Search

Abstract Background Cisplatin-induced ototoxicity (CIO), characterized by irreversible and progressive bilateral hearing loss, is a prevalent adverse effect of cisplatin chemotherapy. Alongside clinical risk factors, genetic variants contribute to CIO and genome-wide association studies (GWAS) have highlighted the polygenicity of this adverse drug reaction. Polygenic scores (PGS), which integrate information from multiple genetic variants across the genome, offer a promising tool for the identification of individuals who are at higher risk for CIO. Integrating large-scale hearing loss GWAS data with single cell omics data holds potential to overcome limitations related to small sample sizes associated with CIO studies, enabling the creation of PGSs to predict CIO risk. Results We utilized a large-scale hearing loss GWAS and murine inner ear single nuclei RNA-sequencing (snRNA-seq) data to develop two polygenic scores: a hearing loss PGS (PGSHL) and a biologically informed PGS for CIO (PGSCIO). The PGSCIO included only variants which mapped to genes that were differentially expressed within cochlear cells that showed differential abundance in the murine snRNA-seq data post-cisplatin treatment. Evaluation of the association of these PGSs with CIO in our target CIO cohort revealed that PGSCIO demonstrated superior performance (P = 5.54 × 10− 5) relative to PGSHL (P = 2.93 × 10− 3). PGSCIO was also associated with CIO in our test cohort (P = 0.04), while the PGSHL did not show a significant association with CIO (P = 0.52). Conclusion This study developed the first PGS for CIO using a large-scale hearing loss dataset and a biologically informed filter generated from cisplatin-treated murine inner ear snRNA-seq data. This innovative approach offers new avenues for developing PGSs for pharmacogenomic traits, which could contribute to the implementation of tailored therapeutic interventions. Further, our approach facilitated the identification of specific cochlear cells that may play critical roles in CIO. These novel insights will guide future research aimed at developing targeted therapeutic strategies to prevent CIO.

Abstract Defining genetic factors impacting chemotherapy failure can help to better predict response and identify drug resistance mechanisms. However, there is limited understanding of the contribution of inherited noncoding genetic variation on inter-individual differences in chemotherapy response in childhood acute lymphoblastic leukemia (ALL). Here we map inherited noncoding variants associated with treatment outcome and/or chemotherapeutic drug resistance to ALL cis-regulatory elements and investigate their gene regulatory potential and target gene connectivity using massively parallel reporter assays and three-dimensional chromatin looping assays, respectively. We identify 54 variants with transcriptional effects and high-confidence gene connectivity. Additionally, functional interrogation of the top variant, rs1247117, reveals changes in chromatin accessibility, PU.1 binding affinity and gene expression, and deletion of the genomic interval containing rs1247117 sensitizes cells to vincristine. Together, these data demonstrate that noncoding regulatory variants associated with diverse pharmacological traits harbor significant effects on allele-specific transcriptional activity and impact sensitivity to antileukemic agents.

Not available.

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

Mechanisms underlying the effects of ecological disturbance on aquatic ecosystems remain uncertain in subtropical regions. Here, we used a proxy-based approach to explore the community dynamics of testate amoebae (Arcellinida and Euglyphida) in two subtropical deep reservoirs (Tingxi and Shidou) in Xiamen, southeastern China, over a three-year period. Specifically, we employed drought and typhoon events recorded by weather station as proxies for ecological disturbance and chlorophyll-a estimated through fluorometry as a proxy for testate amoeba food. We addressed three questions: (1) Does typhoon-induced ecological disturbance affect the distribution patterns of testate amoebae in subtropical reservoirs? (2) Do typhoon- and drought-induced ecological disturbances affect the testate amoeba community across different water layers of subtropical reservoirs similarly? (3) Do stochastic or deterministic processes shaping the testate amoeba community over time exhibit similar patterns in different water layers of subtropical reservoirs? The typhoon-induced ecological disturbance resulted in pronounced shifts in the distribution patterns of testate amoebae, characterized by lower shell influx in surface waters (11-12 ind. mL -1 d -1 ) and higher shell influx in middle and bottom waters (12-22 ind. mL -1 d -1 ). The impact of typhoon-and drought-induced ecological disturbance was more pronounced in surface waters, and its pure explanation accounted for 29.5-35.5 % community variation in a variation partitioning analysis. The effect of stochastic processes revealed by the neutral model increased with water depths, accounting for 63.3-76.5 % of the community variation in the surface, 77.4-82.6 % in the middle, and 82.8-88.1 % in the bottom water. The effect of deterministic processes shown by the null model decreased with water depth and remained relatively low across all water layers. These results suggest contrasting patterns of assembly mechanisms underlying the testate amoeba community responses to ecological disturbance, with the balance perhaps shaped by water depth and the average water residence time in a reservoir., 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.)

A template-directed synthesis of one-dimensional hexagonal PdTe nanowires using Te nanowires as a template through a two-step hydrothermal process is developed, which exhibit excellent mass activity of 4.4 A mg Pd -1 for ethanol electrooxidation in an alkaline medium. This work enriches the controlled synthesis of one-dimensional noble metal chalcogenide nanomaterials.

Rice blast, caused by Pyricularia oryzae, is one of the most destructive fungal diseases in rice, severely impacting rice production worldwide every year. Rapid, accurate and visual detection of P. oryzae is essential for more effective prevention and control. In this study, we developed a recombinase polymerase amplification-lateral flow dipstick (RPA-LFD) assay to detect P. oryzae. Species-specific RPA primer pairs and probe were designed based on target gene MGG_15975. The optimized reaction temperature and time were set at 37 °C and 25 min, respectively. Specificity analysis showed that the assay could specifically detect P. oryzae isolates from rice, whereas other fungal species or Pyricularia species from grasses were not detected. Additionally, this assay demonstrated highly sensitivity, capable of detecting as low as 10-2 ng/µL of P. oryzae genomic DNA, which was found to be 100 times more sensitive than conventional PCR. Furthermore, using this assay, P. oryzae was effectively detected in diseased leaves in rice fields, and could also be identified at an early stage of infection before obvious lesions appeared in artificially inoculated rice seedlings. Therefore, the RPA-LFD assay developed in our study for the detection of P. oryzae is rapid, highly sensitive and efficient, which has the potential application for early diagnosis of P. oryzae infection in rice fields.

Background: The extubation time is critical during the intensive care unit stay in aneurysmal subarachnoid hemorrhage (aSAH) patients. The current conventional parameters for predicting extubation failure (EF) and extubation time may not be suitable for this population. Here, we aimed to identify factors associated with EF in aSAH patients., Methods: From a single-center observational study on aSAH patients with computed tomography angiography from 2019 to 2021, patients who received microsurgery were enrolled and divided into two groups according to whether EF occurred. Multivariable logistic regression was conducted to evaluate disease severity, medical history, and extubation time differences between patients with and without EF., Results: Of 335 patients included, EF occurred with a rate of 0.14. Delayed cerebral ischemia (67.4% vs. 13.5%) and acute hydrocephalus (6.5% vs. 1.4%) were frequently observed in patients with EF. Also, patients who develop EF presented higher disability (65.9% vs. 17.4%) and mortality (10.9% vs. 0.7%) rates. Multivariable analysis demonstrated that age (OR 1.038; 95% CI 1.004-1.073; P = 0.028), onset to admission time (OR 0.731; 95% CI 0.566-0.943; p = 0.016), WFNS grade > 3 (OR 4.309; 95% CI 1.639-11.330; p = 0.003), and extubation time < 24 h (OR 0.097; 95% CI 0.024-0.396; p = 0.001) were significantly associated with EF occurrence., Conclusions: These data provide further evidence that older aSAH patients with onset to admission time < 2 days and WFNS grade > 3 have a high risk of developing EF, which is amplified by the ultra-early extubation. Moreover, in patients with two or more risk factors, a prolonged intubation recommendation requires consideration to avoid the EF., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Research Ethics Committee of Beijing Tiantan Hospital (IRB approval number: KY 2021-008-01) and conducted under the guidance of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (© 2024. The Author(s).)

Mechanosensitive channels of large conductance (MscL) serve as a mechanoelectrical valve of cells in response to the membrane tension. The influence of membrane environments on the MscL channel activity and the underlying mechanism remains unclear. Herein, we developed a new sample preparation protocol that allows for the detection of high-quality 1 H-detected solid-state NMR spectra of MscL in cellular membranes, enabling site-specific analysis of its dynamics. Dipolar order parameters and spin relaxation rates are measured for 51 residues of MscL in synthetic and native membranes. The dynamics data reveal that while MscL maintains a similar rigidity in both membrane environments, it exhibits enhanced slow collective motions in the native cellular membranes. Molecular dynamics simulations demonstrate the critical role of slow motions in the mechanosensitivity of MscL by promoting protein-membrane interactions. This study examines atomic-resolution dynamics of a membrane-protein in cellular membranes and provides novel insights into the functional significance of membrane-protein dynamics.

Electrofusion is an effective method for fusing two cells into a hybrid cell, and this method is widely used in immunomedicine, gene recombination, and other related fields. Although cell pairing and electrofusion techniques have been accomplished with microfluidic devices, the purification and isolation of fused cells remains limited due to expensive instruments and complex operations. In this study, through the optimization of microstructures and electrodes combined with buffer substitution, the entire cell electrofusion process, including cell capture, pairing, electrofusion, and precise separation of the targeted fused cells, is achieved on a single chip. The proposed microfluidic cell electrofusion achieves an efficiency of 80.2 ± 7.5%, and targeted cell separation could be conveniently performed through the strategic activation of individual microelectrodes via negative dielectrophoresis, which ensures accurate release of the fused cells with an efficiency of up to 91.1 ± 5.1%. Furthermore, the survival rates of the cells after electrofusion and release are as high as 94.7 ± 0.6% and 91.7 ± 1.2%, respectively. These results demonstrate that the in situ cell electrofusion and separation process did not affect the cell activity. This chip offers integrated multifunctional manipulation of cells in situ, and can be applied to multiple fields in the future, thus laying the foundation for the field of precise single-cell analysis.

The localized heating technique, which minimizes high-temperature impact on thermally sensitive components and reduces impurity dispersion during encapsulation, has become a focal point in MEMS packaging research. In this study, we propose a method for localized heating at specific positions and shapes. A localized heating device, based on distributed electric field control, is constructed, where a polymer droplet on the lower substrate electrode is driven into a liquid column under the influence of a distributed electric field generated between two parallel substrate electrodes. ITO substrate electrodes with various patterns are fabricated, ensuring the shape of the formed liquid column matches the pattern. Leveraging the principles of heat transfer, the temperature of the polymer droplet is regulated via a heating stage to enable targeted heating of defined shapes and areas. Experiments delve into the impact of driving parameters on heating time and efficiency, with results affirming the proposed method's capability to govern localized heating for particular regions and configurations accurately.

Phthalocyanines (Pcs) are widely developed in cancer phototherapy due to their definite chemical structure and tunable photosensitivity. However, their in vivo application is hampered by low water solubility and non-specific biodistribution. Here,a strategy of sialylation-modulation is developed for the first time to highly improve the bioavailability of Pcs. The sialylated Pcs (ZnPc-4SA) not only has good hydrophilicity, but also can self-assemble into nanoparticles (ZnPc-4SA NPs). These nanoformulations retain the excellent photophysical properties of Pcs, which in turn reflects excellent optoacoustic and phototherapeutic properties. Importantly, ZnPc-4SA NPs exhibit boosted tumor accumulation due to the passive targeting and sialic acid-mediated E-selectin targeting. Besides, the phototoxicity of ZnPc-4SA NPs can effectively trigger cell apoptosis and tumor elimination upon laser irradiation. Therefore, sialylation engineering strategy provides a new option for hydrophobic drugs modification with enhanced tumor theranostics., (© 2024 Wiley‐VCH GmbH.)

Background: Major psychiatric disorders (MPDs) are delineated by distinct clinical features. However, overlapping symptoms and transdiagnostic effectiveness of medications have challenged the traditional diagnostic categorisation. We investigate if there are shared and illness-specific disruptions in the regional functional efficiency (RFE) of the brain across these disorders., Methods: We included 364 participants (118 schizophrenia [SCZ], 80 bipolar disorder [BD], 91 major depressive disorder [MDD], and 75 healthy controls [HCs]). Resting-state fMRI was used to caclulate the RFE based on the static amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality and corresponding dynamic measures indicating variability over time. We used principal component analysis to obtain static and dynamic RFE values. We conducted functional and genetic annotation and enrichment analysis based on abnormal RFE profiles., Results: SCZ showed higher static RFE in the cortico-striatal regions and excessive variability in the cortico-limbic regions. SCZ and MDD shared lower static RFE with higher dynamic RFE in sensorimotor regions than BD and HCs. We observed association between static RFE abnormalities with reward and sensorimotor functions and dynamic RFE abnormalities with sensorimotor functions. Differential spatial expression of genes related to glutamatergic synapse and calcium/cAMP signaling was more likely in the regions with aberrant RFE., Conclusions: SCZ shares more regions with disrupted functional integrity, especially in sensorimotor regions, with MDD rather than BD. The neural patterns of these transdiagnostic changes appear to be potentially driven by gene expression variations relating to glutamatergic synapses and calcium/cAMP signaling. The aberrant sensorimotor, cortico-striatal, and cortico-limbic integrity may collectively underlie neurobiological mechanisms of MPDs.

We introduce a switchable ionic diode modulated by PEG, enabling dynamic control of ion transport and reversible ion flow switching. This system achieves tunable current rectification over two orders of magnitude, simplifying fabrication and offering versatile, scalable solutions for high-performance ionic devices in energy harvesting, nanofluidics, and ionic circuits.

Background: PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease., Methods: This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions., Results: Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 10 9 /L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p < .05)., Conclusions: Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients., Plain Language Summary: Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients., (© 2024 American Cancer Society.)

Current electrolytes of mixing different functional solvents inherit both merits and weaknesses of each solvent, thus cannot simultaneously meet all the requirements of high energy, long cycle life, and high safety for Li metal batteries (LMBs). Here, we design a high voltage and safe electrolyte (VSE) by integrating different functional groups into one molecule. The VSE electrolyte has a wide electrochemical stability window of ~5.6 V enabling a Li anode to achieve high Coulombic efficiency of >99.3%, Li | |LiNi 0.8 Co 0.1 Mn 0.1 O 2 coin cell to maintain capacity retention of 92% after 500 cycles, and the 3.5-Ah-grade Li | |LiNi 0.8 Co 0.1 Mn 0.1 O 2 pouch cell to deliver a high energy density of 531 Wh kg -1 without any flame and expansion after cycled under extreme conditions. The VSE electrolyte even enables 5.0 V Li | |LiNi 0.5 Mn 1.5 O 4 cells to charge/discharge for 200 cycles without capacity decay. This work provides a promising direction for the rational design of high-voltage and intrinsically safe electrolytes for LMBs., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Solid-state nuclear magnetic resonance (ssNMR) is indispensable for studying the structures, dynamics, and interactions of insoluble proteins in native or native-like environments. While ssNMR includes numerous nonselective techniques for general analysis, it also provides various selective methods that allow for the extraction of precise details about proteins. This perspective highlights three key aspects of selective methods: selective signals of protein segments, selective recoupling, and site-specific insights into proteins. These methods leverage protein topology, labeling strategies, and the tailored manipulation of spin interactions through radio frequency (RF) pulses, significantly promoting the field of protein ssNMR. With ongoing advancements in higher magnetic fields and faster magic angle spinning (MAS), there remains an ongoing need to enhance the selectivity and efficiency of selective ssNMR methods, facilitating deeper atomic-level insights into complex biological systems.

Objective: Atherosclerosis(AS) is a vascular disease characterized by the development of plaque in the arteries, and atrial fibrillation (AF) is a common heart arrhythmia. These two conditions share several risk factors in common, such as aging, diabetes, obesity, and hypertension. Ferroptosis is a new mode of non-apoptotic cell death that plays a key role in cardiomyocyte death and has been associated with a variety of cardiac diseases. This study aimed to investigate the ferroptosis biomarkers and underlying biological mechanisms associated with AF and AS., Materials and Methods: The gene expression dataset was obtained from GEO database, differentially expressed genes (DEGs) and ferroptosis expressed genes (FDGs) were obtained by data processing and screening, and then functional enrichment, network construction, transcription factor prediction, identification of biomarkers by LASSO and SVM - RFE algorithms, and also immune infiltration analyses and cellular experiments were performed., Results: In AF and AS, 1627 and 571 DEGs were identified respectively, and 128 were intersected, and 47 common FDGs were also identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs revealed that they were associated with biological processes and pathways such as leukocyte immunity, and FDGs were also involved in specific functions and pathways. Fifteen key genes were identified, CSF1R and ITGAM expression differences were verified, and seven transcription factors were predicted to be differentially expressed. Characterized genes were screened to construct models with good diagnostic efficacy, and immune infiltration showed that NUPR1 was associated with altered immune environments, and WB indicated that NUPR1 was highly expressed in the disease model., Conclusion: Our study demonstrates that the ferroptosis gene NUPR1 plays a role in the pathogenesis of atrial fibrillation and atherosclerosis, and also provides valuable insights into their molecular mechanisms, which may contribute to the development of new targets and strategies for the treatment of these diseases., Competing Interests: The authors declare no potential conflicts of interest., (© 2024 Xu et al.)

Breast cancer (BC), a widespread and lethal neoplasm, is irrespective of the subtype of BC. Metastasis remains a crucial determinant for unfavorable outcome. The identification of novel diagnostic markers is instrumental in optimizing the treatment regime for BC. The direct correlation between anoikis and the progression/outcome of BC is well established. Nevertheless, the contribution of anoikis-related genes (ARGs) in BC remains obscure at present. We implemented the METABRIC dataset to scrutinize and assess differentially expressed ARGs in BC versus healthy breast tissues. An unsupervised consensus clustering approach for ARGs was employed to classify patients into diverse subtypes. ESTIMATE algorithms were utilized to assess immune infiltrative patterns. Prognostic gene expression patterns were derived from LASSO regression and univariate COX regression analysis. Subsequently, these signatures underwent examination via use of the Kaplan-Meier survival curve. 6 pairs of fresh tissue specimens (tumor and adjacent non-tumor) were employed to assess the expression of 7 ARGs genes via qPCR. Notably, DCN and FOS were not expressed in BC tissue, which had been excluded in our subsequent experiments. Also, among remaining 5 ARGs, solely the expression of ADH1A demonstrated a statistically remarkable disparity between freshly collected cancer tissues and the adjacent ones. ADH1A-overexpressed and ADH1A-sh vectors were transfected into MCF-7 and MCF-7-AR cell lines, respectively. The expression status of FABP4, CALML5, ADH1A, C1orf106, CIDEC, β-catenin, N-cadherin, and Vimentin in the clinical samples were scrutinized using RT-qPCR and western blotting techniques. Migration and invasion through transwell chambers were employed to assess the migratory and invasive potential of the cells. Detailed evaluation of cell proliferation was conducted utilizing a Cell Counting Kit-8 (CCK-8) assay. The apoptotic index of the cells was determined by flow cytometry analysis. An innovative anoikis-associated signature consisting of seven genes, namely ADH1A, DCN, CIEDC, FABP4, FOS, CALML5, and C1orf106, was devised to stratify BC patients into high- and low-risk cohorts. This unique risk assessment model, formulated via the distinctive signature approach, has been validated as an independent prognostic indicator. Additional analysis demonstrated that distinct risk subtypes manifested variances in the tumor microenvironment and drug sensitivities. Suppression of ADH1A enhanced the migratory and invasive capacities and reduced these tumorigenesis-related protein levels, underscoring the prognostic role of ADH1A in the progression of BC. Through our meticulous study, we have elucidated the possible molecular markers and clinical implications of ARGs in BC. Our model, which incorporate seven ARGs, has proven to accurately forecast the survival outcomes of BC patients. Moreover, the thorough molecular study of ADH1A has augmented our comprehension of ARGs in BC and opened a novel avenue for guiding personalized and precise therapeutic interventions for BC patients., Competing Interests: Declarations Conflict of interest The authors declare no conflicts of interest. They are solely responsible for the content and writing of this article. Ethics approval and consent to participate Authors conducting experiments on humans or using human tissue samples must ensure that all experiments were conducted in compliance with relevant guidelines and regulations. The study was approved by the Ethics Committee of the First Affiliated Hospital of Kunming Medical University, and all methods were performed in accordance with applicable guidelines and regulations. Consent for publication All authors have reviewed and approved the final manuscript for publication., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Early identification of individuals at high risk for depression is essential for effective implementation of interventions. This study utilized the UK Biobank database to construct an individual depression risk score using nomogram and explored the potential of traditional risk factors and routine biochemical markers for the auxiliary diagnosis of individual depression., Methods: A total of 369,407 participants were included in the study and divided into training and testing sets. LASSO regression was employed to select predictive variables for depression from 16 traditional risk factors and 28 routine biochemical markers. Following variable selection, two multivariable logistic regression models were constructed. Nomograms were then generated to visualize the relationships between these variables and depression risk, and to facilitate the calculation of individual depression risk scores., Results: Twelve traditional risk factors and nine biochemical markers were selected for model building. Model 1, using only traditional risk factors, achieved the area under the curve (AUC) of 0.913 (95 % CI: 0.910-0.915), while Model 2, incorporating both traditional and routine biochemical markers, yielded an AUC of 0.914 (95 % CI: 0.912-0.917). Based on optimal cut-off values, Model 1 exhibited a sensitivity of 81.99 % and a specificity of 83.76 %, while Model 2 demonstrated a sensitivity of 81.54 % and a specificity of 84.31 %., Limitations: External validation is still needed to confirm the model's generalizability., Conclusions: While the depression risk scoring model built using traditional risk factors effectively identifies high-risk individuals for depression and demonstrates good clinical performance, incorporating routine biochemical markers did not significantly improve the model's performance., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Spray-induced gene silencing (SIGS) presents a promising RNA interference (RNAi)-based crop protection strategy against eukaryotic phytopathogens. However, the application of SIGS faces challenges, such as the limited uptake of dsRNA by certain pathogens and the instability of dsRNA in the environment. This study introduces innovative biomimetic nanovesicles, called extracellular vesicle (EV) mimetic chimeric nanovesicles (ECNs), assembled from tomato leaf cell membranes and cationic sterosomes via the freeze-thaw method. Similar to the function of EVs in nucleic acid transport between cells, ECNs serve as a hybrid nanosystem to overcome the challenge of delivering exogenous dsRNA in Phytophthora infestans . When applied to SIGS, the superiority of ECNs in crop protection becomes more apparent, including high loading and protection of dsRNA, improved biosafety, and efficient internalization into pathogen and plant cells, all of which significantly enhance the efficacy of RNAi in preventing early infection of P. infestans to susceptible tomato plants. This study demonstrates that ECNs are promising RNA delivery vehicles and will promote the use of SIGS-based RNA pesticides in sustainable agricultural production.

Background: Renal fibrosis is a key process in the progression from acute kidney injury (AKI) to chronic kidney disease (CKD), while the intricate mechanisms of renal fibrosis remain obscure. While the signal-transducing adaptor protein 2 (STAP2) was well-studied for its notable function in inflammation and immune-related disorders, its specific implication in renal fibrosis remains unclear. This study assessed the mechanism by which STAP2 could promote the progression of renal fibrosis., Methods: The expression level of STAP2 in fibrotic human samples, murine fibrosis models, and cellular fibrosis models was measured, respectively. Subsequently, immunoprecipitation (IP), mass spectrometry, and RNA sequencing (RNA-seq) were employed to identify HSP27 as an interacting protein and the PI3K-AKT signaling pathway. STAP2 was thereafter knocked down or overexpressed in both in vivo and in vitro models to assess the expression levels of pathway-related and fibrosis-related proteins. Finally, the important role of STAP2 in the fibrosis process in animal models induced by ischemia-reperfusion injury (IRI) and cisplatin was validated., Results: Functionally, in vivo assays demonstrated that the genetic knockout of STAP2 could remarkably mitigate epithelial-mesenchymal transition (EMT), diminish inflammatory cell infiltration, and reduce collagen deposition in mice with renal fibrosis. Conversely, in vitro assays employing STAP2-overexpressing cell models exacerbated the expression levels of fibrosis markers. The outcomes uncovered a potential mechanism by which STAP2 could modulate renal fibrosis through its impact on the expression level of phosphorylated HSP27, as well as modulating the PI3K/AKT signaling pathway., Conclusions: This comprehensive investigation delineated the noticeable function of STAP2 in the advancement of renal fibrosis, and the outcomes might contribute to the development of targeted therapies concentrated on STAP2 to mitigate renal fibrosis., Competing Interests: Declarations Ethical approval Animal experiments were approved by Experimental Animal Ethics Committee of Wuhan Third Hospital (WuSanYiShiLun SY2023-003). Collected clinical samples and conducted clinical research were approved by Ethics Committee of Wuhan Third Hospital (WuSanYiLun KY2023-057) and Ethics Committee of Huangshi Central Hospital (2024-17). Conflict of interest The authors confirmed the absence of conflict of interest., (© 2024. The Author(s).)

c-MYC is an important driver of high-risk neuroblastoma. A lack of c-MYC-driven genetically engineered mouse models (GEMM) has hampered the ability to better understand mechanisms of neuroblastoma oncogenesis and to develop effective therapies. Here, we showed that conditional c-MYC induction via Cre recombinase driven by a tyrosine hydroxylase (Th) promoter led to a preponderance of PDX1+ somatostatinoma, a type of pancreatic neuroendocrine tumor (PNET). However, c-MYC activation via an improved Cre recombinase driven by a dopamine β-hydroxylase (Dbh) promoter resulted in neuroblastoma development. The c-MYC murine neuroblastoma tumors recapitulated the pathologic and genetic features of human neuroblastoma and responded to anti-GD2 immunotherapy and DFMO, an FDA-approved inhibitor targeting the MYC transcriptional target ODC1. Thus, c-MYC overexpression results in different but related tumor types depending on the targeted cell. The GEMMs represent valuable tools for testing immunotherapies and targeted therapies for these diseases.

Interleukin-22 (IL-22) is a vital cytokine that is dysregulated in various autoimmune conditions including rheumatoid arthritis (RA), multiple sclerosis (MS), and Alzheimer's disease (AD). As the starting point for the activation of numerous signaling pathways, IL-22 plays an important role in the initiation and development of autoimmune diseases. Specifically, imbalances in IL-22 signaling can interfere with other signaling pathways, causing cross-regulation of target genes which ultimately leads to the development of immune disorders. This review delineates the various connections between the IL-22 signaling pathway and autoimmune disease, focusing on the latest understanding of the cellular sources of IL-22 and its effects on various cell types. We further explore progress with pharmacological interventions related to targeting IL-22, describing how such therapeutic strategies promise to usher in a new era in the treatment of autoimmune disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. 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.)

The introduction of three-dimensional (3D) printing scaffolds has emerged as an effective approach to achieving satisfactory revascularization for bone tissue engineering (BTE). However, there is a notable absence of analytical and descriptive investigations concerning the trajectory, essential research directions, current research scenario, pivotal investigative focuses, and forthcoming perspectives. Hence, the objective of this research is to offer a thorough overview of the advancements achieved in 3D printing structures for vascularized BTE within the last 10 years. Information extracted from the Web of Science repository spans from January 1, 2014, to April 1, 2024. Utilizing advanced analytical instruments, we conducted comprehensive scientometric and visual analyses. The findings underscore the predominant influence of China, representing 59.62 % of the overall publications and playing a pivotal role in shaping research within this field. Notable productivity was evident at various institutions, including Shanghai Jiao Tong University, Chinese Academy of Sciences, and Sichuan University. Wang Jinwu and Wu Chengtie stand out as the most prolific contributors in this domain. The highest number of publications in this area was contributed by the journal Advanced Healthcare Materials . In this study, osteogenesis imperfecta, osteosarcoma, fractures, osteonecrosis, and cartilage diseases were identified as the most significant disorders investigated in this research area. By providing a comprehensive scientometric assessment, this study benefits both experienced researchers and newcomers alike, offering prompt access to essential information and fostering the extraction of innovative concepts within this specific field., Competing Interests: 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., (© 2024 The Author(s).)

We show that PEG-induced macromolecular crowding enhances protein detection in nanopores by increasing capture rate and translocation frequency. Experimental data indicate that a PEG concentration gradient boosts capture efficiency, while our theoretical model attributes this enhancement to osmotic flow, offering insights for improving nanopore-based biosensing.

Lignin has gained significant attention in wastewater treatment due to its abundant resources and good adsorbability. In this work, magnetic lignin micro-nano spheres (Fe 3 O 4 @SiO 2 -LNS) was prepared using alkali lignin as the raw material, and was used as the adsorbent and catalyst to activate peroxymonosulfate (PMS) to build an inhomogeneous catalytic oxidation system (Fe 3 O 4 @SiO 2 -LNS/PMS). The system was then used to remove the stubborn acid blue 9 (AB9) dye in wastewater, and the effects of pH, catalyst dosage, PMS dosage of the system on the removal percentage of AB9 dye and the corresponding degradation mechanism were explored. The results showed that Fe 3 O 4 @SiO 2 -LNS/PMS system had good removal efficiency for AB9 in wastewater, and AB9 dye was completely oxidized and finally degraded into CO 2 and H 2 O. The maximum removal percentage of AB9 was observed when the pH and temperature of the system were 6.0 and 313 K, and the removal percentage of AB9 achieved 100 % when the optimal dosage of Fe 3 O 4 @SiO 2 -LNS and PMS were 3.44 g/L and 53.15 mM, respectively. In addition, Fe 3 O 4 @SiO 2 -LNS had good stability and reusability. This work provides a promising approach for abatement of dyeing wastewater pollution and a new direction for high-value utilization of alkali lignin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The existing efficiency indicators for phytoremediation cannot fully characterise the economic costs and application potential of remediation plants. In this study, we proposed a new strategy for selecting remediation plants based on economic indicators (cost per unit of heavy metal removal). Based on field experiments and data collection, we conducted cost-benefit analyses under various scenarios to compare the application prospects of four cadmium (Cd)-accumulators (Hylotelephium spectabile, Sedum alfredii, Sedum plumbizincicola and tobacco) on slightly Cd-contaminated farmland soil. Utilizing the current screening strategy, which prioritized remediation indicators only, we found that in Cd-contaminated soil, S. plumbizincicola exhibited the best ability to uptake Cd (250 g ha -1 ). However, applying the new strategy that combined economic and remediation indicators, the Monte Carlo simulations results showed that tobacco showed the lowest cost per gram of Cd uptake (546 RMB g -1 ). Combining scenario simulation and cost-benefit analysis, tobacco achieved the earliest positive net present value benefit, indicating a higher application potential in slightly Cd-contaminated soil. Additionally, the spatial distribution and optimal temperature range for tobacco cultivation were found to be superior to those of the other three accumulators, which was consistent with the assessment results of the new screening strategy. The indicator proposed in this study, namely, the cost per unit of heavy metal removal, considers both the remediation efficiency and economic cost. This holds significant value for selecting remediation plants with application potential and provides a crucial basis for decision-making in the development of future phytoremediation strategies and the implementation of large-scale applications., 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.)

It is commonly accepted that batteries perform better at low current densities below the mass-transport limit, which restricts their current rate and capacity. Here, it is demonstrated that the performance of Zn metal electrodes can be dramatically enhanced at current densities and cut-off capacities exceeding the mass-transport limit by using pulsed-current protocols. These protocols achieve cumulative plating/stripping capacities of 11.0 Ah cm -2 and 3.8 Ah cm -2 at record-high current densities of 80 and 160 mA cm -2 , respectively. The study identifies and understands the promoted (002)-textured Zn growth and suppressed hydrogen evolution based on the thermodynamics and kinetics of competing reactions. Furthermore, the over-limiting pulsed-current protocol enables long-life Zn batteries with high mass loading (29 mg cathode cm -2 ) and high areal capacity (7.9 mAh cm -2 ), outperforming cells using constant-current protocols at equivalent energy and time costs. The work provides a comprehensive understanding of the current-capacity-performance relationship in Zn plating/stripping and offers an effective strategy for dendrite-free metal batteries that meet practical requirements for high capacity and high current rates., (© 2024 Wiley‐VCH GmbH.)

As one of the most promising battery systems, the lithium sulfur battery is expected to be widely used in fields of high energy density demands. Owing to the unique solid-solid conversion mechanism, there is no shuttle effect for the Li-SPAN (sulfurized polyacrylonitrile) battery. However, the compatibility between Li anode and carbonate electrolyte has not been resolved, which prevents the SPAN from practical applications. Herein, an organic-inorganic gel carbonate electrolyte is proposed to stabilize interphases and structures of both the anode and cathode, where polyimide (PI) is used for electrolyte gelation, which can assist in the uniform distribution of inorganic components at the electrolyte interface. Furthermore, ZnS nanodots loaded on two-dimensional MoS 2 flakes provide abundant Li-ion diffusion paths, improve the transfer kinetic of Li ions, and induce uniform nucleation and deposition of Li. This gel electrolyte ensures Li symmetric cells a long-term cycle life of more than 900 h under the condition of deep lithium plating/stripping at 5 mAh cm -1 . Li∥Cu cells exhibit a prolonged lifespan of 800 h with a CE of 98.3%. Furthermore, the Li-SPAN battery shows stability of more than 850 cycles, with the capacity retention of 85.1%. This work provides an approach for high-energy Li-SPAN batteries with carbonate-based electrolytes.

The El Niño-Southern Oscillation (ENSO), originating in the central and eastern equatorial Pacific, is a defining mode of interannual climate variability with profound impact on global climate and ecosystems. However, an understanding of how the ENSO might have evolved over geological timescales is still lacking, despite a well-accepted recognition that such an understanding has direct implications for constraining human-induced future ENSO changes. Here, using climate simulations, we show that ENSO has been a leading mode of tropical sea surface temperature (SST) variability in the past 250 My but with substantial variations in amplitude across geological periods. We show this result by performing and analyzing a series of coupled time-slice climate simulations forced by paleogeography, atmospheric CO 2 concentrations, and solar radiation for the past 250 My, in 10-My intervals. The variations in ENSO amplitude across geological periods are little related to mean equatorial zonal SST gradient or global mean surface temperature of the respective periods but are primarily determined by interperiod difference in the background thermocline depth, according to a linear stability analysis. In addition, variations in atmospheric noise serve as an independent contributing factor to ENSO variations across intergeological periods. The two factors together explain about 76% of the interperiod variations in ENSO amplitude over the past 250 My. Our findings support the importance of changing ocean vertical thermal structure and atmospheric noise in influencing projected future ENSO change and its uncertainty., Competing Interests: Competing interests statement:The authors declare no competing interest.

As a pivotal category in the realm of electronics skins, flexible pressure sensors have become a focal point due to their diverse applications such as robotics, aerospace industries, and wearable devices. With the growing demands for measurement accuracy, data reliability, and electrical system compatibility, enhancing sensor's linearity has become increasingly critical. Analysis shows that the nonlinearity of flexible sensors primarily originates from mechanical nonlinearity due to the nolinear deformation of polymers and electrical nonlinearity caused by changes in parameters such as resistance. These nonlinearities can be mitigated through geometric design, material design or combination of both. This work reviews linear design strategies for sensors from the perspectives of structure and materials, covering the following main points: (a) an overview of the fundamental working mechanisms for various sensors; (b) a comprehensive explanation of different linear design strategies and the underlying reasons; (c) a detailed review of existing work employing these strategies and the achieved effects. Additionally, this work delves into diverse applications of linear flexible pressure sensors, spanning robotics, safety, electronic skin, and health monitoring. Finally, existing constraints and future research prospects are outlined to pave the way for the further development of high-performance flexible pressure sensors., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Polarization gradient cooling (PGC) plays an important role in many cold atom applications including the formation of Bose-Einstein condensates (BECs) and cooling of single atoms. Traditional parameter optimization of PGC usually relies on subjective expertise, faces challenges in fine manipulation, and exhibits low optimization efficiency. Here, we propose a segmented control method that differs from the traditional PGC process by expanding the experiment parameters from 3 to 30. Subsequently, the conventional timing optimization problem is reformulated as a Markov decision process (MDP), and the experiment parameters are optimized using a reinforcement learning model. With proper settings of hyperparameters, the learning process exhibits good convergence and powerful parameter exploration capabilities. Finally, we capture ∼4.3 × 10 8 cold atoms, with a phase space density of ∼7.1 × 10 -4 at a temperature of ∼3.7 µK in ∼18.8 min. Our work paves the way for the intelligent preparation of degenerate quantum gas.

In recent years, polysaccharides extracted from berries have received great attention due to their various bioactivities. However, the preparation and application of berry polysaccharides have been greatly limited due to the lack of efficient extraction techniques, unclear structure-activity relationships, and ambiguous functional mechanisms. This review discusses the technological progress in solvent extraction, assisted extraction, critical extraction, and combination extraction. The structure-activity relationship and functional mechanism (antioxidation, hypoglycemic, immunoregulation etc.) of berry polysaccharides are reviewed. After systematic exploration, we believe that industrial production is more suitable for using efficient and low-cost extraction methods, such as ultrasonic assisted extraction and microwave assisted extraction. And some of the bioactivities (antioxidant activity, hypoglycemic activity, etc.) of berry polysaccharides are closely related to their structure (molecular weight, monosaccharide composition, branching structure, etc.). Besides, berry polysaccharides exhibit bioactivities by regulating enzyme activity, cellular metabolism, gene expression, and other pathways to exert their effects on the body. These findings indicate the potential of berry polysaccharides as functional foods and drugs. This paper will contribute to the preparation, bioactivity research, and application of berry polysaccharides., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor heterogeneity is associated with poor prognosis and drug resistance, leading to therapeutic failure. Here, we used tumor evolution analysis to determine the intra- and intertumoral heterogeneity of high-grade serous ovarian cancer (HGSOC) and analyze the correlation between tumor heterogeneity and prognosis, as well as chemotherapy response, through single-cell and spatial transcriptomic analysis. We collected and curated 28 HGSOC patients' single-cell transcriptomic data from five datasets. Then, we developed a novel text-mining-based machine-learning approach to deconstruct the evolutionary patterns of tumor cell functions. We then identified key tumor-related genes within different evolutionary branches, characterized the microenvironmental cell compositions that various functional tumor cells depend on, and analyzed the intra- and intertumoral heterogeneity as well as the tumor microenvironments. These analyses were conducted in relation to the prognosis and chemotherapy response in HGSOC patients. We validated our findings in two spatial and seven bulk transcriptomic datasets (total: 1,030 patients). Using transcriptomic clusters as proxies for functional clonality, we identified a significant increase in tumor cell state heterogeneity that was strongly correlated with patient prognosis and treatment response. Furthermore, increased intra- and intertumoral functional clonality was associated with the characteristics of cancer-associated fibroblasts (CAFs). The spatial proximity between CXCL12-positive CAFs and tumor cells, mediated through the CXCL12/CXCR4 interaction, was highly positively correlated with poor prognosis and chemotherapy resistance in HGSOC. Finally, we constructed a panel of 24 genes through statistical modeling that correlate with CXCL12-positive fibroblasts and can predict both prognosis and the response to chemotherapy in HGSOC patients. Our study offers insights into the collective behavior of tumor cell communities in HGSOC, as well as potential drivers of tumor evolution in response to therapy. There was a strong association between CXCL12-positive fibroblasts and tumor progression, as well as treatment outcomes., (© 2024. The Author(s).)

Magnolia sieboldii , an important ornamental tree native to East Asia, comprises two subspecies in distinct regions, with wild populations facing suboptimal survival. This study aimed to understand the potential habitat distribution of these subspecies under future climate-change conditions to support climate-adaptive conservation. The maximum entropy (MaxEnt) model was used with occurrence and environmental data to simulate the current and future suitable habitats under various climate scenarios. Precipitation in the warmest quarter played a crucial role in shaping the potential habitats of both subspecies; however, they exhibited different sensitivities to temperature-related variables and altitude. Magnolia sieboldii subsp. sieboldii is more sensitive to temperature seasonality and annual mean temperature, whereas Magnolia sieboldii subsp. japonica is more affected by altitude, mean temperature in the driest quarter, and isothermality. Currently, the subsp. sieboldii is predicted to have larger, more contiguous suitable habitats across northeastern China, the Korean Peninsula, and Japan, whereas the subsp. japonica occupies smaller, more disjunct habitats scattered in central and western Japan and the southern Chinese mountains. These two subspecies will respond differently to future climate change. Potentially suitable habitats for subsp. sieboldii are expected to expand significantly northward over time, especially under the SSP585 scenario compared with the SSP126 scenario. In contrast, moderately and highly suitable habitats for the subsp. japonica are projected to contract southward significantly. Therefore, we recommend prioritizing the conservation of the subsp. japonica over that of the subsp. sieboldii . Strategies include in situ and ex situ protection, introduction and cultivation, regional hybridization, and international cooperation. Our study offers valuable insights for the development of targeted conservation strategies for both subspecies of M. sieboldii to counteract the effects of climate change.

Extracellular vesicles (EVs) had been described as a next-generation drug delivery system, due to the compelling evidence that they can facilitate the transfer of a variety of biomolecules between cells. The most frequently used strategy for loading protein cargoes is the endogenous engineering of EVs through genetic fusion of the protein of interest (POI) and scaffold proteins with high EV-sorting ability. However, the lack of scaffold proteins had become a major issue hindering the promotion of this technology. Herein, we proposed novel screening criteria that relax the inclusion requirement of candidate scaffold proteins and eventually identified a new scaffold protein, PLXNA1. The truncated PLXNA1 not only inherits the high EV-sorting ability of its full-length counterpart but also allows the fusion expression of POI in both outer surface and luminal areas, individually or simultaneously. In conclusion, our screening criteria expanded the range of potential scaffold proteins. The identified scaffold protein PLXNA1 showed great potential in developing therapeutic EVs., (© 2024 Echo Biotech Co Ltd. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Protein ubiquitination plays a critical role in protein quality control in response to cellular stress. The excessive accumulation of ubiquitinated conjugates can be detrimental to cells and is recognized as a hallmark of multiple neurodegenerative diseases. However, an in-depth understanding of how the excessive ubiquitin chains are removed to maintain ubiquitin homeostasis post stress remains largely unclear. Here we found that caspase-2 (CASP2) accumulates in a ubiquitin and proteasome-positive biomolecular condensate, which we named ubstressome, following stress and functions as a deubiquitinase to remove overloaded ubiquitin chains on proteins prone to misfolding. Mechanistically, CASP2 binds to the poly-ubiquitinated conjugates through its allosteric ubiquitin-interacting motif-like region and decreases overloaded ubiquitin chains in a protease-dependent manner to promote substrate degradation. CASP2 deficiency in mice results in excessive accumulation of poly-ubiquitinated TAR DNA-binding protein 43, leading to motor defects. Our findings uncover a stress-evoked deubiquitinating activity of CASP2 in the maintenance of cellular ubiquitin homeostasis, which differs from the well-known roles of caspase in apoptosis and inflammation. These data also reveal unrecognized protein quality control functions of condensates in the removal of stress-induced ubiquitin chains., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Ecosystem services play an essential role as intermediaries, linking natural ecosystem resources to socio-economic demands. Understanding their impact on ecological well-being is pivotal for ensuring regional environmental security and promoting sustainable societal and economic development. However, there is insufficient research on the relationship between the two. Accordingly, this study explores the evolutionary relationship between ecological health and ecosystem services by constructing an evaluation system. Regression analysis is used to explore the spatial relationship between ecosystem services and ecological health, providing a reference for maintaining the balance between ecological supply and ecological health. The results show that from 1980 to 2020, an overall improvement was observed in the eco-health index of the Yangtze River Economic Belt's. This improvement was notably marked by substantial growth in the eco-vitality index alongside consistent maintenance of the spatial distribution within the eco-organization index. With regard to distributions of specific ecosystem services, dispersed occurrences characterized areas with high water production and crop yield levels; however, within forested regions, attributes for habitat quality preservation, water purification, soil retention and carbon sequestration were predominant. In the impact of ecosystem services on ecological health, food production held sway over less-developed areas, while soil conservation, water supply and habitat quality exerted greater influence over more-developed regions. This study regards ecosystem services as a bridge connecting humans and the environment not only providing a material basis for society but also reflecting the status of ecological health.

Urban streams play a crucial role in water network connectivity, drainage and urban landscaping, and receive abundant allochthonous dissolved organic matter (DOM), which is derived from nature and human activities. However, the influence of diverse land use types on the spatiotemporal distribution and characteristics of DOM in typical urban streams is still not fully understood. Therefore, the water sample collection and data analysis campaign were carried out in Wuhan in summer and winter. By using parallel factor analysis (PARAFAC) model, two humic-like substances and one protein-like component were eventually identified, and the specific DOM charcteristics of urban streams in industrial area illustrated the impact of allochthonous DOM caused by anthropogenic activities on their properties. The characteristics of DOM presents spatiotemporal distribution differences, and the fluorescence intensity of DOM in summer was significantly higher than that in winter, mainly due to the variation of allochthonous input from precipitation and runoff. Significant differences of the DOM concentration and composition in urban streams under different vegetation coverage were found, indicating that extreme human disturbance and high vegetation coverage can both greatly change DOM characteristics in urban streams. Redundancy analysis (RDA) revealed an indirect driving effect of land use on DOM, and the influence was considerably stronger in summer. The partial least squares structural equation modelling (PLS-SEM) analysis showed that land use can directly affect DOM content of urban streams (-0.147), with anthropogenic land use playing a positive role and natural land use the reverse, and indirectly change DOM concentration by influencing DOM origin (0.128), nutrients (0.022) and heavy metals (0.021). Moreover, human social and economic structure in anthropogenic land use can affect DOM components and sources of urban streams. This study revealed the driving mechanism of land use impact on DOM characteristics and improve our understanding of DOM geochemical cycling in urban streams., 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.)

MYB12 is a key regulator that has been shown to promote the accumulation of various phenylpropanoid compounds in plants. However, the regulation of MYB12 gene is largely unknown. In this study, we found that overexpression of the NtMYB59 gene significantly inhibited the accumulation of chlorogenic acid (CGA), flavonols, and anthocyanins in tobacco, while knock-down and knock-out of NtMYB59 significantly increased the contents of these polyphenol compounds. Transcriptome analysis between WT and NtMYB59-OE plants revealed several differentially expressed genes (DEGs) encoding crucial enzymes in the phenylpropanoid pathway and the transcription factor NtMYB12. ChIP-seq assay further indicated that NtMYB12 might be a direct target of NtMYB59. Subsequent yeast one-hybrid, electrophoretic mobility shift assay, and Dual-Luciferase assays confirmed that NtMYB59 directly binds to the promoter of NtMYB12 to inhibit its expression. Moreover, loss-function of NtMYB59 significantly promoted the accumulation of flavonols and anthocyanins in ntmyb59, but their contents in ntmyb59/ntmyb12 double mutants were significantly lower than that of WT and ntmyb59 plants, indicating that the regulation of NtMYB59 on flavonoids biosynthesis depends on the activity of NtMYB12. Our study revealed that NtMYB59 regulates the expression of NtMYB12, and provided new potential strategies for modulating phenylpropanoids biosynthesis in tobacco., 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 Masson SAS. All rights reserved.)

Spinal disorders pose a significant global health challenge, affecting nearly 5% of the population and incurring substantial socioeconomic costs. Over time, spinal neurosurgery has evolved from basic 19th-century techniques to today's minimally invasive procedures. The recent integration of technologies such as robotic assistance and advanced imaging has not only improved precision but also reshaped treatment paradigms. This review explores key innovations in imaging, biomaterials, and emerging fields such as AI, examining how they address long-standing challenges in spinal care, including enhancing surgical accuracy and promoting tissue regeneration. Are we at the threshold of a new era in healthcare technology, or are these innovations merely enhancements that may not fundamentally advance clinical care? We aim to answer this question by offering a concise introduction to each technology and discussing in depth its status and challenges, providing readers with a clearer understanding of its actual potential to revolutionize surgical practices., 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.)

Inhibiting the shuttle of polysulfides is of great significance for promoting the practical application of lithium-sulfur batteries (LSBs). Here, an imine-linked covalent organic framework@carbon nanotube (COF@CNT) interlayer composed of triazine and boroxine rings is constructed between the sulfur cathode and the separator for polysulfides reception and reutilization. The introduction of CNT imparts the conductor characteristic to the interlayer attributed to electron tunneling in thin COF shell, and creates a hierarchical porous architecture for accommodating polysulfides. The uniform distribution of amphiphilic adsorption sites in COF microporous structure not only enables efficient entrapment of polysulfides while allowing the penetration of Li + ions, but also provides a stable electrocatalytic channel for bidirectional conversion of active sulfur to achieve the substantially improved capacity and stability. The interlayer-incorporated LSBs deliver an ultrahigh capacity of 1446 mA g -1 at 0.1C and an ultralow capacity decay rate of 0.019% at 1C over 1500 cycles. Even at an electrolyte/sulfur ratio of 6 µL mg -1 , an outstanding capacity of 995 mAh g -1 and capacity retention of 74.1% over 200 cycles at 0.2C are obtained. This work offers a compelling polysulfides entrapment and reactivation strategy for stimulating the study on ultra-stable LSBs., (© 2024 Wiley‐VCH GmbH.)

Liver cancer, one of the most common malignant tumors, has seriously threatened people's physical and mental health. The paper was conducted to investigate the functions of two different anesthesia methods on Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and T lymphocyte subsets in patients undergoing liver cancer resection, and to explore the liver function impact of patients undergoing liver cancer surgery. 80 liver cancer patients were split into propofol intravenous anesthesia group and sevoflurane inhalation anesthesia group. The patient's operation-related indicators and changes in TNF-α, CRP and T lymphocyte subsets before anesthesia, after anesthesia, 1 day after anesthesia, and 3 days after anesthesia were calculated. The levels of TNF-α and CRP in the two groups after operation were clearly higher than those before anesthesia, but there was no obvious difference between the two groups. After operation, the TNF-α of the propofol intravenous anesthesia group was lower than the sevoflurane inhalation anesthesia group. The CD3+, CD4+ and CD4+/CD8+ levels in both groups recovered to the pre-anaesthesia level 3 days after the operation. The levels of ALT, AST, ALB and TBIL returned to normal at d4 in both propofol intravenous anesthesia and sevoflurane inhalation anesthesia groups. Compared with evoflurane inhalation anesthesia for patients with liver cancer, intravenous anesthesia with propofol can reduce the body's inflammatory response to a certain extent, has weak inhibitory effect on T lymphocyte immune function, and a smaller effect on liver function.

Objective: Autoinflammation and phospholipase C (PLC) γ2-associated antibody deficiency and immune dysregulation (APLAID) syndrome is an autoinflammatory disease caused by gain-of-function variants in PLCG2. This study investigates the pathogenic mechanism of a novel variant of PLCG2 in a patient with APLAID syndrome., Methods: Whole-exome sequencing and Sanger sequencing were used to identify the pathogenic variant in the patient. Single-cell RNA sequencing, immunoblotting, luciferase assay, inositol monophosphate enzyme-linked immunosorbent assay, calcium flux assay, quantitative PCR, and immunoprecipitation were used to define inflammatory signatures and evaluate the effects of the PLCG2 variant on protein functionality and immune signaling., Results: We identified a novel de novo variant, PLCG2 p.D993Y, in a patient with colitis, pansinusitis, skin rash, edema, recurrent respiratory infections, B-cell deficiencies, and hypogammaglobulinemia. The single-cell transcriptome revealed exacerbated inflammatory responses in the patient's peripheral blood mononuclear cells. Expression of the D993Y variant in HEK293T, COS-7, and PLCG2 knock-out THP-1 cell lines showed heightened PLCγ2 phosphorylation; elevated inositol-1,4,5-trisphosphate production and intracellular Ca 2+ release; and activation of the MAPK, NF-κB, and NFAT signaling pathways compared with control-transfected cells. In vitro experiments indicated that the D993Y variant altered amino acid properties, disrupting the interaction between the catalytic and autoinhibitory domains of PLCγ2, resulting in PLCγ2 autoactivation., Conclusion: Our findings demonstrated that the PLCG2 D993Y variant is a gain-of-function mutation via impairing its autoinhibition, activating multiple inflammatory signaling pathways, thus leading to APLAID syndrome. This study further broadens the molecular underpinnings and phenotypic spectrum of PLCγ2-related disorders., (© 2024 American College of Rheumatology.)

Background: Pleural mesothelioma (PM) is a highly aggressive tumor with poor survival outcomes. The role of additional radiotherapy for PM patients who have received surgery and chemotherapy remains controversial. In this study, we aim to evaluate the impact of age on the effectiveness of additional radiotherapy in order to identify the populations that may benefit from the trimodality therapy., Methods: We designed a case-control study and retrospectively selected PM patients who underwent surgery and chemotherapy, with or without radiotherapy, from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019). Kaplan-Meier curves were performed to compare the overall survival (OS) and cancer-specific survival (CSS) between the surgery + chemotherapy group and the trimodality therapy group. Propensity score matching (PSM) was used to balance the clinical characteristics and reduce potential confounding effects., Results: A total of 745 patients were selected, of which 515 received surgery + chemotherapy and 230 received trimodality therapy. For patients aged 50 to <65 years, additional radiotherapy showed better OS (3-year: 34.78% vs. 23.92%, P=0.02) and CSS (3-year: 36.15% vs. 25.46%, P=0.04) compared to surgery + chemotherapy. Similar results were observed after PSM (3-year OS: 38.76% vs. 26.53%, P=0.02; 3-year CSS: 40.49% vs. 26.92%, P=0.02). No significant benefit of radiotherapy was seen for patients aged <50 and ≥65 years, both before and after PSM., Conclusions: Our findings reveal that trimodality therapy is associated with better OS and CSS compared to surgery + chemotherapy for patients aged 50 to <65 years. These patients might obtain a benefit from additional radiotherapy., 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-24-1111/coif). L.X. receives funding from the Science and Technology Project of the Health Commission of Sichuan Province, China (No. 21PJ008). L.L. receives funding from 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21002). The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Advanced pancreatic ductal adenocarcinomas (PDACs) respond poorly to all therapies, including the first-line treatment, chemotherapy, the latest immunotherapies, and KRAS-targeting therapies. Despite an enormous effort to improve therapeutic efficacy in late-stage PDAC patients, effective treatment modalities remain an unmet medical challenge. To change the status quo, we explored the key signaling networks underlying the universally poor response of PDAC to therapy. Here, we report a previously unknown chemo-induced symbiotic signaling circuit that adaptively confers chemoresistance in patients and mice with advanced PDAC. By integrating single-cell transcriptomic data from PDAC mouse models and clinical pathological information from PDAC patients, we identified Yap1 in cancer cells and Cox2 in stromal fibroblasts as two key nodes in this signaling circuit. Co-targeting Yap1 in cancer cells and Cox2 in stroma sensitized PDAC to Gemcitabine treatment and dramatically prolonged survival of mice bearing late-stage PDAC, whereas simultaneously inhibiting Yap1 and Cox2 only in cancer cells was ineffective. Mechanistically, chemotherapy triggers non-canonical Yap1 activation by nemo-like kinase in 14-3-3ζ-overexpressing PDAC cells and increases secretion of CXCL2/5, which bind to CXCR2 on fibroblasts to induce Cox2 and PGE2 expression, which reciprocally facilitate PDAC cell survival. Finally, analyses of PDAC patient data revealed that patients who received Statins, which inhibit Yap1 signaling, and Cox2 inhibitors (including Aspirin) while receiving Gemcitabine displayed markedly prolonged survival compared to others. The robust anti-tumor efficacy of Statins and Aspirin, which co-target the chemo-induced adaptive circuit in the tumor cells and stroma, signifies a unique therapeutic strategy for PDAC., (© 2024. The Author(s).)