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The synthetic polysaccharides, which have precise structure, can be used to design new drugs by comparing structure-activity relationships (SAR). Improved protein stability may be due to the interaction between the polysaccharides and protein, which includes covalent and noncovalent interactions. It is critical to investigate the SAR of polysaccharides with a precise structure from the perspective of protein stability. Glucans-insulin interaction may be a useful stratagy to solve this problem. This study reports the SAR of the synthesized glucan GLSWA-1 and its substructures 2-4 on insulin secretion and discusses its mechanism. The results showed that although GLSWA-1 and its substructures 2-4 bind insulin to varying degrees, compound 2 improves insulin secretion in a dose-dependent manner. Further research found that compound 2 maintains the thermal stability of insulin better than GLSWA-1 through stronger hydrogen bonding, and molecular dynamics simulations demonstrated that compound 2 can form a "groove-binding model" with insulin. This study considerably improves the research on the SAR of glucan based on insulin thermostability and indicates that compound 2, its linear structure, appropriate chain flexibility ((1 → 6)-glucoside bonds), low molecular weight, and smaller steric hindrance is a potential hypoglycemic agent., 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.)

Cigarette smoke (CS) has detrimental effects on placental growth and embryo development, but the underlying mechanisms remain unclear. This study aims to investigate the impact of CS on trophoblast cell proliferation and regulated cell death (RCD) by examining its interference with iron-sulfur cluster (ISC) proteins and the CIA pathway. Exposure to CS disrupted the cytosolic ISC assembly (CIA) pathway, downregulated ISC proteins, and decreased ISC maturation in the placenta of rats exposed to passive smoking. Studies using HTR-8/Sneo cells demonstrated that cigarette smoke extract (CSE) inhibits trophoblast proliferation, activates autophagy, and induces apoptosis by impairing the CIA pathway and ISC proteins. Molecular docking analysis revealed that nicotine and nicotyrine bind to and promote the autophagic-dependent degradation of MMS19, a key component of the CIA complex. MMS19 KD led to the autophagic degradation of several ISC proteins involved in DNA damage repair and mitochondrial respiratory function, thereby inhibiting cell proliferation. Additionally, MMS19 deficiency resulted in mitochondrial fragmentation, ROS accumulation, and the induction of autosis and apoptosis. Transcriptome analysis indicated that dysregulation of the SMAD pathway mediates mitochondrial damage induced by MMS19 KD. Analysis of placental tissues from maternal smokers further confirmed the disruption of ISC proteins and the SMAD pathway. This study suggests that disruption of the CIA pathway and ISC proteins contributes to placental maldevelopment induced by CS. Targeting the MMS19-SMAD pathway may offer a potential strategy to mitigate adverse pregnancy outcomes caused by CS., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Xiaomei Liu reports financial support was provided by National Natural Science Foundation of China. 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Ecosystem services arise from and are shaped by interactions within social-ecological systems. While network approaches hold promise for conceptualizing and managing ecosystem services, their practical application remains underexplored. This study introduces a novel application of the partial correlation network approach to ecosystem service research, using China's Loess Plateau as a case study to analyze ecosystem services and social-ecological factors within a network framework. Our results reveal significant improvements in key ecosystem services, including soil conservation, carbon sequestration, and food provision, from 2000 to 2020, alongside a non-significant declining trend in water provision. The network analysis uncovers complex interdependencies among ecological restoration activities, landscape pattern changes, socio-ecological processes, and ecosystem services on the Loess Plateau, identifying key nodes and connections within the network. The plant productivity trend exhibits the highest node strength, indicating its pivotal role in driving substantial changes across the entire network configuration. This study highlights the potential of the partial correlation network approach for a comprehensive understanding of the interdependencies between ecosystem services and social-ecological factors, providing valuable insights to inform ecosystem service management and policy-making., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest relevant to this study., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Crisugabalin (HSK16149), a novel VGCC α2δ ligand, has been approved for the treatment of adult diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN). In this study, an LC-MS/MS method was developed for the determination of crisugabalin in rat plasma and tissues homogenate. Samples were extracted by protein precipitation and separated on a Hypersil GOLD aQ column with methanol and 2 mM ammonium acetate in water containing 0.1 % formic acid as mobile phase. Crisugabalin and its internal standard HSK7891 were ionized by electrospray ionization source and detected by multiple reaction monitoring with transitions of m/z 210.9 → 134.4 and m/z 246.0 → 129.3. Over the range of 0.0100-10.0 μg/mL, the selectivity, linearity, precision and accuracy, matrix effect, stability, recovery and dilution integrity of crisugabalin were validated in rat plasma. Validation was also performed in rat liver homogenate at concentrations ranging from 0.0200-20.0 μg/g. The method was then successfully applied to determine the pharmacokinetics and tissue distribution of crisugabalin. In rats, orally administered crisugabalin was completely and rapidly absorbed with a peak time of about 0.57 h, and was mainly distributed to kidney, bladder and liver tissues. Crisugabalin exhibited linear pharmacokinetics over the oral dose range of 3-30 mg/kg., 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.)

Autophagy plays an important role in responding to necrotrophic pathogens and plant signal hormones. Brassinosteroids (BRs) are a class of natural steroidal phytohormones that effectively regulated the disease resistance responses in grape. However, the molecular mechanism of BR-autophagy networks responsible for activation of host defense against gray mold remained to be elucidated. We reported a novel defense mechanism that BR-regulated autophagy in grape berry against gray mold. Exogenous application of 24-epibrassinolide (eBR) enhanced the grape disease resistance. Meanwhile, the endogenous BR was accumulated and BR signaling pathway was activated in the berries. In addition, transcriptome analysis in eBR-treated grapes infected with gray mold showed that the differentially expressed genes (DEGs) were enriched in the metabolic pathway of BR signaling pathway and autophagy. DNA affinity purification sequencing (Dap-seq), Yeast one-hybrid assay (Y1H) and dual luciferase assays (LUC) verified VvBZR1 bound to the promoter of VvATG18a to induce its gene expression. Overexpressing VvATG18a and VvBZR1 improved the resistance of grapes to gray mold. Overall, this study sheds light on the immune mechanisms underlying the involvement of the autophagy in grape innate immunity, highlighting the pivotal role of VvATG18a in enhancing disease resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objectives: Previous studies suggest peripheral blood immune cells associate with the progression and prognosis of lung cancer. The main purpose of this study was to explore the association of peripheral immune cell and its dynamics with the growth of pulmonary nodules., Materials and Method: Of 9280 subjects whom had blood cell counts and chest CT scan in health check-up, 1068 participants were enrolled with the incidental pulmonary nodules of above 5 mm in diameter and subsequently followed up for 2 years. The pulmonary nodules were identified as growth based on the increase of at least 2 mm in the diameters within the two years. The relationships of pulmonary nodules growth with peripheral immune cell dynamics and clinical variables were analyzed using univariable inter-group comparison and multivariable logistic regression analyses., Results: During the two years, 116 (10.9 %) of 1068 participants had the growth pulmonary nodules. Overall, emphysema, nodule diameter and non-solid characteristics associated with the growth of nodules. In the subgroup of pure solid nodules, high baseline eosinophil percentage (OR 1.220; 95 % CI 1.009-1.474; P = 0.040) and the increase of neutrophil count (OR 3.805; 95 % CI 1.027-14.093; P = 0.045) were significant risk factors for the nodule growth. In the subgroup of solid-predominant nodules, the increase of lymphocyte was associated with a lower risk of growth (OR 0.039; 95 % CI 0.002-0.839; P = 0.038)., Conclusions: High baseline eosinophil and increase of neutrophil were associated with the growth of pure solid pulmonary nodules. The decrease of lymphocyte related to the growth of solid-predominant nodules., 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 © 2025 Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study is to explore the process and internal mechanism of patients with diabetes falling into the vicious cycle of medication dependence from the perspective of patients' life., Methods: Employing purposive sampling, 23 patients with type 2 diabetes were interviewed individually at a renowned tertiary hospital in South China. Subsequently, interview data underwent content analysis., Results: Analysis of the collected data yielded three overarching themes: "disease limits me everywhere," "the medications make me feel my life again," and "difficult to get rid of the medication dependence.", Conclusions: Our study reveals the process and underlying causes of the vicious cycle of medication dependence among patients with type 2 diabetes. Diabetes patients, in the process of integrating self-management into their daily lives, often view medication as a shortcut to simplify life. They struggle between comprehensive management and dependence on medication, but influenced by immediate gratification and life rationality, they ultimately fall into an inescapable vicious cycle., Practice Implications: This study can provide information for targeted interventions to enhance patients' comprehensive health management abilities, thereby breaking the vicious cycle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The hAβ-KI and APP SAA -KI are two amyloid models that harbor mutations in the endogenous mouse App gene. Both hAβ-KI and APP SAA -KI mice contain a humanized Aβ sequence, and APP SAA -KI mice carry three additional familial AD mutations. We herein report that the Aβ levels and Aβ42/Aβ40 ratio in APP SAA -KI homozygotes are dramatically higher than those in hAβ-KI homozygotes at 14 months of age. In addition, APP SAA -KI mice display a widespread distribution of amyloid plaques in the brain, whereas the plaques are undetectable in hAβ-KI mice. Moreover, there are no sex differences in amyloid pathology in APP SAA -KI mice. Both APP SAA -KI and hAβ-KI mice exhibit cognitive impairments, wherein no significant differences are found between these two models, although APP SAA KI mice show a trend towards worse cognitive function. Notably, female hAβ-KI and APP SAA -KI mice have a more pronounced cognitive impairments compared to their respective males. Our findings suggest that Aβ humanization contributes to cognitive deficits in APP SAA -KI mice, and that amyloid deposition might not be closely associated with cognitive impairments in APP SAA -KI mice., Competing Interests: Declaration of Competing Interest All authors declare no competing interests. This manuscript is not under consideration for publication elsewhere, and its publication is approved by all authors., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To improve medical students' preclinical skills and enable them to quickly comprehend the procedure of posterior pharyngeal flap surgery, our teaching team developed a surgical simulator specifically for pharyngeal flap surgery., Study Design: Thirteen undergraduate students and 8 first-year residents trained from March to May 2023 participated in simulated surgical training. Initially, multimedia were used to explain and demonstrate to them relevant anatomy, surgical principles, and procedural steps. This was followed by independent simulated surgeries by the students, culminating in the completion of a questionnaire. Independent samples t test was used for statistical analysis., Results: Before the simulated surgery, the residents had a greater understanding of the surgical design compared with the undergraduate students. After the simulated surgery, the residents showed not only significantly greater levels of understanding of the surgical design but also increased familiarity with the surgical process and enhanced confidence in independent surgery compared with the undergraduate students. Both groups showed a notable increase in familiarity with the surgical process and confidence in performing surgery independently after the simulated surgery., Conclusions: The surgical simulator demonstrates high clinical fidelity and provides tactile feedback that closely resembles reality. It significantly enhances the understanding and mastery of surgical techniques for young doctors, ultimately improving their surgical skills., Competing Interests: Declarations of Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Twelve picrotoxane-type sesquiterpenoids were isolated from Dendrobium wardianum, of which dendrowardins K-N (1-4) are new compounds and dendrowardins O and P (9, 10) are new natural products. Notably, the structure of dendrowardin K contains the rarely observed 10,11-γ-lactone ring. The structural configurations of these compounds were determined through comprehensive 1D and 2D nuclear magnetic resonance (NMR), single-crystal X-ray diffraction, and other spectroscopic analyses. Additionally, the hypoglycaemic activities of the picrotoxane-type sesquiterpenes and their analogues were systematically evaluated by determining the antidiabetic activities of these compounds and six others (13-18) obtained from genus Dendrobium. Twelve compounds (1, 2, 4-6, 8, 12, 13 - 15, 17, and 18) significantly improved insulin resistance. Further experiments revealed that compound 6 improved insulin resistance by increasing GLUT-4 expression. The possible mechanism is related to AKT-related pathways, and the effects of treatment with 50 μM compound 6 were comparable to those of the positive control drug metformin. Compounds 4-6 and 13-15, 17 displayed great increases in the secretion of insulin from β-TC-6 cells. On the basis of these findings, the structure-activity relationships (SARs) of picrotoxane-type sesquiterpenoids were discussed for the first time., 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.)

The sirtuin (SIRT) family is a group of seven conserved nicotinamide adenine dinucleotide-dependent histone deacetylases (SIRT1-SIRT7), which play crucial roles in various fundamental biological processes, including metabolism, aging, stress responses, inflammation, and cell survival. The role of SIRTs in neuro-pathophysiology has recently attracted significant attention. Notably, SIRT1-SIRT3 have been identified as key players in neuroprotection as they reduce neuroinflammation and regulate mitochondrial function. This review summarizes the latest research advancements in the role of the SIRT family in neurological diseases, mainly including neurodegenerative diseases, ischemia-related diseases, bleeding-related diseases, nervous system injury and other nervous system diseases, emphasizing their critical functions and associated signaling pathways, (e.g., AMPK/SIRT1/PGC-1α, AMPK/SIRT1/IL-1β/NF-κB, STAT2-SIRT4-mTOR, SIRT3/FOXO3α, and other signaling pathways in disease progression, particularly their protective roles in neurodegenerative diseases, ischemic injuries, and neural damage. Additionally, this review discusses progress in clinical studies targeting SIRT-specific small-molecule agonists and inhibitors. Further research on SIRTs may provide new insights into potential therapeutic strategies for the prevention and treatment of neurological disorders., 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.)

Plants, various biological organisms, and certain marine organisms typically provide biopolymers, like cellulose. Some things that make them unique are that they are non-toxic, biodegradable, have high specific strength and specific modulus, are easy to change the surface of, are highly hydrophilic, and are biocompatible. Significantly, nanocellulose has emerged as a prominent development in the 21st century. The objective of this work was to create a model that can accurately predict and optimize the viscosity, storage modulus (G'), and loss modulus (G″) of sulfate nanocellulose (S-NC) hydrogen materials. These properties were analyzed in different experimental settings. To do this, the researchers used the RSM and multi-layer perceptron (MLP)-ANN techniques to accurately represent and optimize the viscosity, G', and G″ properties. Ultimately, the researchers conducted RSM optimization to identify the optimal patterns of viscosity, G', and G″ characteristics for a new method of producing nanocellulose materials. The results showed that the ANN and RSM methods were very good at predicting how nanocellulose hydrogels would behave while nanocellulose products were being made. Moreover, the ANN technique exhibited superior accuracy in forecasting processes' G' and G' behavior compared to the RSM method. Ultimately, the ideal viscosity state was attained by using a shear rate value of 95 S -1 and including 1.5 wt% of S-NC. The optimal mode for G' and G″ was achieved at a frequency of 14.532 Hz and an S-NC concentration of 1.468 wt%., 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.)

Aims: Human immunodeficiency virus(HIV) co-infection may cause different immune imprinting, which leads to different hybrid immunity and clinical manifestations of coronavirus disease 2019. This study aims to evaluate the immune imprinting from wild-type(WT) vaccination in people living with HIV(PLWH) and analyze its effect on hybrid immunity and clinical manifestations., Materials and Methods: We enrolled 118 PLWH to compared the differences of BA.5-specific immune response in different immune modes. 20 vaccinated healthy individuals(HC) and 30 vaccinated PLWH were matched to compare the differences of the status of Omicron infection, serum neutralizing antibody levels against WT and BA.5, and specific lymphocytes expression, separately., Key Findings: Hybrid immunity had a higher level of BA.5 IgG than either vaccine immunity only or natural immunity only in PLWH but didn't have a higher level of BA.5-specific lymphocytes responses. PLWH had fewer symptoms than HC after breakthrough infection. The neutralizing inhibition rate of PLWH was higher for BA.5 and lower for WT, while the neutralizing inhibition rate of HC was higher for WT and lower for BA.5. The difference value of specific B lymphocytes/memory B cells/follicular helper T cells of PLWH was greater than that of HC., Significance: Hybrid immunity of PLWH has a higher level of Omicron-specific IgG without a higher level of Omicron-specific lymphocytes due to immune imprinting. However, there is a stronger neutralizing ability against variants of PLWH due to the weaker immune imprinting of PLWH than that of healthy people, which may lead to fewer symptoms in PLWH after breakthrough infection., 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.)

Background: Chronic ketamine use leads to cognitive impairments, however, the neural mechanisms underpinning these impairments are still unclear., Aims: Many studies showed Anterior cingulate cortex (ACC)is strongly involved in cognition and drug addiction, as supported by our previous studies. The objective of this study was to assess the variations in resting-state functional connectivity (FC) changes in the right anterior cingulate cortex (ACC) of chronic ketamine users (CKUs) and their relationship with cognitive performance., Methods: The study enrolled 28 chronic ketamine users (CKUs) and 30 healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from both groups. Cognitive functions were evaluated using the MATRICS Consensus Cognitive Battery (MCCB)., Results: CKUs demonstrated significantly poorer cognitive performance than HCs in various cognitive domains, including Visual Learning, Speed of Processing, Working Memory, and the composite score of MCCB. Group-level comparisons revealed that CKUs exhibited enhanced functional connectivity between the right ACC and the right postcentral gyrus (PCG) compared to HCs. There was a positive relationship between the connectivity of right ACC-PCG and reasoning and problem-solving score, but there was no significant association with the characteristics of ketamine use., Conclusion: CKUs showed enhanced connectivity between the right ACC and the right PCG. This enhanced functional connectivity may indicate functional compensation for cognitive deficits in CKUs, especially for reasoning and problem-solving impairments in CKUs., Competing Interests: Declaration of Competing Interest The authors of this paper declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cadonilimab is a first-in-class bispecific PD-1/CTLA-4 antibody. Serine/threonine kinase (STK11) mutation was shown to be related to low PD-L1 expression and objective response rate (ORR) in nonsmall cell lung cancer (NSCLC), resulting in poor progression-free survival (PFS) and overall survival (OS). Herein, we hypothesized that combining cadonilimab with chemotherapy could enhance antitumor immunity and extend survival in these patients. Consequently, we designed this study to explore the clinical activity and safety of cadonilimab combined with chemotherapy in patients with advanced/metastatic NSCLC harboring STK11 alteration., Trial Design: This single-center, open-label, single-arm phase II trial is conducted at the first affiliated hospital of Guangzhou Medical University. Treatment-naïve advanced/metastatic NSCLC patients harboring STK11 mutation will be enrolled in this study. Eligible patients will receive either cadonilimab (10mg/kg on Day 1) plus pemetrexed (500 mg/m 2 ) and carboplatin (AUC = 5) for nonsquamous NSCLC or abraxane (100 mg/m 2 ) and carboplatin (AUC = 5) for squamous NSCLC for 4 cycles, followed by maintenance therapy (cadonilimab plus pemetrexed or abraxane). The treatment will be discontinued when disease progression, intolerability to cadonilimab, and/or chemotherapy occurs. Measurable lesions were assessed according to the Response Evaluation Criteria in Solid Tumors (1.1). The main endpoint is ORR and safety. Subordinate endpoints include PFS, disease control rate, and duration of response., Results: The study commenced enrolment in September 2023, with preliminary findings regarding the primary endpoint anticipated by January 2025., Competing Interests: Disclosures All authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

MicroRNA, as a distinctive biomarker, plays a crucial role in the early prognosis and diagnosis of numerous severe diseases. However, due to its inherent properties such as low abundance, small size, and high sequence similarity, the sensitive and accurate detection of microRNA remains a major challenge. Herein, a dual-mode electrochemical biosensing platform was developed for microRNA detection, based on poly(3,4-ethylenedioxythiophene) (PEDOT) doped with graphene oxide-Fe 3 O 4 (GO-Fe 3 O 4 ) nanocomposite. The GO-Fe 3 O 4 /PEDOT composite demonstrated a porous microstructure, outstanding conductivity, and robust catalytic activity towards nitrite. It was electrodeposited onto the electrode surface in a one-step process using the cyclic voltammetry method (CV). The microRNA biosensor was obtained by anchoring DNA with amino groups to the GO-Fe 3 O 4 /PEDOT layer through the formation of amide bonds. The designed dual-mode microRNA biosensor demonstrated a broad linear range spanning from 10 -15 M to 10 -6 M, with low detection limits of 5.18 × 10 -15 M and 7.36 × 10 -15 M when using chronocoulometry (CC) and amperometric i-t curve (i-t) modes, respectively. Furthermore, a dual-mode electrochemical biosensor has been successfully developed and utilized for the detection of microRNA in human serum, demonstrating its potential for precise and sensitive microRNA detection and its practical application value in clinical medicine., 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.)

Anticancer chemotherapies damage normal tissues, and various drug carriers are under consideration to address this issue. Metal-organic frameworks (MOFs) are promising due to their drug-carrying capacity and tunable properties. Target-inspired surface functionalization may further magnify their potential. In this study, we aim to investigate the anticancer activity of reduced iron-based MOFs (RMOFs) functionalized with ferritin and folic acid and loaded with doxorubicin. Successful synthesis and functionalization are confirmed by electron microscopes, Fourier transform infrared spectroscopy and X-ray diffraction. Anticancer activity is evaluated in different tumor cell lines at various doses. Results indicate that the folic acid functionalized and Dox loaded MOF (FADMOF) showed maximum anticancer potential, leaving only 6 % of 4 T1 cells alive at the highest dose. Ferritin and combo MOFs followed closely, while the plain RMOF lagged behind. Furthermore, in HeLa cells, the RMOF showed the best cytotoxicity, reducing cell viability to a mere 30 % at the highest dose. Similarly, in MCF7 cells, theRMOF) showed the best cytotoxicity, reducing cell viability in a dose-dependent manner and to a mere 25 % at the highest dose. Taken together, this study shows that functionalized MOFs have promising anticancer potential across various cancer cell lines. However, loading with doxorubicin reduces their cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Muhammad Imran Khan, Fenfen Li, Yi Hu and Bensheng Qiu has a patent pending to University of Science and Technology of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The maintenance of cardiac homeostasis necessitates proper protein turnover, which is regulated by the ubiquitin-proteasome system. F-box proteins are one type of E3 ubiquitin ligases, and accumulating evidence suggests that dysregulation of FBPs exacerbates heart diseases. Therefore, in this review, we summarized the F-box proteins present in the heart, which can be divided into three types based on their repeated sequences, namely FBXO (Fbxo32, Fbxo25, Fbxo44, Fbxo27 and Fbxo28), FBXW (Fbxw7 and Fbxw5), and FBXL (Fbxl1, Fbxl10, Fbxl16 and Fbxl2). Moreover, the physiological and pathological roles and the functional mechanisms of these F-box proteins were elucidated within the cardiac context, providing new theories and strategies for the prevention and treatment of heart diseases., Competing Interests: Declaration of Competing Interest All authors declare there are no conflicts of interest regarding the publication of this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Highly urbanized coastal ecosystems are vital in the global carbon budget. However, there are limited researches on carbon flux gradients in these nearshore areas, considering both natural and anthropogenic influences. Through on-site measurements and field samplings during wet-to-dry season in 2023, this study investigated spatial variations and factors affecting carbon fluxes, focusing on the impacts of salinity and eutrophic status in five geographically connected coastal waters of the Guangdong-Hong Kong-Macau Greater Bay Area (GBA). By estimating carbon exchange at land-sea-air interface, dominant processes in carbon dynamics were identified as well. Results showed that partial pressure of CO 2 (pCO 2 ) varied from 391 to 2290 μatm, and sea-air CO 2 exchange fluxes (FCO 2 ) ranged from -3.07 to 70.07 mmol m -2 d -1 , indicating significant geographical distinctions among five coastal waters of the GBA. The total carbon transport from rivers to these nearshore waters was approximated at 6.44 Tg C yr -1 , with the Pearl River (PR) contributing 99.7%, primarily in dissolved forms. Atmospheric CO 2 release was calculated at 0.29 Tg C yr -1 for studied five coastal waters, primarily as carbon sources, except for Dapeng Bay (DPB) as a sink. CO 2 emissions inversely correlated with salinity, yet positively with eutrophication status, particularly in river-dominated estuaries. Moreover, CO 2 flux decreased 23 times as eco-status shift from eutrophic to non-eutrophic. River plumes, terrestrial pollutant inputs, and economic structure were underlying drivers, influencing carbon species concentrations and fluxes. Elevated CO 2 concentrations in eutrophic coastal waters were mainly attributed to terrestrial carbon and nutrients inputs, supporting active biological respiration and microbial decomposition. Conversely, carbon dynamics potentially depend on the balance of respiration and photosynthesis in non-eutrophic coastal waters. This study offers high geographic precision and specificity of carbon species, and provides land-sea integration insight to understand carbon dynamic mechanisms, promoting advancements in water quality management and climate mitigation., 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.)

Detecting dopamine (DA) is critical for early diagnosis of neurological and psychiatric disorders. However, the presence of other catecholamine neurotransmitters with structural similarities to DA causes significant interference in its detection. Herein, we introduce S stripping defects via laser-induced MoS 2 to functionalize MoS 2 electrodes and improve their selectivity for DA electrochemical detection. The sensing results show its excellent immunity to interference from other neurotransmitters, ensuring the preservation of the DA electrochemical signal even in the mixed neurotransmitters such as acetylcholine (ACh), γ-aminobutyric acid (GABA), epinephrine (EP), norepinephrine (NP), and serotonin (5-HT). DFT calculations further reveal that the negatively charged S-stripping defects enhance DA adsorption on the surface of the functionalized MoS 2 electrode, contributing to its excellent performance. Moreover, this functionalized electrodes successfully monitor DA released from living PC12 cells in the presence of other interference, highlighting its potential applicability in intercellular signaling communication., 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.)

Background: During the active phase of urticaria, a decrease in peripheral blood basophils, known as basopenia, is observed. We previously reported that basopenia occurs as a result of basophils migrating to the skin in a contact dermatitis model where a Th2 response is induced with oxazolone., Objective: Although there is currently no established model for urticaria, given that urticaria is an IgE-mediated immediate-type allergic reaction, we aimed to determine whether an IgE-mediated model could reproduce the decrease in basophils in peripheral blood observed during the active phase of urticaria., Methods: Mice were pretreated with 2,4,6-trinitrophenylhaptene (TNP)-specific IgE and basophil dynamics were examined following stimulation with TNP-ovalbumin. Mast cell-deficient WBB6F1-Kit W /Kit W-v mice were used to investigate the role of mast cells in this IgE-mediated model., Results: Following stimulation, we observed immediate ear swelling and basopenia after 0.5 hours. However, the number of basophils observed in the skin lesions was low, while a higher number of basophils were observed in the antigen-draining lymph nodes (LN). In mast cell-deficient mice, no increase in basophils in the LN was observed, reflecting reduced antigen influx into the LN, but basophils remained in the skin., Conclusions: In the IgE-mediated mouse model, basopenia was observed, which coincided with the induction of inflammation in the skin. The migration of basophils to the LN in this model suggests that the systemic immune system, including the LN, should be considered when exploring the pathogenesis of urticaria in humans., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare, (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

The problem of asynchronous fault detection filtering for nonhomogeneous Markov jumping systems with dynamic quantization and hybrid cyber attacks is addressed in this paper. The introduction of polytopic-structure-based transition probabilities is employed to describe the nonhomogeneous Markov process. An asynchronous fault detection filter is proposed, which utilizes the hidden Markov model to achieve comprehensive access to the plant mode information. Prior to transmission to the filter, the measurement output of the system undergoes quantization using a dynamic quantizer. The novel hybrid cyber attacks model being discussed involves four types of attacks: deception attacks, denial-of-service attacks, no attack, and hybrid attacks with both deception and denial-of-service attacks. By constructing Lyapunov functional, sufficient conditions are presented for achieving the stochastic stability with H ∞ performance. Under the complex network environment, the industrial application of the presented asynchronous fault detection filtering model is demonstrated on a non-isothermal continuous stirred tank reactor. The simulation results confirm the practicality of the proposed design method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Rapidly and accurately grasp the change of soil organic carbon content in farmland, which is of great significance in guiding the timely and effective mastery of farmland soil fertility and improvement of soil physical properties. In this study, an ASD FieldSpec 4 spectrometer was used to collect spectral reflectance data on 128 agricultural soil samples taken from Jingbian County, Yulin City, Shaanxi Province, China. Firstly, descriptive statistics of the SOC in the study area were performed, and secondly, after 10 spectral transformations were performed, the correlation analysis and the Boruta algorithm were used to extract the characteristic wavebands of soil organic carbon, respectively, in order to reduce the redundancy of the data. Finally, by comparing the accuracies of different strategies, we constructed a spectral prediction model of soil organic carbon in farmland of the Northwest Agricultural and Animal Husbandry Intertwined Zone that integrates the optimal preprocessing, feature selection strategy and modelling method. The results indicate that: 1) The mean SOC content of the farmland in the study area was low and at the nutrient deficient level, with the standard errors and coefficients of variation for the modelling and validation sets were 1.596 g kg -1 , 1.457 g kg -1 , 54 % and 52 %, respectively; 2) The shape and trend of spectral special curves with different SOC contents show consistency, and the SOC content is negatively correlated with spectral reflectance; 3) CA selects more feature bands, but the feature bands are more homogeneous, while the Boruta algorithm can effectively remove irrelevant variables and improve the SOC feature selection effect; 4) The SOC prediction model based on Boruta-FD-RF can be better for soil organic carbon estimation, with R 2 of 0.899 and 0.748 for the training set and validation set, respectively, RMSE of 1.432 g kg -1 and 1.967 g kg -1 , and RPD of 2.557 and 1.647, respectively. The results show that the SOC model established by integrating optimal spectral pre-processing, feature selection strategy and chemometrics strategy has obvious improvement in prediction accuracy and stability, and this study provides an important reference for the fast and accurate estimation of SOC content in farmland of Agro-pastoral Transitional zone in northwest China., 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.)

Histone deacetylases (HDACs) are zinc-dependent deacetylases that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo and in vitro studies have amply demonstrated the critical role of HDACs in the cell biology of the nervous system during both physiological and pathological processes and have provided new insights into the conduct of research on neurological disease targets. In addition, in vitro and in vivo studies on HDAC inhibitors show promise for the treatment of various diseases. This review summarizes the regulatory mechanisms of HDAC and the important role of its downstream targets in nervous system diseases, and summarizes the therapeutic mechanisms and efficacy of HDAC inhibitors in various nervous system diseases. Additionally, the current pharmacological situation, problems, and developmental prospects of HDAC inhibitors are described. A better understanding of the pathogenic mechanisms of HDACs in the nervous system may reveal new targets for therapeutic interventions in diseases and help to relieve healthcare pressure through preventive measures., 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 Ltd.. All rights reserved.)

Objectives: This study aimed to evaluate the accuracy of computer-aided design and computer-aided manufacturing (CAD-CAM)-assisted templates (CCAT), guiding rod templates (GRT), and freehand (FH) preparation of guide planes., Methods: Forty-five identical maxillary resin casts were divided into three groups, in which the guide planes of the two abutment teeth were prepared using a CCAT (n=15), GRT (n=15), and FH (n=15). The CCAT and GRT were digitally designed on a digital cast of virtually prepared guide planes and fabricated using three-dimensional printing (3DP) technology. To assess the 3D trueness, the prepared guide planes were digitally scanned and compared to the virtually designed guide planes. The angle deviation was measured to assess the trueness of the direction of the guide plane preparation. Shapiro-Wilk and Levene's tests were used to check the normality and equivalence of the variance of the data. The data were compared by using the Kruskal‒Wallis H test (α=0.05)., Results: The CCAT group exhibited significantly better 3D trueness (78.5±19.8 μm) than the GRT group (211.3±42.4 μm, p<0.05) and the FH group (198.9±44.3 μm, p<0.05). Additionally, the CCAT group (1.31±0.50°) showed significantly smaller direction trueness compared to the GRT (4.65±0.72°, p<0.05) and FH (5.64±0.70°, p<0.05) groups., Conclusions: The novel CAD-CAM-assisted template significantly improved the quality of the guide planes compared with the GRT and FH procedures. This enhancement suggests that removable partial dentures can be predictably inserted immediately after guide plane preparation., Clinical Significance: CAD-CAM-assisted templates improve the quality of guide plane preparation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols., 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: Ferroptosis is considered as an immunogenic type of regulated cell death and associated with the pathogenesis of inflammatory skin diseases. However, the involvement and function of ferroptosis in allergic contact dermatitis (ACD) remains unknown., Objective: To explore the role of ferroptosis in ACD. To reveal which type of cells develops ferroptosis in ACD., Methods: We detected the key markers of ferroptosis in 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced ACD mice model. We applicated ferrostatin-1 (Fer-1) to restrain ferroptosis in ACD mice and then compared the severity of dermatitis and the level of inflammation and ferroptosis in dermis and epidermis, respectively. Keratinocyte-specific Gpx4 conditional knockout (cKO) mice were used to investigate the function of keratinocyte ferroptosis in the development of ACD. Single-cell RNA sequencing was conducted to analyze the affection of Fer-1 on different type of cells in ACD., Results: Ferroptosis was involved in DNCB-induced ACD mice. Ferroptosis activation was more remarkable in dermis rather than in epidermis. Gpx4 cKO mice showed similar severity of skin dermatitis as control mice. Fer-1 alleviated skin inflammation in mice and reduced ferroptosis in neutrophils and CD8 + T cells both of which contribute to development of ACD., Conclusion: Ferroptosis was activated in immune cells, especially neutrophils and CD8 + T cells in DNCB-induced ACD mice. Fer-1 treatment inhibited ferroptosis of neutrophils and CD8 + T cells and relieved skin damage in ACD mice., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

HIF-1 activation is protective in acute kidney injury (AKI), but its underlying mechanism is not fully understood. Stress-induced tRNA derived small RNAs play an emerging role in cellular processes. This study investigated the role of HIF-1 associated tiRNA-Lys-CTT-003 (tiR-Lys) in an AKI mouse model. Our sequencing results showed that ischemia can promote the production of renal tiR-Lys by activating HIF-1α. FG-4592, a HIF-1 inducer, can also upregulate the expression of tiR-Lys in renal tubular cells. Both overexpression of tiR-Lys and FG-4592 pre-treatment could improve mitochondrial damage and lipid peroxidation with alleviated renal function and morphological damage in cisplatin-induced AKI mice. While the anti-ferroptosis effect of FG-4592 were largely eliminated by tiR-Lys inhibitor. Notably, tiR-Lys directly alleviated cell death and MDA accumulation induced by the ferroptosis inducer Erastin, accompanied with restored expression of GPX4. RNA-Pulldown and RIP-qPCR results revealed that tiR-Lys can interact with the RNA-binding protein GRSF1.tiR-lys overexpression can preserve protein expression of GRSF1 decreased by cisplatin. Inhibiting Grsf1 via shRNA eliminated the upregulation of GPX4 by tiR-Lys. In conclusion, our study demonstrates that HIF-1α-induced tiR-Lys is protective in cisplatin-induced AKI, primarily by upregulating the level of GPX4 through interaction with GRSF1, thereby inhibiting ferroptosis in renal tubular epithelial cells., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long non-coding RNAs (lncRNAs) have been implicated in dilated cardiomyopathy (DCM). However, the biological functions and regulatory mechanisms of lncRNAs in DCM remain elusive. Using a mouse model of experimental autoimmune myocarditis (EAM) to mimic DCM, we successfully constructed a dynamic lncRNA expression library for EAM by lncRNA microarray and found that the expression of a macrophage-enriched lncRNA, MAAMT, was significantly increased in the myocardial tissue of mice at the acute stage of EAM. Functionally, MAAMT knockdown alleviated the recruitment and proinflammatory activation of macrophages in the heart, spleen, and peripheral blood of mice at the acute stage of EAM, reduced myocardial inflammation and injury, and eventually reversed ventricular remodelling and improved cardiac function in mice at the chronic stage of EAM. Mechanistically, we identified serine/arginine-rich splicing factor 1 (SRSF1) as an MAAMT-interacting protein in macrophages using RNA pull-down assays coupled with mass spectrometry. MAAMT knockdown attenuated the ubiquitination-mediated degradation of SRSF1, increased the protein expression of SRSF1, and restrained the activation of the NF-κB pathway in macrophages, thereby inhibiting the proinflammatory activation of macrophages. Collectively, our results demonstrate that MAAMT is a key proinflammatory regulator of myocarditis that promotes macrophage activation through the SRSF1-NF-κB axis, providing a new insight into early effective treatment strategies for DCM., 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.)

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes a high mortality rate and current treatment focuses on supportive therapies but lacks specific therapeutic targets. Notably, sirtuins (SIRTs) shows potential clinical application in the treatment of sepsis. It has been demonstrated that SIRTs, the nicotinamide adenine dinucleotide + (NAD + )-dependent deacetylases that regulate key signaling pathways in eukaryotes and prokaryotes, are involved in a variety of biological processes. To date, seven mammalian yeast Sir2 homologs have been identified. SIRTs can regulate inflammation, oxidative stress, apoptosis, autophagy, and other pathways that play important roles in sepsis-induced organ dysfunction. However, the existing studies on SIRTs in sepsis are too scattered, and there is no relevant literature to integrate them. This review innovatively summarizes the different mechanisms of SIRTs in sepsis organ dysfunction according to the different systems, and focuses on SIRT agonists, inhibitors, and targeted drugs that have been proved to be effective in the treatment of sepsis, so as to integrate the clinical research and basic research closely. We searched PubMed for all literature related to SIRTs and sepsis since its inception using the following medical subject headings: sirtuins, SIRTs, and sepsis. Data on the mechanisms of SIRTs in sepsis-induced organ damage and their potential as targets for disease treatment were extracted., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To summarize the best evidence related to perioperative non-pharmacologic prophylaxis of venous thromboembolism in patients with pancreatic cancer, and improve the quality of clinical practice., Methods: According to the "6S" evidence pyramid model, we searched guideline networks, professional society websites, and comprehensive databases for clinical decisions, clinical guidelines, expert consensus, evidence summaries, and systematic reviews related to perioperative non-pharmacological prophylaxis of venous thromboembolism in patients with pancreatic cancer. The literature quality assessment followed appropriate tools. If there were any conflicts about the conclusions drawn from different sources of evidence, this study followed the principle of high-quality evidence and the latest published authoritative literature priority. The "JBI Evidence Pre-grading and Evidence Recommendation Level System 2014" was adopted for the evidence lacking a grading system., Results: Nineteen studies were included, including 7 guidelines, 5 expert consensus, 2 clinical decisions, 3 evidence summaries, and 2 systematic reviews. Twenty-three pieces of best evidence were summarized in five aspects: risk assessment, mechanical prophylactic devices, initiation and duration of non-pharmacological prevention, implementation strategies, and health education., Conclusions: The 23 pieces of evidence in five aspects we summarized provide scientific references for clinical caregivers to develop perioperative venous thromboembolism prophylaxis for pancreatic cancer patients. In addition, in order for evidence to be effectively used to improve the quality of clinical practice, clinical caregivers should consider patient preferences and explore barriers to the evidence translation and application., Systematic Review Registration: This study has been registered on the Fudan University Centre for Evidence-based Nursing (Registation No. ES20233506)., (© 2024 The Authors.)

Developing fast, accurate and sensitive triethylamine gas sensors with low detection limits is paramount to ensure the safety of workers and the public. However, sensors based on single metal oxide materials still suffer from drawbacks such as low response sensitivity and long response and recovery times. To address these challenges, in this work, a series of mesoporous CdO/CdGa 2 O 4 microspheres were synthesized. We optimized the sensor's sensing performance to triethylamine by fine-tuning the ratio of CdO to CdGa 2 O 4 . Among them, CdO:3CdGa 2 O 4 -based sensor demonstrates a rapid response time of 2 s to detect 100 ppm of triethylamine, with a high response value of 211 and exceptional selectivity. Furthermore, it exhibits a low detection limit of 20 ppb for triethylamine, making it suitable for practically testing fish freshness. Crucially, electron transfer between the heterojunctions increases the chemically adsorbed oxygen on the materials' surface, thereby enhancing the sensor's response sensitivity to triethylamine. This discovery provides new insights and methodologies for the design of highly efficient triethylamine gas sensors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to explore the involvement of phosphoenolpyruvate carboxykinase 2 (PCK2) in gefitinib-resistant non-small cell lung cancer (NSCLC) cells and assess its feasibility as a therapeutic target against gefitinib resistance., Methods: Gefitinib-resistant cell lines, PC9GR and HCC827GR, were generated through progressive exposure of parental cells to escalating concentrations of gefitinib. Transcriptomic analysis encompassed the treatment of PC9 and PC9GR cells with gefitinib or vehicle, followed by RNA extraction, sequencing, and subsequent bioinformatic analysis. Cell viability was determined via CCK-8 assay, while clonogenic assays assessed colony formation. Apoptosis was detected utilizing the Annexin V-FITC/7AAD kit. Iron ion concentrations were quantified using FerroOrange. mRNA analysis was conducted through quantitative RT-PCR. Western blotting was employed for protein analysis. H&E and immunohistochemical staining were performed on tumor tissue sections., Results: The results revealed that depletion or inhibition of PCK2 significantly enhanced gefitinib's efficacy in inducing cell growth arrest, apoptosis, and ferroptosis in resistant NSCLC. Moreover, PCK2 knockdown led to the downregulation of key ferroptosis-related proteins, GPX4 and SLC7A11, while upregulating ASCL4. Conversely, overexpression of PCK2 in gefitinib-sensitive cells rendered resistance to gefitinib. In vivo experiments using a gefitinib-resistant xenograft model demonstrated that PCK2 silencing not only reduced tumor growth but also considerably increased the anti-tumor effect of gefitinib., Conclusions: In conclusion, our study presents compelling evidence indicating that PCK2 plays a pivotal role in gefitinib resistance in NSCLC. The modulation of ferroptosis-related proteins and the involvement of Akt activation further elucidate the mechanisms underlying this resistance. Consequently, PCK2 emerges as a promising therapeutic target for overcoming gefitinib resistance in NSCLC, offering a new avenue for the development of more effective treatment strategies., 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.)

Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC 50 values ranging from 1.35 to 5.93 μM, which were more effective than the positive control indomethacin (IC 50  = 13.18 μM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The rapidly expanding use of wastewater for public health surveillance requires new strategies to protect privacy rights, while data are collected at increasingly discrete geospatial scales, i.e., city, neighborhood, campus, and building-level. Data collected at high geospatial resolution can inform on labile, short-lived biomarkers, thereby making wastewater-derived data both more actionable and more likely to cause privacy concerns and stigmatization of subpopulations. Additionally, data sharing restrictions among neighboring cities and communities can complicate efforts to balance public health protections with citizens' privacy. Here, we have created an encrypted framework that facilitates the sharing of sensitive population health data among entities that lack trust for one another (e.g., between adjacent municipalities with different governance of health monitoring and data sharing). We demonstrate the utility of this approach with two real-world cases. Our results show the feasibility of sharing encrypted data between two municipalities and a laboratory, while performing secure private computations for wastewater-based epidemiology (WBE) with high precision, fast speeds, and low data costs. This framework is amenable to other computations used by WBE researchers including population normalized mass loads, fecal indicator normalizations, and quality control measures. The Centers for Disease Control and Prevention's National Wastewater Surveillance System shows ∼8 % of the records attributed to collection before the wastewater treatment plant, illustrating an opportunity to further expand currently limited community-level sampling and public health surveillance through security and responsible data-sharing as outlined here., Competing Interests: Declaration of competing interest The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Rapid advancement of the rural digital economy has intensified the demand for leveraging digital tools to foster low-carbon and sustainable agricultural practices, garnering widespread academic and bureaucratic attention. Understanding how the rural digital economy influences agricultural carbon emissions is crucial for unlocking emission reduction potential, facilitating a transition towards sustainable energy usage in rural areas, and nurturing green agricultural development. In this study, we employ the entropy method, a spatial Durbin model, and a panel threshold model to assess the impact of the rural digital economy on agricultural carbon emissions across each province in China from 2010 to 2022. Additionally, we delve into the mechanism through which the rural digital economy facilitates agricultural carbon reduction, particularly in terms of "agricultural socialized services". Our findings reveal several key insights. Firstly, the rural digital economy contributes significantly to reducing agricultural carbon emission intensity. Secondly, there is a non-linear relationship between the rural digital economy and agricultural carbon emissions. With the development of rural digital economy showing a marginal decreasing trend, there is an obvious threshold effect. Thirdly, enhancing agricultural socialized services through the rural digital economy can curb agricultural carbon emissions. Lastly, the carbon reduction effect of the rural digital economy is more significant in more economically developed areas, areas with moderate levels of economic development, and areas with low technological investment; implementation of a "zero growth" policy for fertilizers strengthens this carbon reduction effect. This study sheds light on the mechanisms and effects of agricultural carbon emissions, offering quantitative evidence and theoretical support for the transition towards low-carbon and sustainable agricultural development., 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.)

Terpenoids possess significant physiological activities and are rich in essential oils. Some terpenoids have chiral centers and could form enantiomers with distinct physiological activities. Therefore, the extraction and separation of terpenoids enantiomers are very important and have attracted extensive attention in recent years. Meanwhile, the specific distribution and enantiomer excess results (the excess of one enantiomer over the other in a mixture of enantiomers) could be used as quality markers for illegitimate adulteration, origin identification, and exploring component variations and functional interrelations across different plant tissues. In this study, an overview of the progress in the extraction of terpenoids from essential oils and the separation of their enantiomers over the past two decades has been made. Extraction methods were retrieved by the resultant network visualization findings. The results showed that the predominant methods are hydrodistillation, solvent-free microwave extraction, headspace solid-phase microextraction and supercritical fluid extraction methods. GC-MS combined with chiral chromatography columns is commonly used for the separation of enantiomers, while 2D GC is found to have stronger resolution ability. Finally, some prospects for future research directions in the extraction and separation identification of essential oils are proposed., 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.)

Consumers are more inclined to choose beef with a high intramuscular fat content (IMF), which regulated by lots of factors. It is very significant to find a miRNA that plays a key role in the accumulation of IMF. In our study, we found that bta-miR-330 was highly expressed in Japanese black cattle and differentially expressed at intramuscular pre-adipocytes differentiation processes. Furthermore, we transfected the bta-miR-330 mimic & inhibitor in intramuscular pre-adipocytes. The results showed that bta-miR-330 inhibits the proliferation but promotes the adipogenesis of intramuscular pre-adipocytes. Subsequently, our study showed that bta-miR-330 binds to SESN3, which inhibits the adipogenesis of intramuscular pre-adipocytes. Moreover, we established the mechanism that bta-miR-330 promotes the adipogenesis of intramuscular pre-adipocytes by targeting SESN3 to activate the Akt-mTOR signaling pathway. Overall, our results revealed that bta-miR-330-SESN3-Akt-mTOR axis plays an important role in adipogenesis of intramuscular pre-adipocytes, which provides a molecular basis for increasing IMF content in beef cattle., Competing Interests: Declaration of competing interest We declare that we have no interest in any business or organization. The submitted manuscripts have not been published elsewhere and are not considered for publication elsewhere. All the authors approved the manuscript we submitted., (Copyright © 2024. Published by Elsevier B.V.)

Background: Ferroptosis is an iron-dependent programmed cell death mediated by lipid peroxidation. The purpose was to explore the molecular mechanism by which phosphatidylethanolamine-binding protein 1 (PEBP1) regulates ferroptosis in lung adenocarcinoma (LUAD), hoping to identify novel therapeutic targets for LUAD., Methods: The expression, enrichment pathways and upstream transcription factors of PEBP1 were analyzed using bioinformatics tools. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) experiments were conducted to validate the interaction and binding relationship between PEBP1 and the upstream transcription factor nuclear transcription factor Y subunit α (NFYA). Quantitative reverse transcription PCR (qRT-PCR) was conducted to measure the expression levels of PEBP1 and NFYA mRNA in LUAD cells. Cell viability was detected by cell counting kit-8 assay. In addition, levels of malondialdehyde (MDA), Fe 2+ , and lipid reactive oxygen species (ROS) were assessed to evaluate ferroptosis levels in LUAD cells., Results: PEBP1 was downregulated and significantly enriched in the ferroptosis signaling pathway in LUAD. Overexpression of PEBP1 suppressed cell viability remarkably, while levels of MDA, Fe 2+ , and lipid ROS were increased. Conversely, knockdown of PEBP1 produced the opposite effects. The upstream transcription factor NFYA, predicted to be involved in the regulation of PEBP1, was also upregulated in LUAD. Dual-luciferase reporter assay, ChIP, and molecular experiments revealed that NFYA transcriptionally suppressed the expression of PEBP1, and overexpression of NFYA could reverse the effects caused by PEBP1 overexpression., Conclusion: PEBP1 regulated ferroptosis in LUAD, and the transcription factor NFYA inhibited ferroptosis in LUAD cells by transcriptionally downregulating PEBP1 expression., 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.)

In this study, we examined the persistent pollutant contents [harmful elements (HEs), cadmium (Cd, 0.1 mg/kg) ∼ barium (Ba, 881.1 mg/kg)] and polycyclic aromatic hydrocarbons [PAHs; Acenaphthylene (Acy), Acenaphthene (Ace), Fluorene (Flu), Benzo(k)fluoranthene (BkF), Benzo(a)pyrene (BaP) (0 mg/kg) ∼ BaP (10.2 mg/kg)] in bus stop dust (BSD) from Qingyang, Northwest China. The Nemerow composite pollution index of the eight types of PAHs and ∑ 16 PAHs indicated severe pollution. The carcinogenic risk of the persistent pollutant in BSD to adults was 1.6 times greater than the acceptable upper limit for the human body, while the noncarcinogenic risk was small to five daily bus passenger groups. Clustering and principal component analysis showed that 12 kinds of HEs were mainly derived from coal and fuel combustion and 16 kinds of PAHs were mainly derived from biomass combustion, organic matter decomposition, and chemical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

There is a growing interest in developing highly viscous lipid foods using plant protein and polysaccharide gum-based emulsion technology. However, gaps remain in understanding the rheological, microstructural, and digestive properties of plant proteins like soybean protein isolate (SPI) in combination with various gums. This study investigates how combining SPI and peach gum (PG) affects rheology and lipolysis of oil-in-water (O/W) emulsions containing 20 wt% soybean oil. Emulsions with varying SPI and PG compositions including SPI-PG single and SPI/PG mixed droplet systems were prepared. Heating induced alterations in viscosity (e.g., SPI-PG from 14.88 to 90.27 Pa·s and SPI/PG from 9.66 to 85.32 Pa·s) and microstructure revealing aggregate formation at oil-water interface. The viscosity decreased significantly from the oral to intestinal phase (SPI-PG: 28.10 to 0.19 Pa·s, SPI/PG: 21.27 to 0.10 Pa·s). These changes affected lipid digestion, notably in SPI-PG and SPI/PG emulsions where a compact interface hindered lipolysis during digestion. Interestingly, free fatty acid (FFA) release during small intestinal phase followed a different order: SPI (82.51 %) > SPI-PG (70.77 %) > SPI/PG (63.60 %) > PG (56.09 %). This study provides insights into creating highly viscous O/W spreads with improved rheology, stability, and delayed lipid digestion, offering potential benefits in food product formulation., Competing Interests: Declaration of competing interest The authors declare that they do not possess any competing financial interests for this study to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Bisphenol A (BPA) is an industrial chemical that is commonly found in daily consumer products. BPA is reportedly associated with lung diseases. However, the impact of BPA on pulmonary fibrosis (PF) and its possible mechanisms of action both remain unclear., Methods: A PF mouse model was induced by bleomycin (BLM). Mouse lung fibroblasts (MLG 2908) and mouse alveolar epithelial cells (MLE-12) were treated with BPA to establish a PF cell model. Tissue staining, CCK-8 assays, western blot experiments and relevant indicator kits were used to detect and evaluate the effect of BPA on PF., Results: BPA dose-dependently promoted oxidative stress and induced ferroptosis, leading to PF. The ferroptosis inhibitor Fer-1 partly attenuated the effect of BPA. In addition, among the two main cell types associated with the progression of PF, MLE-12 cells are more sensitive to BPA than are MLG 2908 cells, and BPA induces ferroptosis in MLE-12 cells. Furthermore, BPA promoted autophagy-mediated ferroptosis by activating the AMPK/mTOR signaling pathway, thereby exacerbating the progression of PF. The autophagy inhibitor CQ1 partly attenuated the effect of BPA., Conclusion: BPA promotes the progression of PF by promoting autophagy-dependent ferroptosis in alveolar epithelial cells, which provides a new theoretical basis for understanding BPA-induced PF., 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.)

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn 2+ on the surface of the PET grafts (Cur@Zn 2+ @PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn 2+ from the Cur@Zn 2+ @PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn 2+ @PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1β. Meanwhile, a significant release of Zn 2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn 2+ @PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn 2+ @PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The current one-size-fits-all screening strategy for lung cancer is not suitable for personalized screening., Research Question: What is the risk-adapted starting age of lung cancer screening with comprehensive consideration of risk factors?, Study Design and Methods: The National Lung Cancer Screening program, a multicenter, population-based, prospective cohort study, was analyzed. Information on risk factor exposure was collected during the baseline risk assessment. A Cox proportional hazards model was used to estimate the association between risk factors and lung cancer incidence. Age-specific 10-year cumulative risk was calculated to determine the age at which individuals with various risk factors reached the equivalent risk level as individuals aged ≥ 50 years with active tobacco use and a ≥ 20 pack-year smoking history., Results: Of the 1,031,911 participants enrolled in this study, 3,908 demonstrated lung cancer after a median follow-up of 3.8 years. We identified seven risk factors for lung cancer, including pack-years of smoking, secondhand smoke exposure, family history of lung cancer in first-degree relatives, history of respiratory diseases, occupational hazardous exposure, BMI, and diabetes. The 10-year cumulative risk of lung cancer for people aged ≥ 50 years with active tobacco use and a ≥ 20 pack-year smoking history was 1.37%, which was treated as the risk threshold for screening. Individuals who never smoked and those with active tobacco use and a < 30-pack-year history of smoking reached the equivalent risk level 1 to 14 years later compared with the starting age of 50 years. Men with active tobacco use, a ≥ 30-pack-year history of smoking, and concurrent respiratory diseases or diabetes should be screened 1 year earlier at the age of 49 years., Interpretation: The personalized risk-adapted starting ages for lung cancer screening, based on the principle of equal management of equal risk, can served as an optimized screening strategy to identify high-risk individuals., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)