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A combinative approach of anisotropic bulk etching and modified plasma etching has been successfully employed in a single wafer to fabricate silicon masters for the hot embossing process. The masters hold both pyramid pits and positive profile sidewalls with smooth surfaces and steep angles. The SiO 2 layer is utilized as a etching mask with the aid of photoresist in three steps of photolithography patterning. The first polymethyl-methacrylate (PMMA)-based tunneling transducer with polymer membrane structures is fabricated by hot embossing replication with the silicon master. Consequently, the exponential relations between tunneling currents and applied deflection voltages are also reported. [ABSTRACT FROM AUTHOR]

The toxic effects of tetracycline and glyphosate on hulless barley and its environment, as well as their interrelationship, remain poorly understood. The present study aimed to identify biomarkers reflective of tetracycline and glyphosate toxicity, examine root damage and rhizosphere bacterial communities throughout the growth cycle, and assess the final grain quality. Results indicated that the hydrogen peroxide (H 2 O 2 ) content in the underground parts of barley could serve as a sensitive biomarker for detecting tetracycline and glyphosate toxicity in barley. In addition, a synergistic effect between 5 mg/kg tetracycline and 5 mg/kg glyphosate was observed at the tillering stage, which not only induced H 2 O 2 accumulation across all growth stages but also ultimately reduced seed quality. During the tillering phase, Proteobacteria dominanted, while Actinobacteria showed greater relative abundance during the jointing stage.By the ripening stage, Acidobacteria predominantly colonized the associated soils. Importantly, the study further identified metagenome-assembled genomes containing cytochrome P450 fragments capable of metabolizing these compounds. This study provides novel insights into the transformation of co-contaminants and the adaptive responses of rhizobacteria to tetracycline and glyphosate exposure, offering valuable information for agricultural practices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Chinese agarwood (Aquilaria sinensis) has been a traditional treatment for digestive disorders in South and East Asia. While sesquiterpenes are recognized as the key active constituents of Chinese agarwood, the efficacy and mechanism of the sesquiterpene-enriched extract of Chinese agarwood (PEE) on bile reflux gastritis (BRG) remain unclear., Aim of the Study: To explore the protective impact of PEE against BRG and unveil its underlying mechanism in suppressing apoptosis of gastric mucosal cells., Materials and Methods: A taurocholic acid (TCA)-induced BRG mouse model was used to assess PEE's protective effects on gastric mucosa histopathology. Transcriptomic analysis was conducted to identify the key signaling pathways affected by PEE. The impact of PEE on apoptosis modulation and Wnt/β-catenin signaling in GES-1 cells was examined. Additionally, the influence of PEE on the Wnt/β-catenin pathway in BRG mouse gastric mucosa was evaluated., Results: PEE substantially improved gastric tissue damage and inflammation in BRG mice. Transcriptomic analysis revealed that PEE modulates genes linked to apoptosis and the Wnt/β-catenin pathway. In TCA-induced GES-1 cells, PEE enhanced cell viability and mitigated apoptosis via the Wnt/β-catenin pathway, a process potentially mediated by IWP-2, an antagonist of this pathway. Similar regulatory effects were noted in the gastric mucosa of BRG mice., Conclusion: Our research suggests that PEE exerts a protective effect on the gastric tissue through modulating the Wnt/β-catenin pathway to combat apoptosis, which highlights the potential of PEE as a natural remedy for BRG and warrants further investigation into its therapeutic benefits., 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.)

Sulfur ion (S 2- ) plays a significant and considerable role in many living organisms and ecosystems, while its abnormal content can pose a serious hazard to human health and ecological environment. Hence, it is extremely meaningful to construct a highly sensitive and selective analytical platform for S 2- detection in complex microenvironment, particularly in biological systems. In this study, phosphomolybdic acid and L-Arg were utilized to prepare a new molybdenum doped carbon-dots nanozyme (Mo-CDs) with great peroxidase-like activity by one-step hydrothermal approach. In the presence of H 2 O 2 , Mo-CDs converted 3,3',5,5'-tetramethyl benzidine (TMB) into blue oxTMB, but S 2- strongly reduced the blue solution to colorless and then brown, which established significant selectivity toward S 2- . Mo-CDs illustrated a wide linear range (2.5 μM-900 μM) and low detection limit (LOD = 76 nM) by ultraviolet and smartphone-assisted visualized colorimetric analysis. Especially, the smartphone-assisted analysis platform successfully realized quick, portable, sensitive and visible identification of S 2- with high recovery (95.7-106.7 %) and excellent specificity in water samples. More importantly, Mo-CDs was developed to antibacterial applications based on good peroxidase-like activity. This research not only constructed a new and efficient carbon-dots nanozyme and a low-cost, portable, visual analysis platform for real-time detection of S 2- , but also proposed a novel design strategy and methodology for exploiting multifunctional nanozyme detection tool with great practical application., 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 readiness of leaf-litter to burn in the presence of fire differs greatly between species. Thus, forests composed of different species vary in their susceptibility to fire. Fire susceptibility of forests may also differ from the arithmetic means of flammability of their component species, i.e., non-additive effects exist. Here, we assessed nine indices of flammability and five physicochemical properties of the leaf litter of eight common subtropical tree species in China. We then tested the net effects on litter flammability of different mixtures of the eight species. We measured the following variables: time to ignition, combustion time, spread rate, ignition temperature, mass loss, maximum flame height and three temperature indices, moisture, cellulose, lignin and ash contents, and specific leaf area (SLA). Our results show that the flammability of leaf litter: time to ignition, combustion time, ignition temperature, and flame height, varies widely between the eight species. Time to ignition was short (<3 s) for the three conifer species and Quercus variabilis and Q. aliena, but long (3.5-8.8 s) for Q. fabri, Q. glauca, and Liquidambar formosana. The five species with a short time to ignition all have high cellulose and lignin contents, and SLA, and are highly flammable. In contrast, the three species with long time to ignition have low cellulose and lignin contents, and SLA, and high ash content. Cellulose and lignin contents, and SLA are the major drivers of litter flammability, and ash and moisture contents are important negative drivers. Mixed litters containing species with high cellulose and lignin contents and SLA have positive non-additive effects (synergistic) on overall flammability whereas those containing species with low cellulose and lignin contents, and SLA have negative non-additive effects (antagonistic) on flammability. These results are essential for assessing forest fire-risks and assisting species selection in plantations or fire-break forests as a part of a forest fire-management strategy., Competing Interests: Declaration of competing interest In submitting the manuscript, we would like to make the following statements: (1) No conflict of interest exists in the submission of this manuscript; (2) The manuscript is approved by all authors; (3) The work described was original that has not been published previously, and is not under consideration for publication elsewhere, in whole or in part; (4) All the authors listed have made substantial contributions to research design, or the acquisition, analysis or interpretation of data, or drafting the paper or revising it critically; and (5) Nobody who qualifies for authorship has been excluded., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

China is concurrently facing the dual challenges of air pollution and climate change. Here, we established a coupled modeling framework that integrated a chemical transport model with a health impact assessment model and the human capital method, to quantify the contributions of 150 emission sources (five sectors in 30 provinces) to the CO 2 emissions, and the mortality burdens attributed to O 3 and PM 2.5 . We found that, in 2019, the estimated premature deaths in China attributed to PM 2.5 and O 3 pollution were 1,499,073 and 143,420, respectively. The social cost of air pollution was approximately 232 billion USD (PM 2.5 : 212 billion USD, O 3 : 20 billion USD), comparable to the social cost of CO 2 emissions at 246 billion USD. The social costs of air pollution and carbon emissions attributable to the 150 emission sources exhibited significant heterogeneity. We identified the control priorities and primary control targets for each emission source. Consequently, based on the social costs of air pollution and climate impact, we proposed a synergistic emission control policy that accounted for spatial distribution and sectoral categories. This policy aimed to harmonize the control strategies for PM 2.5 pollution, O 3 pollution, and CO 2 emissions, thereby enhancing the comprehensive benefits of mitigation measures. Our study sheds light on optimizing emission control policies, enhancing the realism of relevant policy-making for synergistic control of air pollution and carbon emissions., 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.)

Ependymal cells line the wall of cerebral ventricles and ensure the unidirectional cerebrospinal fluid (CSF) flow by beating their motile cilia coordinately. The ependymal denudation or ciliary dysfunction causes hydrocephalus. Here, we report that the deficiency of regulator of G-protein signaling 22 (RGS22) results in severe congenital hydrocephalus in both mice and rats. Interestingly, RGS22 is specifically expressed in ependymal cells within the brain. Using conditional knock-out mice, we further demonstrate that the deletion of Rgs22 exclusively in nervous system is sufficient to induce hydrocephalus. Mechanistically, we show that Rgs22 deficiency leads to the ependymal denudation and impaired ciliogenesis. This phenomenon can be attributed to the excessive activation of lysophosphatidic acid receptor (LPAR) signaling under Rgs22 -/- condition, as the LPAR blockade effectively alleviates hydrocephalus in Rgs22 -/- rats. Therefore, our findings unveil a previously unrecognized role of RGS22 in the central nervous system, and present RGS22 as a potential diagnostic and therapeutic target for hydrocephalus., Competing Interests: Compliance and ethics. The authors declare that they have no conflict of interest., (© 2024. Science China Press.)

Background: Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy., Methods: In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity., Results: ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment., Conclusion: Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy., Significance Statement: This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Background: Psychological health is crucial for the physical and mental well-being of primary and secondary school students, however, the research on the interrelationships among negative emotions is still limited. This study aims to investigate the network structure of depression, anxiety, and stress, and explore their correlation with screen time in these populations., Method: This study was conducted from March to July 2022 in 157 counties across 18 cities in Henan Province. The Depression Anxiety Stress Scale (DASS-21) was used to assess the negative emotions experienced by students. Firstly, "Expected Influence" and "Bridge Expected Influence" were considered as key indicators within the symptom network to depict the structure of depressive, anxiety and stress symptoms. Secondly. a case-dropping bootstrap procedure was applied to assess the stability of the network. Finally, this study identified the central and bridge symptoms in the network, and explored their relationships with screen time., Results: The study included 52,782 students with an average age of 11.23±2.56 years. Network analysis showed that feelings of worthlessness, panic, and agitation are the predominant symptoms in the negative emotional networks. Depression, anxiety, and stress were interconnected through feelings of low mood, overreaction, and trembling. Additionally, lack of initiative and dry mouth exhibited the most significant direct associations with screen time., Conclusion: The central and bridge symptoms identified in the negative emotion networks can serve as potential focal points for future research on negative emotions among primary and secondary school students., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This investigation explored the clinical features, pathological outcomes, and biochemical recurrence (BCR) duration among high-risk prostate cancer (HRPC) patients who have undergone neoadjuvant therapy (NAT) in combination with radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Additionally, we identified prognostic indicators that discern pathological complete response (pCR) or minimal residual disease (MRD) and BCR., Methods: In total, we examined 76 HRPC patients, who received NAT with either androgen deprivation therapy (ADT) plus apalutamide or ADT plus abiraterone, with subsequent RP and PLND. We conducted a genetic evaluation of patients receiving neoadjuvant apalutamide. Additionally, patient pathological outcomes, circulating prostate-specific antigen (PSA) response rates, and BCR duration were analyzed. Lastly, we employed uni- and multivariate analyses to screen for prognostic factors that govern pCR or MRD and BCR duration., Results: Patient median age and median PSA at presentation were 69 years (IQR: 66-73), and 47.6 ng/mL (IQR: 24.1-105.75), respectively. We observed marked changes in pCR or MRD rates between the two cohorts. In particular, the ADT plus apalutamide cohort (51.5%) exhibited enhanced rates relative to the ADT plus abiraterone cohort (25.6%) (p = 0.03). The median BCR duration was substantially prolonged among neoadjuvant apalutamide cohort relative to the neoadjuvant abiraterone cohort (261 days vs. 76 days, p = 0.04). Using multivariate analysis, we revealed that the postintervention pre-RP PSA content (≤ 0.1 ng/mL vs. > 0.1 ng/mL) remained a substantial stand-alone indicator of pCR or MRD (odds ratio: 10.712, 95% CI: 2.725-42.105, p < 0.001). Furthermore, supplemental analyses revealed that the ADT plus apalutamide cohort exhibited an augmented serum response rate, which, in turn, reduced the post-intervention pre-RP PSA content. Based on our genetic profiling of the neoadjuvant apalutamide cohort demonstrated high-frequency deleterious changes in the AR axis (30.3%), followed by TP53 mutations (15.15%). Patients with defective AR axis experienced a remarkably shorter median BCR duration relative to patients with other or no genetic alterations (52.5 days vs. 286 and 336 days, respectively, p < 0.0001). Furthermore, using multivariate analysis, we demonstrated that achieving pCR or MRD (hazard ratio [HR]: 0.170, 95% CI: 0.061-0.477, p < 0.001) and presence of defective AR signaling (HR: 11.193, 95% CI: 3.499-35.806, p < 0.001) were strong stand-alone indicators of BCR., Conclusions: Herein, we demonstrated the superior performance of ADT plus apalutamide in achieving pCR or MRD and in extending BCR duration among HRPC patients. Post-intervention pre-RP PSA content as well as genetic shifts, especially in the AR axis, are critical indicators of patient pathological and clinical outcomes. These findings highlight the significance of genetic testing and PSA content monitoring in treating HRPC patients., (© 2024 Wiley Periodicals LLC.)

Ethnopharmacological Relevance: Traditional Chinese medicine (TCM) is frequently used to treat osteoarthritis (OA). Duhuo Jisheng decoction (DHJSD), a Chinese patent medicine, was commonly used Chinese herbal formula for the treatment of OA. In Western medicine, dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme has been proved to be a promising strategy to treat inflammatory diseases with reduced side effects., Aim of the Study: To elucidate the dual action mechanism of DHJSD targeting COX-2 and 5-LOX against OA., Materials and Methods: DHJSD, containing 1495 compounds was screened using a virtual screening approach based on molecular docking. The inhibitory effect of hit compounds against COX-2 and 5-LOX was validated using enzyme-based assays. In vitro, rat chondrocytes were treated with IL-1β (10 ng/mL) for 24 h to induce OA model in vitro. The chondrocyte viability was evaluated using an CCK-8 assay. ELISA was used to detect inflammatory factors expression. Immunofluorescence was used to assess the expression level of collagen II and MMP-13. In addition, a rat cartilage explants culture model was established, and safranin O and HE staining analysis were carried to assess cartilage matrix degradation and cartilage damage, respectively. In vivo, carrageenan-induced paw edema assay was used to examine anti-inflammatory activity, and the gastric ulcerogenic effect was further detected. Finally, Molecular dynamics simulations and binding free energy analysis were carried to explore the binding mechanism., Results: 13 compounds from DHJSD were identified as promising candidates by a virtual screening approach. Among these candidates, three hits 7,4'-dimethoxyisoflavone, genistein, and fraxetin displayed dual inhibition of COX-2 and 5-LOX. Further in vitro assay indicated that 7,4'-dimethoxyisoflavone, genistein, and fraxetin could inhibit PGE2, LTB4, TNF-α, IL-6, or NO production in IL-1β-induced chondrocytes. In addition, the three compounds reduced IL-1β-induced degradation of collagen II and expression of MMP-13 in rat chondrocytes. The results of anti-inflammatory activity of the three compounds in vivo showed that the highest anti-inflammatory activity with edema inhibition percentages of 50.00%, 56.00%, and 51.00% after 3 h, respectively. Moreover, it was found that 7,4'-dimethoxyisoflavone, genistein, and fraxetin have a superior gastric safety profile comparable to indomethacin. Finally, molecular dynamics simulations, binding free energy analysis, and detailed interaction mode demonstrated that 7,4'-dimethoxyisoflavone, genistein, and fraxetin interacted well with both COX-2 and 5-LOX., Conclusions: 7,4'-dimethoxyisoflavone, genistein, and fraxetin from DHJSD with excellent anti-inflammatory effects and no gastric ulceration effects, which helps to explain the dual action mechanism and potential material basis of DHJSD in treating OA and provide evidence to support DHJSD's clinical use., 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.)

To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant Staphylococcus aureus (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound 11 , the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.02-0.04 μg/mL). A mechanistic study of compound 11 revealed that the increase of intracellular ROS and acceleration of the TCA cycle, which reprogrammed the bacterial metabolism, eventually triggered membrane damage and bacterial death. Most importantly, compound 11, with antibacterial and anti-inflammatory properties, accelerated the reconstruction and healing of MRSA-infected cutaneous wounds by decreasing bacterial loads, attenuating inflammation, and promoting angiogenesis. Overall, these findings provide a novel multifunctional chemotype with broad-spectrum antibacterial activity and highlight a promising strategy for MRSA-infected wound healing.

The Warburg effect, characterized by the shift toward aerobic glycolysis, is closely associated with the onset and advancement of tumors, including multiple myeloma (MM). Nevertheless, the specific regulatory mechanisms of glycolysis in MM and its functional role remain unclear. In this study, we identified that growth differentiation factor 15 (GDF15) is a glycolytic regulator, and GDF15 is highly expressed in MM cells and patient samples. Through gain-of-function and loss-of-function experiments, we demonstrated that GDF15 promotes MM cell proliferation and inhibits apoptosis. Moreover, GDF15 enhances Warburg-like metabolism in MM cells, as evidenced by increased glucose uptake, lactate production, and extracellular acidification rate, while reducing oxidative phosphorylation. Importantly, the tumor-promoting effects of GDF15 in MM cells are fermentation-dependent. Mechanistically, GDF15 was found to promote the expression of key glycolytic genes, particularly the glucose transporter GLUT1, through the activation of the TGFβ signaling pathway. Pharmacological inhibition of the TGFβ signaling pathway effectively abrogated the oncogenic activities of GDF15 in MM cells, including cell proliferation, apoptosis, and fermentation. In vivo experiments using a subcutaneous xenotransplanted tumor model confirmed that GDF15 knockdown led to a significant reduction in tumor growth, while GDF15 overexpression promoted tumor growth. Overall, our study provides insights into the molecular mechanisms underlying MM pathogenesis and highlights the potential of targeting GDF15-TGFβ signaling -glycolysis axis as a therapeutic approach for future therapeutic interventions in MM., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Grape (Vitis vinifera) crops encounter significant challenges in overcoming bud endodormancy in warm winter areas worldwide. Research on the mechanisms governing bud dormancy release has focused primarily on stress regulation; however, cell wall regulation of bud meristem regrowth mechanism during the dormancy release remains obscure., Results: In this study, transmission electron microscopy revealed significant changes in the grape bud cell wall following hydrogen cyanamide (HC) treatment, accompanied by an increase in β-1,3-glucanase activity. We then investigated the potential contribution of β-1,3-glucanases (GLUs) to the regulation of cell wall remodeling. Forty-eight VvGLUs distributed in clades α, β, and γ were identified and nominated based on the genome data of V. vinifera. Three γ-clade VvGLUs (VvGLU1, VvGLU16, and VvGLU32) were upregulated by dormancy-releasing stimuli, including HC, sodium azide (AZ), ethylene and hypoxia. Among these, VvGLU1 presented increased gene transcription and protein expression in response to HC and ethylene treatment. The VvGLU1 promoter positively responded to ethylene, and its activity could be activated by VvERF57. Using both immunogold labeling and GFP fusion protein analysis, we observed that VvGLU1 localized in the endoplasmic reticulum, accumulated in the vacuole, and was secreted into the cell wall during HC-triggered dormancy release., Conclusions: Based on these findings, we propose that ethylene-regulated VvGLU1 plays a pivotal role in cell wall remodeling, thereby facilitating the regrowth of the bud meristem., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The electroconversion of CO 2 into ethylene (C 2 H 4 ) offers a promising solution to environmental and energy challenges. Crown ether (CE) modification significantly enhances the C 2 H 4 selectivity of copper-based MOFs, improving C 2 H 4 faradaic efficiency (FE) in CuBTC, CuBDC, and CuBDC-NH 2 by 3.1, 1.7, and 2.4 times, respectively. Among these, CuBTC achieves the highest FE for C 2 H 4 , reaching ca. 52% at 120 mA cm -2 . Control experiments and in situ Fourier transform infrared spectroscopy (FTIR) reveal that CE stabilizes Cu + during the catalyst's in situ reconstruction, promoting the formation of Cu 2 O, which is more favorable for C 2 H 4 production. Furthermore, CE increases the local concentration of K + at the catalyst-electrolyte interface, enhancing *CO adsorption and facilitating C-C coupling reactions. This process promotes the formation of key intermediates, such as *CO*CO, *CO*COH and *COCHO, ultimately boosting C 2 H 4 production.

Lipid nanoparticles (LNP) have shown great promise in clinical applications for delivering mRNA. Targeted delivery of mRNA to particular tissues or organs is essential for precise therapeutic outcomes and minimized side effects in various disease models. However, achieving targeted delivery beyond the liver is a challenge based on current LNP formulations. In this report, we synthesized four ionizable cholesterol analogs by attaching two tertiary amine groups onto the head of a cholesterol-like structure and incorporated them as a fifth component into conventional commercial LNPs based on ALC-0315 or SM-102. Selective targeting delivery of mRNA is achieved by adjusting the proportion of the fifth component in the LNP. Specifically, a spleen-targeted 0315-Ergo-40% formulation demonstrated an impressive 95% delivery efficiency, while a lung-targeted 102-Sito-40% formulation achieved up to 78%. Moreover, when this strategy is applied to a self-developed ionizable lipid named U-101 instead of ALC-0315 or SM-102, the targeting delivery efficiencies to the spleen and lungs reach 96 and 71%, respectively. Multiple assessments suggest that inclusion of the fifth component does not compromise LNP stability, as indicated by consistent particle size, polydispersity index (PDI), and encapsulation efficiency. Furthermore, the test results of liver and kidney function and immunogenicity reveal no increase of toxicity in vivo following the introduction of the fifth component. Additional studies on in vitro cytotoxicity, lysosomal escape, and cellular transfection efficiency confirm that the fifth component does not diminish delivery performance. Taken together, the incorporation of ionizable cholesterol analogs leads to targeting of LNP delivery, which features strong organ selectivity, high safety, and suitability for further evaluation.

Biogenic volatile organic compounds (BVOCs) are emitted by urban vegetation and can interact with anthropogenic pollutants to generate secondary organic aerosols (SOA) that are atmospheric pollutants in urban environments. In urban forests, SOA comprise up to 90 % of all fine aerosols (particulate matter smaller than 1 μm [PM 1 ]) in the summer. PM 1 can greatly affect urban air quality and public health. The formation of SOA is affected by both environmental conditions and the presence of light BVOCs-predominantly isoprene, pentene, butene, and 1,3-butadiene. These factors exhibit complex interactions and nonlinear relationships. In this study, high-frequency field observations were conducted in two urban forest sites in Shanghai during the summers of 2022 and 2023. Data were collected regarding the concentrations of light BVOCs; SOA; and the anthropogenic pollutants NO x , O 3 , and SO 2 , as well as solar radiation, temperature, and humidity. A model was developed to identify the synergistic effects of anthropogenic pollutants, meteorological factors, and BVOCs on SOA concentrations. Increases in short-term SOA concentrations were most strongly correlated with O 3 , which had a synergistic effect alongside NO x . The empirical analysis indicated that 0.144-0.585 μg/m 3 SOA is produced per μg/m 3 of urban BVOCs but can be augmented by 0.072-0.491 μg/m 3 in the presence of O 3 , NOx, and SO 2 . However, long-term feedback mechanisms in urban forests contribute to the maintenance of stable SOA concentrations. The field data and models in this study provide a scientific basis for regulating atmospheric pollutants in urban forests under real-world conditions and offer intuitive and straightforward solutions for managing complex urban air pollution. Synopsis: Anthropogenic pollutants NO x , O 3 , and SO 2 boost BVOCs' SOA production in summer urban forests. Short-term, pollutants are restrictive factors in SOA generation, but long-term forest SOA production exhibits negative feedback., 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.)

A series of flavonoid derivatives containing piperazine sulfonate were designed and synthesized. The results of antiviral experiments in vivo showed that some target compounds had good inhibitory effect on tobacco mosaic virus (TMV). The EC 50 values of S15 and S19 curative activity were 174.5 and 110.4 μg/mL, respectively, which were better than 253.7 μg/mL of Ningnanmycin (NNM). The EC 50 values of S4 and S19 protection activity were 140.3 and 116.1 μg/mL, respectively, better than that of NNM (247.1 μg/mL). Microscale thermophoresis (MST) and molecular docking experiments showed that S19 had a good molecular binding force with TMV. Transmission electron microscopy (TEM) results show that S19 can fracture TMV particles and affect self-assembly. S19 treatment had almost no effect on the growth of seeds and seedlings, and can change the content of chlorophyll malondialdehyde (MDA) and superoxide dismutase (SOD) in tobacco to a certain extent, and improve the disease resistance of tobacco., Competing Interests: Declarations. Conflict of interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Mitochondrial uncouplers dissipate proton gradients and deplete ATP production from oxidative phosphorylation (OXPHOS). While the growth of prostate cancer depends on OXPHOS-generated ATP, the oncogenic pathway mediated by the transcription factor E2F1 is crucial for the progression of this deadly disease. Here, we report that mitochondrial uncouplers, including tizoxanide (TIZ), the active metabolite of the Food and Drug Administration (FDA)-approved anthelmintic nitazoxanide (NTZ), inhibit E2F1-mediated expression of genes involved in cell cycle progression, DNA synthesis, and lipid synthesis. Consequently, NTZ/TIZ induces S-phase kinase-associated protein 2 (SKP2)-mediated G1 arrest while impeding DNA synthesis, lipogenesis, and the growth of prostate cancer cells. The anti-cancer activity of TIZ correlates with its OXPHOS-uncoupling activity. NTZ/TIZ appears to inhibit ATP production, thereby activating the AMP-activated kinase (AMPK)-p38 pathway, leading to cyclin D1 degradation, Rb dephosphorylation, and subsequent E2F1 inhibition. Our results thus connect OXPHOS uncoupling to the inhibition of an essential oncogenic pathway, supporting repositioning NTZ and other mitochondrial uncouplers for prostate cancer therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Composting urban and rural wastes into organic fertilizers for land application is considered the best way to dispose of and recycle waste resources. However, there are some concerns about the long-term effects of applying various organic fertilizers on soils, food safety, and health risks derived from heavy metal(loid)s (HMs). A long-term field experiment was conducted to evaluate the effects of continuous application of chicken manure compost (CM), sewage sludge compost (SSC), and domestic waste compost (DWC) for wheat on the accumulation, transfer, and health risks of HMs. The results revealed that, compared with control or chemical fertilizer treatments, continuous application of CM raised the concentrations of cadmium (Cd), chromium (Cr), copper (Cu), and zinc (Zn) in topsoil by 29 %-38 %, 15 %-16 %,11 %-14 %, and 20 %-36 %, respectively; SSC increased the concentrations of Cd, Cr, Mercury (Hg), arsenic (As), Cu, and Zn by 18 %-26 %, 8 %-9 %, 310 %-329 %, 5 %-8 %, 17 %-21 %, and 19 %-35 %, respectively; and DWC elevated the concentrations of Cd, Cr, Hg, lead (Pb), and Zn by 20 %-28 %, 8 %-9 %, 118 %-118 %, 5 %-10 %, and 3 %-17 %. The HMs concentrations in wheat grain were almost unaffected by the application of the organic fertilizers except for Hg and Pb concentrations. However, the HMs concentrations in both soil and wheat grain remained far below the limits of regulation in China. The long-term application of organic fertilizers did not cause additional noncarcinogenic and carcinogenic risks associated with exposure to HMs. In conclusion, although the long-term application of various urban and rural organic fertilizers increased the concentrations of several HMs in the soil, it almost did not cause any additional adverse effects on wheat grain or increase the health risks., 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. Published by Elsevier B.V.)

Objectives: Ischemic stroke (IS) prevalence rising annually, the necessity of discovering non-interventional genetic influences is progressing. Single nucleotide polymorphism (SNP) plays a pivotal role in stable inheritance of disease susceptibility. Based on the relationship between Alpha- Kinase 1 (ALPK1) and traditional IS risk factors especially hyperuricemia, our study investigated the association and function of ALPK1 SNPs with IS susceptibility., Methods: A case-control study of 1539 patients and 933 controls from northeast China was conducted. Genotyping information of ALPK1 rs2074379 and rs2074388 was collected. Four types of plasmids including rs2074379/rs2074388 G/G, A/G, G/A, and A/A were transfected into 293T cells to observe ALPK1 and SLC22A12 expression. Possible ALPK1 structures of different SNPs were predicted online., Results: Genotype GG (OR = 1.371, CI = 1.029-1.828, P = 0.031) and GA (OR = 1.326, CI = 1.110-1.584, P = 0.002) of rs2074379 and GA of rs2074388 (OR = 1.359, CI = 1.137-1.624, P = 0.001) were found significantly susceptible to IS, with G allele on sites to be a risk allele. Rs2074379 had a multiplicative interaction with hyperuricemia (OR = 1.637, CI = 1.157-2.315, P = 0.005). Uric acid levels differed in genotypes (P < 0.001). The expression of ALPK1 (P < 0.01) and SLC22A12 in membrane urate transporter 1 (URAT1) protein (P < 0.05) functionally changed with G allele on either site. With glycine changing into aspartic acid at rs2074388, the protein secondary structure changed, but the ALPK1 protein subtype remained still., Conclusions: ALPK1 rs2074379 and rs2074388 SNPs were functionally associated with IS susceptibility. The wild allele progressed IS risk probably by reducing ALPK1 expression and inhibiting URAT1 raising the uric acid level, contributing to further exploration of pathogenetic mechanisms of stroke. Chinese Clinical Trial Registration number: ChiCTR-COC-17013559., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The inherent variability of lesions poses challenges in leveraging AI in 3D automated breast ultrasound (ABUS) for lesion detection. Traditional methods based on single scans have fallen short compared to comprehensive evaluations by experienced sonologists using multiple scans. To address this, our study introduces an innovative approach combining the multi-view co-attention mechanism (MCAM) with unsupervised contrastive learning. Rooted in the detection transformer (DETR) architecture, our model employs a one-to-many matching strategy, significantly boosting training efficiency and lesion recall metrics. The model integrates MCAM within the decoder, facilitating the interpretation of lesion data across diverse views. Simultaneously, unsupervised multi-view contrastive learning (UMCL) aligns features consistently across scans, improving detection performance. When tested on two multi-center datasets comprising 1509 patients, our approach outperforms existing state-of-the-art 3D detection models. Notably, our model achieves a 90.3% cancer detection rate with a false positive per image (FPPI) rate of 0.5 on the external validation dataset. This surpasses junior sonologists and matches the performance of seasoned experts., 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.)

To address the concern of optimization problem of China's PM 2.5 control and the limitation of computational efficiencies for traditional air quality models, we developed an integrated analysis framework to efficiently establish the identification and cost-benefit assessment of PM 2.5 control pathways in China by constructing a rapid PM 2.5 exposure response method based on the high-order decoupled direct method (HDDM) and coupling the sequential least square algorithm (SLSQP) and health impact assessment model. Six emission reduction scenarios with varying decision preferences were analyzed. Our study provides a methodological approach for the rapid optimization of emission pathways of major air pollutants in China with flexible options in terms of objectives and constraints, fully considering the diverse differences in environmental, health, and economic impacts among different pollution sources simultaneously. Our findings based on the multi-scenario analysis strengthen the understanding of the importance of diverse species and regions for emission reduction among various decision preferences in China, confirm the necessity of implementing differentiated control strategies for distinct pollution sources from both cost and cost-effectiveness perspectives, and indicate that accelerating PM 2.5 control process in the early stage is a beneficial choice for achieving more health benefits., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background/Objectives: As a widely consumed, nutritious, and affordable food, eggs and their derivatives' impacts on obesity remain inconclusive. In this study, we aimed to determine the association between egg and egg-derived cholesterol consumption, and their change trajectories, with obesity among Chinese adults. Methods : Longitudinal data collected by the China Health and Nutrition Survey from 1997 to 2015 were analyzed. The latent growth mixture model was used to identify eggs and egg-derived cholesterol consumption trajectories. Cox proportional hazard models with shared frailty were used to analyze the association between egg and egg-derived cholesterol consumption, and their change trajectories, with obesity. Results : Data from 10,971 and 9483 participants aged ≥18 years old were used for the analyses of general obesity and central obesity, respectively. Compared to participants with an average egg intake of 0.1-50.0 g/d during the follow-up period, adults who never consumed eggs or those with an average egg intake of 50.1-100.0 g/d and >100.0 g/d had a higher risk of general obesity, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.31 (1.08, 1.58), 1.30 (1.07, 1.60), and 1.98 (1.17, 3.35), respectively, and had a higher risk of central obesity, with HRs (95% CIs) of 1.17 (1.04, 1.31), 1.31 (1.14, 1.50), and 1.64 (1.15, 2.36), respectively. Participants with a "Baseline Low-Significant Rising Pattern" or a "Baseline High-Rising then Falling Pattern" of egg consumption trajectories during the follow-up period had a higher risk of general obesity, with HRs (95% CIs) of 1.56 (1.25, 1.93) and 1.38 (1.13, 1.69), respectively, and central obesity, with HRs (95% CIs) of 1.47 (1.29, 1.68) and 1.52 (1.34, 1.72), respectively. Compared to the second quartile ( Q 2 ) group of the average egg-derived cholesterol intake during the follow-up period, Q 1 , Q 3 , and Q 4 groups had a higher risk of general obesity, with HRs (95% CIs) of 1.28 (1.06,1.54), 1.21 (1.02, 1.44), and 1.43 (1.19, 1.71), respectively, and a higher risk of central obesity, with HRs (95% CIs) of 1.20 (1.08, 1.33), 1.11 (1.01, 1.23), and 1.32 (1.19, 1.46), respectively. Participants with a "Baseline Low-Significant Rising Pattern" or with a "Baseline High-Rising then Falling Pattern" of egg-derived cholesterol consumption during the follow-up period had a higher risk of general obesity, with HRs (95% CIs) of 1.54 (1.25, 1.92) and 1.37 (1.15, 1.64), respectively, and a higher risk of central obesity, with HRs (95% CIs) of 1.46 (1.28, 1.68) and 1.47 (1.32, 1.64), respectively. Conclusions : Both the insufficient and excessive intake of eggs and egg-derived cholesterol tended to be associated with a higher risk of general and central obesity. Suddenly increasing or consistently high levels of egg and egg-derived cholesterol intake seemed to be associated with a higher risk of obesity. To prevent obesity, people should consume a moderate amount of eggs and egg-derived cholesterol., Competing Interests: The authors declare no conflicts of interest.

To expand the applications of hydrophobic silica aerogels derived from rice husk ash (HSA) through simple traditional methods (without adding special materials or processes), this paper employs machine learning to establish mathematical models to identify optimal conditions for extracting water glass and investigates how preparation conditions and heat treatment temperatures affect properties such as the porosity and hydrophobicity of HSA. The results indicate that the decision tree regression model provides the most accurate predictions for the extraction rate and modulus of water glass. Notably, the water contact angle of HSA produced using nitric acid as a catalyst can reach as high as 159.5°, classifying it as a superhydrophobic material. Additionally, while moderately increasing the concentration of the hydrophobic modifier enhances HSA's hydrophobicity, it concurrently reduces its porosity. The HSA maintained hydrophobicity until 500 °C. The pore structure of HSA collapsed gradually with the increase in heat temperature. After treatment at 700 °C, HSA lost its hydrophobicity and the porous structure was severely damaged. Compared with silica aerogel using traditional silicon sources, the damage to pore structure and the crystallization occurred at lower temperatures, but the hydrophobicity remained at higher temperatures.

Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems. This study employs the "equation-free" multiscale computational method to accelerate the relaxation of all-atom simulations of MT tips toward their putative equilibrium conformation. Using large MT lattice systems (14 protofilaments × 8 heterodimers) comprising ∼21-38 million atoms, we applied this multiscale approach to leapfrog through time and nearly double the computational efficiency in realizing relaxed all-atom conformations of GDP- and GTP-complexed MT tips. Commencing from an initial 4 μs unbiased all-atom simulation, we interleave coarse projective "equation-free" jumps with short bursts of all-atom molecular dynamics simulation to realize an additional effective simulation time of 1.875 μs. Our 5.875 μs of effective simulation trajectories for each system expose the subtle yet essential differences in the structures of MT tips as a function of whether β-tubulin monomer is complexed with GDP or GTP, as well as the lateral interactions within the MT tip, offering a refined understanding of features underlying MT dynamic instability. The approach presents a robust and generalizable framework for future explorations of large biomolecular systems at atomic resolution., (Copyright © 2025 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

n-butane (n-C 4 H 10 ) and isobutane (i-C 4 H 10 ) are important raw materials in chemical industry. The separation of the two hydrocarbon isomers via distillation is challenging and energy-consuming. Herein we report the adsorption behavior of a microporous cobalt formate framework [Co 3 (HCOO) 6 ] for potential kinetic separation of butane isomers. Under ambient condition, [Co 3 (HCOO) 6 ] shows near adsorption capacity for n-C 4 H 10 (1.77 mmol g -1 ) and i-C 4 H 10 (1.36 mmol g -1 ) with different adsorption kinetics. Study on the adsorption kinetics for butane indicates that the smaller isomer is adsorbed at a higher diffusion rate, resulting in a high kinetic selectivity of 193 for n-C 4 H 10 /i-C 4 H 10 separation. Analyses of adsorption kinetics and breakthrough experiment have validated the separation potential of [Co 3 (HCOO) 6 ] for butane purification., (© 2025 Wiley-VCH GmbH.)