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Background: Hypertrophic cardiomyopathy (HCM) is typically manifested as a hereditary disorder, with 30 %-60 % of cases linked to cardiac sarcomere gene mutations. Despite numerous identified TNNI3 mutations associated with HCM, their severity, prevalence, and disease progression vary. The link between TNNI3 variants and phenotypes remains largely unexplored. This study aims to elucidate the impact of the TNNI3 c.235C > T mutation on HCM through clinical research and cell experiments and to explore its mechanism in HCM development., Methods: We screened an HCM family for pathogenic gene mutations using gene sequencing. The proband and family members were assessed through electrocardiography, echocardiography, and cardiac MRI, and a pedigree map was created for disease prediction analysis. Mutant plasmids were constructed with the TNNI3 c.235C > T mutation and transfected into the AC16 human cardiomyocyte cell line to investigate the mutation's effects., Results: The TNNI3 c.235C > T mutation was identified as the disease-causing variant in the family. This mutation led to the upregulation of hypertrophy-associated genes ANP, BNP, and MYH7, increased cardiomyocyte size, and activation of the ERK signaling pathway. Further investigations revealed that the TNNI3 c.235C > T mutation impaired mitochondrial function, disrupted cardiomyocyte metabolism, and increased cellular autophagy and apoptosis., Conclusions: The TNNI3 c.235C > T gene mutation may be a pathogenic factor for HCM, showing heterogeneous features and clinical phenotypes. This mutation induces myocardial hypertrophy, activates the ERK signaling pathway, and exacerbates mitochondrial dysfunction, apoptosis, and autophagy in cardiomyocytes. These findings provide insights into the mechanism of HCM caused by gene mutations and may inform HCM treatment strategies., Competing Interests: Declaration of competing interest The authors reported no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The chemical instability of traditional organically-decorated superhydrophobic metal surfaces is a significant issue, severely limiting practical applications. This is due to the susceptibility of low surface energy coatings to ion permeation, decomposition, and exfoliation, especially in harsh environments. Here, organic coating-free, durable superhydrophobic surfaces on Al alloys by developing the paracrystalline state of a bionic anthill tribe structure is successfully achieved, using femtosecond laser element-doping microstructuring followed by repetitive annealing processes. Remarkably, the inherent superhydrophobic properties of the sample are maintained for ≈2000 h in a corrosive 3.5 wt.% NaCl aqueous solution, significantly surpassing the performance of traditional organic coatings. Moreover, this inherent superhydrophobicity remains nearly unchanged, even after rigorous electrochemical reaction measurements. Additional tests involving UV irradiation (>100 h), freezing cycles (>100 cycles), and acid/alkali resistance (>65 h) further demonstrate that the environmental adaptability of the surface far exceeds that of silane-coated surfaces. Ab initio calculations reveal that the formation of the paracrystalline state reduces surface energy and enhances chemical stability, thereby extending the durability of the superhydrophobic metal. These findings offer a powerful strategy for utilizing atomic-level structural rearrangements to design inherent superhydrophobic surfaces without the need for organic coatings., (© 2024 Wiley‐VCH GmbH.)

Co-delivering multiple drugs or circumventing the drug efflux mechanism can significantly decrease multidrug resistance (MDR), a major cause of cancer treatment failure. In this study, we designed and fabricated a universal "three-in-one" self-delivery system for synergistic cancer therapy using a computer-aided strategy. First, we engineered two glutathione (GSH)-responsive heterodimers, ERL-SS-CPT (erlotinib [ERL] linked with camptothecin [CPT] via a disulfide bond [SS]) and CPT-SS-ERI (CPT conjugated with erianin [ERI]), which serve as both cargo and carrier material. Next, molecular dynamics simulations indicated that multiple noncovalent molecular forces, including π-π stacking, hydrogen bonds, hydrophobic interactions, and sulfur bonds, drive the self-assembly process of these heterodimers. We then explored the universality of the heterodimers and developed a "triadic" drug delivery platform comprising 40 variants. Subsequently, we conducted case studies on docetaxel (DTX)-loaded ERL-SS-CPT nanoparticles (denoted as DTX@ERL-SS-CPT NPs) and curcumin (CUR)-loaded ERL-SS-CPT NPs (identified as CUR@CPT-SS-ERI NPs) to comprehensively investigate their self-assembly mechanism, physicochemical properties, storage stability, GSH-responsive drug release, cellular uptake, apoptosis effects, biocompatibility, and cytotoxicity. Both NPs exhibited well-defined spherical structures, high drug loading rates, and excellent storage stability. DTX@ERL-SS-CPT NPs exhibited the strongest cytotoxicity in A549 cells, following the order of DTX@ERL-SS-CPT NPs > ERL-SS-CPT NPs > CPT > DTX > ERL. Conversely, DTX@ERL-SS-CPT NPs showed negligible cytotoxicity in normal human bronchial epithelium cell line (BEAS-2B), indicating good biocompatibility and safety. Similar observations were made for CUR@CPT-SS-ERI NPs regarding biocompatibility and cytotoxicity. Upon endocytosis and encountering intracellular overexpressed GSH, the disulfide-bond linker is cleaved, resulting in the release of the versatile NPs into three parts. The spherical NPs enhance water solubility, reduce the required dosage of free drugs, and increase cellular drug accumulation while suppressing P-glycoprotein (P-gp) expression, leading to apoptosis. This work provides a computer-aided universal strategy-a heterodimer-based "triadic" drug delivery platform-to enhance anticancer efficiency while reducing multidrug resistance., 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.)

Microbial fermentation is an effective method to improve the functional activity of oats (Avena sativa L.), while there are some limitations to the advantages of single microbial fermentation. In this study, a microbial co-culture fermentation system with Monascus anka, Saccharomyces cerevisiae and Bacillus subtilis to release and conversion oat phenolics was established. Results showed that the optimal microbial co-fermentation system was obtained by adding Saccharomyces cerevisiae on the fourth day and Bacillus subtilis on the eighth day during Monascus anka fermentation (MF + 4S + 8B). The phenolic content was reached 26.93 mg GAE/g DW, which increased 41.08 times compared to un-fermented oats (UF). In the process of co-fermentation systems, cellulase and β-glucosidase (r 2  = 0.97, p < 0.01) had a positive correlation with the release of phenolics. SEM combined with HPLC showed that the complex enzyme system produced by microbial co-fermentation enhanced the disruption of oat cell structure, as well as altered the phenolics fractions and facilitated the conversion of bound phenolics to free phenolics, especially the content of chlorogenic acid and vanillic acid in the free forms was increased 31.42 and 14.15 times, respectively. Additionally, the phenolic contents were increased and the components were changed with the microbial co-fermentation of crude enzyme solution further added, which validated the positive influence of complex enzyme system of MF + 4S + 8B in the phenolic release and transformation of oats. Therefore, this study systematically investigated the phenolic mobilization in oats during the co-fermentation period, which provides a viable option for improving the functional properties of cereal products, as well as the application of microbial cell factories., Competing Interests: Declarations. Conflicts of interest: The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hepatocellular carcinoma (HCC) is a serious health issue due to its low early diagnosis rate, resistance to chemotherapy, and poor five-year survival rate. Therefore, it is crucial to explore novel diagnostic and therapeutic approaches tailored to the characteristics of HCC. Aggregation-induced emission (AIE) is a phenomenon where the luminescence of certain molecules, typically non-luminescent or weakly luminescent in solution, is significantly enhanced upon aggregation. AIE has been extensively applied in bioimaging, biosensors, and therapy. Fluorophore materials based on AIE (AIEgens) have a wide range of application scenarios and potential for clinical translation. This review focuses on recent advances in AIE-based strategies for diagnosing and treating HCC. First, the specific functional mechanism of AIE is described. Next, we summarize recent progress in the application of AIE for multimodal imaging, biosensor detection, and phototherapy. Finally, prospects and challenges for the AIE-based application in the diagnosis and therapy of HCC are discussed., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

RNA interference (RNAi) is an evolutionarily conserved pathway that defends against viral infections in diverse organisms. Caenorhabditis elegans mutations that enhance RNAi have revealed pathways that may regulate antiviral defense. A genetic screen for C. elegans mutations that fail to up-regulate a defense response reporter transgene detected mutations that enhance RNAi to silence this reporter gene in the inositol polyphosphate multikinase impk-1 , the synMuv B gene lin-15B, and the pathogen defense response gene pals-22 . Using other assays for enhanced RNAi, we found that the impk-1 alleles and an ippk-1 gene inactivation of a later step in inositol hexaphosphate (IP 6 ) synthesis, and the lin-15B and pals-22 alleles enhance RNAi. IP 6 has been known for decades to bind and stabilize human adenosine deaminase that acts on RNA (ADAR) as well as the paralog tRNA editing ADAT. We show that the C. elegans IP 6 pathway is also required for mRNA and tRNA editing. Thus, a deficiency in two axes of RNA editing enhances the already potent C. elegans RNAi antiviral defense, suggesting adenosine to inosine RNA editing may normally moderate this siRNA antiviral defense pathway. The C. elegans IP 6 -deficient mutants are synthetic lethal with a set of enhanced RNAi mutants that act in the polyploid hypodermis to regulate collagen secretion and signaling from that tissue, implicating IP 6 signaling especially in this tissue. This enhanced antiviral RNAi response uses the C. elegans RIG-I-like receptor DRH-1 to activate the unfolded protein response (UPR). The production of primary siRNAs, rather than secondary siRNAs, contributes to this activation of the UPR through XBP-1 signaling. The gon-14 and pal-17 mutants that also emerged from this screen act in the mitochondrial defense pathway rather than by enhancing RNAi., Competing Interests: Competing interests statement:The authors declare no competing interest.

Klebsiella pneumoniae (KP) is a zoonotic conditionally pathogenic bacterium with a high prevalence of infection. It often induces purulent inflammation of the rabbit lungs, kidneys and other tissues, with high morbidity and mortality. Bacillus coagulans (BC) has the ability to regulate the balance of host intestinal flora and improve host immunity. However, the mechanism of the protective effect of BC on KP-induced kidney injury in rabbits is not clear. To explore this, we randomly divided fifty 35-day-old Eyplus rabbits into five groups: control, KP, low-dose BC (LBC), medium-dose BC (MBC) and high-dose BC (HBC). On the 1st day of the experiment, rabbits in LBC, MBC and HBC groups were fed diets containing 1 × 10 6 CFU/g, 5 × 10 6 CFU/g and 1 × 10 7 CFU/g BC, respectively, and rabbits in CK and KP groups were fed basal diets. On the 8th day, each rabbit in the KP, LBC, MBC and HBC groups was infused with 4 mL of 1 × 10 11  CFU/mL KP bacterial solution, and the CK group was infused with the same amount of sterilised saline for a total of 7 days. Rabbit kidney tissues were collected on the 15th d. HE staining was used to observe the pathological changes of rabbit kidney tissues, oxidative stress-related indexes were detected by biochemical kits, and the content of inflammatory factors and apoptosis-related factors in kidney tissues were detected by ELISA. The results showed that KP disrupts the normal structure of the kidney, induces oxidative stress and inflammatory responses, and mediates apoptosis by regulating the levels of Bcl-2 family proteins. BC pretreatment significantly reduced kidney structural damage, oxidative stress, inflammatory response, and apoptosis in rabbits. To alleviate KP-induced kidney injury by increasing the activity of antioxidant enzymes and the content of anti-apoptotic proteins. Compared with the LBC group and the HBC group, the remission effect was more pronounced in the MBC group. Therefore, in this study, the effect of 5 × 10 6 CFU/g BC was more significant., 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.)

Objectives: To analyse the prognostic factors for visual acuity in acute retinal necrosis (ARN) patients treated non-surgically., Methods: The clinical data of ARN patients who visited our hospital from January 2010 to January 2023 were retrospectively analysed., Results: Twenty-four patients (29 eyes) were included. Aqueous humour samples were collected from 20 out of 29 eyes, and PCR confirmed that 85% (17/20) of the eyes had VZV infection, 10% (2/20) had CMV infection, and 5% (1/20) had HSV infection. All patients were treated with intravenous antiviral agents. Intravitreal ganciclovir and oral corticosteroids were given according to the patients' wishes. A comparison of visual acuity at the time of first identification of inactive ARN with that at the first visit revealed that 16 (55.2%) eyes improved and 13 (44.8%) did not improve. Logistic regression analysis revealed that risk factors for failure to improve vision after treatment included retinal detachment (odds ratio [OR],33.75; 95% CI, 3.245-351.067; P = 0.003), necrotising retinitis involving the posterior pole (odds ratio [OR],8.167; 95% CI, 1.297-51.403, P = 0.025), and arteritis involving the large retinal arteries (odds ratio [OR],9.167; 95% CI, 1.493-56.297; P = 0.017). The VZV viral load in the aqueous humour at initial presentation was significantly associated with visual prognosis (r = 0.688, P = 0.013), retinal detachment (τ = 0.597, P = 0.021) and the extent of retinal necrosis (τ = 0.57, P = 0.027). The neutrophil to lymphocyte ratio (NLR) of VZV-infected patients at first presentation was significantly correlated with the prognosis of visual acuity (r = 0.616, P = 0.033) and retinal detachment (τ = 0.728, P = 0.004)., Conclusions: High NLR and viral DNA copy number in the aqueous humour at the initial presentation, as well as subsequent retinal detachment, necrotising retinitis involving the posterior pole, and arteritis involving the large retinal arteries were risk factors for poor visual prognosis in VZV-infected ARN patients., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objectives: This study aimed to determine the genetic environment and characterize plasmid carrying a novel VIM-type β-lactamase (VIM-84) in a multidrug-resistant Pseudomonas monteilii (P. monteilii) isolate obtained from the human gut through whole-genome sequencing., Methods: DNA extraction of P. monteilii L2757hy was performed using the Genomic DNA Isolation Kit (QIAGEN, Hilden, Germany). Whole-genome sequencing was performed by Illumina NovaSeq 6000 and Oxford Nanopore platforms. The transferability of resistance genes was screened as single clonal on Mueller Hinton Agar (MHA) plates containing rifampicin and meropenem. Verification was performed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI/TOF-MS) and polymerase chain reaction (PCR) with Pseudomonas aeruginosa PAO1Ri as the recipient strain., Results: L2757hy was identified as P. monteilii through sequencing and average nucleotide identity (ANI) analysis. The genome was assigned as ST147 and comprised a 6, 130, 057 bp chromosome with a GC content of 61.8% and a 49, 704 bp plasmid. Several resistance genes, including bla IMP-1 , aac(6')-IIa and tmexCD-toprJ, as well as virulence genes, such as iroN and wzaJ, were identified on the chromosome. A novel VIM-type bla VIM-84 was found on the plasmid, which was previously identified in Pseudomonas aeruginosa. Plasmid harboring bla VIM-84 was untypable, and it could be transferred to P. aeruginosa PAO1Ri and was associated with a class I integron with the genetic environment intI1-bla VIM-84 -tniR-tniQ-tniB-tniA, likely derived from Tn402., Conclusions: Our study revealed that the novel bla VIM-84 gene was harbored by P. monteilii rather than P. aeruginosa. We suggested that P. monteilii may serve as a reservoir for resistance genes. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy., Competing Interests: Competing interests The authors report no conflicts of interest in this work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Heavy metal pollution causes irreversible damage to plants, animals, and humans. Therefore, it is meaningful to develop facile, fast, and efficient strategies for heavy metal ion (HMI) detection. Here, a portable composite film (CPSE) was designed for HMI detection with high sensitivity and wide detection range. The CPSE was prepared by using cellulose nanofibers (CNF)/polyvinyl alcohol (PVA) as the matrix and utilizing modified starch (HPS) to assist disodium calcium ethylenediaminetetraacetate (EDTA-Ca) to form stable complexes with HMI. The R, G and B values (the three primary colors of light) were captured using an image acquisition system to produce an HMI standard color card successfully. Specifically, the composite film can effectively distinguish Cu 2+ , Pb 2+ and Fe 3+ . The response time of the composite film to HMI was 2-4 s, and the detection ranges of Cu 2+ and Fe 3+ were 5-700 ppm and 10-1000 ppm, respectively. Additionally, the synergistic effect of HPS and EDTA-Ca led to the increase in tensile strength (1.59-1.71 times), tear strength (3.29-3.57 times), and glass transition temperature (~ 6 °C) compared to CNF/PVA/HPS and CNF/PVA/EDTA-Ca films. This study confirms the value of CPSE films as materials for HMI detection and suggests innovative ideas for designing similar biomass detection materials in the future., 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.)

Background: Several blood proteins might be associated with the development of colorectal cancer (CRC), but many studies on this topic are often biased. By using genetic variation data, which is less influenced by environmental factors, we can better determine the causal relationship between specific blood proteins and the occurrence of colorectal cancer., Methods: Data from a genome-wide association study (GWAS) on blood proteins, encompassing 1,478 proteins, and colorectal cancer (CRC) GWAS data, covering 637,693 subjects, were collected and organized. Additionally, GWAS data for obesity, diabetes mellitus (DM), and smoking were obtained for further analysis. Single nucleotide polymorphisms (SNPs) significantly associated with the exposure factors (blood proteins) were selected to ensure their independence from other confounding factors and outcomes (CRC onset), and that they only affected outcomes through blood proteins. The causal effects of Mendelian Randomization (MR) were primarily estimated using the inverse variance weighted (IVW) method, with other methods serving as supplementary approaches. The Cochran's Q-test assessed heterogeneity among SNP estimates; the MR Egger method evaluated pleiotropy; and the leave-one-out test examined the sensitivity of individual SNPs. Obesity, DM, and smoking were included in the multivariate MR analysis., Result: A total of 31 SNPs and 8 blood protein exposure factors were identified, specifically TNFRSF16 (4 SNPs), RNF8 (4 SNPs), MRM3 (4 SNPs), ST6GALNAC1 (4 SNPs), TIE1 (4 SNPs), CBP (4 SNPs), DNAJB9 (4 SNPs), and EDN2 (3 SNPs). The IVW results showed a significant causal relationship between all 8 exposure factors and colorectal cancer (P < 0.05). Among these, TNFRSF16, TIE1, and EDN2 were identified as risk factors, while the remaining five served as protective factors. The causal inference in this study was not influenced by pleiotropy or environmental factors such as obesity, diabetes, and smoking. Therefore, the results were both stable and reliable., Conclusion: Eight blood proteins (or genes) have been identified as having a causal relationship with the onset of colorectal cancer, suggesting their potential use as screening biomarkers and treatment targets., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Informed consent: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Cell analysis is crucial to contemporary biomedical research, as it plays a pivotal role in elucidating life processes and advancing disease diagnosis and treatment. Raman spectroscopy, harnessing distinctive molecular vibrational data, provides a non-destructive method for cell analysis. This review surveys the progress of Raman spectroscopy in cellular analysis, emphasizing its utility in identifying individual cells, monitoring biomolecules, and assessing intracellular environments. A significant focus is placed on the novel application of triple-bond molecules as Raman tags, which enhance imaging capabilities by creating a distinctive signature with minimal background noise. The summary of Raman spectroscopy studies provides a forward-looking perspective on its applications., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Persons with physical disabilities are more likely to suffer from psychological symptoms and inferiority feelings, and social support plays an important role in improving those symptoms. However, the interaction between psychological symptoms, inferiority feelings and social support is yet to be understood., Methods: A cross-sectional study was conducted to investigate anxiety, depression, and inferiority feelings among individuals with physical disabilities in a Chinese sample. The questionnaire included the Generalized Anxiety Disorder 7, Patient Health Questionnaire 9, Self-designed Disability Questionnaire, and Social Support Rating Scale including three dimensions: subjective social support, objective social support and utilization of social support., Results: Out of the 1,453 respondents with physical disabilities, 49.7, 60.4, and 62.5% reported experiencing anxiety, depression, and inferiority feelings, respectively. Factors such as time since identification of physical disabilities, comorbidities, daily travel, social interaction, internet use, subjective social support, and inferiority feelings were found to be associated with anxiety or depression symptoms among physically disabled individuals. Subjective social support was found to be associated with inferiority feelings, which partly mediated the effect of subjective social support on anxiety symptoms by 37.4% and depression symptoms by 28.7%., Conclusion: This study highlights the importance of addressing the psychological well-being of physically disabled individuals in addition to their physical rehabilitation. Psychological intervention strategies should focus on improving subjective social support and reducing inferiority feelings, particularly among vulnerable groups., 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 Liu, Xu, Liu, Song, Li, Li and Chen.)

Introduction: Groundcover management plays a crucial role in improving water retention and soil nutrition in orchard systems, thereby preventing environmental constrains by non-point source pollution. However, effectiveness of groundcover management in citrus orchards developed on sloping farmland with eroded purple soil has not been studied in detail. In particular, information on the soil nutrient losses, e.g. , nitrogen (N) and phosphorus (P), through interflow and its effects on growth and nutrition of citrus plants has not been reported., Methods: The present study evaluated the effects of different cover crops, i.e. , Lolium perenne L. (Lolium), Vicia villosa Roth (Vicia) and Orychophragmus violaceus (Ory), on nutrition and growth of citrus trees as well as water, soil and nutrient retention in an orchard developed in sloping farmland during two consecutive years., Results and Discussion: The results show that the groundcover species Lolium and Vicia mediated nursing effects on nutrition and growth of citrus trees. These nursing effects included enhanced foliar levels of carbon(C), N and P as well as increased tree height, stem diameter, and crown width. Groundcover management generally reduced the annual surface runoff, interflow, soil loss, total N loss and total P loss. Among the cover crop species studied, Lolium and Vicia were overall more efficient than Ory in this context. Lolium reduced the average annual total loss of N and P by 42.53% and 49.23%, respectively, compared with clean tillage. The estimated annual reduction potentials of soil, N and P losses in Southwestern China were 16.3, 3.4 and 8.5 million tons yr -1 , respectively. Obviously, Lolium and Vicia provide highly beneficial ground coverage on sloping farmland and, thus, can be used for future sustainable development of citrus orchards., 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 Liu, Zhang, Wang, Zhang, Xu, Zhang, Zhang, Hu, Shi and Rennenberg.)

Background: At present, the severity and grade of anterior scleritis are judged mainly based on the area and location of involvement, whether there is necrosis, etc. Quantitative measurement of sclera and surrounding tissues will help to accurately assess the severity of scleritis and provide quantitative indicators for the choice of treatment., Methods: We retrospectively analyzed the thickness of sclera and ciliary bodies detected by ultrasound biological microscopy (UBM) in noninfectious anterior scleritis patients who subsequently were treated with topical or systemic treatment, and visited our hospital from March 2014 to March 2021. Age- and sex-matched normal individuals were used as controls., Results: A total of 185 patients (50 males and 135 females) with noninfectious anterior scleritis and 84 (31 males and 53 females) controls were included. In patients with noninfectious scleritis, the thickness of sclera and the ciliary body were significantly greater than those in the control group ( p  < 0.05). Before treatment, the thickness of sclera and the ciliary body in systemic treatment group was significantly higher than that in topical treatment group ( p  < 0.05). After treatment, both thicknesses of sclera and the ciliary body decreased significantly ( p  < 0.05). The ratio of ciliary body thickness from the site of inflammation to the normal position was significantly higher in the systemic treatment group than in the topical treatment group., Conclusions: UBM quantitatively shows a decrease in AST/CBT in patients with anterior scleritis after treatment. The ratio of ciliary body thickness at the site of information to that at the normal position may be a reference for the choice of treatment.

The morphology of the active layer is crucial for highly efficient organic solar cells (OSCs), which can be regulated by selecting a rational third component. In this work, the highly crystalline nonfullerene acceptor BTP-eC9 is selected as the morphology regulator in OSCs with PM6:BTP-BO-4Cl as the main system. The addition of BTP-eC9 can prolong the nucleation and crystallization progress of acceptor and donor molecules, thereby enhancing the order of molecular arrangement. Meanwhile, the nucleation and crystallization time of the donor is earlier than that of the acceptors after introducing BTP-eC9, which is beneficial for obtaining a better vertical structural phase separation. The exciton dissociation, charge transport, and charge collection are promoted effectively by the optimized morphology of the active layer, which improves the short-circuit current density and filling factor. After introducing BTP-eC9, the power conversion efficiencies (PCEs) of the ternary OSCs are improved from 17.31% to 18.15%. The PCE is further improved to 18.39% by introducing gold nanopyramid (Au NBPs) into the hole transport layer to improve photon utilization efficiency. This work indicates that the morphology can be optimized by selecting a highly crystalline third component to regulate the nucleation and crystallization progress of the acceptor and donor molecules., (© 2024 Wiley‐VCH GmbH.)

Background: Obesity is a well-known risk factor for developing malignant tumors and promoting tumor cell growth and spread. However, recent studies have shown that obese cancer patients, who typically have a worse prognosis than nonobese cancer patients, show a significant improvement in survival after receiving immune checkpoint inhibitor (ICI) therapy. This phenomenon is known as the "obesity paradox". However, this phenomenon is influenced by tumor type and sex. Therefore, this study aimed to explore the impact of obesity on immunotherapy efficacy from multiple perspectives, aiming to verify this paradox and provide new scientific evidence on the effect of obesity on ICI efficacy., Methods: This retrospective study evaluated the data of patients who received ICI therapy between June 2019 and August 2023. Automatic segmentation of skeletal muscle, subcutaneous fat, and visceral fat was performed using Slice-O-Matic software, and the corresponding skeletal muscle index (SMI), subcutaneous fat index (SFI) and visceral fat index (VFI) were calculated. The neutrophil-to-lymphocyte ratio (NLR) was determined by dividing the neutrophil count by the lymphocyte count. Univariate and multivariate Cox regression analyses were used to evaluate the correlation between body mass index (BMI), body composition parameters, and the NLR with overall survival (OS) and progression-free survival (PFS) in obese patients receiving ICI therapy., Results: We analyzed 219 patients with a median age of 60 years (IQR 53-69 years; 155 men and 64 women). Obese patients, particularly those with visceral fat accumulation, exhibited extended OS after ICI therapy (log-rank P = 0.027). Cox multivariate analysis revealed that the NLR (HR = 1.036; 95% CI: 0.996 to 1.078; P = 0.002) was independently associated with OS. Patients with a high NLR had worse OS than those with a low NLR., Conclusions: This study corroborates the veracity of the "obesity paradox" under specific conditions and identifies NLR as an independent prognostic factor, with elevated NLR indicative of a poor prognosis., (© 2024. The Author(s).)

High-entropy alloy (HEA) electrocatalysts have exhibited remarkable catalytic performance because of their synergistic interactions among multiple metals. However, the growth mechanism of HEAs remains elusive, primarily due to the constraints imposed by the current synthesis methodologies for HEAs. In this work, an innovative electrodeposition method was developed to fabricate Pt-based nanocomposites (Pt 1 Bi 2 Co 1 Cu 1 Ni 1 /CC), comprising HEA nanosheets and carbon cloths (CCs). The reaction system could be effectively monitored by taking samples out from the system during the reaction process, facilitating in-depth insight into the growth mechanism underlying the material formation. In particular, Pt 1 Bi 2 Co 1 Cu 1 Ni 1 /CC nanocomposites show superior methanol oxidation reaction (MOR) performance (mass activity up to 5.02 A mg Pt -1 ). Upon structural analysis, the d-band center of Pt 1 Bi 2 Co 1 Cu 1 Ni 1 /CC is lower in comparison with that of Pt 1 Bi 2 /CC and Pt/CC, demonstrating the formation of a rich-electron structure. Both the uniformity of HEAs and the carbon-supported effect could provide additional active sites. These findings suggest that the strong electronic interaction within HEAs and additional active sites can effectively modulate the catalytic structure of Pt, which benefits the enhanced CO tolerance and MOR performance.

It is urgent to develop new therapeutic strategies for ovarian cancer (OC). Long-noncoding RNAs (lncRNAs) have participated in multiple biological processes including tumor recurrence and progression. This study aimed to determine the effects and potential regulatory mechanism of lncRNA FOXD2-AS1 in OC progression. Levels of lncRNA FOXD2-AS1 and miR-324-3p in OC tissues and cell lines were analyzed using quantitative real-time PCR (qRT-PCR). The direct target between FOXD2-AS1 or miR-324-3p was determined using bioinformatics tools and further verified by dual-luciferase reporter assay. Cell viability, apoptosis, migration, along invasion were assessed by MTT, flow cytometry, as well as Transwell assays, respectively. In addition, the levels of miR-324-3p, PCNA, MMP9, Bax, Bcl-2, and SOX4 in OC cells were evaluated using qRT-PCR and western blot assays. We observed that lncRNA FOXD2-AS1 was up-regulated while miR-324-3p was down-regulated in OC tissues and cell lines, especially in SKOV3 cells. Moreover, miR-324-3p was a direct target of lncRNA FOXD2-AS1. Meanwhile, SOX4 interacted with miR-324-3p and was negatively regulated by miR-324-3p in SKOV3 cells. Function assays confirmed that lncRNA FOXD2-AS1 silenced depressed cell proliferation, migration, and invasion while accelerating apoptosis. These functions of lncRNA FOXD2-AS1 were attenuated by miR-324-3p inhibition. Our research demonstrated that FOXD2-AS1 silencing restrained cell growth and metastasis of OC via regulating miR-324-3p/SOX4 axis, indicating that lncRNA FOXD2-AS1 could be a novel potential therapeutic target for OC., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Hyperuricemia (HUA), caused by purine disorders, can lead to gouty arthritis (GA). Kaempferol (KPF), a natural flavonoid, has anti-inflammatory properties, though its mechanism in treating HUA combined with GA remains unclear. This study used a mouse model of HUA combined with GA and in vitro models with HK-2 and THP-1 cells to explore KPF's effects. Cells were treated with KPF or inhibitors of ABCG2, ROS, NLRP3 inflammasome, and nuclear factor κB (NF-κB) pathway. Quantitative assays measured uric acid (UA), creatinine, oxidative stress biomarkers, and pro-inflammatory cytokines. Histopathological analyses showed KPF improved renal and joint inflammation caused by HUA and GA. KPF alleviated oxidative stress, reduced pro-inflammatory cytokines, and regulated UA levels through the modulation of urate transporters, NLRP3 inflammasome, and NF-κB pathway. KPF's actions, partly mediated by ROS reduction, suggest it is a promising candidate for treating HUA combined with GA., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Introduction: Water and salt conditions are key factors influencing vegetation growth on shell island in the Yellow River Delta. However, the effects of the depth of underground brine on the photosynthetic characteristics and antioxidant system of halophytes remain unclear., Methods: The laboratory simulation experiment was carried out to investigate the effect of the changes of underground brine depth on Suaeda salsa using four levels of groundwater: 0 cm, 15 cm, 30 cm and 45 cm., Results: The results showed that different underground brine depths had significant impacts on the photosynthetic characteristics and antioxidant system of S. salsa , and 0-30 cm underground brine depth was suitable for S. salsa growth. The net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), light utilization efficiency (LUE) and carboxylation efficiency (CE) of S. salsa increased first and then decreased with increasing depth of underground brine. The stomatal limitation value (Ls) and WUE of S. salsa reached the peak value at the groundwater depth of 0 cm, and water use efficiency was reduced by 19.4%, 8.0% and 8.6% at 15 cm, 30 cm, and 45 cm, respectively, compared to the 0 cm treatment. With the deepening of underground brine depth, the value of LUE and CE firstly increased and then decreased, and reached the peak value when the depth was 30 cm. The antioxidant enzyme (SOD, POD and CAT) activities of S. salsa decreased and then increased with the increase of underground brine depth. The enzyme activities were the lowest when the underground brine depth was 30 cm. As the groundwater depth increased, MDA content decreased and then increased. The highest degree of membrane peroxidation in S. salsa leaves was observed at the depth of 45 cm., Discussion: Our study reveals that the antioxidant capacity of S. salsa was weakened at the underground brine depth of 45 cm and the growth of S. salsa was inhibited., 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 Wang, Xu, Zhang, Fu, Li and Sun.)

Zearalenone (ZEA) is a mycotoxin produced by Fusarium spp. fungi and is widely found in moldy corn, wheat, barley, and other grains. ZEA is distributed to the whole body via blood circulation after metabolic transformation in animals. Through oxidative stress, immunosuppression, apoptosis, autophagy, and mitochondrial dysfunction, ZEA leads to hepatitis, neurodegenerative diseases, cancer, abortion, and stillbirth in female animals, and decreased sperm motility in male animals. In recent years, due to the influence of climate, storage facilities, and other factors, the problem of ZEA pollution in global food crops has become particularly prominent, resulting in serious problems for the animal husbandry and feed industries, and threatening human health. Resveratrol (RSV) is a natural product with therapeutic activities such as anti-inflammatory, antioxidant, and anticancer properties. RSV can alleviate ZEA-induced toxic effects by targeting signaling pathways such as NF-κB, Nrf2/Keap1, and PI3K/AKT/mTOR via attenuating oxidative damage, inflammatory response, and apoptosis, and regulating cellular autophagy. Therefore, this paper provides a review of the protective effect of RSV against ZEA-induced toxicity and its molecular mechanism, and discusses the safety and potential clinical applications of RSV in the search for natural mycotoxin detoxification agents.

UPLC-Q-TOF-MS combined with mass defect filtering strategies were applied for the phytochemical investigation of Harrisonia perforata, leading to the isolation of thirteen undescribed limonoids named haperforatones A-M (1-13) and seventeen known compounds (14-30). Particularly, haperforatones D-E (4-5) have an unprecedented A, B, C, D-seco-6, 7-nor-C-24-limonoid skeleton, structurally stripped of the five-membered lactone ring B and formed a double bond at the C-5 and C-10 positions. Their 2D structures and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 4, and 6 were established via X-ray diffraction crystallography. All 30 compounds were evaluated for anti-inflammatory potential in LPS-induced Raw 264.7 cell lines. Among those tested compounds, the most potent activity against LPS-induced NO generation was demonstrated by haperforatone F (6), with the IC 50 value of inhibition NO production of 7.2 µM. Additionally, 6 could significantly inhibit IL-1β and IL-6 release and markedly downregulate the protein expression level of iNOS in the LPS-stimulated RAW264.7 cells at 10 µM. The possible mechanism of NO inhibition of 6 was also investigated using molecular docking, which revealed the interaction of compound 6 with the iNOS protein., 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.)

Based on the basic idea of expanding the interlayer spacing of MXene, utilizing the effect of gallic acid-modified cellulose nanofibers for rapid moisture separation, the flexible sensing and driving composite film with a perfect balance among humidity signal response and mechanical properties was prepared. Inspired by the stacking of autumn fallen leaves, the cellulose nanofibers-based composite films were formed by self-assembly under vacuum filtration of blending gallic acid-modified cellulose nanofibers with MXene. The enhanced mechanical properties (tensile strength 131.1 MPa, puncture load 0.88 N, tearing strength 165.55 N/mm, and elongation at break 16.14 %), humidity sensing (the stable induced voltage 63.7 mV and response/recovery time 3.2/5.1 s), and humidity driving (154.7° bending angle) properties were observed. The synergistic effect of hydrogen bonds, the "pinning effect" arising from the side chains, and the hierarchical layered microstructure contributed to the enhanced performance. This work exemplifies the application of green natural product for preparing intelligent sensing, wearable devices, and biomimetic robots., 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.)

Purpose: The long-term fertility impact of cancer treatments is a significant concern for young breast cancer survivors. These reproductive concerns often become a persistent source of stress, negatively affecting their quality of life. This study aims to explore the reproductive concerns experienced by young breast cancer survivors post-treatment and the factors influencing their perceptions., Methods: This phenomenological study utilized semi-structured interviews to collect data. Eighteen participants were recruited from a tertiary hospital in Mainland China. The interviews were transcribed verbatim and analyzed using Colaizzi's method., Results: Data analysis revealed five themes and fourteen subthemes: (1) multiple emotional burdens interwoven with concerns about fertility; (2) concerns about risks associated with reproduction; (3) dilemma of childrearing; (4) the significance of reproduction; (5) support needs from family, peers, and professionals., Conclusion: Young breast cancer survivors in China face significant challenges related to reproductive issues. Reproductive health is a crucial aspect of breast cancer survivorship care. Healthcare providers must be attentive to the reproductive concerns of survivors, recognize the importance of multidimensional support for positive adaptation, and offer tailored and ongoing interventions to manage reproductive health in young breast cancer survivors., Competing Interests: Conflict of interest The authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

This study aimed to explore the association between genetic polymorphisms in the chromosome region 9q21 and the risk of pelvic organ prolapse (POP) in Northwestern Chinese women. A case-control study was conducted with 241 POP patients and 268 healthy controls, analyzing ten single nucleotide polymorphisms (SNPs) across five genes using PCR amplification and Sequenom MassArray. The results revealed significant associations between three SNPs-rs2297002 in GOLM1, rs7450 in MAK10, and rs3814535 in TLE1-and POP. Specifically, the TC genotype of rs2297002, the GA genotype of rs7450, and the AA genotype of rs3814535 were linked to an increased or decreased risk of POP. The study suggests that these genetic variants might contribute to the pathogenesis of POP in this population, offering potential markers for early diagnosis and further investigation into the molecular mechanisms underlying POP., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2024.)

Background: Amnestic mild cognitive impairment (aMCI) is an important window of opportunity for early intervention and rehabilitation in dementia. The aim of this study was to investigate the feasibility and effect of delivering transcutaneous electrical acupuncture stimulation (TEAS) intervention to elders with aMCI., Methods: A total of 61 aMCI patients were randomly allocated into the intervention group (receiving a 12-week TEAS) and control group (receiving health education). The feasibility outcomes included recruitment rate, retention rate, adherence rate, and an exploration of patients' views and suggestions on the research. The effective outcomes included cognitive function, sleep quality, and life quality, which were measured by the Montreal cognitive assessment scale (MoCA), auditory verbal learning test-Huashan version (AVLT-H), Pittsburgh sleep quality index (PSQI), and quality of life short-term-12 (QoL SF-12)., Results: The recruitment rate, retention rate, and adherence rate were 67.35%, 92.42%, and 85.29%, respectively. Most aspects of the research design and administration of the TEAS intervention were acceptable. The quantitative analysis suggests that compared with the control group, the scores of MoCA, AVLT-H, and SF-12 (mental component summary) were significantly better ( p < 0.05); however, the differences were not statistically significant in PSQI and SF-12 (physical component summary) ( p > 0.05)., Conclusions: The findings demonstrated that the study was feasible. TEAS awas possible for enhancing cognitive function and mental health in people with aMCI.

Acupoints are the local initial response sites of acupuncture therapeutic effects. As a biomarker, histamine is released into the acupoint region and plays its role concurrently as acupuncture needles are inserted into acupoints. Hence, real-time monitoring of histamine at acupoints is important to elucidate the effectiveness of the acupoint-activation process in acupuncture. Therefore, we developed highly sensitive acupuncture/Au particles/graphene biosensors by electrodeposition, brushing, and annealing methods based on bare acupuncture needles. We achieved a histamine detection limit of approximately 4.352 (±3.419) × 10 -12 mol L -1 and good sensitivity of approximately 6.296 (±3.873) μA μM -1 , with satisfactory specificity, repeatability, and stability in vitro , rendering them more competitive and suitable for real-time monitoring in vivo without causing additional damage. Subsequently, we conducted real-time histamine monitoring at non-acupoint and acupoint PC6 in rats, respectively. Our results showed minimal changes at the non-acupoint, whereas a trend of initial increase followed by a decrease was observed at acupoint PC6. The change in histamine concentration at acupoint PC6 reflected its involvement in the acupoint-activation procedure. Moreover, its peak position at ∼18 min could provide guidance for optimizing needle retaining time for maximum therapeutic effect. This work presents the first real-time in vivo monitoring of histamine at acupoints with high sensitivity and underscores the specificity of histamine release between non-acupoint and acupoint PC6, demonstrating great potential for elucidating the acupoint-activation mechanisms in acupuncture. Additionally, this work expands the application of nanomaterials in the integration of medicine and engineering, which is an important aspect of the future development of materials science.

The presence of livestock inside protected areas, or "livestock encroachment," is a global conservation concern because livestock is broadly thought to negatively affect wildlife. The Maasai Mara National Reserve (MMNR), Kenya, exemplifies this tension as livestock is believed to have resulted in the declining wildlife populations, contributing to the strict and sometimes violent exclusion measures targeting Maasai pastoralists. However, research embedded in the real-world setting that draws insights from the social-ecological contexts is lacking. In this study, we conducted 19 mo of ecological monitoring covering 60 sites in MMNR and found that cattle presence inside the reserve did not significantly impact most co-occurring wild herbivores at the current intensity. Using the Hierarchical Modeling of Species Communities and Gaussian copula graphic models, we showed that cattle had no direct associations-neither negative nor positive-with nearly all wild herbivores despite frequently sharing the same space. Moreover, we did not detect resource degradation correlated with cattle presence near the MMNR boundary. Given the colonial legacy and land use history of Mara, entering MMNR becomes the only viable option for many herders. These results corroborate the emerging perspective that the ecological impacts of extensively herded livestock on wildlife might be more nuanced than previously thought. To effectively balance the needs of people, livestock, and wildlife, the current rigid livestock exclusion measures need to be reassessed to holistically consider herbivore ecology, local land use history, and modern politics of protected area management., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Dysregulation of vascular homeostasis can induce cardiovascular diseases and increase global mortality rates. Although lineage tracing studies have confirmed the pivotal role of modulated vascular smooth muscle cells (VSMCs) in the progression of pathological vascular remodeling, the underlying mechanisms are still unclear., Methods: The expression of Tudor-SN was determined in VSMCs of artery stenosis, PDGF-BB-treated VSMCs and atherosclerotic plaque. Loss- and gain-of-function approaches were used to explore the role of Tudor-SN in the modulation of VSMCs phenotype both in vivo and in vitro., Results: In this study, we demonstrate that Tudor-SN expression is significantly elevated in injury-induced arteries, atherosclerotic plaques, and PDGF-BB-stimulated VSMCs. Tudor-SN deficiency attenuates, but overexpression aggravates the synthetic phenotypic switching of VSMCs and pathological vascular remodeling. Loss of Tudor-SN also reduces atherosclerotic plaque formation and increases plaque stability. Mechanistically, PTEN, the major regulator of the MAPK and PI3K-AKT signaling pathways, plays a vital role in Tudor-SN-mediated regulation on proliferation and migration of VSMCs. Tudor-SN facilitates the polyubiquitination and degradation of PTEN via NEDD4-1, thus exacerbating vascular remodeling under pathological conditions. BpV (HOpic), a specific inhibitor of PTEN, not only counteracts the protective effect of Tudor-SN deficiency on proliferation and migration of VSMCs, but also abrogates the negative effect of carotid artery injury-induced vascular remodeling in mice., Conclusions: Our findings reveal that Tudor-SN deficiency significantly ameliorated pathological vascular remodeling by reducing NEDD4-1-dependent PTEN polyubiquitination, suggesting that Tudor-SN may be a novel target for preventing vascular diseases., (© 2024. The Author(s).)

The absence of effective extracellular matrix to mimic the natural tumor microenvironment remains a significant obstacle in cancer research. Matrigel, abundant in various biological matrix components, is limited in its application due to its high cost. This has prompted researchers to explore alternative matrix substitutes. Here, we have investigated the effects of the extracellular matrix derived from pig small intestinal submucosa (ECM-SIS) in xenograft tumor modeling. Our results showed that the pig-derived ECM-SIS effectively promotes the establishment of xenograft tumor models, with a tumor formation rate comparable to that of Matrigel. Furthermore, we showed that the pig-derived ECM-SIS exhibited lower immune rejection and fewer infiltrating macrophages than Matrigel. Gene sequencing analysis demonstrated only a 0.5% difference in genes between pig-derived ECM-SIS and Matrigel during the process of tumor tissue formation. These differentially expressed genes primarily participate in cellular processes, biological regulation, and metabolic processes. These findings emphasize the potential of pig-derived ECM-SIS as a cost-effective option for tumor modeling in cancer research., (Creative Commons Attribution license.)

Angiosperm trees usually develop tension wood (TW) in response to gravitational stimulation. TW comprises abundant gelatinous (G-) fibers with thick G-layers primarily composed of crystalline cellulose. Understanding the pivotal factors governing G-layer formation in TW fiber remains elusive. This study elucidates the role of a Populus trichocarpa COBRA family protein, PtrCOB3, in the G-layer formation of TW fibers. PtrCOB3 expression was upregulated, and its promoter activity was enhanced during TW formation. Comparative analysis with wild-type trees revealed that ptrcob3 mutants, mediated by Cas9/gRNA gene editing, were incapable of producing G-layers within TW fibers and showed severely impaired stem lift. Fluorescence immunolabeling data revealed a dearth of crystalline cellulose in the tertiary cell wall (TCW) of ptrcob3 TW fibers. The role of PtrCOB3 in G-layer formation is contingent upon its native promoter, as evidenced by the comparative phenotypic assessments of pCOB11::PtrCOB3, pCOB3::PtrCOB3, and pCOB3::PtrCOB11 transgenic lines in the ptrcob3 background. Overexpression of PtrCOB3 under the control of its native promoter expedited G-layer formation within TW fibers. We further identified 3 transcription factors that bind to the PtrCOB3 promoter and positively regulate its transcriptional levels. Alongside the primary TCW synthesis genes, these findings enable the construction of a 2-layer transcriptional regulatory network for the G-layer formation of TW fibers. Overall, this study uncovers mechanistic insight into TW formation, whereby a specific COB protein executes the deposition of cellulose, and consequently, G-layer formation within TW fibers., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Copper-based nanoparticles (NPs) are gradually being introduced as sustainable agricultural nanopesticides. However, the effects of NPs on plants requires carefully evaluation to ensure their safe utilization. In this study, leaves of 2-week-old lettuce (Lactuca sativa L.) were exposed to copper oxide nanoparticles (CuO-NPs, 0 [CK], 100 [T1], and 1000 [T2] mg/L) for 15 days. A significant Cu accumulation (up to 1966 mg/kg) was detected in lettuce leaves. The metabolomics revealed a total of 474 metabolites in lettuce leaves, and clear differences were observed in the metabolite profiles of control and CuO-NPs treated leaves. Generally, phenolic acids and alkaloids, which are important antioxidants, were significantly increased (1.26-4.53 folds) under foliar exposure to NPs; meanwhile, all the significantly affected flavonoids were down-regulated after CuO-NP exposure, indicating these flavonoids were consumed under oxidative stress. Succinic and citric acids, which are key components of the tricarboxylic acid cycle, were especially increased under T2, suggesting the energy and carbohydrate metabolisms were enhanced under high-concentration CuO-NP treatment. There was also both up- and down-regulation of fatty acids, suggesting cell membrane fluidity and function responded to CuO-NPs. Galactinol, which is related to galactose metabolism, and xanthosine, which is crucial in purine and caffeine metabolism, were down-regulated under T2, indicating decreased stress resistance and disturbed nucleotide metabolism under the high CuO-NP dose. Moreover, the differentially accumulated metabolites were significantly associated with plant growth and its antioxidant ability. Future work should focus on controlling the overuse or excessive release of NPs into agricultural ecosystems to limit their adverse effects., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Frailty is a severe, common co-morbidity associated with congestive heart failure (CHF). This retrospective cohort study assesses the association between frailty and the risk of mortality in critically ill CHF patients., Methods: Eligible patients with CHF from the Medical Information Base for Intensive Care IV database were retrospectively analyzed. The frailty index based on laboratory tests (FI&#95;Lab) index was calculated using 33 variables to assess frailty status. The primary outcomes were in-hospital mortality and one-year mortality. The secondary outcomes were the incidence of acute kidney injury (AKI) and the administration of renal replacement therapy (RRT) in patients with concurrent AKI. Survival disparities among the FI&#95;Lab subgroups were estimated with Kaplan-Meier survival analysis. The association between the FI&#95;Lab index and mortality was examined with Cox proportional risk modeling., Results: A total of 3273 adult patients aged 18 years and older were enrolled in the study, with 1820 men and 1453 women included. The incidence rates of in-hospital mortality and one-year mortality rate were 0.96 per 1,000 person-days and 263.8 per 1,000 person-years, respectively. Multivariable regression analysis identified baseline FI&#95;Lab > 0.45 as an independent risk factor predicting in-hospital mortality (odds ratio = 3.221, 95% CI 2.341-4.432, p < 0.001) and one-year mortality (hazard ratio=2.152, 95% CI: 1.730-2.678, p < 0.001). In terms of predicting mortality, adding FI&#95;Lab to the six disease severity scores significantly improved the overall performance of the model (all p < 0.001)., Conclusions: We established a positive correlation between the baseline FI&#95;Lab and the likelihood of adverse outcomes in critical CHF patients. Given its potential as a reliable prognostic tool for such patients, further validation of FI&#95;Lab across multiple centers is recommended for future research., 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 Shi, Lin, Zhang, Xu, Lan, Jiang, Chen and Lu.)

Recently, Computer-Aided Diagnosis (CAD) systems have emerged as indispensable tools in clinical diagnostic workflows, significantly alleviating the burden on radiologists. Nevertheless, despite their integration into clinical settings, CAD systems encounter limitations. Specifically, while CAD systems can achieve high performance in the detection of lung nodules, they face challenges in accurately predicting multiple cancer types. This limitation can be attributed to the scarcity of publicly available datasets annotated with expert-level cancer type information. This research aims to bridge this gap by providing publicly accessible datasets and reliable tools for medical diagnosis, facilitating a finer categorization of different types of lung diseases so as to offer precise treatment recommendations. To achieve this objective, we curated a diverse dataset of lung Computed Tomography (CT) images, comprising 330 annotated nodules (nodules are labeled as bounding boxes) from 95 distinct patients. The quality of the dataset was evaluated using a variety of classical classification and detection models, and these promising results demonstrate that the dataset has a feasible application and further facilitate intelligent auxiliary diagnosis., (© 2024. The Author(s).)

In order to improve the effectiveness of tumor treatment and reduce the toxic side effects of drugs, we formed carrier-free multifunctional nanoparticles (BI NPs) by noncovalent interaction of berberine hydrochloride and IR780. BI NPs possessed the synergistic effects of promoting apoptosis, inhibiting proliferation and metastasis of tumors, and phototherapeutic treatment. Dispersive and passive targeting ability retention (EPR) effects of BI NPs on tumor sites in vivo could be monitored by fluorescence imaging. In addition, BI NPs exhibited effective reactive oxygen species (ROS) generation and photothermal conversion capabilities, photodynamic therapy (PDT), and photothermal therapy (PTT). Importantly, BI NPs inhibit tumor suppression through the AMPK/PI3K/AKT signaling pathway to inhibit tumor proliferation and metastasis. BI NPs not only have efficient in vivo multimodal therapeutic effects but also have good biosafety and potential clinical applications.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly tumors; however, its pathogenic mechanism remains largely elusive. In-depth researches are needed to reveal the expression regulatory mechanisms and functions of the RNA-binding protein RALY in HCC. Here, we identify RALY as a highly expressed oncogenic factor that affects HCC cells proliferation both in vitro and in vivo . O-GlcNAcylation of RALY at Ser176 enhances its stability by protecting RALY from TRIM27-mediated ubiquitination, thus maintaining hyper-expression of the RALY protein. Mechanistically, RALY interacts with USP22 messenger RNA, as revealed by RNA immunoprecipitation, to increase their cytoplasmic localization and protein expression, thereby promoting the proliferation of HCC cells. Furthermore, we develop a novel RALY protein degrader based on peptide proteolysis-targeting chimeras, named RALY-PROTAC, which we chemically synthesize by linking a RALY-targeting peptide with the E3 ubiquitin ligase recruitment ligand pomalidomide. In conclusion, our findings demonstrate a novel mechanism by which O-GlcNAcylation/RALY/USP22 mRNA axis aggravates HCC cells proliferation. RALY-PROTACs as degraders of the RALY protein exhibit potential as therapeutic drugs for RALY-overexpressing HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A total of 769 wheat kernels collected from six provinces in China were analyzed for beauvericin (BEA) and four enniatins (ENNs), namely, ENA, ENA 1 , ENB and ENB 1 , using a solid phase extraction (SPE) technique with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results show that the predominant toxin was BEA, which had a maximum of 387.67 μg/kg and an average of 37.69 μg/kg. With regard to ENNs, the prevalence and average concentrations of ENB and ENB 1 were higher than those of ENA and ENA 1 . The geographical distribution of BEA and ENNs varied. Hubei and Shandong exhibited the highest and lowest positive rates of BEA and ENNs (13.46% and 87.5%, respectively). However, no significant difference was observed among these six provinces. There was a co-occurrence of BEA and ENNs, and 42.26% of samples were simultaneously detected with two or more toxins. Moreover, a significant linear correlation in concentrations was observed between the four ENN analogs ( r range: 0.75~0.96, p < 0.05). This survey reveals that the contamination and co-contamination of BEA and ENNs in Chinese wheat kernels were very common.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is characterized by a high death rate and a poor prospect for survival. Anoikis, which is a kind of programmed cell apoptosis, is an important factor in the advancement of tumors. Nonetheless, the function of anoikis-related lncRNAs (ARLRs) in LUAD is still not well understood. The TCGA database was queried for genomic and clinical information. A prognostic signature for ARLRs was established via the use of coexpression analysis and Cox regression. Validation of the model's accuracy was conducted utilizing K-M curves and receiver operating characteristic (ROC) curves, and the signature was utilized to develop a nomogram. LncRNAs were implicated in the progression of tumors, as determined by functional enrichment analysis. There was an improvement in prognosis, increased immune cell infiltration, and higher immune scores among the low-risk patients. Additionally, we found that the two groups had varied anticancer drug sensitivities, which could help guide treatment. The impact of one ARLR, AC026355.2, on migration and invasion was validated by in vitro experiments in LUAD cells. Herein, a new lncRNA signature associated with anoikis was identified and estimated, potentially serving as a prognostic indicator for LUAD patients.

Sjögren's disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren's syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, -6.3 ± 0.6; PBO, -4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, -1.8 ± 0.2; PBO, -0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164 ., (© 2024. The Author(s).)

Thaumatin-like proteins (TLPs) in plants are involved in diverse biotic and abiotic stresses, including antifungal activity, low temperature, drought, and high salinity. However, the roles of the TLP genes are rarely reported in early flowering. Here, the TLP gene family was identified in P. trichocarpa . The 49 PtTLP genes were classified into 10 clusters, and gene structures, conserved motifs, and expression patterns were analyzed in these PtTLP genes. Among 49 PtTLP genes, the PtTLP6 transcription level is preferentially high in stems, and GUS staining signals were mainly detected in the phloem tissues of the PtTLP6 pro::GUS transgenic poplars. We generated transgenic Arabidopsis plants overexpressing the PtTLP6 gene, and its overexpression lines showed early flowering phenotypes. However, the expression levels of main flowering regulating genes were not significantly altered in these PtTLP6 -overexpressing plants. Our data further showed that overexpression of the PtTLP6 gene led to a reactive oxygen species (ROS) burst in Arabidopsis , which might advance the development process of transgenic plants. In addition, subcellular localization of PtTLP6 -fused green fluorescent protein (GFP) was in peroxisome, as suggested by tobacco leaf transient transformation. Overall, this work provides a comprehensive analysis of the TLP gene family in Populus and an insight into the role of TLPs in woody plants.

Background: Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs., Methods: Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers., Results: Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy., Conclusions: Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment., (© 2024. The Author(s).)

Background: Prostate cancer (PCa) incidence and mortality rates are rising. Our previous research has shown that the combination of icariin (ICA) and curcumol (CUR) induced autophagy and ferroptosis in PCa cells, and altered lipid metabolism. We aimed to further explore the effects of the combination of ICA and CUR on gut microbiota, metabolism, and immunity in PCa., Methods: A mouse subcutaneous RM-1 cell tumor model was established. 16 S rRNA sequencing was performed to detect changes in fecal gut microbiota. SCFAs in mouse feces, and the effect of ICA-CUR on T-cell immunity, IGFBP2, and DNMT1 were examined. Fecal microbiota transplantation (FMT) was conducted to explore the mechanism of ICA-CUR. Si-IGFBP2 and si/oe-DNMT1 were transfected into RM-1 and DU145 cells, and the cells were treated with ICA-CUR to investigate the mechanism of ICA-CUR on PCa development., Results: After treatment with ICA-CUR, there was a decrease in tumor volume and weight, accompanied by changes in gut microbiota. ICA-CUR affected SCFAs and DNMT1/IGFBP2/EGFR/STAT3/PD-L1 pathway. ICA-CUR increased the positive rates of CD3 + CD8 + IFN-γ, CD3 + CD8 + Ki67 cells, and the levels of IFN-γ and IFN-α in the serum. After FMT (with donors from the ICA-CUR group), tumor volume and weight were decreased. SCFAs promote tumor development and the expression of IGFBP2. In vitro, DNMT1/IGFBP2 promotes cell migration and proliferation. ICA-CUR inhibits the expression of DNMT1/IGFBP2., Conclusions: ICA-CUR mediates the interaction between gut microbiota and the DNMT1/IGFBP2 axis to inhibit the progression of PCa by regulating immune response and metabolism, suggesting a potential therapeutic strategy for PCa., (© 2024. The Author(s).)

This study was aimed to investigate the effect of hydrogen-rich solution (HRS) on acute radiation pneumonitis (ARP) in rats. The ARP model was induced by X-ray irradiation. Histopathological changes were assessed using HE and Masson stains. Inflammatory cytokines were detected by ELISA. Immunohistochemistry and flow cytometry were performed to quantify macrophage (CD68) levels and the M2/M1 ratio. Western blot analysis, RT-qPCR, ELISA and flow cytometry were used to evaluate mitochondrial oxidative stress injury indicators. Immunofluorescence double staining was performed to colocalize CD68/LC3B and p-AMPK-α/CD68. The relative expression of proteins associated with autophagy activation and the adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were detected by western blotting. ARP decreased body weight, increased the lung coefficient, collagen deposition and macrophage infiltration and promoted M1 polarization in rats. After HRS treatment, pathological damage was alleviated, and M1 polarization was inhibited. Furthermore, HRS treatment reversed the ARP-induced high levels of mitochondrial oxidative stress injury and autophagy inhibition. Importantly, the phosphorylation of AMPK-α was inhibited, the phosphorylation of mTOR and ULK1 was activated in ARP rats and this effect was reversed by HRS treatment. HRS inhibited M1 polarization and alleviated oxidative stress to activate autophagy in ARP rats by regulating the AMPK/mTOR/ULK1 signaling pathway., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

This study aimed to establish a high-performance liquid chromatography (HPLC) method to investigate the residues of patulin in apples, hawthorns, and their products. A total of 400 samples were collected from online shopping plats and supermarkets in China, including apples (n = 50), hawthorns (n = 50), and their products (apple juice, apple puree, apple jam, hawthorn juice, hawthorn chips, and hawthorn rolls, n = 300). In this experiment, this method had good linearity and a recovery of 82.3-94.4% for patulin. The limit of detection (LOD) was 0.2 µg/kg for liquid samples, while it was 0.3 µg/kg for solid and semi-fluid samples. The frequencies of patulin were 79.8% in 400 samples, and the patulin concentration is from 0.6 to 126.0 µg/kg. Two samples (0.5%) for patulin exceeded the regulatory limit (50 µg/kg) in 400 samples. The frequencies of patulin in kinds of samples were 32.0-98.0% (p < 0.05), and the percentage of samples exceeding the limit was not more than 2.0%. The frequencies of patulin in domestic samples were 83.0%, while they were 57.7% in imported samples. Two domestic samples (0.6%) contained patulin above the regulatory limit, while none of the imported samples exceeded the limit. Among the online and offline samples, the frequencies of patulin were 76.4 and 82.1%. Two online samples (1.0%) for patulin exceeded the regulatory limit, whereas none of the offline samples exceeded the limit. These results showed it is important to monitor regularly the content of patulin in apples, hawthorns, and their products to ensure consumer food safety., (© 2024. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

Human-wildlife interactions are increasing in severity due to climate change and proliferating urbanization. Regions where human infrastructure and activity are rapidly densifying or newly appearing constitute novel environments in which wildlife must learn to coexist with people, thereby serving as ideal case studies with which to infer future human-wildlife interactions in shared landscapes. As a widely reviled and behaviorally plastic apex predator, the spotted hyena ( Crocuta crocuta ) is a model species for understanding how large carnivores navigate these human-caused 'landscapes of fear' in a changing world. Using high-resolution GPS collar data, we applied resource selection functions and step selection functions to assess spotted hyena landscape navigation and fine-scale movement decisions in relation to social-ecological features in a rapidly developing region comprising two protected areas: Lake Nakuru National Park and Soysambu Conservancy, Kenya. We then used camera trap imagery and Barrier Behavior Analysis (BaBA) to further examine hyena interactions with barriers. Our results show that environmental factors, linear infrastructure, human-carnivore conflict hotspots, and human tolerance were all important predictors for landscape-scale resource selection by hyenas, while human experience elements were less important for fine-scale hyena movement decisions. Hyena selection for these characteristics also changed seasonally and across land management types. Camera traps documented an exceptionally high number of individual spotted hyenas (234) approaching the national park fence at 16 sites during the study period, and BaBA results suggested that hyenas perceive protected area boundaries' semi-permeable electric fences as risky but may cross them out of necessity. Our findings highlight that the ability of carnivores to flexibly respond within human-caused landscapes of fear may be expressed differently depending on context, scale, and climatic factors. These results also point to the need to incorporate societal factors into multiscale analyses of wildlife movement to effectively plan for human-wildlife coexistence., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Many breast cancer patients suffer from fear of cancer recurrence (FCR). However, effective physical intervention for FCR has been scarce. Previous studies have confirmed that repetitive transcranial magnetic stimulation (rTMS) can help improve patients' anxiety, depression, fear, and stress level. Therefore, this study aims to assess the efficacy of rTMS in the treatment of FCR in breast cancer patients and explore its underlying neural mechanism., Methods and Analysis: and analysis: Fifty breast cancer patients with high FCR (FCR total score >27), and fifty age- and gender-matched patients with low FCR (FCR total score <7) will be recruited to participate in this study. Patients in the high FCR group will be randomly assigned to receive 4-week low-frequency rTMS targeting the right dorsolateral prefrontal cortex (rDLPFC) + treatment as usual (TAU) (n = 25), or to receive sham stimulation + TAU (n = 25). Patients in the low FCR group will only receive TAU. All participants will take a baseline fMRI scan to examine the local activities and interactions of brain activity between the prefrontal cortex (DLPFC), amygdala and hippocampus. Fear of Cancer Recurrence Questionnaire (FCRQ7), Patient Health Questionnaire (PHQ9), Generalize Anxiety Disorder (GAD7), Numeric Rating Scale (NRS), and Insomnia Severity Index (ISI7) will be used to measure an individual's FCR, depression, anxiety, pain, and insomnia symptoms at week 0 (baseline), week 4 (the end of intervention), week 5 (1 week post-treatment), week 8 (1 month post-treatment), and week 16 (3 months post-treatment). Participants in the high FCR group will receive a post-treatment fMRI scan within 24 h after intervention to explore the neural mechanisms of rTMS treatment. The primary outcome of the study, whether the rTMS intervention is sufficient in relieving FCR in breast cancer patients, is measured by FCRQ7. Additionally, task activation, local activity and functional connectivity of the DLPFC, amygdala and hippocampus will be compared, between high and low FCR group, and before and after treatment., Discussion: Studies have shown that low-frequency rTMS can be used to treat patient's FCR. However, there is a lack of relevant evidence to support the efficacy of rTMS on FCR in cancer patients, and the neural mechanisms underlying the effects of rTMS on FCR need to be further investigated., Ethics and Dissemination: Ethical approval for the study has been obtained from the Ethics Committee of Guangdong Provincial People's Hospital (reference number: KY-N-2022-136-01). The results of the investigation will be published in scientific papers. The data from the investigation will be made available online if necessary., Trial Registration: NCT05881889 (ClinicalTrials.gov). Date of registration: May 31, 2023., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)