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This paper proposes a new impulse excitation technique using a square plate. First, the functional relationship between the modal frequency of the specimen and the geometrical dimensions and mechanical parameters was established by using the finite element method. Then, the continuous functional relationship derived by a homotopy method allowed the frequency ratios to be related to the thickness-to-length ratio and Poisson's ratio. By measuring the frequency ratios and thickness-to-length ratio, Poisson's ratio could be calculated using this functional relationship. When the density and Poisson's ratio were known, Young's modulus could be identified inversely in conjunction with the finite element analysis. Finally, a comparison test between this method and the traditional impulse excitation technique was designed and implemented, and the results showed that this method has advantages in both testing efficiency and accuracy. The study provides a new idea for system identification, which has important application value and promotion significance., (© 2024. The Author(s).)

Abstract: Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Large pieces of plastic are transformed into microplastic particles through weathering, abrasion, and ultraviolet radiation, significantly impacting the soil ecosystem. However, studies on biodegradable microplastics replacing traditional microplastics as agricultural mulching films to drive the biogeochemical processes influenced by GHG are still in their initial stages, with limited relevant reports available. This study sought to investigate the effects of microplastic and straw addition on CO 2 and N 2 O emissions in different soils. Herein, yellow-brown soil (S1) and fluvo-aquic soil (S2) were utilized, each treated with three different concentrations of PLA (polylactic acid) microplastics (0.25%, 2%, and 7% w/w) at 25 °C for 35 days, with and without straw addition. The results showed that straw (1% w/w) significantly increased soil CO 2 by 4.1-fold and 3.2-fold, respectively, and N 2 O by 1.8-fold and 1.8-fold, respectively, in cumulative emissions in S1 and S2 compared with the control. PLA microplastics significantly increased CO 2 emissions by 71.5% and 99.0% and decreased N 2 O emissions by 30.1% and 24.7% at a high concentration (7% w/w, PLA3) in S1 and S2 compared with the control, respectively. The same trend was observed with the addition of straw and microplastics together. Structural equation modeling and redundancy analysis confirmed that soil physiochemical parameters, enzyme and microbial activities are key factors regulating CO 2 and N 2 O emissions. The addition of microplastics is equivalent to the addition of carbon sources, which can significantly affect DOC, MBC, SOC and the abundance of carbon-associated bacteria (CbbL), thereby increasing soil CO 2 emissions. The addition of microplastics alone inhibited the activity of nitrogen cycling enzymes (urease activity), increasing the abundance of denitrifying microbes. However, adding a high amount of microplastics and straw together released plastic additives, inhibiting microbial abundance and reducing the nitrogen cycle. These effects decreased NH 4 + -N and increased NO 3 - -N, resulting in decreased N 2 O emissions. This study indicates that biodegradable microplastics could reduce soil plastic residue pollution through degradation. However, their use could also increase CO 2 emissions and decrease N 2 O emissions. Consequently, this research lays the groundwork for further investigation into the implications of utilizing biodegradable microplastics as agricultural mulch, particularly concerning soil geochemistry and GHG emissions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shan lin reports financial support was provided by National Key Research and Development Program of China. Shan lin reports financial support was provided by The Scientific and Technological Talents and Platform of Yunnan Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Glycosaminoglycans (GAGs) are a family of structurally complex heteropolysaccharides that play pivotal roles in biological functions, including the regulation of cell proliferation, enzyme inhibition, and activation of growth factor receptors. Therefore, the synthesis of GAGs is a hot research topic in drug development. The enzymatic synthesis of GAGs has received widespread attention due to their eco-friendly nature, high regioselectivity, and stereoselectivity. The enhancement of the enzymatic synthesis process is the key to its industrial applications. In this review, we overviewed the construction of more efficient in vitro biomimetic synthesis systems of glycosaminoglycans and presented the different strategies to improve enzyme catalysis, including the combination of chemical and enzymatic methods, solid-phase synthesis, and protein engineering to solve the problems of enzyme stability, separation and purification of the product, preparation of structurally defined sugar chains, etc., and discussed the challenges and opportunities in large-scale green synthesis of GAGs., 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.)

Additive manufacturing (AM) enables the production of complex, lightweight, and customized components with superior quality. Selecting the right materials considering their thermal properties, printability, and layer adhesion is crucial in melting-based AM techniques. This study investigates Droplet Deposition Modelling (DDM), an innovative material extrusion process that utilizes thermoplastic granules. DDM is distinguished by its shorter manufacturing times and a wider range of materials, setting it apart from traditional material extrusion methods such as fused filament fabrication. We investigated the printability and part quality in DDM using two common pharmaceutical excipients: Polyvinylpyrrolidone/vinyl acetate 6:4 (PVP/VA), which is highly brittle, and Polycaprolactone (PCL), known for its low solubility and role in controlled drug release. Different ratios of PVP/VA and PCL were compounded via hot melt extrusion (HME) and used in DDM to study the impact of ingredient content on printability and part quality, employing geometrical models to assess material compatibility and printability. The study revealed that increasing PVP/VA content leads to higher viscosity, reduced flowability, and uneven deposition, with formulations of 80 % and 100 % PVP/VA showing poor processability. In contrast, formulations with 60 % and 40 % PVP/VA exhibited smooth processing and compatibility with DDM. We identified processing temperature and Drop Aspect Ratio (DAR) as key factors influencing material printability and part quality. Elevated processing temperatures and reduced DAR were found to increase interface temperatures, reduce diffusion, and potentially cause the 'elephant feet' issue. Additionally, smaller droplet sizes and material characteristics, such as higher interfacial tension in PCL, could lead to coalescence. Our findings highlight the complexities in optimizing DDM processing parameters and material blends, underscoring the need for careful formulation design to achieve high-quality 3D printed products., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Organophosphate flame retardants (OPFRs) pose the significant risks to the environment and human health and have become a serious public health issue. Tricresyl phosphates (TCPs), a group of aryl OPFRs, exhibit neurotoxicity and endocrine disrupting toxicity. However, the binding mechanisms between TCPs and human serum albumin (HSA) remain unknown. In this study, through fluorescence and ultraviolet-visible (UV-vis) absorption spectroscopy, molecular docking and molecular dynamics (MD), tri-para-cresyl phosphate (TpCP) was selected to explore potential interactions between HSA and TCPs. The results of the fluorescence spectroscopy demonstrated that a decrease in the fluorescence intensity of HSA and a blue shift were observed with the increasing concentrations of TpCP. The binding constant (K a ) was 2.575 × 10 4  L/mol, 4.701 × 10 4  L/mol, 5.684 × 10 4  L/mol and 9.482 × 10 4  L/mol at 293 K, 298 K, 303 K, and 310 K, respectively. The fluorescence process between HSA and TpCP involved a mix of static and dynamic quenching mechanism. The gibbs free energy (ΔG 0 ) of HSA-TpCP system was -24.452 kJ/mol, -25.907 kJ/mol, -27.363 kJ/mol, and - 29.401 kJ/mol at 293 K, 298 K, 303 K, and 310 K, respectively, suggesting that the HSA-TpCP reaction was spontaneous. The enthalpy change (ΔH 0 ) and thermodynamic entropy change (ΔS 0 ) of the HSA-TpCP system were 60.83 kJ/mol and 291.08 J/(mol·>k), respectively, indicating that hydrophobic force was the major driving force in the HSA-TpCP complex. Furthermore, multispectral analysis also revealed that TpCP could alter the microenvironment of tryptophan residue and the secondary structure of HSA and bind with the active site I of HSA. Molecular docking and MD simulations confirmed that TpCP could spontaneously form a stable complex with HSA, which was consistent with the fluorescence experimental results. This study provides novel insights into the mechanisms of underlying the transportation and distribution of OPFRs in humans., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phytoene desaturase (PDS) is a key rate-limiting enzyme in the carotenoid biosynthesis pathway. Although commercial PDS inhibitors have been developed for decades, it remains necessary to develop novel PDS inhibitors with higher bioactivity. In this work, we used the scaffold hopping and linker modification approaches to design and synthesize a series of compounds ( 7a - 7o , 8a - 8l , and 14a - 14d ). The postemergence application assay demonstrated that 8e and 7e separately showed the best herbicidal activity at 750 g a.i./ha and lower doses (187.5 g, 375g a.i./ha) without no significant toxicity to maize and wheat. The surface plasmon resonance revealed strong binding affinity between 7e and Synechococcus PDS ( Syn PDS). The HPLC analysis confirmed that 8e at 750 g a.i./ha caused significant phytoene accumulation in Arabidopsis seedlings. This work demonstrates the efficacy of structure-guided optimization through scaffold hopping and linker modification to design potent PDS inhibitors with enhanced bioactivity and crop safety.

The magneto-optical response of chiral materials holds significant potential for applications in physics, chemistry, and biology. However, exploration of the near-infrared (NIR) magneto-optical response remains limited. Herein, we report the synthesis and strong NIR-II magneto-optical activity of three pairs of chiral 3 d- 4 f clusters of R/S -Ln 15 Cu 54 (Ln = Sm, Gd, and Dy). Structural analysis reveals that R/S -Ln 15 Cu 54 features a triangular prism cage with C 3 symmetry. Interestingly, magnetic circular dichroism (MCD) spectra exhibit remarkable magneto-optical response in the NIR-II region, driven by the f-f transition. The maximum g -factor of R/S -Sm 15 Cu 54 reaches 5.5 × 10 -3 T -1 around 1300-1450 nm, surpassing values associated with Dy III and Cu II ions. This remarkable NIR-II magneto-optical activity may be attributed to strong magnetic-dipole-allowed f-f transitions and helix chirality of the structure. This work not only presents the largest Ln-Cu clusters to date but also demonstrate the key role of magnetic-dipole-allowed transitions on magneto-optical activity.

Carbon monoxide (CO), a significant gas transmitter, plays a vital role in the intricate functioning of living systems and is intimately linked to a variety of physiological and pathological processes. To comprehensively investigate CO within biological system, researchers have widely adopted CORM-3, a compound capable of releasing CO, which serves as a surrogate for CO. It aids in elucidating the physiological and pathological effects of CO within living organisms and can be employed as a therapeutic drug molecule. Therefore, the pivotal role of CORM-3 necessitates the development of effective probes that can facilitate the visualization and tracking of CORM-3 in living systems. However, creating fluorescent probes for real-time imaging of CORM-3 in living species has proven to be a persisting challenge that arises from factors such as background interference, light scattering and photoactivation. Herein, the BNDN fluorescent probe, a brand-new near-infrared is proposed. Remarkably, the BNDN probe offers several noteworthy advantages, including a substantial Stokes shift (201 nm), heightened sensitivity, exceptional selectivity, and an exceedingly low CORM-3 detection limit (0.7 ppb). Furthermore, the underlying sensing mechanism has been meticulously examined, revealing a process that revives the fluorophore by reducing the complex Cu 2+ to Cu + . This distinctive NIR fluorescence "turn-on" character, coupled with its larger Stokes shift, holds great promise for achieving high resolution imaging. Most impressively, this innovative probe has demonstrated its efficacy in detecting exogenous CORM-3 in living animal. It is important to underscore that these endeavors mark a rare instance of a near-infrared probes successfully detecting exogenous CORM-3 in vivo. These exceptional outcomes highlighted the potential of BNDN as a highly promising new tool for in vivo detection of CORM-3. Considering the impressive imaging capabilities demonstrated by BNDN presented in this study, we anticipate that this tool may offer a compelling avenue for shedding light on the roles of CO in future research endeavors., 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.)

M2-like macrophages promote tumor growth and cancer immune evasion. This study used an in vitro model to investigate how hypoxia and tumor metabolism affect macrophage polarization. Liver cancer cells (HepG2 and VX2) and macrophages (THP1) were cultured under hypoxic (0.1% O 2 ) and normoxic (21% O 2 ) conditions with varying glucose levels (2 g/L or 4.5 g/L). Viability assays and extracellular pH (pHe) measurements were conducted over 96 hours. Macrophages were exposed to the tumor-conditioned medium (TCM) from the cancer cells, and polarization was assessed using arginase and nitrite assays. GC-MS-based metabolic profiling quantified TCM meta-bolites and correlated them with M2 polarization. The results showed that pHe in TCMs decreased more under hypoxia than normoxia ( p < 0.0001), independent of glucose levels. The arginase assay showed hypoxia significantly induced the M2 polarization of macrophages (control group: p = 0.0120, 0.1% VX2-TCM group: p = 0.0149, 0.1% HepG2-TCM group: p < 0.0001, 0.1% VX2-TCM HG group: p = 0.0001, and 0.1% HepG2-TCM HG group: p < 0.0001). TCMs also induced M2 polarization under normoxic conditions, but the strongest M2 polarization occurred when both tumor cells and macrophages were incubated under hypoxia with high glucose levels. Metabolomics revealed that several metabolites, particularly lactate, were correlated with hypoxia and M2 polarization. Under normoxia, elevated 2-amino-butanoic acid (2A-BA) strongly correlated with M2 polarization. These findings suggest that targeting tumor hypoxia could mitigate immune evasion in liver tumors. Lactate drives acidity in hypoxic tumors, while 2A-BA could be a therapeutic target for overcoming immunosuppression in normoxic conditions.

Introduction: The aim of this work is to develop a deep learning (DL) system for rapidly and accurately screening for intraocular tumor (IOT), retinal detachment (RD), vitreous hemorrhage (VH), and posterior scleral staphyloma (PSS) using ocular B-scan ultrasound images., Methods: Ultrasound images from five clinically confirmed categories, including vitreous hemorrhage, retinal detachment, intraocular tumor, posterior scleral staphyloma, and normal eyes, were used to develop and evaluate a fine-grained classification system (the Dual-Path Lesion Attention Network, DPLA-Net). Images were derived from five centers scanned by different sonographers and divided into training, validation, and test sets in a ratio of 7:1:2. Two senior ophthalmologists and four junior ophthalmologists were recruited to evaluate the system's performance., Results: This multi-center cross-sectional study was conducted in six hospitals in China. A total of 6054 ultrasound images were collected; 4758 images were used for the training and validation of the system, and 1296 images were used as a testing set. DPLA-Net achieved a mean accuracy of 0.943 in the testing set, and the area under the curve was 0.988 for IOT, 0.997 for RD, 0.994 for PSS, 0.988 for VH, and 0.993 for normal. With the help of DPLA-Net, the accuracy of the four junior ophthalmologists improved from 0.696 (95% confidence interval [CI] 0.684-0.707) to 0.919 (95% CI 0.912-0.926, p < 0.001), and the time used for classifying each image reduced from 16.84 ± 2.34 s to 10.09 ± 1.79 s., Conclusions: The proposed DPLA-Net showed high accuracy for screening and classifying multiple ophthalmic diseases using B-scan ultrasound images across mutiple centers. Moreover, the system can promote the efficiency of classification by ophthalmologists., (© 2024. The Author(s).)

Deep carbon cycle is crucial for mantle dynamics and maintaining Earth's habitability. Recycled carbonates are a strong oxidant in mantle carbon-iron redox reactions, leading to the formation of highly oxidized mantle domains and deep carbon storage. Here we report high Fe 3+ /∑Fe values in Cenozoic intraplate basalts from eastern China, which are correlated with geochemical and isotopic compositions that point to a common role of carbonated melt with recycled carbonate signatures. We propose that the source of these highly oxidized basalts has been oxidized by carbonated melts derived from the stagnant subducted slab in the mantle transition zone. Diamonds formed during the carbon-iron redox reaction were separated from the melt due to density differences. This would leave a large amount of carbon (about four times of preindustrial atmospheric carbon budget) stored in the deep mantle and isolated from global carbon cycle. As such, the amounts of subducted slabs stagnated at mantle transition zone can be an important factor regulating the climate.

Neutrophil hyperexpression is recognized as a key prognostic factor for inflammation and is closely related to the emergence of a wide range of cardiovascular disorders. In recent years, S100 calcium binding protein A8/A9 (S100A8/A9) derived from neutrophils has attracted increasing attention as an important warning protein for cardiovascular disease. This article evaluates the utility of S100A8/A9 protein as a biomarker and therapeutic target for diagnosing cardiovascular diseases, considering its structural features, fundamental biological properties, and its multifaceted influence on cardiovascular conditions including atherosclerosis, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure., 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., (© 2024 Sun, Xu, Gao, Deng, Song, Li and Liu.)

Background: Developmental dysplasia of the hip (DDH) is a common cause of childhood disability, and the incidence of DDH shows significant familial aggregation. As the genetic factors of DDH remain unknown, the correlation between five candidate single nucleotide polymorphisms (SNPs) and DDH was evaluated in the Han Chinese population of Southwest China., Methods: A case‒control association study was conducted in 276 patients with DDH and 318 healthy controls. SNP genotyping in the case and control groups was performed by SNPshot and multiple PCR. SNPs were genotyped in the case and control groups by multiplex PCR. The relationship between DDH and candidate SNPs was evaluated using the χ2 test., Results: The genotype distributions of rs291412 in HIBCH and rs769956 in FTCDNL1 were different between the case and control groups (P < 0.05). After genetic model analysis, logistic regression analysis revealed that the C allele of rs291412 had a protective effect on DDH (OR = 0.605, P = 0.010) and that the G allele of rs769956 was a risk factor (OR = 2.939, P = 0.010).s., Conclusion: These SNPs could be associated with susceptibility to DDH but larger population-based studies should confirm the current results., (© 2024. The Author(s).)

Background: The role of selinexor, a targeted inhibitor of exportin 1 (XPO1), in the treatment of cholangiocarcinoma is not yet fully understood. This study conducted comprehensive in vitro and in vivo investigations to elucidate the effects of selinexor on cholangiocarcinoma, with a focus on its mechanistic relationship with the cellular localization of Paternally Expressed Gene 3 (PEG3)., Methods: A patient-derived xenograft (PDX) model was established using samples from a cholangiocarcinoma patient in immunodeficient mice to assess the in vivo effects of selinexor. Additionally, cholangiocarcinoma cell lines HuCC-T1 and BRE were cultured to evaluate selinexor's impact on cell proliferation, invasion, migration, cell cycle, and apoptosis. HuCC-T1 cells were also implanted in immunodeficient mice for further investigation. Immunofluorescence and Western blotting were employed to observe the expression and localization of the PEG3 protein., Results: The results demonstrated that selinexor significantly inhibited tumor growth in the cholangiocarcinoma PDX model and promoted the accumulation of PEG3 protein within the nuclei of tumor cells. In vitro experiments showed that selinexor effectively suppressed cholangiocarcinoma cell proliferation, invasion, and migration, while also impeding the cell cycle and inducing apoptosis. Notably, selinexor markedly facilitated the nuclear accumulation of PEG3 protein in cholangiocarcinoma cells. However, when PEG3 expression was knocked down, the effects of selinexor on cholangiocarcinoma were significantly reversed., Conclusion: These findings suggest that selinexor inhibits the progression of cholangiocarcinoma by targeting XPO1 and promoting the nuclear accumulation of PEG3 protein, thereby hindering the cell cycle and inducing apoptosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The therapeutic effect of anlotinib on neuroblastoma is still not fully understood. This study aims to explore the differentiation therapeutic effects of anlotinib on neuroblastoma and its potential association with the neural development regulatory protein collapsin response mediator protein 5 (CRMP5), both in vivo and in vitro. A patient-derived xenograft (PDX) model was established to observe the therapeutic effect of anlotinib. Neuroblastoma cell lines SK-N-SH and SK-N-AS were cultured to observe the morphological impact of anlotinib. Transwell assay was used to evaluate the cell invasion, and Western blot analysis and immunohistochemistry were employed to detect the expressions of neuronal differentiation-related proteins. Results indicate that anlotinib effectively inhibited tumor growth in the PDX model, modulated the expressions of neuronal differentiation markers. In vitro, anlotinib treatment induced neurite outgrowth in neuroblastoma cells and inhibited their invasive ability, reflecting a change in neuronal marker expression patterns consistent with the PDX model. Similarly, in the SK-N-AS mouse xenograft model, anlotinib demonstrated comparable tumor-suppressing effects and promoted neuronal-like differentiation. Additionally, anlotinib significantly downregulated CRMP5 expression in neuroblastoma both in vivo and in vitro. Overexpression of CRMP5 significantly reversed the differentiation therapy effect of anlotinib, exacerbating the aggressiveness and reducing the differentiation level of neuroblastoma. These findings highlight the potential of anlotinib as an anti-neuroblastoma agent. It may suppress tumor proliferation and invasion by promoting the differentiation of tumor cells towards a neuronal-like state, and this differentiation therapy effect involves the inhibition of CRMP5 signaling., (© 2024 Wiley Periodicals LLC.)

Integrated MFC-MBR systems effectively remove antibiotics and control the release of antibiotic resistance genes (ARGs). However, the fouling layers on membranes can potentially act as reservoirs for ARGs. This study aims to elucidate the roles of membrane fouling layers and levels in influencing sulfamethoxazole (SMX) removal and ARGs control within an MFC-MBR system. Our findings demonstrate that low-intensity bioelectricity (400-500 mV) mitigates membrane fouling rates. The membrane fouling layer significantly contributes (39%-47%) to SMX removal compared to the cathode/anode zones. Higher extracellular polymeric substance (EPS) content and a lower protein/polysaccharide (PN/PS) ratio favor SMX removal by the membrane fouling layer. Across different levels of membrane fouling, the PN/PS ratio rather than EPS concentration plays a crucial role in SMX removal efficiency. The MFC-MBR with low fouling achieved superior SMX removal (69.1%) compared to medium (54.3%) and high fouling conditions (46.8%). The presence of ARGs in the membrane fouling layer increases with fouling formation, with intrinsic ARGs prevailing. Dense membrane fouling layers effectively retain ARGs, thereby reducing the risk of extracellular ARGs (eARGs) diffusion in effluents. These results provide insights into controlling ARGs in MFC-MBR systems and underscore the significant role of membrane fouling layers in antibiotics and ARGs removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Reduced endometrium thickness and receptivity are two important reasons for recurrent implantation failure (RIF). In order to elucidate differences between these two types of endometrial defects in terms of molecular signatures, cellular interactions, and structural changes, we systematically investigated the single-cell transcriptomic atlas across three distinct groups: RIF patients with thin endometrium (≤ 6 mm, TE-RIF), RIF patients with normal endometrium thickness (≥ 8 mm, NE-RIF), and fertile individuals (Control)., Methods: The late proliferative and mid-secretory phases of the endometrium were collected from three individuals in the TE-RIF group, two in the NE-RIF group, and three in the control group. The study employed a combination of advanced techniques. Single-cell RNA sequencing (scRNA-seq) was utilized to capture comprehensive transcriptomic profiles at the single-cell level, providing insights into gene expression patterns within specific cell types. Scanning and transmission electron microscopy were employed to visualize ultrastructural details of the endometrial tissue, while hematoxylin and eosin staining facilitated the examination of tissue morphology and cellular composition. Immunohistochemistry techniques were also applied to detect and localize specific protein markers relevant to endometrial receptivity and function., Results: Through comparative analysis of differentially expressed genes among these groups and KEGG pathway analysis, the TE-RIF group exhibited notable dysregulations in the TNF and MAPK signaling pathways, which are pivotal in stromal cell growth and endometrial receptivity. Conversely, in the NE-RIF group, disturbances in energy metabolism emerged as a primary contributor to reduced endometrial receptivity. Additionally, using CellPhoneDB for intercellular communication analysis revealed aberrant interactions between epithelial and stromal cells, impacting endometrial receptivity specifically in the TE-RIF group., Conclusion: Overall, our findings provide valuable insights into the heterogeneous molecular pathways and cellular interactions associated with RIF in different endometrial conditions. These insights may pave the way for targeted therapeutic interventions aimed at improving endometrial receptivity and enhancing reproductive outcomes in patients undergoing ART. Further research is warranted to validate these findings and translate them into clinical applications for personalized fertility treatments., Trial Registration: Not applicable., (© 2024. The Author(s).)

Glycine- and arginine-rich (GAR) motifs, commonly found in RNA-binding and -processing proteins, can be symmetrically (SDMA) or asymmetrically (ADMA) dimethylated at the arginine residue by protein arginine methyltransferases. Arginine-methylated protein motifs are usually read by Tudor domain-containing proteins. Here, using a GFP-Trap, we identify a non-Tudor domain protein, squamous cell carcinoma antigen recognized by T cells 3 (SART3), as a reader for SDMA-marked GAR motifs. Structural analysis and mutagenesis of SART3 show that aromatic residues lining a groove between two adjacent aromatic-rich half-a-tetratricopeptide (HAT) repeat domains are essential for SART3 to recognize and bind to SDMA-marked GAR motif peptides, as well as for the interaction between SART3 and the GAR-motif-containing proteins fibrillarin and coilin. Further, we show that the loss of this reader ability affects RNA splicing. Overall, our findings broaden the range of potential SDMA readers to include HAT domains., Competing Interests: Declaration of interests M.T.B. is the co-founder of EpiCypher., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Multinary metal sulfides (MMSs) are highly suitable candidates for the application of electrocatalysis as they offer numerous parameters for optimizing the electronic structure and catalytic sites. Herein, a stable nanoarchitecture consisting of MMSs ((NiCoCrMnFe)S x ) nanoparticles embedded in S, N-codoped carbon (SNC) layers derived from metal organic framework (MOF) and supported on carbonized wood fibers (CWF) was fabricated by directly carbonization. Benefiting from this carbon-coated configuration, along with the synergistic effects within multinary metal systems, (NiCoCrMnFe)S x @SNC/CWF delivers an exceptionally low overpotential of 260 mV at a high current density of 1000 mA cm -2 , a small Tafel slope of 48.5 mV dec -1 , and robust electrocatalytic stability. Furthermore, the (NiCoCrMnFe)S x @SNC/CWF used as the cathode of rechargeable Zn-air batteries demonstrates higher power density and remarkable durability, surpassing that of commercial RuO 2 . Thus, we showcase the feasibility and advantages of employing highly efficient and durable MMSs materials for low-cost and sustainable energy conversion., 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.)

Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests., (© 2024. The Author(s).)

Over the past decades, the field of organic solar cells (OSCs) has witnessed a significant evolution in materials chemistry, which has resulted in a remarkable enhancement of device performance, achieving efficiencies of over 19%. The photoactive layer materials in OSCs play a crucial role in light absorption, charge generation, transport and stability. To facilitate the scale-up of OSCs, it is imperative to address the photostability of these electron acceptor and donor materials, as their photochemical degradation process remains a challenge during the photo-to-electric conversion. In this review, we present an overview of the development of electron acceptor and donor materials, emphasizing the crucial aspects of their chemical stability behavior that are linked to the photostability of OSCs. Throughout each section, we highlight the photochemical degradation pathways for electron acceptor and donor materials, and their link to device degradation. We also discuss the existing interdisciplinary challenges and obstacles that impede the development of photostable materials. Finally, we offer insights into strategies aimed at enhancing photochemical stability and discuss future directions for developing photostable photo-active layers, facilitating the commercialization of OSCs.

Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice. Although the VMHvl innervates the pSI unidirectionally through both excitatory and inhibitory connections, it is the excitatory VMHvl-pSI projections that are strengthened in males to promote aggression, whereas the inhibitory connections that reduce aggressive behavior are strengthened in females. Consequently, the convergent hypothalamic input onto the pSI leads to heightened pSI activity in males, resulting in male-biased aggression. Our findings reveal a sexually distinct excitation-inhibition balance of a hypothalamic-amygdala circuit that underlies sexually dimorphic aggression., Competing Interests: Declaration of interests S.D. is a member of the advisory board of Neuron., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified. Employing a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are synchronously activated during social fear expression. Moreover, optogenetic inhibition of the mPFC-LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal-habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear. These results unravel a crucial role of the prefrontal-habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptom often observed in many psychiatric disorders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. 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.)

Background: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration., Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments., Results: The US irradiation condition of 0.8 W/cm 2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice., Conclusion: The application of US (0.8 W/cm 2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Xiang et al.)

Purpose: Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE)., Patients and Methods: Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher's exact and t -test, Kaplan-Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson's correlation., Results: OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed., Conclusion: The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone., Competing Interests: The authors state that this work has not received any funding. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Outside the submitted work, RS received a stipend from Berliner Krebsgesellschaft e.V.. CAH and LJS are currently fellows of the BIH Charité (Junior Digital) Clinician Scientist Program funded by the Charité-Universitätsmedizin Berlin and the Berlin Institute of Health. HX and YH are fellows of the Chinese Scholarship Council. LJS receives research grants from the Berliner Krebsgesellschaft e.V., the Collaborative Research Center (CRC) 1340 “Matrix in Vision” funded by the Deutsche Forschungsgemeinschaft (DFG), the DFG research unit 5628 “Multiscale MRE: in vivo physics of cancer”, and Guerbet, and honoraria and travel support from Guerbet. Outside the submitted work, BG reports honoraria and travel support in the last 10 years from Parexel/CALYX, C.R. BARD/BD, SIRTex Medical, St. Jude Medical, COOK, AngioDynamics, Pharmcept, Guerbet, Ewimed, Siemens, VARIAN, Terumo, Roche, Merck, 3M, Beacon Bioscience/ICON, IPSEN, Bayer, Pfizer, Eisai, MSD, and INARI; grants from INARI, Siemens, SIRTeX, BARD/BD. The authors report no other conflicts of interest in this work., (© 2024 Schmidt et al.)

Objective: We aimed to develop a deep learning system capable of identifying subjects with cognitive impairment quickly and easily based on multimodal ocular images., Design: Cross sectional study., Subjects: Participants of Beijing Eye Study 2011 and patients attending Beijing Tongren Eye Center and Beijing Tongren Hospital Physical Examination Center., Methods: We trained and validated a deep learning algorithm to assess cognitive impairment using retrospectively collected data from the Beijing Eye Study 2011. Cognitive impairment was defined as a Mini-Mental State Examination score < 24. Based on fundus photographs and OCT images, we developed 5 models based on the following sets of images: macula-centered fundus photographs, optic disc-centered fundus photographs, fundus photographs of both fields, OCT images, and fundus photographs of both fields with OCT (multimodal). The performance of the models was evaluated and compared in an external validation data set, which was collected from patients attending Beijing Tongren Eye Center and Beijing Tongren Hospital Physical Examination Center., Main Outcome Measures: Area under the curve (AUC)., Results: A total of 9424 retinal photographs and 4712 OCT images were used to develop the model. The external validation sets from each center included 1180 fundus photographs and 590 OCT images. Model comparison revealed that the multimodal performed best, achieving an AUC of 0.820 in the internal validation set, 0.786 in external validation set 1, and 0.784 in external validation set 2. We evaluated the performance of the multi-model in different sexes and different age groups; there were no significant differences. The heatmap analysis showed that signals around the optic disc in fundus photographs and the retina and choroid around the macular and optic disc regions in OCT images were used by the multimodal to identify participants with cognitive impairment., Conclusions: Fundus photographs and OCT can provide valuable information on cognitive function. Multimodal models provide richer information compared with single-mode models. Deep learning algorithms based on multimodal retinal images may be capable of screening cognitive impairment. This technique has potential value for broader implementation in community-based screening or clinic settings., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Electroacupuncture is often used to treat insomnia., Objective: To evaluate the efficacy and safety of electroacupuncture for insomnia., Search Strategy: Databases including PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data and VIP Full-text e-Journals Database were searched up to January 15, 2023., Inclusion Criteria: Randomized clinical trials were included if they compared the clinical efficacy and safety of electroacupuncture with sham acupuncture, no treatment or usual care (UC) and general acupuncture., Data Extraction and Analysis: The full texts of the studies were reviewed to remove ineligible literature. The extracted data included authors, publication year, diagnostic criteria, sample size, population characteristics, interventions and outcomes. The above steps were performed independently by two reviewers and the data were cross-checked. Stata15.0 software was used to analyze the extracted outcome data. For continuous data (Pittsburgh Sleep Quality Index [PSQI] score and Insomnia Severity Index score), weighted mean difference (WMD) was calculated and 95% confidence interval (CI) was reported when the same scale was applied. For dichotomous variables (clinical response rate and adverse events), a meta-analysis was performed using risk ratio (RR) as the effect indicator., Results: Thirty-one trials with 2226 subjects were included. The meta-analysis suggested that electroacupuncture was more effective in improving insomnia compared with the control group (sham acupuncture, no treatment, UC and general acupuncture) (RR = 1.21; 95% CI: [1.16, 1.27]), significantly reducing the PSQI score in insomnia patients after treatment and at follow-up (WMD = -3.23; 95% CI: [-4.29, -2.17]; P < 0.001). There was no significant difference in the incidence of adverse events between the EA and control groups (sham acupuncture and no treatment or UC. RR = 1.48; 95% CI: [0.91, 2.40]; P = 0.117). In addition, the regression results revealed that receiving electroacupuncture for seven to nine weeks provided the best efficacy (P < 0.05)., Conclusion: Electroacupuncture can significantly promote better sleep quality in insomnia patients and is suitable for the treatment of various types of insomnia. However, the articles included were single-center trials with small sample sizes, and some articles were of poor quality. Therefore, further research is still needed to confirm these findings. Please cite this article as: Xu HY, Wu LN, Zhang Y, Ba T, Zhao XF. Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis. J Integr Med. 2024; 22(4): 460-473., 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.)

The unique superconductivity and charge density wave transition characteristics of NbSe 2 make it worthy of exploring its electrochemical performance and potential applications in the field of batteries. Herein, the bulk NbSe 2 was successfully exfoliated into few-layered NbSe 2 nanostructures by wet grinding exfoliation approach, which solved the issues of its long activation period and poor cycle stability. The strong Nb-Se bond in the plane and weak van der Waals force between the adjacent layers could render the fast Na + diffusion, provide abundant reaction sites and multi-directional migration paths, thus accelerate the ionic conductivity. The theoretical calculations verified the high Na + adsorption tendency between the NbSe 2 interlayers stemming from the continuous region of charge accumulation. Thanks to the unique electronic and two-dimensional few-layered structures, the exfoliated NbSe 2 exhibited a high cyclic stability with a capacity of 502 mA h g -1 over 2800 cycles at 10 A/g. In addition, the reaction mechanism was studied by in-situ X-ray diffraction and other tests, indicating a reaction mechanism containing of simultaneous intercalation (NbSe 2 ↔Na x NbSe 2 ↔NaNbSe 2 ↔Na 1+x NbSe 2 ) and conversion processes in NbSe 2 . This parallelly running mechanism not only alleviates the volume change but also ensures a high specific capacity. Additionally, different lattice planes of the NaNbSe 2 intermediate in the intercalation process experience varying degrees of contraction and expanding in d-spacing due to the influence of Coulombic force., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To compare clinical outcomes of high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) for anterior medial osteoarthritis (AMOA) as well as offer surgical recommendations through age stratification., Methods: Between May 2019 and May 2021, 68 cross-indicated AMOA patients were analyzed. The patients were divided into HTO and UKA groups and further into two age groups of 55-60 and 60-65 years. Additionally, general data, visual analog scale (VAS) score, and Hospital for Special Surgery knee score (HSS) were analyzed., Results: All the patients were followed up for 18 months. Knee joint HSS significantly improved, and VAS score decreased in both groups (P < 0.05). In the 55-60 age group, HTO showed superior knee HSS at 1 and 3 months (P < 0.05), with no significant difference at 6, 12, and 18 months. HTO had a significantly lower VAS score at one month, and the VAS scores of the two groups decreased gradually with no significant difference. In the 60-65 age group, the UKA group showed superior knee joint HSS at one month, with no significant difference at 3, 6, 12, and 18 months. The UKA group had a significantly lower VAS score at one month, and both groups' VAS scores decreased gradually with no significant difference., Conclusion: Both methods yield satisfactory results for AMOA cross-indications, improving knee joint function. The observed recovery trends have implications for personalized surgical recommendations, guiding interventions based on age-specific considerations for optimal outcomes in anterior medial osteoarthritis cases., (© 2024. The Author(s).)

Integrating multiple single-cell datasets is essential for the comprehensive understanding of cell heterogeneity. Batch effect is the undesired systematic variations among technologies or experimental laboratories that distort biological signals and hinder the integration of single-cell datasets. However, existing methods typically rely on a selected dataset as a reference, leading to inconsistent integration performance using different references, or embed cells into uninterpretable low-dimensional feature space. To overcome these limitations, a reference-free method, Beaconet, for integrating multiple single-cell transcriptomic datasets in original molecular space by aligning the global distribution of each batch using an adversarial correction network is presented. Through extensive comparisons with 13 state-of-the-art methods, it is demonstrated that Beaconet can effectively remove batch effect while preserving biological variations and is superior to existing unsupervised methods using all possible references in overall performance. Furthermore, Beaconet performs integration in the original molecular feature space, enabling the characterization of cell types and downstream differential expression analysis directly using integrated data with gene-expression features. Additionally, when applying to large-scale atlas data integration, Beaconet shows notable advantages in both time- and space-efficiencies. In summary, Beaconet serves as an effective and efficient batch effect removal tool that can facilitate the integration of single-cell datasets in a reference-free and molecular feature-preserved mode., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objective: To present the real-world status and explore the predictors of the efficacy and prognosis of first-line treatment for unresectable hepatocellular carcinoma (uHCC)., Methods: Real-world data of uHCC patients who underwent first-line treatment at 4 hospitals in Northern Anhui, China, from July 2019 to December 2022 were retrospectively collected. The clinicopathological features, haematological indicators, including superoxide dismutase (SOD) and vascular endothelial growth factor-A (VEGF-A), efficacy and safety data were analysed., Results: A total of 153 patients were enrolled and most of them treated with targeted therapy combined with immunotherapy (TI). Compared to patients treated with TI, patients who were administrated with TI plus locoregional therapy (TIL) showed longer median progression-free survival (mPFS) and median overall survival (mOS) times (both p  < 0.05), with manageable safety profiles. Moreover, compared to patients with low baseline serum levels of SOD, patients with high baseline serum SOD levels had a better treatment efficacy and had longer mPFS and mOS times (all p  < 0.05). Subgroup analyses indicated that patients with low SOD levels had longer mPFS times when receiving TIL than when receiving TI ( p =  0.005), but, among patients with high SOD levels, their prognoses were not substantially different between TIL and TI ( p  > 0.05). Additionally, patients in the low-VEGF-A group had a longer mOS time than patients in the high-VEGF-A group ( p  = 0.004). In comparison with TI, TIL can improve the survival time among patients with high VEGF-A levels but not among patients with low VEGF-A levels., Conclusions: TI was the most commonly first-line systemic therapy for uHCC patients, with better efficacy and outcomes when combined with locoregional therapy in a certain population. Baseline serum SOD and VEGF-A were found to be potential predictive biomarkers for decision-making, treatment response, and outcome in patients with uHCC in the primary care setting.

Synaptotagmin-1 (Syt1) is a calcium sensor that regulates synaptic vesicle fusion in synchronous neurotransmitter release. Syt1 interacts with negatively charged lipids and the SNARE complex to control the fusion event. However, it remains incompletely understood how Syt1 mediates Ca2+-trigged synaptic vesicle fusion. Here, we discovered that Syt1 undergoes liquid-liquid phase separation (LLPS) to form condensates both in vitro and in living cells. Syt1 condensates play a role in vesicle attachment to the PM and efficiently recruit SNAREs and complexin, which may facilitate the downstream synaptic vesicle fusion. We observed that Syt1 condensates undergo a liquid-to-gel-like phase transition, reflecting the formation of Syt1 oligomers. The phase transition can be blocked or reversed by Ca2+, confirming the essential role of Ca2+ in Syt1 oligomer disassembly. Finally, we showed that the Syt1 mutations causing Syt1-associated neurodevelopmental disorder impair the Ca2+-driven phase transition. These findings reveal that Syt1 undergoes LLPS and a Ca2+-sensitive phase transition, providing new insights into Syt1-mediated vesicle fusion., (© 2024 Zhu et al.)

This study investigated the effects of different external circuit loading mode on pollutants removal and power generation in microbial fuel cells (MFC). The results indicated that MFC exhibited distinct characteristics of higher maximum power density (P max ) (named MFC-HP) and lower P max (named MFC-LP). And the capacitive properties of bioanodes may affect anodic electrochemistry. Reducing external load to align with the internal resistance increased P max of MFC-LP by 54.47 %, without no obvious effect on MFC-HP. However, intermittent external resistance loading (IER) mitigated the biotoxic effects of sulfamethoxazole (SMX) (a persistent organic pollutant) on chemical oxygen demand (COD) and NH 4 + -N removal and maintained high P max (424.33 mW/m 2 ) in MFC-HP. Meanwhile, IER mode enriched electrochemically active bacteria (EAB) and environmental adaptive bacteria Advenella, which may reduce antibiotic resistance genes (ARGs) accumulation. This study suggested that the external circuit control can be effective means to regulate electrochemical characteristics and pollutants removal performance of MFC., 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.)

Water stress, a significant abiotic stressor, significantly hampers crop growth and yield, posing threat to food security. Despite the promising potential of nanoparticles (NPs) in enhancing plant stress tolerance, the precise mechanisms underlying the alleviation of water stress using O-Carboxymethyl chitosan nanoparticles (O-CMC-NPs) in maize remain elusive. In this study, we synthesized O-CMC-NPs and delved into their capacity to mitigate water stress (waterlogging and drought) in maize seedlings. Structural characterization revealed spherical O-CMC-NPs with a size of approximately 200 nm. These NPs accumulated near the seed embryo and root tip, resulting in a substantial increase in fresh and dry weights. The application of O-CMC-NPs to water-stressed maize seedlings remarkedly elevated the chlorophyll content and activity of various antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO). The malondialdehyde (MDA) content was significantly reduced compared to the untreated control. Additionally, the expression of stress-responsive genes, such as ZmSOD, ZmCAT, ZmPOD, ZmTIFY, ZmACO, ZmPYL2, ZmNF-YC12, and ZmEREB180, were significantly upregulated in the O-CMC-NPs treated seedlings. These findings unveil the novel role of O-CMC-NPs in enhancing plant stress tolerance, suggesting their potential application in safeguarding maize seedlings under water stress conditions and facilitating the recovery from oxidative damage., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio, and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ovarian cancer is an aggressive malignancy with high mortality known for its considerable metastatic potential. This study aimed to explore the expression and functional role of Unc-51 like autophagy activating kinase 2 (ULK2) in the progression of ovarian cancer., Methods: ULK2 expression patterns in ovarian cancer tissues as well as benign tumor control samples obtained from our institution were evaluated using immunohistochemistry. Cell counting kit 8 and Transwell assays were applied to assess the effects of ULK2 overexpression on cell proliferation, migration and invasion, respectively. RNA sequencing was performed to explore potential mechanisms of action of ULK2 beyond its classical autophagy modulation., Results: Our experiments showed significant downregulation of ULK2 in ovarian cancer tissues. Importantly, low expression of ULK2 was markedly correlated with decreased overall survival. In vitro functional studies further demonstrated that overexpression of ULK2 significantly suppressed tumor cell proliferation, migration, and invasion. RNA sequencing analysis revealed a potential regulatory role of ULK2 in the insulin signaling pathway through upregulation of insulin-like growth factor binding protein-3 (IGFBP3) in ovarian cancer cells., Conclusions: In summary, the collective data indicated that ULK2 acted as a tumor suppressor in ovarian cancer by upregulating the expression of IGFBP3. Our study underscores the potential utility of ULK2 as a valuable prognostic marker for ovarian cancer., Competing Interests: The authors declare that they have no competing interests., (© 2024 Chen et al.)

While conventional cancer modalities, such as chemotherapy and radiotherapy, act through direct killing of tumor cells, cancer immunotherapy elicits potent anti-tumor immune responses thereby eliminating tumors. Nevertheless, promising outcomes have not been reported in patients with glioblastoma (GBM) likely due to the immune privileged status of the central nervous system and immunosuppressive micro-environment within GBM. In the past years, several exciting findings, such as the re-discovery of meningeal lymphatic vessels (MLVs), three-dimensional anatomical reconstruction of MLV networks, and the demonstration of the promotion of GBM immunosurveillance by lymphatic drainage enhancement, have revealed an intricate communication between the nervous and immune systems, and brought hope for the development of new GBM treatment. Based on conceptual framework of the updated cancer-immunity (CI) cycle, here we focus on GBM antigen drainage and immune activation, the early events in driving the CI cycle. We also discuss the implications of these findings for developing new therapeutic approaches in tackling fatal GBM in the future., (© 2024. The Author(s).)

Fairness is a fundamental value in human societies, with individuals concerned about unfairness both to themselves and to others. Nevertheless, an enduring debate focuses on whether self-unfairness and other-unfairness elicit shared or distinct neuropsychological processes. To address this, we combined a three-person ultimatum game with computational modeling and advanced neuroimaging analysis techniques to unravel the behavioral, cognitive, and neural patterns underlying unfairness to self and others. Our behavioral and computational results reveal a heightened concern among participants for self-unfairness over other-unfairness. Moreover, self-unfairness consistently activates brain regions such as the anterior insula, dorsal anterior cingulate cortex, and dorsolateral prefrontal cortex, spanning various spatial scales that encompass univariate activation, local multivariate patterns, and whole-brain multivariate patterns. These regions are well-established in their association with emotional and cognitive processes relevant to fairness-based decision-making. Conversely, other-unfairness primarily engages the middle occipital gyrus. Collectively, our findings robustly support distinct neurocomputational signatures between self-unfairness and other-unfairness., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10. Behavioral tests and single-nucleus RNA sequencing (snRNA-seq) of the PFC were conducted from PNDs 31 to 37. Mechanistic exploration included clustering analysis, identification of differentially expressed genes (DEGs), enrichment analyses, single-cell trajectory analysis, and genome-wide association studies (GWAS). Sevoflurane anesthesia resulted in sociability and cognition impairments in mice. Novel specific marker genes identified 8 distinct cell types in the PFC. Most DEGs between the control and sevoflurane groups were unique to specific cell types. Re-defining 15 glutamatergic neuron subclusters based on layer identity revealed their altered expression profiles. Notably, sevoflurane disrupted the trajectory from oligodendrocyte precursor cells (OPCs) to oligodendrocytes (OLs). Validation of disease-relevant candidate genes across the main cell types demonstrated their association with social dysfunction and working memory impairment. Behavioral results and snRNA-seq collectively elucidated the cellular atlas in the PFC of young male mice, providing a foundation for further mechanistic studies on developmental neurotoxicity induced by anesthesia., (© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient., (© 2024 The Author(s). Ecology Letters published by John Wiley & Sons Ltd.)

Individuals with social anxiety often exhibit atypical processing of facial expressions. Previous research in social anxiety has primarily emphasized cognitive bias associated with face processing and the corresponding abnormalities in cortico-limbic circuitry, yet whether social anxiety influences early perceptual processing of emotional faces remains largely unknown. We used a psychophysical method to investigate the monocular advantage for face perception (i.e., face stimuli are better recognized when presented to the same eye compared to different eyes), an effect that is indicative of early, subcortical processing of face stimuli. We compared the monocular advantage for different emotional expressions (neutral, angry and sad) in three groups (N = 24 per group): individuals clinically diagnosed with social anxiety disorder (SAD), individuals with high social anxiety in subclinical populations (SSA), and a healthy control (HC) group of individuals matched for age and gender. Compared to SSA and HC groups, we found that individuals with SAD exhibited a greater monocular advantage when processing neutral and sad faces. While the magnitudes of monocular advantages were similar across three groups when processing angry faces, individuals with SAD performed better in this condition when the faces were presented to different eye. The former findings suggest that social anxiety leads to an enhanced role of subcortical structures in processing nonthreatening expressions. The latter findings, on the other hand, likely reflect an enhanced cortical processing of threatening expressions in SAD group. These distinct patterns of monocular advantage indicate that social anxiety altered representation of emotional faces at various stages of information processing, starting at an early stage of the visual system., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Traditional atmospheric chemistry posits that sulfur dioxide (SO 2 ) can be oxidized to sulfate (SO 4 2- ) through aqueous-phase reactions in clouds and gas-phase oxidation. Despite adequate knowledge of traditional mechanisms, several studies have highlighted the potential for SO 2 oxidation within aerosol water. Given the widespread presence of tropospheric aerosols, SO 4 2- production through aqueous-phase oxidation in aerosol water could have a pervasive global impact. Here, we quantify the potential contributions of aerosol aqueous pathways to global sulfate formation based on the GEOS-Chem simulations and subsequent theoretical calculations. Hydrogen peroxide (H 2 O 2 ) oxidation significantly influences continental regions both horizontally and vertically. Over the past two decades, shifts in the formation pathways within typical cities reveal an intriguing trend: despite reductions in SO 2 emissions, the increased atmospheric oxidation capacities, like rising H 2 O 2 levels, prevent a steady decline in SO 4 2- concentrations. Abating oxidants would facilitate the benefit of SO 2 reduction and the positive feedback in sulfate mitigation., (© 2024. The Author(s).)

A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.

Objectives: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China., Methods: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed., Results: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis., Conclusions: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Severe immunosuppression is a hallmark of colorectal cancer (CRC). Myeloid-derived suppressor cells (MDSCs), one of the most abundant components of the tumor stroma, play an important role in the invasion, metastasis, and immune escape of CRC. MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells, including T and natural killer cells, as well as by inducing the proliferation of immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages, which, in turn, promote the growth of cancer cells. Thus, MDSCs are key contributors to the emergence of an immunosuppressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity. In this narrative review, we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment, the current therapeutic approaches and technologies targeting MDSCs, and the therapeutic potential of modulating MDSCs in CRC treatment. This study provides ideas and methods to enhance survival rates in patients with CRC., Competing Interests: Conflict-of-interest statement: 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., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)