RNA protein binding sites are both cost-effective and expeditious. This review synthesizes already existing computational methods, summarizing commonly used databases for predicting RNA protein binding sites. In addition, applications and innovations of computational methods using traditional machine learning and deep learning for RNA protein binding site prediction during 2018-2023 are presented. These methods cover a wide range of aspects such as effective database utilization, feature selection and encoding, innovative classification algorithms, and evaluation strategies. Exploring the limitations of existing computational methods, this paper delves into the potential directions for future development. DeepRKE, RDense, and DeepDW all employ convolutional neural networks and long and short-term memory networks to construct prediction models, yet their algorithm design and feature encoding differ, resulting in diverse prediction performances., Competing Interests: Declaration of competing interest none declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Plant fiber-reinforced polylactic acid (PLA) composites are extensively utilized in eco-friendly packaging, sports equipment, and various other applications due to their environmental benefits and cost-effectiveness. However, PLA suffers from brittleness and poor toughness, which restricts its use in scenarios demanding high toughness. To expand the application range of plant fiber-reinforced PLA-based composites and enhance their poor toughness, this study employed a two-step process involving wheat straw fiber (WF) to improve the interfacial compatibility between WF and PLA. Additionally, four elastomeric materials-poly (butylene adipate-co-terephthalate) (PBAT), poly (butylene succinate) (PBS), polycaprolactone (PCL), and polyhydroxyalkanoate (PHA)-were incorporated to achieve a mutual reactive interface enhancement and elastomeric toughening. The results demonstrated that Fe 3+ /TsWF/PLA/PBS exhibited a tensile strength, elongation at break, and impact strength of 34.01 MPa, 14.23 %, and 16.2 kJ/m 2 , respectively. These values represented a 2.4 %, 86.7 %, and 119 % increase compared to the unmodified composites. Scanning electron microscopy analysis revealed no fiber exposure in the cross-section, indicating excellent interfacial compatibility. Furthermore, X-ray diffraction and differential scanning calorimetry tests confirmed improvements in the crystalline properties of the composites. This work introduces a novel approach for preparing fiber-reinforced PLA-based composites with exceptional toughness and strength., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Endothelial dysfunction is the most common pathological feature of cardiovascular diseases, including diabetes mellitus, hypertension and atherosclerosis. It affects both macro- and micro-vasculatures, causing functional impairment of multiple organs. Pien Tze Huang (PZH) is a well-studied traditional Chinese medicine (TCM) with multiple pharmacological properties that produces therapeutic benefits against colorectal cancer, non-alcoholic steatohepatitis and neurodegenerative diseases. However, it is unknown how PZH affects vascular function under pathological conditions. Therefore, this study aimed to investigate the effect of PZH on endothelial function and the underlying mechanisms in db/db diabetic mice. The results showed that chronic treatment of PZH (250 mg/kg/day, 5 weeks) improved endothelial function by restoring endothelium-dependent relaxation through the activation of the Akt-eNOS pathway and inhibition of endothelial oxidative stress, which increased nitric oxide bioavailability. Furthermore, PZH treatment increased insulin sensitivity and suppressed inflammation in diabetic mice. These new findings suggest that PZH may have vaso-protective properties and the potential to protect against diabetic vasculopathy by preserving endothelial function., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The technology of capturing circulating tumor cells (CTCs) plays a crucial role in the diagnosis, evaluation of therapeutic efficacy, and prediction of prognosis in lung cancer. However, the presence of complex blood environment often results in severe nonspecific protein adsorption and interferences from blood cells, which negatively impacts the specificity of CTCs capture. There is a great need for development of novel nanomaterials for CTCs capture with prominent anti-nonspecific adsorptions from proteins or blood cells., Results: We present a novel immune magnetic probe Fe 3 O 4 @(PEI/AA) 4 @Apt. The surface of Fe 3 O 4 particles was modified with four layers of PEI/AA composite by layer-by-layer assembly. Furthermore, aptamers targeting epithelial marker EpCAM (SYL3C) and mesenchymal marker CSV (ZY5C) were simultaneously connected on Fe 3 O 4 @(PEI/AA) 4 to improve the detection of different phenotypic CTCs and reduce false negatives. The results demonstrated that the (PEI/AA) 4 coatings not only minimized non-specific protein adsorptions, but also significantly reduced the adsorption rate of red blood cells to a mere 1 %, as a result of which, the Fe 3 O 4 @(PEI/AA) 4 @Apt probe achieved a remarkably high capture efficiency toward CTCs (95.9 %). In the subsequent validation of clinical samples, the probe was also effective in capturing rare CTCs from lung cancer patients., Significance and Novelty: A (PEI/AA) polymerized composite with controllable layers was fabricated by layer-by-layer self-assembly technique, which displayed remarkable anti-nonspecific adsorption capabilities toward proteins and cells. Importantly, Fe 3 O 4 @(PEI/AA) 4 @Apt probe significantly improved CTCs capture purity in lung cancer patients to 89.36 %. For the first time, this study combined controllable (PEI/AA) layers with magnetic separation to innovatively build a resistant interface that significantly improves the specific capture performances of CTCs, broadening the application of this polymerized composite., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nitrogen removal is essential for restoring eutrophic lakes. Microorganisms and aquatic plants in lakes are both crucial for removing excess nitrogen. However, microplastic (MP) pollution and the invasion of exotic aquatic plants have become increasingly serious in lake ecosystems due to human activity and plant-dominant traits. This field mesocosm study explored how the diversity of invasive submerged macrophytes affects denitrification (DNF), anammox (ANA), and dissimilatory nitrate reduction to ammonium (DNRA) in lake sediments with varying MPs. Results showed that invasive macrophytes suppressed DNF rates, but DNRA and ANA were less sensitive than DNF to the diversity of invasive species. Sediment MPs increased the biomass of invasive species more than native species, but did not affect microbial processes. The effects of MPs on nitrate dissimilatory reduction were process-specific. MPs increased DNF rates and the competitive advantage of DNF over DNRA by changing the sediment environment. The decoupling of DNF and ANA was also observed, with increased DNF rates and decreased ANA rates. The study findings suggested new insights into how the invasion of exotic submerged macrophytes affects the sediment nitrogen cycle complex environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To develop predictive nomograms based on clinical and ultrasound features and to improve the clinical strategy for US BI-RADS 4A lesions., Methods: Patients with US BI-RADS 4A lesions from 3 hospitals between January 2016 and June 2020 were retrospectively included. Clinical and ultrasound features were extracted to establish nomograms CE (based on clinical experience) and DL (based on deep-learning algorithm). The performances of nomograms were evaluated by receiver operator characteristic curves, calibration curves and decision curves. Diagnostic performances with DL of radiologists were analyzed., Results: 1616 patients from 2 hospitals were randomly divided into training and internal validation cohorts at a ratio of 7:3. Hundred patients from another hospital made up external validation cohort. DL achieved more optimized AUCs than CE (internal validation: 0.916 vs. 0.863, P < .01; external validation: 0.884 vs. 0.776, P = .05). The sensitivities of DL were higher than CE (internal validation: 81.03% vs. 72.41%, P = .044; external validation: 93.75% vs. 81.25%, P = .4795) without losing specificity (internal validation: 84.91% vs. 86.47%, P = .353; external validation: 69.14% vs. 71.60%, P = .789). Decision curves indicated DL adds more clinical net benefit. With DL's assistance, both radiologists achieved higher AUCs (0.712 vs. 0.801; 0.547 vs. 0.800), improved specificities (70.93% vs. 74.42%, P < .001; 59.3% vs. 81.4%, P = .004), and decreased unnecessary biopsy rates by 6.7% and 24%., Conclusion: DL was developed to discriminate US BI-RADS 4A lesions with a higher diagnostic power and more clinical net benefit than CE. Using DL may guide clinicians to make precise clinical decisions and avoid overtreatment of benign lesions., Competing Interests: Disclosure The authors declare that they have no conflict interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated significant efficacy in achieving complete remission (CR) in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, a considerable number of patients experience relapse within 1 year after CAR T-cell therapy, leading to an extremely poor prognosis, particularly in patients without bridging transplantation., Materials and Methods: In our study, we investigated 42 children with R/R B-ALL who underwent anti-CD19 CAR T-cell therapy without bridging transplantation at our center. All patients were included in the response analysis and evaluated for survival and toxicity., Results: The cohort that received the CAR T-cell infusion exhibited a 100% CR rate by day 28 (d28). The overall survival (OS) at 4 years was 61.3% ± 8.5%, and the event-free survival (EFS) was 55.9% ± 7.9%, with a median follow-up duration of 50.1 months. Minimal residual disease (MRD) ≥1% was associated with inferior outcomes, resulting in lower 4-year OS (P = .033) and EFS (P = .014) compared to MRD<1%. The incidences of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity were 26.8% and 23.8%, respectively. Furthermore, MRD≥1% was identified as an independent factor associated with increased severity of CRS and occurrence of neurotoxicity., Conclusion: These findings suggest that reducing the pre-infusion MRD could serve as an effective treatment strategy to enhance the outcomes of CAR T-cell therapy., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Perioperative nociception-antinociception balance is essential for the prevention of adverse postoperative events. Estimating the nociception level helps optimize intraoperative management. In the past two decades, various nociception monitoring devices have been developed for the identification of intraoperative nociception. However, each type of nociception monitoring device has advantages and disadvantages, limiting their clinical application in particular patients and settings. Therefore, this review aimed to summarize the information on nociceptor monitoring in current clinical settings, explore each technique's particularities, and possible future directions to provide a reference for clinicians and researchers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Given the detrimental impact of global warming on crop production, it is particularly important to understand how plants respond and adapt to higher temperatures. Using the non-invasive micro-test technique and laser confocal microscopy, we found that the cascade process of early signals (K + , H 2 O 2 , H + , and Ca 2+ ) ultimately resulted in an increase in the cytoplasmic Ca 2+ concentration when Arabidopsis was exposed to heat stress. Quantitative real-time PCR demonstrated that heat stress significantly up-regulated the expression of CAM1, CAM3 and HSFA2; however, after CAM1 and CAM3 mutation, the upregulation of HSFA2 was reduced. In addition, heat stress affected the expression of LOX3 and OPR3, which was not observed when HSFA2 was mutated. Luciferase reporter gene expression assay and electrophoretic mobility shift assay showed that HSFA2 regulated the expression of both genes. Determination of jasmonic acid (JA) content showed that JA synthesis was promoted by heat stress, but was damaged when HSFA2 and OPR3 were mutated. Finally, physiological experiments showed that JA reduced the relative electrical conductivity of leaves, enhanced chlorophyll content and relative water content, and improved the survival rate of Arabidopsis under heat stress. Together, our results reveal a new pathway for Arabidopsis to sense and transmit heat signals; HSFA2 is involved in the JA synthesis, which can act as a defensive compound improving Arabidopsis heat tolerance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Artocarpus nanchuanensis, the northernmost species in the jackfruit genus, has great economic and horticultural value due to its nutritious fruit and beautiful tree shape. Calcineurin B-like proteins (CBLs) act as plant-specific Ca 2+ sensors and participate in regulating plant responses to various abiotic stresses by interacting with CBL-interacting protein kinases (CIPKs). However, the characteristics and functions of the CBL and CIPK genes in A. nanchuanensis are still unclear. Here, we identified 14 CBL and 33 CIPK genes from the A. nanchuanensis genome, and based on phylogenetic analysis, they were divided into 4 and 7 clades, respectively. Gene structure and motif analysis indicated that the AnCBL and AnCIPK genes were relatively conserved. Colinear analysis showed that segmental duplication contributed to the expansion of the AnCBL and AnCIPK gene families. Expression analysis showed that AnCBL and AnCIPK genes were widely expressed in various tissues of A. nanchuanensis and exhibited tissue-specific expression. In addition, three genes (AnCBL6, AnCIPK7/8) may play important roles in response to salt, cold, and drought stresses. In summary, this study lays an important foundation for the improvement of stress resistance in A. nanchuanensis and provides new insight for the functional research on CBL and CIPK gene families., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The vast majority of processes in the carbon and nitrogen cycles are driven by microorganisms. The nitrite-dependent anaerobic oxidation of methane (N-DAMO) process links carbon and nitrogen cycles, offering a novel approach for the simultaneous reduction of methane emissions and nitrite pollution. However, there is currently no comprehensive summary of the current status of the N-DAMO process in natural aquatic environments. Therefore, our study aims to fill this knowledge gap by conducting a comprehensive review of the global research trends in N-DAMO processes in various aquatic environments (excluding artificial bioreactors). Our review mainly focused on molecular identification, global study sites, and their interactions with other elemental cycling processes. Furthermore, we performed a data integration analysis to unveil the effects of key environmental factors on the abundance of N-DAMO bacteria and the rate of N-DAMO process. By combining the findings from the literature review and data integration analysis, we proposed future research perspectives on N-DAMO processes in global aquatic environments. Our overarching goal is to advance the understanding of the N-DAMO process and its role in synergistically reducing carbon emissions and removing nitrogen. By doing so, we aim to make a significant contribution to the timely achievement of China's carbon peak and carbon neutrality targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The bioavailability and toxicity of organic pollutants in aquatic organisms can be largely affected by the co-existed nanoparticles. However, the impacts of such combined exposure on the visual system remain largely unknown. Here, we systematically investigated the visual toxicity in zebrafish larvae after single or joint exposure to titanium dioxide nanoparticles (n-TiO 2 ) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) at environmentally relevant levels. Molecular dynamics simulations revealed the enhanced transmembrane capability of the complex than the individual, which accounted for the increased bioavailability of both TBPH and n-TiO 2 when combined exposure to zebrafish. Transcriptome analysis showed that co-exposure to n-TiO 2 and TBPH interfered with molecular pathways related to eye lens structure and sensory perception of zebrafish. Particularly, n-TiO 2 or TBPH significantly suppressed the expression of βB1-crystallin and rhodopsin in zebrafish retina and lens, which was further enhanced after co-exposure. Moreover, we detected disorganized retinal histology, stunted lens development and significant visual behavioral changes of zebrafish under co-exposure condition. The overall results suggest that combined exposure to water borne n-TiO 2 and TBPH increased their bioavailability, resulted in severer damage to optic nerve development and ultimately abnormal visual behavior patterns, highlighting the higher potential health risks of co-exposure to aquatic vertebrates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The widespread occurrence of organic antibiotic pollution in the environment and the associated harmful effects necessitate effective treatment method. Heterogeneous electro-Fenton (hetero-EF) has been regarded as one of the most promising techniques towards organic pollutant removal. However, the preparation of efficient cathode still remains challenging. Herein, a novel metal-organic framework (MOF)-derived Fe/Ni@C marigold-like nanosheets were fabricated successfully for the degradation of oxytetracycline (OTC) by serving as the hetero-EF cathode. The FeNi 3 @C (Fe/Ni molar ratio of 1:3) based hetero-EF system exhibited 8.2 times faster OTC removal rate than that of anodic oxidation and possessed many advantages such as excellent OTC degradation efficiency (95.4% within 90 min), broad environmental adaptability (satisfactory treatment performance for multiple antibiotics under various actual water matrixes), good stability and reusability, and significant toxicity reduction. The superior hetero-EF catalytic performance was mainly attributed to: 1) porous carbon and Ni existence were both conducive to the in-situ generation of H 2 O 2 from dissolved O 2 ; 2) the synergistic effects of bimetals together with electron transfer from the cathode promoted the regeneration of ≡ Fe II /Ni II , thereby accelerating the production of reactive oxygen species; 3) the unique nanosheet structure derived from the precursor two-dimensional Fe-Ni MOFs enhanced the accessibility of active sites. This work presented a promising hetero-EF cathode for the electrocatalytic treatment of antibiotic-containing wastewaters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cellular micro-environment analysis via fluorescence probe has become a powerful method to explore the early-stage cancer diagnosis and pathophysiological process of relevant diseases. The polarity change of intracellular lipid droplets (LDs) is closely linked with disorders or diseases, which result in various physiological and pathological processes. However, the efficient design strategy for lipid droplet polarity probes with high sensitivity is lacking. To overcome this difficulty, two kinds of LDs-targeting and polarity-sensitive fluorescent probes containing carbazole and siloxane groups were rationally designed and synthesized. With the carbazole-based rotor and bridge-like siloxanes, two probes (P1 and P2) behave high sensitivity to polarity changes and show different fluorescent intensity in normal and cancer cells. Notably, polysiloxanes groups promoted the response sensitivity of the probes dramatically for the polymeric microenvironment. In addition, due to the polarity changes of LDs in cancer cells, the distinct fluorescent intensities in different channels of laser scanning confocal microscope were observed between NHA cell and U87 cells. This work could offer an opportunity to monitor the dynamic behaviors of LDs and further provide a powerful tool to be potentially applied in the early-stage diagnosis of cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Several simple secondary structures could form complex and diverse functional proteins, meaning that secondary structures may contain a lot of hidden information and are arranged according to certain principles, to carry enough information of functional specificity and diversity. However, these inner information and principles have not been understood systematically. In our study, we designed a structure-function alphabet of helix based on reduced amino acid clusters to describe the typical features of helices and delve into the information. Firstly, we selected 480 typical helices from membrane proteins, zymoproteins, transcription factors, and other proteins to define and calculate the interval range, and the helices are classified in terms of hydrophilicity, charge and length: (1) hydrophobic helix (≤43%), amphiphilic helix (43%∼71%), and hydrophilic helix (≥71%). (2) positive helix, negative helix, electrically neutral helix and uncharged helix. (3) short helix (≤8 aa), medium-length helix (9-28 aa), and long helix (≥29 aa). Then, we designed an alphabet containing 36 triplet codes according to the above classification, so that the main features of each helix can be represented by only three letters. This alphabet not only preliminarily defined the helix characteristics, but also greatly reduced the informational dimension of protein structure. Finally, we present an application example to demonstrate the value of the structure-function alphabet in protein functional determination and differentiation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Abstract: Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Polarity plays a critical role in biology and materials science, serving as a complex parameter. Imbalances in polarity within subcellular organelles are closely associated with various diseases. Moreover, volatile organic compounds (VOC) with low polarity pose significant health and safety risks, therefore, researchers have shown great interest in accurately detecting polarity. However, precise observation of polarity changes within organisms and identification of low-polarity volatile organic solvents are formidable challenges. To overcome these difficulties, we developed a versatile polymeric twisting intramolecular charge transfer (TICT) effect Polysiloxane-n (PDMS-n), utilizing polysiloxane molecular chains as "smart guides" to connect TICT molecules, inspired by the concept of "threading a needle." With the aid of PDMS-n, the process of polarity changes during cellular lipophagy was monitored in situ with high accuracy. Remarkably, the polarity changes of the local microstructure of the PDMS films were successfully visualized. PDMS-Films were also constructed, which enabled the recognition of Dichloromethane (DCM) gas during swelling. This work will contribute to the understanding of changes in cellular physiological processes, and facilitate the sensitive detection of VOCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)