Search

Chronic kidney disease (CKD) is a global public health problem, involving about 10% of the global population. Unfortunately, there are currently no effective drugs. Kidney fibrosis is the main pathology of CKD, where integrins play crucial roles in renal fibrogenesis. Recently, Bexotegrast (PLN-74809) as a dual integrin αvβ1/αvβ6 inhibitor could reduce the degree of lung fibrosis in patients with idiopathic pulmonary fibrosis. However, the role of PLN-74809 remains unclear in fibrotic kidney disease. Here, we have revealed that PLN-74809 administration dose-dependently delayed the progression of renal fibrosis in both adenine diet- and unilateral ureteral obstruction (UUO)-induced mice. Mechanistically, PLN-74809 targeted integrin αvβ1/αvβ6 to inhibit FAK/Src/Akt/β-catenin cascade in fibrotic kidneys. In summary, our results for the first time highlighted the αvβ1/αvβ6 inhibitor PLN-74809 exerted potential therapeutic against kidney fibrosis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Flos Chrysanthemi Indici (FCI), the flower of Chrysanthemum Indicum L., is a popular traditional Chinese medicine (TCM) for treatment of inflammatory diseases in China. FCI is also a functional food, and is widely used as herbal tea for clearing heat and detoxicating., Aim of the Study: To explore quality control markers of FCI based on the optimal harvest period., Materials and Methods: First, UPLC-Q-TOF/MS based untargeted metabolomics was applied to explore the chemical profiles of FCIs collected at bud stages (BS), initial stages (IS), full bloom stages (FS) and eventual stages (ES) from eight cultivated regions in China. Subsequently, lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model and carrageenan-induced rat paw edema model were used to confirm the anti-inflammatory effect of FCIs collected at IS/FS. Then, UPLC-PDA targeted metabolomics was used to quantitatively analyze 9 constituents with anti-inflammatory activity (7 flavonoids and 2 phenolic acids) changed significantly (VIP > 4) during flowering stages. Finally, ROC curves combined with PCA analysis based on the variation of 9 active constituents in FCIs from different flowering stages were applied to screen the quality markers of FCI., Results: FCIs at IS/FS had almost same chemical characteristics, but quite different from those at BS and ES. A total of 32 constituents in FCIs including flavonoids and phenolic acids were changed during flowering development. Most of the varied constituents had the highest or higher contents at IS/FS compared with those at ES, indicating that the optimal harvest period of FCI should be at IS/FS. FCI extract could effectively suppress nitric oxide (NO) production in LPS-induced RAW264.7 cells and regulate the abnormal levels of cytokines and PGE 2 in carrageenan-induced paw edema model rat. The results of quantitatively analysis revealed that the variation trends of phenolic acids and flavonoids in FCIs were different during flowering development, but most of them had higher contents at IS/FS than those at ES in all FCIs collected from eight cultivated regions, except one sample from Anhui. Finally, linarin, luteolin, apigenin and 3,5-dicaffeoylquinic acid were selected as the Q-markers based on the contribution of their AUC values in ROC and clustering of PCA analysis., Conclusions: Our study demonstrates the optimal harvest period of FCI and specifies the multi-constituents Q-markers of FCI based on the influence of growth progression on the active constituents using untargeted/targeted metabolomics. The findings not only greatly increase the utilization rate of FCI resources and improve quality control of FCI products, but also offer new strategy to identify the Q-markers of FCI., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although the nonmonotonic variation in the diffusion coefficients of alcohol and water with changing alcohol concentrations in aqueous solutions has been reported for many years, the underlying physical mechanisms remain unclear. Using molecular dynamics simulations, we investigated the molecular diffusion mechanisms in aqueous methanol solutions. Our findings reveal that the molecular diffusion is co-influenced by hydrogen bonding and the hydrophobic ends of methanol molecules. A stronger hydrogen bond (HB) network and a higher concentration of hydrophobic ends of methanol molecules both enhance molecular correlations, thereby slowing molecular diffusion in the solution. As methanol concentration increases, the HB network weakens, facilitating molecular diffusion. However, the increased concentration of hydrophobic ends counteracts this effect. Consequently, the diffusion coefficients of water and methanol molecules exhibit nonmonotonic changes. Previous studies have only focused on the role of HB networks. For the first time, we have identified the impact of the hydrophobic ends of alcohol on molecular diffusion in aqueous alcohol solutions. Our research contributes to a better understanding and manipulation of the properties of aqueous alcohol solutions and even liquids with complex compositions., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

In the current electrolytic manganese industry, iron separation and reuse from iron-rich manganese ore leachate (IRMOL) has become one of the most pressing challenges. This study aimed to investigate the optimal conditions for iron separation from IRMOL and to assess the economic and practical advantages of iron separation or removal in industrial manufacturing. To identify more cost-effective and technologically advanced production circumstances, we examined five key elements that weaken Fe(OH) 3 colloidal production conditions in enterprises: reaction temperature, pH, crystal species, aging and reaction time. The screening results showed that when the conditions were optimized, the efficiency of reducing manganese loss decreased from 6.15% to 4.69%. Additionally, the generation of iron-rich electrolytic manganese residue (IREMR) was decreased by 44.32%, and the filtration velocity of IREMR increased from 0.0030 to 0.0220 mL/(s·cm 2 ) compared to the production conditions before optimization at the enterprises. Through multiphase equilibria modeling with Visual MINTEQ, we have determined that raising the temperature and pH levels increases the expenses associated with chemicals and energy usage and results in an elevation of Fe(OH) 2 + concentration. This can lead to the creation of Fe(OH) 3 colloidal, causing a high water content in IREMR, inefficient filtration, and significant loss of manganese. This strategy is highly significant for the production of electrolytic manganese and the reduction of electrolytic manganese residue., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Two-dimensional (2D) semiconducting ferromagnet Fe 3 GeTe 2 holds great promise for advanced spintronic applications because of its gate-tunable ferromagnetic ordering at room temperature, whereas the controllable growth of large-area single crystals remains very challenging due to its ternary nature and variable stoichiometry inducing many competitive phases. Here, we theoretically probe the mechanism of selective growth of monolayer Fe 3 GeTe 2 on various epitaxial substrates. Thermodynamic analysis shows that the corresponding phase-pure chemical potential windows for the selective growth of Fe 3 GeTe 2 can be reasonably attained in ternary phase space on insulating and chemically inert c-plane sapphire and Ga 2 O 3 (0001) substrates by properly modulating the interfacial interaction and employing suitable feedstocks to avoid competitive growth of possible impurity phases with different stoichiometry ratios. It is also revealed that both the weak edge-substrate interaction and interlayer coupling of Fe 3 GeTe 2 together lead to a surface-dominated nucleation behavior and, thereby, energetically favor lateral growth of the monolayer rather than vertical growth of the multilayer. Importantly, straight protocols for the experimentally selective growth of phase-pure ternary Fe 3 GeTe 2 are also provided by establishing the relationship between the feedstock chemical potential and growth parameters on a thermochemical basis. Our insightful study can also be reasonably extended to guide future experimental design for the selective growth of other multicomponent 2D materials.

Durable and functional regeneration of the airway epithelium in vivo with transplanted stem cells has the potential to reconstitute healthy tissue in diseased airways, such as in cystic fibrosis or primary ciliary dyskinesia. Here, we present detailed protocols for the preparation and culture expansion of murine primary and induced pluripotent stem cell-derived airway basal stem cells (iBCs) and methods for their intra-airway transplantation into polidocanol-conditioned murine recipients to achieve durable in vivo airway regeneration. Reconstitution of the airway tissue resident epithelial stem cell compartment of immunocompetent mice with syngeneic donor cells leverages the extensive self-renewal and multipotent differentiation properties of basal stem cells (BCs) to durably generate a broad diversity of mature airway epithelial lineages in vivo. Engrafted donor-derived cells re-establish planar cell polarity as well as functional ciliary transport. By using this same approach, human primary BCs or iBCs transplanted into NOD-SCID gamma recipient mice similarly display engraftment and multilineage airway epithelial differentiation in vivo. The time to generate mouse or human iBCs takes ~60 d, which can be reduced to ~20 d if previously differentiated cells are thawed from cryopreserved iBC archives. The tracheal conditioning regimen and cell transplantation procedure is completed in 1 d. A competent graduate student or postdoctoral trainee should be able to perform the procedures listed in this protocol., (© 2024. Springer Nature Limited.)

Condensable particulate matter (CPM) and filterable particulate matter (FPM) emitted from industrial sources have been well studied, but their emissions from vehicles have not yet been covered. This study explores the emission characteristics of CPM and FPM from typical diesel vehicles under various driving conditions. The emission factors (EFs) of CPMs under driving conditions were 5.4-10.4 times higher than those of FPMs, while CPMs EFs under transient driving conditions were about 2.5 times higher than those under steady driving conditions. CPM and FPM are mainly composed of organic matter accounting for 53.3 %-92.9 %, while the intermediate and semi-volatile organic compounds dominate the organic matter accounting for 86.3 %-98.6 %. Similar to industrial sources, alkanes are the predominant organic species emitted by diesel vehicles, comprising 42.0 %-64.0 % of the detected organic components. Inorganic CPM is primarily composed of NH 4 + , representing 84.9 %-87.6 % of the total, in contrast to industrial sources where SO 4 2- and Cl - dominate. Interestingly, the air pollution control devices installed on diesel vehicles under steady driving conditions perform better in removing organic CPM and producing higher inorganic CPM emissions than those under transient driving conditions. These findings will enhance the comprehensive understanding of particulate matter emitted from diesel vehicles and provide a scientific foundation for the development of related control technologies., 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.)

Cancer is one of the most serious health problems worldwide. Because cancer has no specific symptoms in its early stages, it is often not diagnosed until it is in advanced stages, reducing the likelihood of successful treatment. Therefore, early diagnosis of cancer is a formidable challenge. Mass spectrometry-based proteomics offers a robust technical foundation for cancer diagnosis. However, mass spectrometry data are characterized by high dimensionality, large data volume, and noise interference, which can lead to diagnostic errors in clinical applications. To address this challenge, an improved algorithm combining principal component analysis (PCA) with a convolutional neural network (CNN) algorithm (denoted as PCA-1DSE-ResCNN) was proposed to assist in analyzing high-dimensional mass spectral data. The algorithm initially reduced the dimensionality of the data through the PCA technique. Subsequently, the convolutional neural network algorithm (1DSE-ResCNN) integrating residual blocks and squeeze-and-excitation blocks was used as a classifier. This approach can not only alleviate the issues of overfitting and gradient vanishing caused by deep network layers but also reduce redundant information, enabling the algorithm to effectively learn high-dimensional data features and deal with nonlinear relationships. To validate the effectiveness of the algorithm, the high-dimensional ovarian cancer mass spectrometry dataset was selected as an example to examine its application performance in early diagnosis of ovarian cancer. The experimental results demonstrated that the PCA-1DSE-ResCNN algorithm outperforms other methods in terms of accuracy, specificity, and sensitivity on three high-dimensional ovarian cancer datasets. This study will contribute to the rapid diagnosis and early detection of cancer.

Postoperative gastrointestinal dysfunction, including temporary nonmechanical suppression of gastrointestinal motility (known as postoperative ileus), occurs in about 10% surgeries of abdominal tumors. Since these complications can prolong hospitalization and affect eating, it is important to understand their risk factors and identify effective interventions to manage or prevent them. The present review comprehensively examined the relevant literature to describe risk factors for postoperative ileus and effective interventions. Risk factors include old age, open surgery, difficulty of surgery, surgery lasting longer than 3 hours, preoperative bowel treatment, infection, and blood transfusion. Factors that protect against postoperative ileus include early enteral nutrition, minimally invasive surgery, and multimodal pain treatment. Interventions that can shorten or prevent such ileus include minimally invasive surgery, early enteral nutrition as well as use of chewing gum, laxatives, and alvimopan. Most of these interventions have been integrated into current guidelines for enhanced recovery of gastrointestinal function after surgery. Future high-quality research is needed in order to clarify our understanding of efficacy and safety., Competing Interests: J.-H. Z received speaker fees for Bayer, BeiGene, AstraZeneca, MSD, Roche, Innovent, and HengRui. But none of them are related to this project at all. The other authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Fat greatly impacts the overall texture and flavor of pork belly. Twice-cooked pork bellies (TPB), typically boiled and sliced before "back to pot" being stir-fried, is a classic Sichuan cuisine among stir-fried dishes. In this study, the effects of substituting conventional pan-frying (PCV) with superheated steam (SHS) technology on the sensory, texture, microstructure and flavor of the fat layers were investigated. SHS was used as an alternative to boiling (120 °C for 15, 20, 25, and 30 min), and "back to pot" stir-frying was also by SHS. TPB precooked for 25 min (P25) with SHS performed better quality characteristics than PCV, with less collagen fiber disruption and lipid droplet area, resulting in a lower hardness and higher shear force. Besides, the low-oxygen environment of SHS retarded the lipid peroxidation, showing a significantly lower MDA content than PCV. Differently, PCV exhibited more grassy and fatty flavors, while P25 exhibited a unique aroma of fruity and creamy due to its higher UFA/SFA ratios in the pre-cooking stage. Overall, the sensory scores of P25 were comparable to those of PCV (with no significant difference), revealing that SHS is expected to be applied to the industrial production of stir-fried dishes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to be declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Nanocelluloses (NCs) isolated from lignocellulosic resources usually require harsh chemical pretreatments to remove lignin, which face constraints such as high energy consumption and inefficient resource utilization. An alternative strategy involving the partial retention of lignin can be adopted to endow NCs with better versatility and functionality. The resulting lignin-containing nanocelluloses (LNCs) generally possess better mechanical property, thermal stability, barrier property, antioxidant activity, and surface hydrophobicity than lignin-free NCs, which have attracted extensive interest as a promising green nanomaterial for numerous applications. This review provides a comprehensive overview of the recent advances in the preparation, properties, and food application of LNCs. The effect of residual lignin on the preparation and properties of LNCs is discussed. Furthermore, the key roles of lignin in the properties of LNCs, including particle size, crystalline structure, dispersibility, thermal, mechanical, antibacterial, rheological and adhesion properties, are summarized comprehensively. Furthermore, capitalizing on their dietary fiber and nanostructure properties, the food applications of LNCs in the forms of films, gels and emulsions are also discussed. Finally, the challenges and opportunities regarding the development of LNCs are provided., 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.)

Advancements in biomaterial-based spinal cord tissue engineering technology have profoundly influenced regenerative medicine, providing innovative solutions for both spinal cord organoid development and engineered spinal cord injury (SCI) repair. In spinal cord organoids, biomaterials offer a supportive microenvironment that mimics the natural extracellular matrix, facilitating cell differentiation and organization and advancing the understanding of spinal cord development and pathophysiology. Furthermore, biomaterials are essential in constructing engineered spinal cords for SCI repair. The incorporation of biomaterials with growth factors, fabrication of ordered scaffold structures, and artificial spinal cord assemblies are critical insights for SCI to ensure structural integrity, enhance cell viability, and promote neural regeneration in transplantation. In summary, this review summarizes the contribution of biomaterials to the spinal cord organoids progression and discusses strategies for biomaterial-based spinal cord engineering in SCI therapy. These achievements underscore the transformative potential of biomaterials to improve treatment options for SCI and accelerate future clinical applications., (© 2024 Wiley‐VCH GmbH.)

Objective: To investigate the association between early blood pressure drop and worsening renal function (WRF) in ICU patients with liver failure and to evaluate their clinical outcomes., Design: Retrospective observational study., Setting: Intensive Care Medicine., Patients: Patients admitted to the ICU for the first time during their first hospitalization; diagnosed with liver failure according to the International Classification of Diseases, Ninth and Tenth Revision codes; and aged ≥18 years were included. Patients with a peak systolic blood pressure (SBP) drop of <0 mmHg were excluded., Intervention: We analyzed data of ICU patients with liver failure from the Medical Information Mart for Intensive Care IV version 2.2 database. Descriptive statistics, analysis of variance, Kruskal-Wallis test, and chi-square test were employed for analysis. Multivariate linear regression models were used to assess the determinants of blood pressure decline. Cox proportional hazards and generalized additive models were used to evaluate MAIN VARIABLES OF INTEREST: The relationship between blood pressure decline, WRF, and 60-day in-hospital mortality were evaluated, along with subgroup analyses., Results: Peak SBP drop was independently associated with higher risks of WRF (P < 0.001) and 60-day in-hospital mortality (P < 0.001), even after adjusting for potential confounders, including baseline SBP. The independent risk relationship observed between peak diastolic blood pressure, mean arterial pressure drop, and the occurrence of WRF and 60-day in-hospital mortality was similar., Conclusions: In ICU patients with liver failure, a significant early drop in blood pressure was associated with a higher incidence of WRF, increased risk of 60-day in-hospital mortality, and poorer prognoses., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Background: Transcutaneous electrical acupoint stimulation (TEAS) may contribute to blood pressure (BP) control, but the evidence remains insufficient. Our objectives were to evaluate the impact of TEAS on hypertension and determine the optimal frequency., Methods: A total of 120 hypertensive patients were randomly allocated to the TEAS-2Hz group, TEAS-10Hz group, or usual care control group in a 1:1:1 ratio. All patients were advised to continue their usual antihypertensive regimen. Additionally, patients in the TEAS groups received TEAS therapy 3 times per week for 4 weeks, with a 4-week follow-up., Results: The primary outcome was the change in systolic BP (SBP) from baseline to week 4. Secondary outcomes included changes in diastolic BP (DBP), mean arterial pressure (MAP), heart rate (HR), heart rate variability (HRV), and 12-item health survey (SF-12) at different time points. Both TEAS groups showed reductions in SBP relative to control (TEAS-2Hz group vs. control, -4.70mmHg [95% CI, -7.00 to -2.40mmHg]; P < 0.001; TEAS-10Hz group vs. control, -8.66mmHg [95% CI, -10.97 to -6.36mmHg]; P < 0.001). TEAS-10Hz provided a significant decrease in SBP than TEAS-2Hz (-3.96mmHg [95% CI, -1.66 to -6.26mmHg]; P < 0.001). TEAS groups also exhibited reductions in DBP, MAP, HR, LF/HF ratio（LF/HF）, very low frequency (VLF), and normalized low frequency (LF norm), and an increase in normalized high frequency (HF norm) than control. No differences were observed among groups in low frequency (LF), high frequency (HF), total power (TP), very low frequency (VLF), and SF-12., Conclusion: TEAS might be a promising adjunctive therapy for hypertension, and the recommended frequency is 10Hz, which should be confirmed in larger trials., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Type A aortic dissection (TAAD) is an acute onset disease with a high mortality rate. TAAD is caused by a tear in the aortic intima and subsequent blood infiltration. The most prominent characteristics of TAAD are aortic media degeneration and inflammatory cell infiltration, which disturb the structural integrity and function of nonimmune and immune cells in the aortic wall. However, to date, there is no systematic evaluation of the interactions between nonimmune cells and immune cells and their effects on metabolism in the context of aortic dissection. Here, multiomics, including bulk RNA-seq, single-cell RNA-seq, and lipid metabolomics, was applied to elucidate the comprehensive TAAD lipid metabolism landscape. Normally, monocytes in the stress response state secrete a variety of cytokines. Injured fibroblasts lack the ability to degrade lipids, which is suspected to contribute to a high lipid environment. Macrophages differentiate into fatty acid binding protein 5-positive (FABP5+) macrophages under the stimulation of metabolic substrates. Moreover, the upregulation of Fabp5+ macrophages were retrospectively validated in TAAD model mice and TAAD patients. Finally, Fabp5+ macrophages can generate a wide range of proinflammatory cytokines, which possibly contribute to TAAD pathogenesis., 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.)

Triple-negative breast cancer (TNBC) is currently the only subtype lacking efficient targeted therapies. Taxol is the primary chemotherapeutic agent for TNBC. However, Taxol resistance often develops in the treatment of TNBC patients, which importantly contributes to high mortality and poor prognosis in TNBC patients. Recent preclinical studies have shown that the inhibition of Notch pathway by γ-secretase inhibitors can slow down the progression of TNBC. Our studies in bioinformatic analysis of breast cancer patients and TNBC/Taxol cells in vitro showed that there was high correlation between the activation of Notch pathway and Taxol resistance in TNBC. Increased γ-secretase activity (by the overexpression of catalytic core PSEN-1) significantly reduced Taxol sensitivity of TNBC cells, and enhanced biological characteristics of malignancy in vitro, and tumour growth in vivo. Mechanistically, increased γ-secretase activity led to the accumulation of NICD in the nucleus, promoting the interaction between NICD and PXR to activate PXR, which triggered the transcription of PXR downstream associated drug resistance genes. Furthermore, we showed that pharmacological inhibition of γ-secretase with γ-secretase inhibitors (Nirogacestat and DAPT) can reverse Taxol resistance in vivo and in vitro. Our results for the first time demonstrate that the activation of γ -secretase/NCD-PXR/Notch pathway is one of important mechanisms to cause Taxol resistance in TNBC, and the blockades of this pathway may represent a new therapeutic strategy for overcoming Taxol resistance in TNBC., 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.)

Etching effects by lipase on polylactic acid (PLA) could induce the exposure of active sites and promote the attachment of betanin nanocomplexes (BR-Ch) to obtain red color. 3D printing, regarded as emerging, innovative packaging fabrication technique, was applied to potentially develop creative, red PLA products for food application. BR-Ch was prepared based on betanin and nano chitin via electrostatic interaction and hydrogen bonding, obtaining nanocomplexes with excellent thermal stability. Pre-treatments mattered greatly in PLA functionalization, and especially, lipase pre-treatment 30 min promoted BR-Ch modification on PLA. Final PLA exhibited excellent red color characteristics (CIElab, Hue-Saturation-Brightness, K/S and CMYK), elongation at break and stable thermal resistance, ultimately achieving outstanding dyeing effect. This work indicates that BR-Ch can potentially replace synthetic pigments to functionalize lipase-pretreated PLA, and the dyed PLA demonstrate the excellent packaging application prospects in food field by 3D-printed products., Competing Interests: Declaration of competing interest The authors confirm that they have no conflicts of interest with respect to the work described in this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

ConspectusTwo-dimensional (2D) semiconducting transition metal dichalcogenides (TMDs), in particular molybdenum disulfide (MoS 2 ), have recently attracted huge interest due to their proper bandgap, high mobility at 2D limit, and easy-to-integrate planar structure, which are very promising for extending Moore's law in postsilicon electronics technology. Great effort has been devoted toward such a goal since the demonstration of protype MoS 2 devices with high room-temperature on/off current ratios, ultralow standby power consumption, and atomic level scaling capacity down to sub-1-nm technology node. However, there are still several key challenges that need to be addressed prior to the real application of MoS 2 -based electronics technology. The controllable growth of wafer-scale single-crystal MoS 2 on industry-compatible insulating substrates is the prerequisite of application while the currently synthesized MoS 2 films mostly are polycrystalline with limited sizes of single-crystal domains and may involve metal substrates. The precise layer-control is also very important for MoS 2 growth since its electronic properties are layer-dependent, whereas the layer-by-layer growth of multilayer MoS 2 dominated by the van der Waals (vdW) epitaxy leads to poor thickness uniformity and noncontinuously distributed domains. High density up to 10 13 cm -2 of sulfur vacancies (SVs) in grown MoS 2 can cause unfavorable carrier scatting and electronic properties variations and will inevitably disturb the device performance. The dangling-bond-free surface of MoS 2 gives rise to an inherent vdW gap at metal-semiconductor (M-S) contact, which leads to high electrical resistance and poor current-delivery capability at the contact interface and thereby substantially limits the performances of MoS 2 devices.In this Account, we briefly review recent experimental and theoretical attempts for addressing the aforementioned challenges and present our own insights from atomistic simulations. We theoretically revealed the vital role of substrate steps for guiding unidirectional nucleation of monolayer MoS 2 and uniform nucleation and edge-aligned growth of bilayer MoS 2 by advanced simulations. The established thermodynamic mechanisms have successfully directed the experimental works on the controllable growth of 2 in. single-crystal monolayer and centimeter-scale uniform bilayer MoS 2 . The postgrowth repair mechanism of SV defect in MoS 2 via thiol chemistry treatment has been theoretically explored with the consideration of side reaction of surface functionalization to help experimentally reduce SV defect density by 75%. Beyond the atomic level understanding, theoretical simulations proposed the electronic states hybridization mechanism across the semimetal-MoS 2 vdW interface, thereby guiding experimental effort for realizing Ohmic contact at the MoS 2 -Sb(0112) vdW interface with record-low contact resistance.These advances provide a sound basis with an atomic-level understanding for addressing the related issues. However, there are still notable gaps in terms of system size and time scale of dynamics between atomistic simulations and experimental observations for the studies of MoS 2 growth and interfaces. The combination of multiscale simulations and artificial intelligence technology is expected to narrow these gaps and provide a more insightful understanding of the controllable growth and interfacial properties modulation of MoS 2 . We conclude the Account with the standing challenges and outlook on future research directions from the theoretical perspective.

Objective: Hematological indicators in the early stage of PD-1 inhibitor treatment may show superior predictive ability of the occurrence of immune related adverse event (irAE) compared to the pre-treatment indicators, as the immune response is modulated during the PD-1 inhibitor treatment. The objective of this study was to investigate the predictive capabilities of biomarkers in the early treatment stage for immune related thyroid dysfunction (irTD), and explore the potential predictive cytokines., Methods: Medical records and blood test results of cancer patients treated with PD-1 inhibitor at a certain medical institution were collected. Logistic regression analysis was utilized to identify the predictive factors of irTD, ROC curves were plotted and the area under the curves (AUC) was calculated. Serum samples were collected before and during early treatment phase, cytokine detection was performed to explore potential predictive cytokines., Results: A total of 264 patients were enrolled, 58 developed irTD (21.97%), including 31 patients with thyrotoxicosis and 27 with hypothyroidism. There were no significant differences in demographic characteristics, tumor types and PD-1 inhibitors between patients with and without irTD. Multivariate logistic analysis showed that anti-thyroglobulin antibody (TgAb) (OR=2.831, 95%CI: 1.077-7.443, P =0.035) and anti-thyroperoxidase antibody (TPOAb) (OR=9.565, 95%CI: 3.399-26.921, P =0.000) in the early treatment phase were independent predictive factors for irTD, the AUC of early-stage biomarkers was larger than that of pre-treatment (0.655 vs 0.571); low level of TSH at the early stage (OR=0.162, 95%CI: 0.077-0.341, P =0.000) was significantly correlated with thyrotoxicosis; female (OR=3.889, 95%CI: 1.457-10.380, P =0.007) and positive TPOAb (OR=8.678, 95%CI: 2.656-28.357, P =0.000) at the early stage were significantly correlated with hypothyroidism. The AUCs of early-stage biomarkers were larger than that of pre-treatment both in thyrotoxicosis (0.812 vs 0.637) and hypothyroidism patients (0.728 vs 0.710). The increase of IL-16 (adjusted P =0.004), IL-12p70 (adjusted P =0.014), IL-17 (adjusted P =0.014), CCL-15 (adjusted P =0.014) and IL-1a (adjusted P =0.021) in the early treatment phase were positively correlated with irTD., Conclusions: Biomarkers at the early stage of PD-1 inhibitor treatment could predict irTD, and demonstrated stronger predictive ability compared to pre-treatment biomarkers. IL-16, IL-12p70, IL-17, CCL-15 and IL-1a could serve as potential predictive biomarkers for irTD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Chen, Li, Cai, Ma, Yang, Zhang, Bai, Wu, Tang and Wang.)

Chronic kidney disease (CKD) is a condition characterized by functional deterioration with sustained inflammation and progressive fibrosis of the kidneys affecting over 800 million people worldwide. The P2X7 receptor (P2X7R) plays a key role in CKD progression. Our previous P2X7R antagonists demonstrated good efficacy for treating kidney injury but were limited by low oral exposure and short half-life, restricting their application. This study reports the optimization of P2X7R antagonists for better oral pharmacokinetics. The candidate compound 13a with the respective IC 50 of 34.86 and 25.28 nM against human and murine P2X7R, administered orally at 10 mg/kg in mice, exhibits a remarkably long half-life of 161.64 h, with a high exposure of 1,163,980.55 μg·h/L. Oral administration of 13a (0.3 or 1.0 mg/kg, twice weekly) significantly reduced renal injury and fibrosis in unilateral ureteral obstruction and adenine diet-induced mice models, highlighting its potential for delaying the progression of CKD.

Animals spend a considerable proportion of their life span at rest. However, resting status has often been overlooked when investigating how species respond to environmental conditions. This may induce a large bias in understanding the local adaptation of species across environmental gradients and their vulnerability to potential environmental change. Here, we conducted an empirical study on montane agamid lizards, combined with mechanistic modeling, to compare elevational variations in body temperature and metabolisms (cumulative digestion and maintenance cost) between resting and active status. Our study on three populations of an agamid lizard along an elevational gradient revealed a trend of decreasing body temperature toward higher elevations, the main contributor of which was resting status of the lizards. Using population-specific reaction norms, we predicted greater elevational variation in hourly and cumulative digestion for resting lizards than for active lizards. Climate-change impacts, estimated as the change in cumulative digestion, also show greater elevational variation when resting status is factored into the analysis. Further, our global analysis of 98 agamid species revealed that in about half of their combined distributional range, the contribution of resting status in determining the elevational variation in cumulative digestion and maintenance cost of lizards was greater than the contribution made by a lizard's active status. Our study highlights the importance of considering resting status when investigating how species respond to environmental conditions, especially for those distributed over tropical and subtropical mountain areas., (© 2024 The Ecological Society of America.)

Molecularly imprinted polymers (MIPs) show significant promise as effective alternatives to antibodies in disease diagnosis and therapy. However, the challenging process of screening extensive libraries of monomer combinations and synthesis conditions to identify formulations with enhanced selectivity and affinity presents a notable time constraint. The need for expedient methods becomes clear in accelerating the strategic development of MIPs tailored for precise molecular recognition purposes. In this study, an innovative high-throughput screening methodology designed to identify the optimal MIP formulation for targeting tumors is presented. Employing a microtiter plate format, over 100 polymer syntheses are conducted, incorporating diverse combinations of functional monomers. Evaluation of binding performance utilizes fluorescence-based assays, focusing on an epitope of the epidermal growth factor receptor (EGFR). Through this meticulously structured screening process, synthesis conditions that produced MIP nanoparticles exhibiting substantial specificity for EGFR targeting (K D = 10 -12  m) are identified. These "bionic antibodies" demonstrate selective recognition of cancer cells in whole blood samples, even at concentrations as low as 5 cells mL -1 . Further validation through fluorescent imaging confirms the tumor-specific localization of the MIPs in vivo. This highly efficient screening approach facilitates the strategic synthesis of imprinted polymers functioning as precision bioprobes., (© 2024 Wiley‐VCH GmbH.)

A high-quality filler within mixed matrix membranes, coupled with uniform dispersity, endows a high-efficiency transfer pathway for the significant improvement on separation performance. In this work, a zeolite-typed MCM-22 filler is reported that is doped into polydimethylsiloxane (PDMS) matrix by ultrafast photo-curing technique. The unique structure of nanosheets assembly layer by layer endows the continuous transfer channels towards penetrate molecules because of the inter-connective nanosheets within PDMS matrix. Furthermore, an ultrafast freezing effect produced by fast photo-curing is used to overcome the key issue, namely filler aggregation, and further eliminates defects. When pervaporative separating a 5 wt% ethanol aqueous solution, the resulting MCM-22/PDMS membrane exhibits an excellent membrane flux of 1486 g m -2 h -1 with an ethanol separation factor of 10.2. Considering a biobased route for ethanol production, the gas stripping and vapor permeation through this membrane also shows a great enrichment performance, and the concentrated ethanol is up to 65.6 wt%. Overall, this MCM-22/PDMS membrane shows a high separation ability for ethanol benefited from a unique structure deign of fillers and ultrafast curing speed of PDMS, and has a great potential for bioethanol separation from cellulosic ethanol fermentation., (© 2024 Wiley‐VCH GmbH.)

Nanocellulose has been favored as one of the most promising sustainable nanomaterials, due to its competitive advantages and superior performances such as hydrophilicity, renewability, biodegradability, biocompatibility, tunable surface features, excellent mechanical strength, and high specific surface area. Based on the above properties of nanocellulose and the advantages of hydrogels such as high water absorption, adsorption, porosity and structural adjustability, nanocellulose based hydrogels integrating the benefits of both have attracted extensive attention as promising materials in various fields. In this review, the main fabrication strategies of nanocellulose based hydrogels are initially discussed in terms of different crosslinking methods. Then, the typical properties of nanocellulose based hydrogels are comprehensively summarized, including porous structure, swelling ability, adsorption, mechanical, self-healing, smart response performances. Especially, relying on these properties, the general application of nanocellulose based hydrogels in food field is also discussed, mainly including food packaging, food detection, nutrient embedding delivery, 3D food printing, and enzyme immobilization. Finally, the safety of nanocellulose based hydrogel is summarized, and the current challenges and future perspectives of nanocellulose based hydrogels are put forward., Competing Interests: Declaration of competing interest The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Sepsis-associated acute kidney injury (SA-AKI) is one of common critical illnesses with high morbidity and mortality. At present, effective therapeutic drugs for SA-AKI are remain lacking. SKLB023 is a synthetic small-molecule compound which exerts potent anti-inflammatory effects in our previous studies. Here, this study aimed to characterize the protective effect of SKLB023 on SA-AKI and explore its underlying mechanism. The SA-AKI experimental models have been established by cecum ligation/puncture (CLP) and lipopolysaccharide (LPS) injection in male C57BL/6J mice. SKLB023 was administered by gavage (50 or 25 mg/kg in CLP model and 50 mg/kg in LPS model) daily 3 days in advance and 30 min earlier on the day of modeling. Our results confirmed SKLB023 treatment could improve the survival of SA-AKI mice and ameliorate renal pathological injury, inflammation, and apoptosis in the two types of septic AKI mice. Mechanically, SKLB023 deceased the expression of TLR4 in LPS-triggered renal tubular epithelial cells, and inhibited the activation of downstream pathways including NF-κB and MAPK pathways. Our study suggested that SKLB023 is expected to be a potential drug for the prevention and treatment of septic AKI., 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: Several inflammatory indicators have been reported to have predictive value in many types of malignant cancer. This research was aimed to explore the ability of the monocyte-to-lymphocyte ratio (MLR) to predict prognosis in patients with intrahepatic cholangiocarcinoma (ICC) who subjected to curative hepatectomy., Methods: This retrospective analysis included 196 patients with ICC who underwent curative hepatectomy between May 2018 and April 2023. The predictive abilities of the preoperative MLR in assessing overall survival (OS) and disease-free survival (DFS) in those patients were compared with other inflammation-based scores, including monocyte-to-white ratio, neutrophil-to-lymphocyte ratio, neutrophil-to-white ratio, platelet-to-lymphocyte ratio, platelet-to-white ratio, and systemic immune-inflammation index, as well as tumor markers, like carcinoembryonic antigen (CEA) and carbohydrate antigen 19 - 9 (CA19-9)., Results: The area under the time-dependent receiver operating characteristic curve indicated that the preoperative MLR had higher predictive efficiency in contrast with other inflammation-based scores and tumor markers in assessing OS and DFS. Stratifying patients according to the optimal cut-off value for the preoperative MLR, the data showed that both OS and DFS in the high MLR group were significantly worse than those in the low MLR group (p < 0.05 for all). Univariable and multivariable Cox analyses revealed that the preoperative MLR was an independent risk factor for OS and DFS in patients with ICC. In addition to predicting OS in patients with high CEA levels and predicting DFS in patients with high CA19-9 levels, patients with different CEA and CA19-9 levels were divided into completely different OS and DFS subgroups based on the risk stratification of the preoperative MLR., Conclusions: Our results demonstrated that the preoperative MLR was a good prognosis indicator to predict DFS and OS following curative hepatectomy in patients with ICC., (© 2024. The Author(s).)

Predicting performance responses of insects to climate change is crucial for biodiversity conservation and pest management. While most projections on insects' performance under climate change have used macro-scale weather station data, few incorporated the microclimates within vegetation that insects inhabit and their feeding behaviors (e.g., leaf-nesting: building leaf nests or feeding inside). Here, taking advantage of relatively homogenous vegetation structures in agricultural fields, we built microclimate models to examine fine-scale air temperatures within two important crop systems (maize and rice) and compared microclimate air temperatures to temperatures from weather stations. We deployed physical models of caterpillars and quantified effects of leaf-nesting behavior on operative temperatures of two Lepidoptera pests: Ostrinia furnacalis (Pyralidae) and Cnaphalocrocis medinalis (Crambidae). We built temperature-growth rate curves and predicted the growth rate of caterpillars with and without leaf-nesting behavior based on downscaled microclimate changes under different climate change scenarios. We identified widespread differences between microclimates in our crop systems and air temperatures reported by local weather stations. Leaf-nesting individuals in general had much lower body temperatures compared to non-leaf-nesting individuals. When considering microclimates, we predicted leaf-nesting individuals grow slower compared to non-leaf-nesting individuals with rising temperature. Our findings highlight the importance of considering microclimate and habitat-modifying behavior in predicting performance responses to climate change. Understanding the thermal biology of pests and other insects would allow us to make more accurate projections on crop yields and biodiversity responses to environmental changes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

This study examines how plant genotype can influence the microbiome by comparing six tomato genotypes ( Solanum lycopersicum ) based on their traditional vs. commercial backgrounds. Using Illumina-based sequencing of the V6-V8 regions of 16S and ITS2 rRNA genes, we analyzed and compared the endophytic bacterial and fungal communities in stems to understand how microbiota can differ and be altered in plant genotypes and the relation to human manipulation. Our results reflect that traditional genotypes harbor significantly more exclusive microbial taxa and a broader phylogenetic background than the commercial ones. Traditional genotypes were significantly richer in Eurotiomycetes and Sordariomycetes fungi, while Lasiosphaeriaceae was more prevalent in commercial genotypes. TH-30 exhibited the highest bacterial abundance, significantly more than commercial genotypes, particularly in Actinomycetia, Bacteroidia , and Gammaproteobacteria . Additionally, traditional genotypes had higher bacterial diversity, notably in orders like Cytophagales, Xanthomonadales , and Burkholderiales . Moreover, we performed an evaluation of the impact of a systemic fungicide (tebuconazole-dichlofluanide) to simulate a common agronomic practice and determined that a single fungicide treatment altered the stem endophytic microbiota. Control plants had a higher prevalence of fungal orders Pleosporales, Helotiales , and Glomerellales , while treated plants were dominated by Sordariomycetes and Laboulbeniomycetes . Fungal community diversity significantly decreased, but no significant impact was observed on bacterial diversity. Our study provides evidence that the background of the tomato variety impacts the fungal and bacterial stem endophytes. Furthermore, these findings suggest the potential benefits of using of traditional genotypes as a source of novel beneficial microbiota that may prove highly valuable in unpredicted challenges and the advancement in sustainable agriculture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu-Xu, Ma, Farvardin, García-Agustín and Llorens.)

Osteoarthritis (OA) is defined by articular cartilage degeneration, synovial membrane inflammation, and abnormal bone remodeling. Recent study has discovered that OA development is linked to an aberrant epigenetic modification of OA-related genes. Our previous research showed that DNA demethylation in ADAMTS-5 promoter region had a substantial impact on ADAMTS-5 expression in the mouse OA model. This process facilitated the binding of Spi-1 to ADAMTS-5 promoter. While alterations in histone methylation have been documented during embryonic development and cancer development, there is a paucity of data on the change in OA pathogenesis. Even no data have been reported on the role of histone modifications in ADAMTS-5 activation in OA. Following our previous study on the role of DNA methylation, we aimed to examine the contribution of histone H3K9 dimethylation in ADAMTS-5 activation in OA. Additionally, we aimed to elucidate the molecular mechanisms underlying the cooperative interaction between DNA methylation and histone H3K9 dimethylation. The potential for anti-OA intervention therapy which is based on modulating histone H3K9 dimethylation is also explored. We demonstrated that a reduction in histone H3K9 dimethylation, along with DNA demethylation of the Spi-1 binding site, had a role in ADAMTS-5 activation in the articular cartilage of OA mice. Significantly, the conditional deletion of histone demethylase to be identified as lysine-specific demethylase 1 (LSD1) in articular cartilage could alleviate the degenerative features of OA mice. Our study demonstrates the direct impact of histone H3K9 dimethylation on gene expression, which in turn contributes to OA development. This research enhances our understanding of the underlying causes of OA., (© 2024 Wiley Periodicals LLC.)

The regulation of genes can be mathematically described by input-output functions that are typically assumed to be time invariant. This fundamental assumption underpins the design of synthetic gene circuits and the quantitative understanding of natural gene regulatory networks. Here, we found that this assumption is challenged in mammalian cells. We observed that a synthetic reporter gene can exhibit unexpected transcriptional memory, leading to a shift in the dose-response curve upon a second induction. Mechanistically, we investigated the cis-dependency of transcriptional memory, revealing the necessity of promoter DNA methylation in establishing memory. Furthermore, we showed that the synthetic transcription factor's effective DNA binding affinity underlies trans-dependency, which is associated with its capacity to undergo biomolecular condensation. These principles enabled modulating memory by perturbing either cis- or trans-regulation of genes. Together, our findings suggest the potential pervasiveness of transcriptional memory and implicate the need to model mammalian gene regulation with time-varying input-output functions. A record of this paper's transparent peer review process is included in the supplemental information., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The increasing complexity and difficulty of surgical procedures have led to a rise in medical errors within clinical settings in recent years. Gastrointestinal diseases, in particular, present significant medical challenges and impose substantial economic burdens, underscoring the urgent need for experiential, high-fidelity gastrointestinal surgical training tools. This study leverages patient-specific computed tomography (CT) and magnetic resonance imaging (MRI) data, combined with 3D printed manufacturing, to develop hydrogel organ models with tunable performance and tissue-mimicking softness. These properties are achieved by regulating the freeze-thaw cycles, cross-linking agents, and the concentration of incorporated antibacterial nanoparticles in DN hydrogels. Through the application of indirect 3D printing and the "sacrificial material method", we successfully fabricate organ tissues such as the stomach, intestines, and blood vessels with high precision. In ex vivo surgical training demonstrations, these tissue-like soft hydrogels provide an effective platform for preoperative simulation and surgical training in digestive surgery, accommodating various surgical procedures and accurately simulating intraoperative bleeding. The development of advanced bionic organ models with specific and tunable characteristics based on DN hydrogels is poised to significantly advance surgical training, medical device testing, and the reform of medical education.

Key Messages: Sixty-nine quantitative trait nucleotides conferring maize resistance to Gibberella ear rot were detected, including eighteen novel loci. Four candidate genes were predicted, and four kompetitive allele-specific PCR markers were developed. Maize Gibberella ear rot (GER), caused by Fusarium graminearum, is one of the most devastating diseases in maize-growing regions worldwide. Enhancing maize cultivar resistance to this disease requires a comprehensive understanding of the genetic basis of resistance to GER. In this study, 334 maize inbred lines were phenotyped for GER resistance in five environments and genotyped using the Affymetrix CGMB56K SNP Array, and a genome-wide association study of resistance to GER was performed using a 3V multi-locus random-SNP-effect mixed linear model. A total of 69 quantitative trait nucleotides (QTNs) conferring resistance to GER were detected, and all of them explained individually less than 10% of the phenotypic variation, suggesting that resistance to GER is controlled by multiple minor-effect genetic loci. A total of 348 genes located around the 200-kb genomic region of these 69 QTNs were identified, and four of them (Zm00001d029648, Zm00001d031449, Zm00001d006397, and Zm00001d053145) were considered candidate genes conferring susceptibility to GER based on gene expression patterns. Moreover, four kompetitive allele-specific PCR markers were developed based on the non-synonymous variation of these four candidate genes and validated in two genetic populations. This study provides useful genetic resources for improving resistance to GER in maize., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Peritoneal dialysis (PD) is currently one of the effective methods for treating end-stage renal disease (ESRD). However, long-term exposure to high concentration glucose in peritoneal dialysis environment could lead to peritoneal fibrosis (PF), impaired peritoneal filtration function, decreased peritoneal dialysis efficiency, and even withdrawal from peritoneal dialysis in patients. Considerable evidence suggests that peritoneal fibrosis after peritoneal dialysis is related to crucial factors such as mesothelial-to-mesenchymal transition (MMT), inflammatory response, and angiogenesis, etc. In our review, we summarize the pathophysiological mechanisms and further illustrate the future strategies against PF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kang, Liu, Fu and Ma.)

Small cell lung cancer (SCLC) is an aggressive pulmonary neuroendocrine malignancy featured by cold tumor immune microenvironment (TIME), limited benefit from immunotherapy, and poor survival. The spatial heterogeneity of TIME significantly associated with anti-tumor immunity has not been systemically studied in SCLC. We performed ultra-high-plex Digital Spatial Profiling on 132 tissue microarray cores from 44 treatment-naive limited-stage SCLC tumors. Incorporating single-cell RNA-sequencing data from a local cohort and published SCLC data, we established a spatial proteo-transcriptomic landscape covering over 18,000 genes and 60 key immuno-oncology proteins that participate in signaling pathways affecting tumorigenesis, immune regulation, and cancer metabolism across 3 pathologically defined spatial compartments (pan-CK-positive tumor nest; CD45/CD3-positive tumor stroma; para-tumor). Our study depicted the spatial transcriptomic and proteomic TIME architecture of SCLC, indicating clear intra-tumor heterogeneity dictated via canonical neuroendocrine subtyping markers; revealed the enrichment of innate immune cells and functionally impaired B cells in tumor nest and suggested potentially important immunoregulatory roles of monocytes/macrophages. We identified RE1 silencing factor (REST) as a potential biomarker for SCLC associated with low neuroendocrine features, more active anti-tumor immunity, and prolonged survival., (© 2024. The Author(s).)

We report an anomalous structural transformation of a Cu(I) cluster into two different types of copper-silver (CuAg) alloy nanoclusters. Different from previous reports, we demonstrate that under specifically designed reaction conditions, the Ag-doping could induce a substantial growth of the starting Cu 15 and a Ag 13 Cu 20 nanocluster was obtained via the unexpected insertion of an Ag 13 kernel inside the Cu(I)-S shell. Ag 13 Cu 20 demonstrates high activity to initiate the photopolymerization of previously hard-to-print inorganic polymers in 3D laser microprinting. Interestingly, a slight modification of the reaction condition leads to the formation of another Ag 18-x Cu x S (8≤x) nanocluster templated by a central S 2- anion, which possesses a unique electronic structure compared to conventional template-free CuAg nanoclusters. Overall, this work unveils the intriguing doping chemistry of Cu clusters, as well as their capability to create different types of alloy nanoclusters with previously unobtainable structures and multifunctionality., (© 2024 Wiley-VCH GmbH.)

Efficient drug delivery across the blood-brain barrier is imperative for treating glioblastoma (GBM). This study utilized the GBM cell membrane to construct a biomimetic targeted nanosystem (GMNPs@AMD/RAPA) that hierarchically releases the CXCR4 antagonist AMD3100 and the mTOR pathway inhibitor rapamycin (RAPA) for reprogramming the tumor immune microenvironment and suppressing the progression of GBM. By initially inhibiting the CXCL12/CXCR4 axis, the tumor microenvironment (TME) was reprogrammed to enhance the infiltration of cytotoxic T lymphocytes (CTLs) into the TME while suppressing tumor cell survival, proliferation, and angiogenesis. Subsequently, through further cellular uptake and degradation of the nanoparticles, the mTOR pathway inhibitor RAPA was released, further suppressing the tumor progression. This study successfully combined chemotherapy and immunotherapy, achieving effective synergistic therapeutic effects, and suppressing the progression of GBM., 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 Authors.)

Climate change severely affects crop production. Cotton is one of the primary fiber crops in the world and its production is susceptible to various environmental stresses, especially drought and salinity. Development of stress tolerant genotypes is the only way to escape from these environmental constraints. We identified sixteen homologs of the Arabidopsis JUB1 gene in cotton. Expression of GhJUB1&#95;3-At was significantly induced in the temporal expression analysis of GhJUB1 genes in the roots of drought tolerant (H177) and susceptible (S9612) cotton genotypes under drought. The silencing of the GhJUB1&#95;3-At gene alone and together with its paralogue GhJUB1&#95;3-Dt reduced the drought tolerance in cotton plants. The transgenic lines exhibited tolerance to the drought and salt stress as compared to the wildtype (WT). The chlorophyll and relative water contents of wildtype decreased under drought as compared to the transgenic lines. The transgenic lines showed decreased H 2 O 2 and increased proline levels under drought and salt stress, as compared to the WT, indicating that the transgenic lines have drought and salt stress tolerance. The expression analysis of the transgenic lines and WT revealed that GAI was upregulated in the transgenic lines in normal conditions as compared to the WT. Under drought and salt treatment, RAB18 and RD29A were strongly upregulated in the transgenic lines as compared to the WT. Conclusively, GhJUB1&#95;3-At is not an auto activator and it is regulated by the crosstalk of GhHB7, GhRAP2-3 and GhRAV1. GhRAV1, a negative regulator of abiotic stress tolerance and positive regulator of leaf senescence, suppresses the expression of GhJUB1&#95;3-At under severe circumstances leading to plant death., (© 2024 Scandinavian Plant Physiology Society.)

Mycorrhizal associations are key mutualisms that shape the structure of forest communities and multiple ecosystem functions. However, we lack a framework for predicting the varying dominance of distinct mycorrhizal associations in an integrated proxy of multifunctionality across ecosystems. Here, we used the datasets containing diversity of mycorrhizal associations and 18 ecosystem processes related to supporting, provisioning, and regulating services to examine how the dominance of ectomycorrhiza (EcM) associations affects ecosystem multifunctionality in subtropical mountain forests in Southwest China. Meanwhile, we synthesized the prevalence of EcM-dominant effects on ecosystem functioning in forest biomes. Our results demonstrated that elevation significantly modified the distributions of EcM trees and fungal dominance, which in turn influenced multiple functions simultaneously. Multifunctionality increased with increasing proportion of EcM associations, supporting the ectomycorrhizal-dominance hypothesis. Meanwhile, we observed that the impacts of EcM dominance on individual ecosystem functions exhibited different relationships among forest biomes. Our findings highlight the importance of ectomycorrhizal dominance in regulating multifunctionality in subtropical forests. However, this ectomycorrhizal feedback in shaping ecosystem functions cannot necessarily be generalized across forests. Therefore, we argue that the predictions for ecosystem multifunctionality in response to the shifts of mycorrhizal composition could vary across space and time., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

A new pimarane-type diterpene, ent-8(14),15-pimaradiene-2β,19-diol (JXE-23), was isolated from the fern plant Aleuritopteris albofusca by our previous work; however, the biological activity of this diterpene remains unclear. In the present study, the anti-cancer potential of JXE-23 in various cancer cells was investigated. Among MCF-7 breast cancer cells, A549 lung cancer cells, and HepG2 liver cancer cells, JXE-23 displayed significant cytotoxicity to HepG2 cells with an IC 50 value of 17.20 ± 1.73 µM, while showing no obvious toxicity in normal hepatocytes HL7702. JXE-23 inhibited cell growth and colony formation in HepG2 cells. A cell cycle distribution analysis showed that JXE-23 caused G2/M cell cycle arrest. Besides, JXE-23 also suppressed the migration of HepG2 cells. Interestingly, an increase of light chain 3 II (LC3II) and Beclin 1 and a decrease of P62 have occurred in JXE-23-treated cells, as well as the formation of GFP-LC3 dots, indicative of autophagy induction by JXE-23. When combined with autophagy inhibitor 3-methyladenine and chloroquine, the cell viability was significantly reduced, suggesting that JXE-23 triggered protective autophagy in hepatoma cells. Further study showed that JXE-23 inactivated the CIP2A/p-AKT/c-Myc signaling axis in HepG2 cells. Our data provided evidence that JXE-23 inhibited cell growth, arrested cells at the G2/M phase, and induced protective autophagy in HepG2 hepatocellular carcinoma cells. JXE-23 may be a potential lead compound for anti-cancer drug development, and autophagy inhibitor treatment may provide an effective strategy for improving its anti-cancer effect., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Phase junctions exhibit great potential in photocatalytic energy conversion, yet the narrow light response region and inefficient charge transfer limit their photocatalytic performance. Herein, an anatase/rutile phase junction modified by plasmonic TiN and oxygen vacancies (TiN/(A-R-TiO 2 -Ov)) is prepared through an in-situ thermal transformation from TiN for efficient photothermal-assisted photocatalytic hydrogen production for the first time. The content of TiN, oxygen vacancies, and phase components in TiN/(A-R-TiO 2 -Ov) hybrids can be well-adjusted by tuning the heating time. The as-prepared photocatalysts display a large specific area and wide light absorption due to the synergistic effect of plasmonic excitation, oxygen vacancies, and bandgap excitations. Meanwhile, the multi-interfaces between TiN, anatase, and rutile provide built-in electric fields for efficient separation of photoinduced carriers and hot electron injection via ohmic contact and type-Ⅱ band arrangement. As a result, the TiN/(A-R-TiO 2 -Ov) photocatalyst shows an excellent photocatalytic hydrogen generation rate of 15.07 mmol/g/h, which is 20.6 times higher than that of titanium dioxide P25. Moreover, temperature-dependent photocatalytic tests reveal that the excellent photothermal conversion caused by plasmonic heating and crystal lattice vibrations in TiN/(A-R-TiO 2 -Ov) has about 25 % enhancement in photocatalysis (18.84 mmol/g/h). This work provides new inspiration for developing high-performance photocatalysts by optimizing charge transfer and photothermal 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. Published by Elsevier Inc.)

Neurologic and neuropsychiatric disorders substantially impact the pediatric population, but there is a lack of dedicated devices for monitoring the developing brain in animal models, leading to gaps in mechanistic understanding of how brain functions emerge and their disruption in disease states. Due to the small size, fragility, and high water content of immature neural tissue, as well as the absence of a hardened skull to mechanically support rigid devices, conventional neural interface devices are poorly suited to acquire brain signals without inducing damage. Here, the authors design conformable, implantable, conducting polymer-based probes (NeuroShanks) for precise targeting in the developing mouse brain without the need for skull-attached, rigid mechanical support structures. These probes enable the acquisition of high spatiotemporal resolution neurophysiologic activity from superficial and deep brain regions across unanesthetized behavioral states without causing tissue disruption or device failure. Once implanted, probes are mechanically stable and permit precise, stable signal monitoring at the level of the local field potential and individual action potentials. These results support the translational potential of such devices for clinically indicated neurophysiologic recording in pediatric patients. Additionally, the role of organic bioelectronics as an enabling technology to address questions in developmental neuroscience is revealed., (© 2024 The Authors. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Modern implantable bioelectronics demand soft, biocompatible components that make robust, low-impedance connections with the body and circuit elements. Concurrently, such technologies must demonstrate high efficiency, with the ability to interface between the body's ionic and external electronic charge carriers. Here, a mixed-conducting suture, the e-suture, is presented. Composed of silk, the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), and insulating jacketing polymers,the resulting e-suture has mixed-conducting properties at the interface with biological tissue as well as effective insulation along its length. The e-suture can be mechanically integrated into electronics, enabling the acquisition of biopotentials such as electrocardiograms, electromyograms, and local field potentials (LFP). Chronic, in vivo acquisition of LFP with e-sutures remains stable for months with robust brain activity patterns. Furthermore, e-sutures can establish electrophoretic-based local drug delivery, potentially offering enhanced anatomical targeting and decreased side effects associated with systemic administration, while maintaining an electrically conducting interface for biopotential monitoring. E-sutures expand on the conventional role of sutures and wires by providing a soft, biocompatible, and mechanically sound structure that additionally has multifunctional capacity for sensing, stimulation, and drug delivery., (© 2024 Wiley‐VCH GmbH.)

Objectives: This study aims to analyze the efficacy of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA) in hepatocellular carcinoma (HCC)., Methods: A retrospective analysis was conducted on 632 patients with HCC at Barcelona Clinic Liver Cancer Staging (BCLC) System stages 0, A, and B from Beijing You'an Hospital affiliated with Capital Medical University. The primary outcomes analyzed were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes included one-, three-, and five-year OS rates among different groups., Results: The median follow-up period for 632 cases identified with HCC was 52.1 months (range: 3-162 months), while 127 patients died during follow-up. The one-, three-, and five-year OS rates were 97.1 %, 89.5 %, and 80.4 %, respectively. Moreover, the one-, three-, and five-year PFS rates were 58.1 %, 29.3 %, and 19.8 %, respectively. Multivariate analysis revealed that the BCLC stages and complete ablation were independent predictors of OS and PFS (all p < 0.05). Subgroup analysis showed no difference in OS rate among TACE-RFA, TACE-MWA, and TACE-CA groups, but TACE-CA showed better efficacy in improving the PFS rate (all p < 0.05)., Conclusions: The combination of TACE and ablation is effective in early-stage HCC and BCLC stage B. Complete ablation and BCLC stages are significant prognostic factors for PFS and OS. Further research, including randomized controlled trials, is needed to validate these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Individual brains vary greatly in morphology, connectivity and organization. Individualized brain parcellation is capable of precisely localizing subject-specific functional regions. However, most individualization approaches have examined single modalities of data and have not generalized to nonhuman primates. The present study proposed a novel multimodal connectivity-based individual parcellation (MCIP) method, which optimizes within-region homogeneity, spatial continuity and similarity to a reference atlas with the fusion of personal functional and anatomical connectivity. Comprehensive evaluation demonstrated that MCIP outperformed state-of-the-art multimodal individualization methods in terms of functional and anatomical homogeneity, predictability of cognitive measures, heritability, reproducibility and generalizability across species. Comparative investigation showed a higher topographic variability in humans than that in macaques. Therefore, MCIP provides improved accurate and reliable mapping of brain functional regions over existing methods at an individual level across species, and could facilitate comparative and translational neuroscience research.

Background: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined., Methods: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses., Results: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs . 46.6%, p  <  0. 001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p  < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality ( p  = 0.004), need for renal replacement therapy ( p =  0.011), and developing stage-3 AKI (p =  0.040) according to the adjusted models., Conclusions: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

Repairing and regenerating articular cartilage defects (ACDs) have long been challenging for physicians and scientists. The rise of injectable materials provides a novel strategy for minimally invasive surgery to repair ACDs. In this study, we successfully developed injectable materials based on collagen type II, achieving hyaline cartilage repair and regeneration of ACDs. Analysis was conducted on the regenerated cartilage after materials injection. The histology staining demonstrated complete healing of the ACDs with the attainment of a hyaline cartilage phenotype. The biochemical and biomechanical properties are similar to the adjacent native cartilage without noticeable adverse effects on the subchondral bone. Further transcriptome analysis found that compared with the Native cartilage adjacent to the defect area, the Regenerated cartilage in the defect area repaired with type II collagen-based injection materials showed changes in cartilage-related pathways, as well as down-regulation of T cell receptor signaling pathways and interleukin-17 signaling pathways, which changed the immune microenvironment of the ACD area. Overall, these findings offer a promising injectable approach to treating ACDs, providing a potential solution to the challenges associated with achieving hyaline cartilage in situ repair and regeneration while minimizing damage to the surrounding cartilage., Competing Interests: 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., (Copyright © 2024 Zhen Zhang et al.)

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized., Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development., Results: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups., Conclusion: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology., (© 2024. The Author(s).)

Background: Enterobacter cloacae insecticidal proteins have been reported to kill Galleria mellonella larvae through affecting their midgut microbiome. However, the mechanisms involved remain unclear. Here we aim to investigate how the insecticidal proteins act on the midgut Duox-ROS system and microbial community of G. mellonella larvae., Methods: Reverse transcription qPCR and fluorescence probes were utilized to assess the Duox expression levels and to evaluate quantitative changes of the ROS levels. Sequencing of the 16S rRNA gene sequences of the midgut bacteria of G. mellonella larvae was conducted for further analyses of bacterial diversity, composition, and abundance., Results: After the injection of the insecticidal proteins, the Duox expression levels first increased within 28 h, then dramatically peaked at 36 h, and slowly decreased thereafter. Simultaneously, the ROS levels increased significantly at 36 h, peaked at 48 h, and rapidly declined to the normal level at 60 h. Responsive to the change of the ROS levels, the structure of the midgut microbial community was altered substantially, compared to that of the untreated larvae. The relative abundance of Enterobacteriaceae and other specific pathogenic bacteria increased significantly, whereas that of Lactobacillus decreased sharply. Importantly, notable shifts were observed in the crucial midgut predicted metabolic functions, including membrane transportation, carbohydrate metabolism, and amino acid metabolism., Conclusion: Insecticidal proteins of E. cloacae kill G. mellonella larvae mainly through generation of high oxidative stress, alterations of the midgut microbial community and function, and damage to the physiological functions. These findings provide insights into the inhibition mechanism of E. cloacae insecticidal proteins to G. mellonella larvae., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Taotao Li reports financial support was provided by Henan University of Urban Construction. Chao Hu reports a relationship with Pingdingshan Academy of Agricultural Sciences that includes: employment. 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.)

Background: Stroke is the leading cause of acquired disability and the second leading cause of death worldwide. Its rate of incidence, disability, mortality, and recurrence is high, and the patients experience various symptoms of discomfort, which not only affect their rehabilitation function but also reduce their ability to perform daily activities and their quality of life. Nowadays, with the improvement of China's medical standards, patients are increasingly attentive to their quality of life and health status. However, diagnostic techniques and effective treatments for patients with stroke are still limited but urgently required., Objective: This study aimed to evaluate the quality of life during hospitalization using a stroke patient-reported outcomes (PROs) scale and additionally to recognize potential factors and risk indicators that may impact recurrent events, facilitating early intervention measures., Methods: This is a registry-based, retrospective observational cross-sectional study on patients with stroke. A convenient sampling method was used to select various indicators of patients. The Stroke-PRO scale was then used to assess patients' conditions across physical, psychological, social, and therapeutic domains. Multiple linear regression analysis was applied to identify factors influencing stroke PROs, while correlation analysis was conducted to explore the relationship between these outcomes and blood lipid levels., Results: The mean Stroke-PRO score in this study was 4.09 (SD 0.29) points. By multiple linear regression analysis, residence, occupation, physical exercise, Barthel index, Braden scale, National Institutes of Health Stroke Scale scores at admission, and stroke type were the risk factors for reported outcomes of patients with stroke (P<.05). Correlation analysis showed that serum triglyceride, total cholesterol, and low-density lipoprotein were negatively correlated with Stroke-PRO scores in patients with stroke (P<.05), while high-density lipoprotein was positively correlated with patients with stroke (P<.05). The 95% CI was -0.31 to -0.03 for triglyceride, 0.17-0.44 for high-density lipoprotein, -0.29 to -0.01 for cholesterol, -0.30 to -0.02 for low-density lipoprotein, and -0.12 to 0.16 for blood glucose., Conclusions: Patients with stroke have a low level of health, and their reported outcomes need to be improved. Accordingly, nursing staff should pay attention to the quality of life and blood lipid indexes of patients with stroke, actively assess their actual health status, and take early intervention measures to promote their recovery., (©Jia Sun, Liang Ma, Xiao Miao, Hui Sun, SuSu Zhu, Ran Zhang, LeLe Fan, TingTing Hu. Originally published in JMIR Formative Research (https://formative.jmir.org), 26.08.2024.)