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Background: The detection of tyrosine kinase inhibitors (TKIs) in biological fluids is essential due to their critical role in cancer therapy and the variability in individual drug metabolism, which necessitates precise dosing. Traditional methods for analyzing TKIs in biological fluids, such as blood plasma, typically involve complex sample preparation techniques that can be resource-intensive, environmentally burdensome, and not sufficiently sensitive for low-concentration analytes. There is a pressing need for more efficient, economical, and environmentally friendly methods that can enhance sensitivity and throughput without compromising accuracy., Results: This study explores the use of melt-blown polypropylene nonwoven (MBPP), commonly found in face masks, as a novel sorbent for pipette-tip micro-solid phase extraction (PT-μSPE). MBPP demonstrated excellent hydrophobicity and significant mesoporous adsorption capacity. An extraction device was fashioned by inserting a segment of MBPP (15 mg) into a 200 μL disposable plastic pipette tip, which was then attached to a 2.5 mL disposable plastic syringe. The MBPP's fabric form removes the need for a frit, allowing the extraction process to be completed in just 3 min through simple plunger manipulation. The method achieved extraction recoveries ranging from 60.5 % to nearly 100 %. Subsequent method validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed satisfactory linearity (coefficient of determination R 2  > 0.993), accuracy (relative recoveries: 86.3%-114.8 %), and precision (relative standard deviation: 3.4%-11.3 %), with detection limits between 0.022 and 0.135 ng mL -1 ., Significance: The introduction of MBPP for PT-μSPE represents a significant advancement in the bioanalytical detection of TKIs, offering a highly efficient, cost-effective, and environmentally sustainable method. It compares favorably with existing techniques, offering advantages in terms of cost, environmental impact, and ease of use. This approach has the potential to be widely adopted for routine monitoring of TKIs in clinical settings., 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.)

Aristolochic acid I (AAI) is strongly nephrotoxic and can cause "Aristolochic acid nephropathy (AAN)". Aristolochic acid nephropathy is characterized by extensive renal interstitial fibrosis. However, the exact mechanism by which it occurs has not been fully elucidated. lt has been reported that indoleamine 2,3-dioxygenase-1 (IDO1) promotes renal fibrosis in renal disorders, but it is unclear how IDO1 functions in AAI-induced kidney fibrosis. In this work, we systematically examined the role of IDO1 in AAI-induced renal tubulointerstitial fibrosis. The results showed that AAI induced upregulation of IDO1 expression in renal tubular epithelial cells and mouse kidney. Inhibition of IDO1 expression reduced the levels of fibrosis-associated markers α-SMA, COL-I and FN and ameliorated renal tubular epithelial cell fibrosis. It also improved renal function, reduced collagen deposition, and ameliorated interstitial fibrosis in mice. Moreover, we discovered that inhibition of IDO1 decreased the expression of the apoptotic protein BAX, raised the expression of BCL-2 protein, and reduced apoptosis. The above studies suggest that IDO1 is a target of action in renal tubulointerstitial fibrosis caused by AAI, and inhibition of IDO1 may be a viable approach for the therapy of AAI-induced renal tubulointerstitial fibrosis., 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. 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.)

Vitiligo is an acquired chronic depigmentary skin disorder which results from the destruction of melanocytes. The clinical characteristic of vitiligo is the development of white macules due to the loss of functioning melanocytes in the skin or hair. Vitiligo in the genital area brings about a serious psychological impact on individuals. However, the choices of treatment for genital vitiligo are scarce. This study sheds light on the leverage of 5-ALA (5-Aminolevulinic Acid) Photodynamic Therapy (PDT) for the management of genital vitiligo. Nine patients with genital vitiligo who underwent 20% ALA-PDT treatment were reported. The results revealed that the treatment protocol simulated melanocyte regeneration in the patients effectively. ALA-PDT exerts significant anti-inflammatory effects by reducing pro-inflammatory cytokines and inducing regulatory T cells, which may help suppress the autoimmune response involved in vitiligo pathogenesis. Notably, five patients who were defined as responders showed moderate to excellent improvement in repigmentation and the treatment was well tolerated in all cases. Our findings suggest that ALA-PDT is a potential treatment option for genital vitiligo., (Copyright © 2024. Published by Elsevier B.V.)

The expression of TRIM47, a member of the TRIM protein and E3 ubiquitin ligase families, is elevated in various cancers, such as non-small cell lung cancer and colorectal cancer, and is linked to poor prognosis. This study aimed to investigate the role of TRIM47 in gastric cancer development. Using The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset and analysis of 20 patient samples from our center, TRIM47 was found to be significantly up-regulated in gastric cancer tissues and associated with advanced N-stage and poor prognosis. We constructed stable TRIM47 knockdown and overexpressing gastric cancer cell lines. CCK8, EDU, colony formation, wound healing, and Transwell tests were used to evaluate the effects on cell proliferation, invasion, and migration. The results showed that TRIM47 knockdown inhibited the proliferation, migration and invasion of gastric cancer cells, while TRIM47 overexpression promoted these behaviors. These results were further confirmed in vivo. In the mechanism part, we found that TRIM47 interacts with CYLD protein. Moreover, TRIM47 promotes K48-linked ubiquitination, leading to the degradation of CYLD by the proteasome, thereby activating the NF-κB pathway and regulating the biological behavior of gastric cancer cells. Taken together, our study demonstrated that TRIM47 is involved in the proliferation and metastasis of gastric cancer through the CYLD/NF-κB pathway., (© 2024. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis. Gemcitabine-based chemotherapy has emerged as a first-line treatment for PDAC. However, the development of gemcitabine resistance often results in therapeutic failure. In order to uncover the underlying mechanisms of gemcitabine resistance, gemcitabine-resistant PDAC cell lines and patient-derived xenograft (PDX) models are established and subjected to RNA sequencing. It is found that CMTM6 is closely related to gemcitabine resistance in PDAC. Multi-omics analysis revealed that EP300-mediated H3K27ac modification is involved in the transcriptional activation of CMTM6, which maintains IGF2BP1 expression by preventing its ubiquitination. The m 6 A reader IGF2BP1 stabilizes the EP300 and MYC mRNAs by recognizing m 6 A modifications, forming a positive feedback loop that enhances tumor stemness and ultimately contributes to PDAC resistance. The combined application of the EP300 inhibitor inobrodib and gemcitabine exerts a synergistic effect on PDAC. Overall, these findings reveal that the EP300-CMTM6-IGF2BP1 positive feedback loop facilitates gemcitabine resistance via epigenetic reprogramming and the combined use of inobrodib and gemcitabine represents a promising strategy for overcoming chemoresistance in PDAC, warranting further investigation in clinical trials., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Biochar amendments are effective in stabilizing soil aggregates and improving soil organic carbon (SOC) content. However, the effects of biochar on highly acidic soil and their relation with soil SOC stability remain understudied. The study aimed to investigate the impact of biochar on changes of aggregate distribution and SOC stability in a highly acidic tea plantation soils over an eight-year period. Soil samples were collected from plots with varying biochar application amounts (0, 2.5 t ha -1 , 5 t ha -1 , 10 t ha -1 , 20 t ha -1 and 40 t ha -1 ). The content of SOC, iron bound organic carbon (OC-Fe), particulate organic carbon (POC), mineral-associated organic carbon (MAOC) and the functional group composition of SOC was analyzed. The results indicated that in the biochar application treatments, the value of soil pH, SOC, POC and MAOC contents were increased from 3.92 to 4.28, 6.68%-187.02%, 8.31%-66.78% and 13.07%-236.47% respectively, compared with CK, while the content of macro-aggregate (particle size>0.25 mm) and soil aggregates mean weight diameter (MWD) significantly increased with higher biochar application amounts. But dissolved organic carbon (DOC) and OC-Fe content exhibited downward trend, decreased from 2.43% to 6.97% and 4.18%-19.91%. Furthermore, aromatic-C levels increased, with increased biochar application amounts. The integration of biochar not only bolstered soil aggregate stability but also amplified the presence of aromatic-C, thereby enhancing the resilience of organic carbon in highly acidic tea garden soil (BC40 > BC20 > BC5>BC2.5 > BC10 > CK), with increases ranging from 6% to 47%. The principal component analysis and structural equation modeling identified soil pH, TN, SOC, POC, MAOC, R > 0.25 and MWD as key factors of soil organic carbon stability. These findings provide crucial insights into the mechanism underlying biochar's efficiency in fortifying organic carbon stability, particularly in the context of highly acidic soil., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yixiang Wang reports financial support was provided by Fujian Provincial Department of Science and Technology. If there are other authors, they 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 Ltd. All rights reserved.)

Triplex DNA structures, formed when a third DNA strand wraps around the major groove of DNA, are key molecular regulators and genomic threats. However, the regulatory network governing triplex DNA dynamics remains poorly understood. Here we reveal the binding and functional repertoire of proteins that interact with triplex DNA through chemoproteomic profiling in living cells. We develop a chemical probe that exhibits exceptional specificity towards triplex DNA. By employing a co-binding-mediated proximity capture strategy, we enrich triplex DNA interactome for quantitative proteomics analysis. This enables the identification of a comprehensive list of proteins that interact with triplex DNA, characterized by diverse binding properties and regulatory mechanisms in their native chromatin context. As a demonstration, we validate DDX3X as an ATP-independent triplex DNA helicase to unwind substrates with a 5' overhang to prevent DNA damage. Overall, our study provides a valuable resource for exploring the biology and translational potential of triplex DNA., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Compared to conventional nucleic acid detection methods, label-free single nucleotide polymorphism (SNP) detection presents challenging due to the necessity of discerning single base mismatches, especially in the field of enzyme-free detection. In this study, we introduce a novel bulged-type DNA duplex probe designed to significantly amplify single-base differences. This probe is integrated with programmable DNA-based nanostructures to develop a sensitive, label-free biosensor for nonenzymatic SNP detection. The duplex probe with one bulge could selectively identify wild-typed DNA (WT) and mutant-type DNA (MT) based on a competitive strand displacement reaction mechanism. The hyperbranched HCR (HHCR) by incorporating of hairpin DNA into the DNA tetrahedron and surface-tethering on the portable screen printing electrode (SPCE) significantly favor the formation of negatively charged DNA nanostructure. We harnessed strong repulsion of DNA nanostructure towards the electroactive [Fe(CN)₆]³⁻/⁴⁻ in combination with electrochemical technique to create a label-free biosensor. This simple, enzyme-free and label-free biosensor could detect MT with a detection limit of 56 aM, even in multiple sequence backgrounds. The study served as the proof-of-concept for the integration of enzyme-free competitive mechanism and label-free strategy, which can be extended as a powerful tool to various fields., 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 evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard., Methods: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SI lt  - SI pre )/(SI ea  - SI pre ), where SI pre , SI ea, and SI lt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves., Results: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001)., Conclusion: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC., Clinical Relevance Statement: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC., Key Points: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC., (© 2024. The Author(s).)

Gamma irradiation-based mutant creation is one of the most important methods for rice plant mutagenesis breeding and molecular biology research. Although median lethal dose irradiation severely damages rice seedlings, applying brassinolide (BR) can increase the survival rate of irradiated seedlings. In this study, we investigated the effects of soaking seeds in solutions containing different BR concentrations (0.001, 0.01, 0.1, 1.0, and 5.0 μmol/L) and then spraying the resulting seedlings twice with 0.1 μmol/L BR. The combined BR treatments markedly decreased the superoxide anion (O 2 •- ), hydrogen peroxide (H 2 O 2 ), and malondialdehyde contents but increased the chlorophyll content. An appropriate BR treatment of gamma-irradiated samples substantially increased the activities of the antioxidant enzymes superoxide dismutase, peroxidase, and ascorbate peroxidase as well as the proline, ascorbic acid, and glutathione contents in rice seedling shoots. The BR treatment also promoted the growth of seedlings derived from irradiated seeds and increased the shoot and root fresh and dry weights. Most notably, soaking seeds in 0.01 or 0.1 μmol/L BR solutions and then spraying seedlings twice with 0.1 μmol/L BR significantly increased the final seedling survival rate and decreased mutant loss. The study results suggest that exogenous BR treatments can protect rice seedlings from gamma irradiation stress by enhancing antioxidant metabolism.

Chronic rhinosinusitis (CRS) is a prevalent inflammatory airway disease affecting over 10% of the global population, leading to considerable socio-economic impacts, especially in developing countries. The pathogenesis of CRS is multifactorial, involving potential contributions from both genetic and environmental factors. While the influence of allergic and autoimmune diseases on CRS has been observed, the causal relationships between these diseases and CRS remain unclear. We extracted data from large-scale genome-wide association studies (GWAS) and utilized a bidirectional two-sample Mendelian randomization (MR) analysis to explore the causal relationships between CRS and ten autoimmune and allergic diseases, including asthma, allergic rhinitis (AR), atopic dermatitis (AD), psoriasis, type 1 diabetes (T1D), hypothyroidism, celiac disease (CeD), multiple sclerosis (MS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Additionally, we conducted colocalization analysis to determine whether the allergic/autoimmune diseases showing statistical causal relationships with CRS are driven by the same genetic variants. The MR analysis identified that AR (OR = 1.30; 95% CI = 1.21-1.40; P = 3.26E-13), asthma (OR = 1.35; 95% CI = 1.25-1.45; P = 1.35E-14), and AD (OR = 1.17; 95% CI = 1.06-1.30; P = 0.003) were significantly associated with an increased risk of developing CRS. Interestingly, psoriasis (OR = 0.05; 95% CI = 0.01-0.37; P = 0.004) appeared to have a protective effect against CRS. Associations for T1D and hypothyroidism were also suggestive as potential risk factors for CRS. No significant associations in the reverse MR analysis, suggesting a one-directional relationship. Colocalization analysis indicated that asthma (PP.H4 = 0.99) shared the same genetic variant (IL-33 rs3939286) with CRS. In conclusion, our study confirmed the causal relationships between allergic and autoimmune diseases (AR, asthma, AD, and psoriasis) and CRS. Notably, we identified a shared genetic variant, rs3939286 in the IL-33 gene, between asthma and CRS, suggesting that targeting the IL-33 pathway may provide a therapeutic strategy for both diseases., (© 2024. The Author(s).)

Repair and preservation of the injured meniscus has become paramount in clinical practice. However, the complexities of various clinic stitching techniques for meniscus repair pose challenges for grassroots doctors. Hence, there is a compelling interest in innovative therapeutic strategies such as bioadhesives. An ideal bioadhesive must cure quickly in aqueous and blood environments, bind strongly, endure arthroscopic washing pressures, and degrade appropriately for tissue regeneration. Here, we present a tetra-poly (ethylene glycol) (PEG)-based hydrogel bioadhesive, boasting high biocompatibility, ultrafast gelation, facile injectable operation, and favorable mechanical strength. In view of the synergistic effects of chemical anchor and physical chain entanglement to tightly bind the meniscus, a seamless interface was formed between the surrounding meniscal tissues and hydrogels, enabling the longitudinal tear of the meniscus fused in situ to withstand large tensile force with the adhesive strength of 541.5 ± 31.4 kPa and arthroscopic washout resistance of 29.4 kPa. Superior to existing commercial adhesives, ours allows sutureless application and arthroscopic assistance, without requiring specialized clinical skills. This research is expected to significantly impact our understanding of meniscal healing and ultimately promote a simpler process for achieving functional and structural recovery in torn menisci., Competing Interests: The authors declare they have no conflicts of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Rationale and Objectives: The study aimed to analyze the patterns and frequency of Level V lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC), identify its risk factors, and construct predictive models for assessment., Methods: We conducted a retrospective analysis of 325 PTC patients who underwent thyroidectomy and therapeutic unilateral bilateral modified radical neck dissection from October 2020 to January 2023. Patients were randomly allocated into a training cohort (70%) and a validation cohort (30%). The radiomics signature model was developed using ultrasound images, applying the minimum Redundancy-Maximum Relevance and Least Absolute Shrinkage and Selection Operator regression to extract high-throughput quantitative features. Concurrently, the clinic signature model was formulated based on significant clinical factors associated with Level V LNM. Both models were independently translated into nomograms for ease of clinical use., Results: The radiomics signature model, without the inclusion of clinical factors, showed high discriminative power with an area under the curve (AUC) of 0.933 in the training cohort and 0.912 in the validation cohort. Conversely, the clinic signature model, composed of tumor margin, simultaneous metastasis, and high-volume lateral LNM, achieved an AUC of 0.749 in the training cohort. The radiomics signature model exhibited superior performance in sensitivity, specificity, positive predictive value, negative predictive value across both cohorts. Decision curve analysis demonstrated the clinical utility of the radiomics signature model, indicating its potential to guide more precise treatment decisions., Conclusion: The radiomics signature model outperformed the clinic signature model in predicting Level V LNM in PTC patients. The radiomics signature model, available as a nomogram, offers a promising tool for preoperative assessment, with the potential to refine clinical decision-making and individualize treatment strategies for PTC patients with potential Level V LNM., Competing Interests: Declaration of Competing Interest This manuscript has not been published nor submitted for publication elsewhere. All authors have contributed significantly, and agree with the content of the manuscript. The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR's effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR's solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism., Methods: The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms., Results: After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC 0-t ) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects., Conclusion: MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Mao et al.)

Aristolochic acid I (AAI) is one of the nephrotoxic and carcinogenic compounds in Aristolochic acids (AAs). Recent studies have reported its promoting effect on hepatocellular carcinoma. However, the underlying mechanisms of AAI for the development of HCC is still unclear. Here, we found that AAI exposure caused alterations in mitochondrial function, which featured with increased ATP level and mitochondrial membrane potential, accumulation of mitochondrial Ca 2+ and mitochondrial ROS (MitoROS) in Hepa1-6 and HepG2 cells. The restriction of mitochondrial Ca 2+ uptake alleviated these effects. Our results showed that increased MitoROS was associated with AAI-induced migration and invasion in HCC cells. MitoROS/Src/FAK pathway was involved in the AAI-induced migration and invasion of HCC cells. In summary, our study showed that AAI affected mitochondrial metabolism of HCC cells by promoting the accumulation of mitochondrial Ca 2+ . These effects resulted in the activation of the MitoROS/SRC/FAK pathway in AAI-treated HCC cells, which in turn induced cell migration and invasion., 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: The achievement of an optimal return to sport (RTS) has remained a key goal after sports-related injuries, with the ongoing debate on the effectiveness of different surgical approaches for anterior cruciate ligament (ACL) rupture. This study aims to assess clinical outcomes and RTS across various surgical methods, such as anatomical single-bundle reconstruction (ASBR), central-axial single-bundle reconstruction (CASBR), and double-bundle reconstruction (DBR)., Methods: A randomized clinical trial was conducted, comprising 191 patients who underwent ACL rupture. These patients were divided into three groups based on the ACL reconstruction techniques they received (ASBR, CASBR, DBR). Over the 2-year follow-up period, the study assessed RTS through four single-hop tests, isokinetic extension tests, and limb asymmetry indices. Postoperative graft status was determined using the signal-to-noise quotient (SNQ), while knee function was evaluated using the International Knee Documentation Committee 2000 (IKDC-2000) score, Lysholm score, Tegner score, and degree of knee laxity. A binary logistic regression model was developed to forecast the factors influencing ideal RTS., Results: DBR (67.63%) and CASBR (58.00%) exhibited higher RTS passing rates compared to ASBR (30.39%; χ2 = 19.57, P <0.05). Quadriceps strength symmetry in the lower limbs was identified as the key determinant of RTS (χ2 = 17.08, P <0.05). The RTS rate was influenced by SNQs of the graft's tibial site (odds ratio: 0.544) and quadriceps strength of the reconstructed knee joint at 60°/s (odds ratio: 6.346). Notably, the DBR group showed enhanced knee stability, evidenced by superior results in the Lachman test (χ2 = 13.49, P <0.01), objective IKDC-2000 (χ2 = 27.02, P = 0.002), and anterior instability test (χ2 = 9.46, P <0.01). Furthermore, DBR demonstrated superior clinical outcomes based on the Lysholm score (DBR: 89.57 ± 7.72, CASBR: 83.00 ± 12.71, ASBR: 83.21 ± 11.95; F = 10.452, P <0.01) and IKDC-2000 score (DBR: 90.95 ± 7.00, CASBR: 84.64 ± 12.68, ASBR: 83.63 ± 11.41; F = 11.78, P <0.01)., Conclusion: For patients with ACL rupture, more ideal RTS rate and clinical outcomes were shown in the DBR group than in the ASBR and CASBR groups. Autograft status and quadriceps strength are postively related to RTS., Trial Registration: ClinicalTrials.gov (NCT05400460)., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of various diseases, such as infectious diseases, autoimmune disorders, metabolic diseases, and cancers. In this context, IRFs display a dichotomous nature, functioning as both tumor suppressors and promoters, contingent upon the specific disease milieu. Post-translational modifications of IRFs, including phosphorylation and ubiquitination, play a crucial role in modulating their function, stability, and activation. As prospective biomarkers and therapeutic targets, IRFs present promising opportunities for disease intervention. Further research is needed to elucidate the precise mechanisms governing IRF regulation, potentially pioneering innovative therapeutic strategies, particularly in cancer treatment, where the equilibrium of IRF activities is of paramount importance., (© 2024. The Author(s).)

Tumor-derived small extracellular vesicle (sEV) microRNAs (miRNAs) are emerging biomarkers for cancer diagnostics. Conventional sEV miRNA detection methods necessitate the lysis of sEVs, rendering them laborious and time-consuming and potentially leading to damage or loss of miRNAs. Membrane fusion-based in situ detection of sEV miRNAs involves the preparation of probe-loaded vesicles ( e.g. , liposomes or cellular vesicles), which are typically sophisticated and require specialist equipment. Membrane perforation methods employ chemical treatments that can induce severe miRNA degradation or leaks. Inspired by previous studies that loaded nucleic acids into EVs or cells using hydrophobic tethers for therapeutic applications, herein, we repurposed this strategy by conjugating a hydrophobic tether onto molecular beacons to aid their transportation into sEVs, allowing for in situ detection of miRNAs in a fusion-free and multiplexing manner. This method enables simultaneous detection of multiple miRNA species within serum-derived sEVs for the diagnosis of prostate cancer, breast cancer, and gastric cancer with an accuracy of 83.3%, 81.8%, and 100%, respectively, in a cohort of 66 individuals, indicating that it holds a high application potential in clinical diagnostics.

Fokienia hodginsii (F. hodginsii), belonging to the genus Fokienia of the Cupressaceae. F. hodginsii has significant application value due to its wood properties and great research value in evolutionary studies as a gymnosperm. However, the genome of F. hodginsii remains unknown due to the large size of gymnosperms genome. Pacific Bioscience sequencing, Hi-C mapping, whole-genome Bisulfite Sequencing (BS-Seq), long-read isoform sequencing (Iso-Seq), direct RNA sequencing (DRS), quantitative proteomics, and metabonomics analysis are employed to facilitate genome assembly, gene annotation, and investigation into epigenetic mechanisms. In this study, the 10G F. hodginsii genome is assembled into 11 chromosomes. Furthermore, 50 521 protein-coding genes are annotated and determined that 65% of F. hodginsii genome comprises repetitive sequences. It is discovered that transposable element (TE)-including introns is associated with higher expression. The DNA methylome of F. hodginsii reveals that xylem has a higher DNA methylation level compared to callus. Moreover, DRS reveals the significant alterations in RNA full-length ratio, which potentially associated with poly(A) length (PAL) and alternative polyadenylation (APA). Finally, the morphology measurement and metabonomics analysis revealed the difference of 14 cultivars. In summary, the genomes and epigenetics datasets provide a molecular basis for callus formation in the gymnosperm family., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Lipid metabolism reprogramming stands as a fundamental hallmark of cancer cells. Unraveling the core regulators of lipid biosynthesis holds the potential to find promising therapeutic targets in pancreatic ductal adenocarcinoma (PDAC). Here, it is demonstrated that platelet-derived growth factor C (PDGFC) orchestrated lipid metabolism, thereby facilitated the malignant progression of PDAC. Expression of PDGFC is upregulated in PDAC cohorts and is corelated with a poor prognosis. Aberrantly high expression of PDGFC promoted proliferation and metastasis of PDAC both in vitro and in vivo. Mechanistically, PDGFC accelerated the malignant progression of PDAC by upregulating fatty acid accumulation through sterol regulatory element-binding protein 1 (SREBP1), a key transcription factor in lipid metabolism. Remarkably, Betulin, an inhibitor of SREBP1, demonstrated the capability to inhibit proliferation and metastasis of PDAC cell lines, along with attenuating the process of liver metastasis in vivo. Overall, the study underscores the pivotal role of PDGFC-mediated lipid metabolism in PDAC progression, suggesting PDGFC as a potential biomarker for PDAC metastasis. Targeting PDGFC-induced lipid metabolism emerges as a promising therapeutic strategy for metastatic PDAC, with the potential to improve clinical outcomes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Talquetamab is a bispecific antibody targeting the multiple myeloma-associated antigen G protein-coupled receptor family C group 5 member D (GPRC5D). In the phase 1/2 MonumenTAL-1 trial (NCT03399799/NCT04634552), overall responses rates were > 71% in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). Due to the distribution of the target antigen, a unique pattern of GPRC5D-associated adverse events (AEs) was observed, together with T-cell redirection-associated AEs. Management strategies for talquetamab-associated AEs are described., Discussion: GPRC5D-associated AEs included dermatologic (rash, nonrash, and nail toxicities) and oral AEs (dysgeusia, dysphagia, and dry mouth). The incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were consistent with other T-cell redirection therapies. The incidence of high-grade infections was lower than observed with B-cell maturation antigen-targeting bispecific antibodies, with less frequent use of intravenous immunoglobulin required. GPRC5D-associated AEs were mostly low grade and led to few discontinuations. Skin toxicities were managed with emollients, topical corticosteroids, and oral corticosteroids (for high-grade, persistent, or AEs that progress). Nail toxicities were commonly managed with emollients. Based on investigator experience, dose modification may be effective for controlling oral events. Observation for potential weight changes is required. Infections were managed per standard of care. CRS and ICANS were effectively managed, consistent with other trials of T-cell redirection therapies., Conclusion: Although talquetamab had a distinct safety profile, AEs were considered clinically manageable and mostly low grade. With appropriate education and support, health care practitioners can ensure patients with RRMM maintain quality of life and treatment adherence. VIDEO ABSTRACT., (Copyright © 2024. Published by Elsevier Inc.)

Imaging live cells under stable culture conditions is essential to investigate cell physiological activities and proliferation. To achieve this goal, typically, a specialized incubation chamber that creates desired culture conditions needs to be incorporated into a microscopy system to perform cell monitoring. However, such imaging systems are generally large and costly, hampering their wide applications. Recent advances in the field of miniaturized microscopy systems have enabled incubator cell monitoring, providing a hospitable environment for live cells. Although these systems are more cost-effective, they are usually limited in imaging modalities and spatial temporal resolution. Here, we present a dual-mode, image-enhanced, miniaturized microscopy system (termed MiniCube) for direct monitoring of live cells inside incubators. MiniCube enables both bright field imaging and fluorescence imaging with single-cell spatial resolution and sub-second temporal resolution. Moreover, this system can also perform cell monitoring inside the incubator with tunable time scales ranging from a few seconds to days. Meanwhile, automatic cell segmentation and image enhancement are realized by the proposed data analysis pipeline of this system, and the signal-to-noise ratio (SNR) of acquired data is significantly improved using a deep learning based image denoising algorithm. Image data can be acquired with 5 times lower light exposure while maintaining comparable SNR. The versatility of this miniaturized microscopy system lends itself to various applications in biology studies, providing a practical platform and method for studying live cell dynamics within the incubator., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ning Hu reports a relationship with National Natural Science Foundation of China that includes: funding grants. Diming Zhang reports a relationship with Zhejiang Provincial Natural Science Foundation of China that includes: funding grants. Chunlian Qin reports a relationship with National Natural Science Foundation of China that includes: funding grants. Ning Hu reports a relationship with Hangzhou Agricultural Social Development Research Key Project that includes:. Chunlian Qin reports a relationship with China Postdoctoral Science Foundation Funded Project that includes: funding grants. If there are other authors, they 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: One lung ventilation (OLV) is an essential method of lung isolation to protect the ventilated lung from soiling by the contralateral lung and obtain optimal surgical exposure in thoracic surgery. This study aims to examine the trends and developments in OLV research from 1982 to 2024 through bibliometric analysis., Methods: The literature on OLV was systematically searched in the Web of Science Core Collection database for this study. VOSviewer and CiteSpace were utilized to perform comprehensive bibliometric and visual analyses of global publication/trends, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords in the field of OLV., Results: A total of 1,682 articles and reviews on OLV research were identified, which showed an overall growing trend from 1982 to 2024. The United States was the leader in this field, accounting for the largest number of publications (n=299). Among all institutions, Yonsei University had the largest number of publications (n=23), but National Taiwan University Hospital had the highest number of cited publications (n=876). The papers related to OLV were mainly published in Journal of Cardiothoracic and Vascular Anesthesia (n=147) and the most productive author was Cheng YJ (n=15). After keywords analysis, "infants", "dexmedetomidine", "inflammation", and "airway management" were newly emergent research hotspots., Conclusions: Through bibliometric and visualization methods, we undertook a comprehensive analysis in the field of OLV. The United States maintained a top position in this field, the emerging hotspots of OLV changed from basic research to clinical research and the further innovation of OLV management. This study provides new ideas for scholars in their future works., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-645/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objectives: This study aimed to investigate the psychological stress experienced by frontline medical staff during the Yangbi Earthquake and to understand how coping strategies and social support influence stress responses., Methods: From days 3 to 14 post-earthquake, online questionnaires were administered to frontline medical staff to assess perceived social support, coping strategies, and psychological stress responses using the Perceived Social Support Scale (PSSS), Trait Coping Strategies Questionnaire (TCSQ), and Stress Response Questionnaire (SRQ). Data analysis included correlation analysis to explore relationships between variables, multiple linear regression to identify key predictors of stress, and path analysis to determine direct and indirect effects., Results: A total of 253 valid questionnaires were analyzed, with a participant composition of 81.82% females and 18.18% males, and the majority being nurses (62.06%). Psychological stress responses varied by gender and age, with females and older age groups showing higher physical stress responses (P < 0.05). Correlation and regression analyses indicated that negative coping and lower levels of social support were associated with increased stress responses (P < 0.05). Path analysis revealed that intra-family and extra-family support influenced stress responses directly and indirectly through coping strategies (P < 0.05)., Conclusion: This study suggests that perceived social support directly influences stress responses in frontline medical personnel during disasters, with coping strategies mediating this effect. Future research should explore these dynamics over time through longitudinal studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Ye, Yang, Sun, Yan, Yuan, Peng and Tang.)

Background: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients., Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis., Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways., Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long-term depression, retrograde endocannabinoid signaling, and so on., Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression., Competing Interests: The authors declare that they do not possess any known conflicting financial interests or personal relationships that could have influenced the work reported in this manuscript., (© 2024 Ye et al.)

This project utilized both field experiment and laboratory analyses to address the gap in understanding regarding the alterations in properties and functions of biochar, and the impact of heavy metal passivation in soil over long-term natural field aging. The study aimed to examine the changes in the physical and chemical characteristics of biochar over an extended period of natural aging. Additionally, it sought to analyze the impact and mechanisms of biochar in reducing of the harmful effects of the heavy metal cadmium (Cd) during the aging process. Both original and aged biochar conformed to the pseudo-second-order kinetics model and the Langmuir model. The aging process enhanced the adsorption of Cd by biochar and mitigated the leaching of Cd 2+ into the soil. These findings provide a scientific basis for evaluating biochar's environmental behavior and its potential use in the remediation of soil contaminated with heavy metals., (© 2024. The Author(s).)

Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H 2 O 2 production, but also NADPH down-regulation, intensifying redox damage to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harm to normal cells mainly due to metabolic vulnerability of the former. Once administered into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety.

The structural integrity of the sperm flagellum is essential for proper sperm function. Flagellar defects can result in male infertility, yet the precise mechanisms underlying this relationship are not fully understood. CCDC181, a coiled-coil domain-containing protein, is known to localize on sperm flagella and at the basal regions of motile cilia. Despite this knowledge, the specific functions of CCDC181 in flagellum biogenesis remain unclear. In this study, Ccdc181 knockout mice were generated. The absence of CCDC181 led to defective sperm head shaping and flagellum formation. Furthermore, the Ccdc181 knockout mice exhibited extremely low sperm counts, grossly aberrant sperm morphologies, markedly diminished sperm motility, and typical multiple morphological abnormalities of the flagella (MMAF). Additionally, an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified, with CCDC181 regulating the localization of LRRC46 within sperm flagella. These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

Infertility represents a significant health concern, with sperm quantity and quality being crucial determinants of male fertility. Oligoasthenoteratozoospermia (OAT) is characterized by reduced sperm motility, lower sperm concentration, and morphological abnormalities in sperm heads and flagella. Although variants in several genes have been implicated in OAT, its genetic etiologies and pathogenetic mechanisms remain inadequately understood. In this study, we identified a homozygous nonsense mutation (c.916C>T, p.Arg306*) in the coiled-coil domain containing 146 ( CCDC146 ) gene in an infertile male patient with OAT. This mutation resulted in the production of a truncated CCDC146 protein (amino acids 1-305), retaining only two out of five coiled-coil domains. To validate the pathogenicity of the CCDC146 mutation, we generated a mouse model ( Ccdc146 mut/mut ) with a similar mutation to that of the patient. Consistently, the Ccdc146 mut/mut mice exhibited infertility, characterized by significantly reduced sperm counts, diminished motility, and multiple defects in sperm heads and flagella. Furthermore, the levels of axonemal proteins, including DNAH17, DNAH1, and SPAG6, were significantly reduced in the sperm of Ccdc146 mut/mut mice. Additionally, both human and mouse CCDC146 interacted with intraflagellar transport protein 20 (IFT20), but this interaction was lost in the mutated versions, leading to the degradation of IFT20. This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility, potentially by disrupting axonemal protein transportation. These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

Background: Mitochondrial dysfunction is an important factor in the pathogenesis of schizophrenia. However, the relationship between mitophagy and schizophrenia remains to be elucidated., Methods: Single-cell RNA sequencing datasets of peripheral blood and brain organoids from SCZ patients and healthy controls were retrieved. Mitophagy-related genes that were differentially expressed between the two groups were screened. The diagnostic model based on key mitophagy genes was constructed using two machine learning methods, and the relationship between mitophagy and immune cells was analyzed. Single-cell RNA sequencing data of brain organoids was used to calculate the mitophagy score (Mitoscore)., Results: We found 7 key mitophagy genes to construct a diagnostic model. The mitophagy genes were related to the infiltration of neutrophils, activated dendritic cells, resting NK cells, regulatory T cells, resting memory T cells, and CD8 T cells. In addition, we identified 12 cell clusters based on the Mitoscore, and the most abundant neurons were further divided into three subgroups. Results at the single-cell level showed that Mitohigh&#95;Neuron established a novel interaction with endothelial cells via SPP1 signaling pathway, suggesting their distinct roles in SCZ pathogenesis., Conclusion: We identified a mitophagy signature for schizophrenia that provides new insights into disease pathogenesis and new possibilities for its diagnosis and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Lian, Ye, Cheng and Xu.)

G-Quadruplex/thioflavin (G4/THT) has become a very promising label-free fluorescent luminescent element for nucleic acid detection due to its good programmability and compatibility. However, the weak fluorescence efficiency of single-molecule G4/THT limits its potential applications. Here, we developed an entropy-driven catalytic (EDC) G4 (EDC-G4) cycle amplification technology as a universal label-free signal amplification and output system by properly programming classical EDC and G4 backbone sequences, preintegrated ligase chain reaction (LCR) for label-free sensitive detection of single nucleotide polymorphisms (SNPs). First, the positive strand LCR enabled specific transduction and preliminary signal amplification from single-base mutation information to single-strand information. Subsequently, the EDC-G4 cycle amplification reaction was activated, accompanied by the production of a large number of G4/THT luminophores to output fluorescent signals. The EDC-G4 system was proposed to address the weak fluorescence of G4/THT and obtain a label-free fluorescence signal amplification. The dual-signal amplification effect enabled the LCR-EDC-G4 detection system to accurately detect mutant target (MT) at concentrations as low as 22.39 fM and specifically identify 0.01% MT in a mixed detection pool. Moreover, the LCR-EDC-G4 system was further demonstrated for its potential application in real biological samples. Therefore, this study not only contributes ideas for the development of label-free fluorescent biosensing strategies but also provides a high-performance and practical SNP detection tool in parallel.

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses., Importance: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro . In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research., Competing Interests: The authors declare no conflict of interest.

Rationale: Stroke induces metabolic changes in the body, and metabolites have become potential biomarkers for stroke. However, the specific metabolites involved in stroke and the mechanisms underlying brain injury during stroke remain unclear. Methods: Surface-enhanced Raman spectroscopy (SERS) and liquid chromatography-mass spectrometry (LC‒MS) analysis of clinical serum samples from 69 controls and 51 ischemic stroke patients who underwent reperfusion within 24 hours were performed to identify differentially abundant metabolites. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) and then intravenously injected with hypoxanthine. The infarct area was evaluated via tetrazolium chloride (TTC) staining, and behavior tests were conducted. Blood-brain barrier (BBB) leakage was assessed by Evans blue and IgG staining. Human blood vessel organoids were used to investigate the mechanism of hypoxanthine-induced pyroptosis of endothelial cells. Results: SERS and LC‒MS revealed the metabolic profiles of serum from stroke patients and controls with high sensitivity, speed and accuracy. Hypoxanthine levels were significantly elevated in the acute stage of ischemic stroke in both patients and mice (p < 0.001 after Bonferroni correction). In addition, increasing hypoxanthine increased the infarct area and aggravated BBB leakage and neurobehavioral deficits in mice after ischemic stroke. Further mechanistic studies using endothelial cells, human blood vessel organoids, and stroke mice demonstrated that hypoxanthine-mediated gasdermin E (GSDME)-dependent pyroptosis of endothelial cells occurs through intracellular Ca 2+ overload. Conclusion: Our study identified hypoxanthine as an important metabolite that induces vascular injury and BBB disruption in stroke through triggering GSDME-dependent pyroptosis of endothelial cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in "photosynthesis" and "photosynthesis, light reaction" in Sedum alfredii Hance leaves. Moreover, the "plant hormone signal transduction" pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants., 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.)

Polysaccharides from sea cucumbers are known for their biological activities, but little is known about those from sea cucumber viscera. The present study isolated a sulfated polysaccharide (SCVP-2) from the viscera of Apostichopus japonicas, which had a molecular weight of 209.1 kDa. SCVP-2 comprised 66.3 % total sugars, 2.1 % uronic acid, 4.5 % proteins, and 25.5 % sulfate groups, containing glucosamine, galactosamine, glucose, galactose, and fucose. FT-IR and NMR analyses identified SCVP-2 as a fucoidan sulfate with sulfation patterns of the fucose branches as Fuc2S, Fuc4S, and Fuc0S. SEM and AFM analyses showed irregular clusters and linear conformations. SCVP-2 demonstrated strong anti-inflammatory properties both in vitro and in vivo. In lipopolysaccharide (LPS)-induced inflammation in macrophage RAW264.7 cells, SCVP-2 significantly reduced nitric oxide (NO) and cytokine secretion (IL-1β, IL-6, TNF-α). Additionally, it downregulated the expression of these cytokine genes. Furthermore, the anti-inflammatory mechanism of SCVP-2 was related to the inhibition of the MAPKs and NF-κB pathways. SCVP-2's anti-inflammatory capacity was confirmed in acute inflammation models, including xylene-induced ear swelling and acetic acid-induced peritoneal capillary permeability, and in high-fat diet-induced systemic low-grade chronic inflammation. In conclusion, SCVP-2 exhibits significant anti-inflammatory activity, suggesting its potential for development as a functional food ingredient or therapeutic agent for inflammation-related diseases., 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: The close relationship between bile acid (BA) metabolism and sepsis has been investigated in recent years, as knowledge of the role of the gut microbiome and metabolomics in sepsis has grown and become more comprehensive., Methods: Patients with sepsis who were admitted to the PICU of the Children's Hospital, Zhejiang University School of Medicine from January 2016 to December 2021 were enrolled in this study. Preoperative non-infectious pediatric patients undergoing elective surgeries in our hospital's department of surgery were recruited as controls during the same period. Clinical data were collected and analyzed., Results: 702 children were enrolled, comprising 538 sepsis survivors, 164 sepsis fatalities, and 269 non-infected controls. Statistical analysis revealed that total BA (TBA) increased in both the early and severe stages of pediatric sepsis. In the severe stage, TBA (OR = 2.898, 95% CI 1.946-4.315, p < 0.05) was identified as a risk factor for sepsis. A clinical model identified TBA (the cut-off value is >17.95 µmol/L) as an independent predictor of sepsis mortality with an AUC of 0.842 (95% CI 0.800-0.883), sensitivity of 54.9%, specificity of 96.6%, and HR = 7.658 (95% CI 5.575-10.520)., Conclusions: The study showed that elevated TBA was associated with a heightened risk of mortality in pediatric sepsis., Impact: Many clinical indicators show differences between children with sepsis and the control group, among which the difference in serum total bile acid levels is the most significant. During the hospitalization of the patients, the overall bile acid levels in the sepsis death group were higher and exhibited greater fluctuations compared to the survival group, with significant differences. Serum total bile acid levels can serve as effective biomarker for predicting the prognosis of children with sepsis., (© 2024. The Author(s).)

In the vanguard of neuromorphic engineering, we develop a paradigm of biocompatible polymer memcapacitors using a seamless solution process, unleashing comprehensive synaptic capabilities depending on both the stimulation form and history. Like the human brain to learn and adapt, the memcapacitors exhibit analogue-type and evolvable capacitance shifts that mirror the complex flexibility of synaptic strengthening and weakening. With increasing frequency and intensity of the stimulation, the memcapacitors demonstrate an evolution from short-term plasticity (STP) to long-term plasticity (LTP), and even to metaplasticity (MP) at a higher level. A physical picture, featuring the stimulus-controlled spatiotemporal ion redistribution in the polymer, elaborates the origin of the memcapacitive prowess and resultant versatile synaptic plasticity. The distinctive MP behavior endows the memcapacitors with a dynamic learning rate (LR), which is utilized in an artificial neural network. The superiority of implementing a dynamic LR compared with conventional practices of using constant LR shines light on the potential of the memcapacitors to exploit organic neuromorphic computing hardware.

Introduction: Trauma is a significant global public health concern and the leading cause of morbidity and mortality in children. This study aimed to assess the independent predictors of trauma severity as well as mortality in pediatric patients admitted to the intensive care unit (ICU)., Methods: In this cross-sectional study, following the STROBE checklist, we retrospectively analyzed the clinical and baseline characteristics of pediatric patients with trauma injuries admitted to the ICU of Children's Hospital of Zhejiang University School of Medicine, China, over a decade., Results: 951 pediatric patients with a mean age of 4.79 ± 3.24 years (60.78% Boys) were studied (mortality rate 8.41%). Significant associations were observed between ISS and place of residence (p = 0.021), location of the injury (p = 0.010), year of injury (p <0.001), and injury mechanism (p <0.001). The two independent factors of trauma severity were the year of injury (β = 0.47; 95%CI: 0.28 - 0.65) and injury mechanism (β = -0.60; 95%CI: -0.88 - -0.31). Significant differences were observed between survived and non-survived regarding age (p <0.001), ISS score (p <0.001), time elapsed from injury to ICU (p <0.001), duration of mechanical ventilation (p <0.001), GCS score (p <0.001), and the proportion of patients requiring mechanical ventilation (p <0.001 ). The results of multivariate analysis indicated that age (OR = 0.805; 95%CI: 0.70 - 0.914; p = 0.001) and GCS score at ICU admission (OR = 0.629; 95%CI: 0.53 - 0.735; p < 0.001) acted as protective factors, whereas mechanical ventilation in the ICU (OR = 7.834; 95%CI: 1.766 - 34.757; p = 0.007) and ISS score at ICU admission (OR = 1.088; 95%CI: 1.047 - 1.130; p < 0.001) served as risk factors for mortality., Conclusion: Automobile-related injuries represent the leading cause of trauma in children, with escalating severity scores year over year among pediatric patients admitted to the ICU with trauma injuries. Based on the findings the independent predictors of mortality of pediatric trauma patients admitted to the ICU were age, GCS score at ICU admission; mechanical ventilation in the ICU, and ISS score at ICU admission. Also, the year of injury and injury mechanism were independent predictors of trauma severity., Competing Interests: The authors declare no conflicts of interest.

Pediatric trauma plays a crucial role in pediatric mortality, with traffic injuries and falls frequently cited as leading causes of significant injuries among children. A comprehensive investigation, including geographical factors, is essential for developing effective strategies to prevent injuries and alleviate the burden of pediatric trauma. This study involved a retrospective analysis of clinical data from pediatric patients admitted to our hospital's intensive care unit (ICU) due to trauma over a 10-year period. Comprehensive analyses were conducted to elucidate trends, demographics, injury patterns, and risk factors associated with these admissions. This retrospective study included 951 pediatric patients (mean age: 4.79 ± 3.24 years; mean weight: 18.45 ± 9.02 kg; median time to ICU admission post-injury: 10.86 ± 14.95 h). Among these patients, 422 (44.4%) underwent emergency surgery, and 466 (49%) required mechanical ventilation support, with a mean duration of 70.19 ± 146.62 h. The mean duration of ICU stay was 6.24 ± 8.01 days, and the overall mean hospitalization duration was 16.08 ± 15.56 days. The predominant cause of unintentional injury was traffic accidents (47.9%), followed by falls (42.5%) and burns/scalds (5.3%). Most incidents involved children aged 0-6 years (70.7%), with males comprising 60.0% of patients. Injury incidents predominantly occurred between 12 and 6 PM (44.5%) and on non-workdays (37.6%). The most common locations where injuries occurred were roadsides (49%) and rural areas (64.35%). Single-site injuries (58.78%) were more prevalent than multiple-site injuries (41.22%), and head injuries were the most common among single-site injuries (81.57%). At ICU admission, the mean injury severity score was 18.49 ± 8.86. Following active intervention, 871 patients (91.59%) showed improvement, while 80 (8.41%) succumbed to their injuries. Traffic injuries remain the primary cause of pediatric trauma leading to ICU admission, underscoring the importance of using appropriate child restraint systems and protective gear as fundamental preventive measures. The increased incidence of injuries among children aged < 6 years and those residing in rural areas highlights the need for targeted preventive strategies, necessitating tailored interventions and public policy formulations that address these high-risk populations., (© 2024. The Author(s).)

Background: To evaluate the association between the pulmonary vein (PV) entry site morphology after total anomalous pulmonary vein repair (TAPVC) and postoperative pulmonary vein stenosis (PVS)., Methods: Computed tomography (CT) examination was performed to determine the PV entry site morphology. The width of the PV confluence was divided by the width of the left atrium (LA) to obtain the cPV/LA index. The cPV/LA index was compared between patients with and without postoperative PVS., Results: Fifty-one patients who had undergone CT after TAPVC repair were included, with a median cPV/LA index of 0.5 (interquartile range (IQR) = 0.349-0.654). Among them, 27 patients developed postoperative PVS. The median cPV/LA index after primary TAPVC repair was significantly lower in patients with PVS compared to those without PVS (0.367, IQR = 0.308-0.433 vs. 0.657, IQR = 0.571-0.783, P < 0.0001). Additionally, the cPV/LA index after surgical re-intervention for PVS was significantly smaller in patients who developed recurrent stenosis compared to those who remained free-from re-stenosis after surgical relief (0.459, IQR = 0.349-0.556; vs. 0.706, IQR = 0.628-0.810, P = 0.0045)., Conclusion: A small PV confluence width is associated with the development of postoperative PVS and recurrent stenosis after surgical relief of PVS. Our results suggest that adequate bilateral pulmonary vein lateralization during TAPVC surgery is crucial., Competing Interests: Declaration of competing interest All the authors reported no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Objective To explore the effects of iron overload on neutrophil function and peritonitis, as well as the possible mechanisms. Methods C57BL/6 mice were randomly divided into a control group and an iron overload group (10 mice in each group). Acute peritonitis model was induced by intraperitoneal injection of E.coli. The iron deposition in liver and spleen was assessed using H&E staining and the iron level in neutrophils was quantified by colorimetric analysis. The proportion and morphology of neutrophils were evaluated by blood cell counting plate and MGG staining, and the cellular aging of neutrophils was determined by senescence-associated β-galactosidase (SA-β-Gal) staining. The protein expression levels of P16 in neutrophils was detected using Western blot analysis and the bactericidal function of neutrophils was detected by LB smears. The mitochondrial membrane potential and mitochondrial function of neutrophils were detected by JC-1 staining and ATP kit, respectively. Results Compared with the control group, mice in the iron overload group exhibited following effects, including significantly higher iron content in the liver and spleen, a shorter survival time, significantly reduced bactericidal ability of neutrophil with no significant differences in the quantity or morphology, aggravated aging in neutrophils (indicated by increased expression of P16 and a higher number of SA-β-Gal positive cells), and decreased mitochondrial membrane potential and ATP levels. Conclusion Iron overload aggravates peritonitis by reducing the bactericidal ability of neutrophils.

To date, computed tomography experiments, carried-out at synchrotron radiation facilities worldwide, pose a tremendous challenge in terms of the breadth and complexity of the experimental datasets produced. Furthermore, near real-time three-dimensional reconstruction capabilities are becoming a crucial requirement in order to perform high-quality and result-informed synchrotron imaging experiments, where a large amount of data is collected and processed within a short time window. To address these challenges, we have developed and deployed a synchrotron computed tomography framework designed to automatically process online the experimental data from the synchrotron imaging beamlines, while leveraging the high-performance computing cluster capabilities to accelerate the real-time feedback to the users on their experimental results. We have, further, integrated it within a modern unified national authentication and data management framework, which we have developed and deployed, spanning the entire data lifecycle of a large-scale scientific facility. In this study, the overall architecture, functional modules and workflow design of our synchrotron computed tomography framework are presented in detail. Moreover, the successful integration of the imaging beamlines at the Shanghai Synchrotron Radiation Facility into our scientific computing framework is also detailed, which, ultimately, resulted in accelerating and fully automating their entire data processing pipelines. In fact, when compared with the original three-dimensional tomography reconstruction approaches, the implementation of our synchrotron computed tomography framework led to an acceleration in the experimental data processing capabilities, while maintaining a high level of integration with all the beamline processing software and systems., (open access.)

Graphene-based nanomaterials have attracted significant attention for their potentials in biomedical and biotechnology applications in recent years, owing to the outstanding physical and chemical properties. However, the interaction mechanism and impact on biological activity of macro/micro biomolecules still require more concerns and further research in order to enhance their applicability in biosensors, etc. Herein, an integrated method has been developed to predict the protein bioactivity performance when interacting with nanomaterials for protein-based biosensor. Molecular dynamics simulation and molecular docking technique were consolidated to investigate several nanomaterials: C60 fullerene, single-walled carbon nanotube, pristine graphene and graphene oxide, and their effect when interacting with protein. The adsorption behavior, secondary structure changes and protein bioactivity changes were simulated, and the results of protein activity simulation were verified in combination with atomic force spectrum, circular dichroism spectrum fluorescence and electrochemical experiments. The best quantification alignment between bioactivity obtained by simulation and experiment measurements was further explored. The two proteins, RNase A and Exonuclease III, were regarded as analysis model for the proof of concept, and the prediction accuracy of protein bioactivity could reach up to 0.98. The study shows an easy-to-operate and systematic approach to predict the effects of graphene-based nanomaterials on protein bioactivity, which holds guiding significance for the design of protein-related biosensors. In addition, the proposed prediction model is not limited to carbon-based nanomaterials and can be extended to other types of nanomaterials. This facilitates the rapid, simple, and low-cost selection of efficient and biosafe nanomaterials candidates for protein-related applications in biosensing and biomedical systems., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Diming Zhang reports financial support was provided by Natural Science Foundation of Zhejiang Province. Xiaoyu Zhao reports financial support was provided by National Natural Science Foundation of China. Xiaoyu Zhao reports financial support was provided by Fundamental Research Funds for the Provincial Universities of Zhejiang. Xiaoyu Zhao reports financial support was provided by National Natural Science Youth Foundation. Diming Zhang reports a relationship with Natural Science Foundation of Zhejiang Province that includes: funding grants. Xiaoyu Zhao reports a relationship with National Natural Science Foundation of China that includes: funding grants. Xiaoyu Zhao reports a relationship with Fundamental Research Funds for the Provincial Universities of Zhejiang that includes: funding grants. Xiaoyu Zhao reports a relationship with National Natural Science Youth Foundation that includes: funding grants. If there are other authors, they 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.)

Microplastics (MPs), discovered in oceans, lakes, and rivers, can infiltrate the food chain through ingestion by organisms, potentially posing health risks. Our research is the first to study the composition and distribution of MPs in Bosten Lake's sediment. In May, the average abundance of MPs was 0.95±0.72 particles per 10 gs, and in October, it was 0.90±0.61 particles per 10 gs. Bohu Town had the highest MP abundance, with 1.75±0.35 particles per 10 gs in spring and 2 ± 0 particles per 10 gs in autumn. In May, 53 % of the MPs were transparent, while in October, black MPs constituted 58 %. The predominant morphology was fibrous, accounting for 61 % of the total. MPs in the size range of 0.2-1 mm made up 91 % and 66 % of the total in May and October, respectively. The most common types of MPs in May were polyethylene terephthalate (PET) at 40 % and polyethylene (PE) at 26 %. In October, PET was the most prevalent at 71 %, followed by poly(ether-ether-ketone)(PEEK) at 11 %. Certain microbial taxa, such as Actinobacteriota, Pseudomonas, and Vicinamibacteraceae, associated with MP degradation or complex carbon chain breakdown, were notably enriched in sediment areas with high MP concentrations. A significant positive correlation was observed between the abundance of MPs in sediments and Actinobacteriota. Additionally, the abundance of Thiobacillus, Ca.competibacter, and other bacteria involved in soil element cycling showed a significant positive correlation with the organic matter content in the sediments. Anaerobic bacteria like Thermoanaerobacterium displayed a significant positive correlation with water depth. Our study reveals the presence, composition, and distribution of MPs in Bosten Lake's sediments, shedding light on their potential ecological impact., 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 Ltd.)

The neuronal excitotoxicity that follows reoxygenation after a hypoxic period may contribute to epilepsy, Alzheimer's disease, Parkinson's disease and various disorders that are related to inadequate supplement of oxygen in neurons. Therefore, counteracting the deleterious effects of post-hypoxic stress is an interesting strategy to treat a large spectrum of neurodegenerative diseases. Here, we show that the expression of the key telomere protecting protein Trf2 decreases in the brain of mice submitted to a post-hypoxic stress. Moreover, downregulating the expression of Terf2 in hippocampal neural cells of unchallenged mice triggers an excitotoxicity-like phenotype including glutamate overexpression and behavioral alterations while overexpressing Terf2 in hippocampal neural cells of mice subjected to a post-hypoxic treatment prevents brain damages. Moreover, Terf2 overexpression in culture neurons counteracts the oxidative stress triggered by glutamate. Finally, we provide evidence that the effect of Terf2 downregulation on excitotoxicity involves Sirt3 repression leading to mitochondrial dysfunction. We propose that increasing the level of Terf2 expression is a potential strategy to reduce post-hypoxic stress damages., 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.)

In this study, a sustainable and environmentally friendly method was developed for the enrichment and purification of phycocyanin from Spirulina platensis. This was achieved by utilizing a temperature-sensitive polymer, Pluronic F68, in an aqueous two-phase solvent system. The phase behavior of the temperature-sensitive polymer-based biphasic system was evaluated. The extraction conditions were optimized by both single-factor experiments and response surface methodology. Under the optimal conditions, the upper polymer-rich phase was recycled for sustainable phycocyanin extraction, resulting in a grade of 3.23 during the third extraction cycle. Pluronic F68 could be efficiently recovered and reused during the extraction process. The interaction mechanism between Pluronic F68 and phycocyanin was systematically studied using FT-IR and fluorescence analysis. This was further complemented by static and dynamic calculation of molecular motion through molecular docking and molecular dynamics simulation, indicating that hydrophobic segment of Pluronic F68 played a key role in the binding process with phycocyanin., 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 Ltd. All rights reserved.)

Background: MicroRNA (miRNA) has gradually become an emerging biomarker for early diagnosis and prognosis of various diseases due to its specific gene expression and high stability. With the development of molecular diagnosis and point-of-care testing (POCT) technology, developing simple, fast, sensitive, efficient, and low-cost miRNA sensors is of great significance for clinical applications and emergency rapid diagnosis. At present, entropy-driven toehold mediated chain displacement reaction, as a promising enzyme free isothermal amplification technique, is an important tool for ultra-sensitive biosensing applications., Results: In this study, we used gold nanoparticles (AuNPs) as carriers and quenchers, modified them using self-assembled triple chain composite substrates AuNPs@A@B1/B2, and used dual reporter molecules for cascade cyclic amplification to amplify fluorescence signals, which proposed a fluorescent biosensor based on this reaction and build an intelligent fluorescence sensing platform for rapid detection of miRNA. We designed a highly specific self-programmable sensor using the acute ischemic stroke (AIS) biomarker miRNA-125a-5p as a sample, and achieved sensitive detection of miRNA in the range of 0.01 μM∼10 μ M under optimal conditions. It broke through the traditional detection limitations of weak signals and liberated the fluorescence detection environment., Significance: In summary, this creative miRNA biosensor combined with POCT has demonstrated extraordinary detection potential, broad application prospects in the early diagnosis and prognosis monitoring of AIS, provides a novel miRNA universal detection strategy for the fields of biological and life sciences., 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.)