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Purpose: The panimmune-inflammatory value (PIV) is a novel inflammatory indicator. However, its role in maintenance hemodialysis (MHD) remains unclear. Our goal was to explore the predictive value of PIV for cardiovascular and all-cause mortality in MHD patients., Methods: In this retrospective cohort study, 507 patients receiving MHD between November 2017 and December 2022 were enrolled. The PIV value was calculated as follows: neutrophil count × monocyte count × platelet count/lymphocyte count. Patients were divided into two groups on the basis of the median PIV. Propensity score matching (PSM) was used to adjust for imbalances in baseline information between groups. Kaplan‒Meier curves, Cox regression, the Fine‒Gray competing risk model, and restricted cubic spline (RCS) curves were used to analyze the relationship between PIV and mortality., Results: By the end of follow-up, 126 deaths had occurred, 91 of which were due to cardiovascular disease. The Kaplan‒Meier curves demonstrated that MHD patients with higher PIV levels had a poorer prognosis for all-cause death (p = 0.019). PIV levels were linked to all-cause death in multivariate Cox proportional risk regression (HR = 1.76; 95% CI 1.14, 2.72; p = 0.011). The Fine‒Gray model revealed a greater cumulative incidence of cardiovascular death in the higher PIV group (p = 0.035). PIV levels were linked to cardiovascular mortality in the Fine‒Gray competing risk model (HR = 2.06; 95% CI 1.25, 3.42; p = 0.005). The RCS revealed a nonlinear relationship between PIV and mortality risk (p < 0.05). Using 63 years of age as the threshold, we observed a multiplicative interaction effect between age and PIV for all-cause mortality (p = 0.006)., Conclusion: In MHD patients, PIV is an independent hazard factor for cardiovascular-related mortality and all-cause mortality., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Soil salinity is a major contributor to crop yield losses. To improve our understanding of root responses to salinity, we developed and exploited a real-time salt-induced tilting assay. This assay follows root growth upon both gravitropic and salt challenges, revealing that root bending upon tilting is modulated by Na+ ions, but not by osmotic stress. Next, we measured this salt-specific response in 345 natural Arabidopsis (Arabidopsis thaliana) accessions and discovered a genetic locus, encoding the cell wall-modifying enzyme EXTENSIN ARABINOSE DEFICIENT TRANSFERASE (ExAD) that is associated with root bending in the presence of NaCl (hereafter salt). Extensins are a class of structural cell wall glycoproteins known as hydroxyproline (Hyp)-rich glycoproteins, which are posttranslationally modified by O-glycosylation, mostly involving Hyp-arabinosylation. We show that salt-induced ExAD-dependent Hyp-arabinosylation influences root bending responses and cell wall thickness. Roots of exad1 mutant seedlings, which lack Hyp-arabinosylation of extensin, displayed increased thickness of root epidermal cell walls and greater cell wall porosity. They also showed altered gravitropic root bending in salt conditions and a reduced salt-avoidance response. Our results suggest that extensin modification via Hyp-arabinosylation is a unique salt-specific cellular process required for the directional response of roots exposed to salinity., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Exposure to fine particulate matter (PM) disrupts the function of airway epithelial barriers causing cellular stress and damage. However, the precise mechanisms underlying PM-induced cellular injury and the associated molecular pathways remain incompletely understood. In this study, we used intratracheal instillation of PM in C57BL6 mice and PM treatment of the BEAS-2B cell line as in vivo and in vitro models, respectively, to simulate PM-induced cellular damage and inflammation. We collected lung tissues and bronchoalveolar lavage fluids to assess histopathological changes, necroptosis, and airway inflammation. Our findings reveal that PM exposure induces necroptosis in mouse airway epithelial cells. Importantly, concurrent administration of a receptor interacting protein kinases 3 (RIPK3) inhibitor or the deletion of the necroptosis effector mixed-lineage kinase domain-like protein (MLKL) effectively attenuated PM-induced airway inflammation. PM exposure dose-dependently induces the expression of Parkin, an E3 ligase we recently reported to play a pivotal role in necroptosis through regulating necrosome formation. Significantly, deletion of endogenous Parkin exacerbates inflammation by enhancing epithelial necroptosis. These results indicate that PM-induced Parkin expression plays a crucial role in suppressing epithelial necroptosis, thereby reducing airway inflammation. Overall, these findings offer valuable mechanistic insights into PM-induced airway injury and identify a potential target for clinical intervention., Competing Interests: Declaration of competing interest The authors declare that they have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Gene transfection, defined by the delivery of nucleic acids into cellular compartments, stands as a crucial procedure in gene therapy. While branched polyethylenimine (PEI) is widely regarded as the "gold standard" for nonviral vectors, its cationic nature presents several issues, including nonspecific protein adsorption and notable cytotoxicity. Additionally, it often fails to achieve high transfection efficiency, particularly with hard-to-transfect cell types. To overcome these challenges associated with PEI as a vector for plasmid DNA (pDNA), the photothermal agent indocyanine green (ICG) is integrated with PEI and pDNA to form the PEI/ICG/pDNA (PI/pDNA) complex for more efficient and safer gene transfection. The negatively charged ICG serves a dual purpose: neutralizing PEI's excessive positive charges to reduce cytotoxicity and, under near-infrared irradiation, inducing local heating that enhances cell membrane permeability, thus facilitating the uptake of PI/pDNA complexes to boost transfection efficiency. Using pDNA encoding vascular endothelial growth factor as a model, our system shows enhanced transfection efficiency in vitro for hard-to-transfect endothelial cells, leading to improved cell proliferation and migration. Furthermore, in vivo studies reveal the therapeutic potential of this system in accelerating the healing of infected wounds by promoting angiogenesis and reducing inflammation. This approach offers a straightforward and effective method for gene transfection, showing potentials for tissue engineering and cell-based therapies.

Bacterial biofilms present a profound challenge to global public health, often resulting in persistent and recurrent infections that resist treatment. Chemodynamic therapy (CDT), leveraging the conversion of hydrogen peroxide (H 2 O 2 ) to highly reactive hydroxyl radicals (•OH), has shown potential as an antibacterial approach. Nonetheless, CDT struggles to eliminate biofilms due to limited endogenous H 2 O 2 and the protective extracellular polymeric substances (EPS) within biofilms. This study introduces a multifunctional nanoplatform designed to self-supply H 2 O 2 and generate nitric oxide (NO) to overcome these hurdles. The nanoplatform comprises calcium peroxide (CaO 2 ) for sustained H 2 O 2 production, a copper-based metal-organic framework (HKUST-1) encapsulating CaO 2 , and l-arginine (l-Arg) as a natural NO donor. When exposed to the acidic microenvironment within biofilms, the HKUST-1 layer decomposes, releasing Cu 2+ ions and l-Arg, and exposing the CaO 2 core to initiate a cascade of reactions producing reactive species such as H 2 O 2 , •OH, and superoxide anions (•O 2 - ). Subsequently, H 2 O 2 catalyzes l-Arg to produce NO, which disperses the biofilm and reacts with •O 2 - to form peroxynitrite, synergistically eradicating bacteria with •OH. In vitro assays demonstrated the nanoplatform's remarkable antibiofilm efficacy against both Gram-positive Methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, significantly reducing bacterial viability and EPS content. In vivo mouse model experiments validated the nanoplatform's effectiveness in eliminating biofilms and promoting infected wound healing without adverse effects. This study represents a breakthrough in overcoming traditional CDT limitations by integrating self-supplied H 2 O 2 with NO's biofilm-disrupting capabilities, offering a promising therapeutic strategy for biofilm-associated 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.)

Porcine epidemic diarrhea virus (PEDV) belongs to the Alphacoronavirus genus within the Coronavirus family, causing severe watery diarrhea in piglets and resulting in significant economic losses. Medium-chain acyl-CoA dehydrogenase (ACADM) is an enzyme participating in lipid metabolism associated with metabolic diseases and pathogen infections. Nonetheless, the precise role of ACADM in regulating PEDV replication remains uncertain. In this study, we identified ACADM as the host binding partner of NSP4 via immunoprecipitation-mass spectrometry analysis. The interaction between ACADM and NSP4 was subsequently corroborated through coimmunoprecipitation and laser confocal microscopy. Following this, a notable upsurge in ACADM expression was observed during PEDV infection. ACADM overexpression effectively inhibited virus replication, whereas ACADM knockdown facilitated virus replication, suggesting ACADM has negative regulation effect on PEDV infection. Furthermore, we demonstrated fatty acid β-oxidation affected PEDV replication for the first time, inhibition of fatty acid β-oxidation reduced PEDV replication. ACADM decreased PEDV-induced β-oxidation to suppress PEDV replication. Mechanistically, ACADM reduced cellular free fatty acid levels and subsequent β-oxidation by hindering AMPK-mediated lipophagy. In summary, our results reveal that ACADM plays a negative regulatory role in PEDV replication by regulating lipid metabolism. The present study introduces a novel approach for the prevention and control of PEDV infection., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Trauma and tumor removal usually cause bone defects; in addition, the related postoperative infection also shall be carefully considered clinically. In this study, polylactic acid (PLLA) composite fibers containing Cerium oxide (CeO 2 ) are first prepared by electrospinning technology. Then, the PLLA/CeO 2 @PDA/Ag composite materials are successfully prepared by reducing silver ion (Ag + ) to nano-silver (AgNPs)  coating in situ and binding AgNPs to the materials surface by mussel structure liked polydopamine (PDA). In the materials, Ag + can be slowly released in simulated body fluids. Based on the photothermal performance of AgNPs, the photothermal conversion efficiency of the materials is 21%, under NIR 808 nm illumination. The effective photothermal conversion can help materials fighting with E. coli and S. aureus in 3 h, with an antibacterial rate of 100%. Additionally, the sustained Ag + release contributes to the antibacterial in long term. Meanwhile, the materials can mimic the bio-behavior of superoxide dismutase and catalase in decreasing the singlet oxygen level and removing the excess reactive oxygen species. Furthermore, the materials are beneficial for cell proliferation and osteogenic differentiation in vitro. In this study, a promising bone-regenerated material with high photothermal conversion efficiency and antibacterial and anti-oxidation properties, is successfully constructed., (© 2024 Wiley‐VCH GmbH.)

Purpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored., Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays., Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3., Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Zhang et al.)

Background: Post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) is an uncommon complication after colorectal endoscopic submucosal dissection (ESD). This study aimed to explore the risk factors of PEECS for superficial colorectal lesions based on the latest and consistent diagnostic criteria and to establish a predictive nomogram model., Methods: This retrospective analysis included patients with superficial colorectal lesions who underwent endoscopic submucosal dissection (ESD) between June 2008 and December 2021 in our center. The independent risk factors of PEECS for superficial colorectal lesions were identified using least absolute shrinkage and selection operator (LASSO) logistic regression analysis, as well as univariate analysis and multivariate logistic regression, and derived predictive nomogram model was constructed., Results: Among the 555 patients with superficial colorectal lesions enrolled, PEECS occurred in 45 (8.1%) patients. Multivariate logistic regression revealed that female sex (OR 3.94, P < 0.001), age > 50 years (OR 4.28, P = 0.02), injury to muscle layer (OR 10.38, P < 0.001), non-lifting sign (OR 2.20, P = 0.04) and inadequate bowel preparation (OR 5.61, P < 0.001) were independent risk factors of PEECS for superficial colorectal lesions. A predictive nomogram model was constructed based on the above five predictors. For this model, the area under the receiver operating characteristic (ROC) curve was 0.855, the calibration curve exhibited good consistency between the prediction and the actual observation, and the C-index was confirmed as 0.843 by bootstrap method., Conclusion: Female sex, age > 50 years, injury to muscle layer, non-lifting sign and inadequate bowel preparation were independent risk factors of PEECS for superficial colorectal lesions. The proposed nomogram could accurately predict the risk of PEECS for superficial colorectal lesions., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

PEDV, a single-stranded RNA virus, causes significant economic losses in the pig industry. Sin3-associated protein 18 (SAP18) is known for its role in transcriptional inhibition and RNA splicing. However, research on SAP18's involvement in PEDV infection is limited. Here, we identified an interaction between SAP18 and PEDV nonstructural protein 10 (Nsp10) using immunoprecipitation-mass spectrometry (IP-MS) and confirmed it through immunoprecipitation and laser confocal microscopy. Additionally, PEDV Nsp10 reduced SAP18 protein levels and induced its cytoplasmic accumulation. Overexpressing SAP18 suppressed PEDV replication, meanwhile its knockdown via short interfering RNA (siRNA) enhanced replication. SAP18 overexpression boosted IRF3 and NF-κB P65 phosphorylation, nuclear translocation, and IFN-β antiviral response. Furthermore, SAP18 upregulated RIG-I expression and facilitated its dephosphorylation, while SAP18 knockdown had the opposite effect. Finally, SAP18 interacted with phosphatase 1 (PP1) catalytic subunit alpha (PPP1CA), promoting PPP1CA-RIG-I interaction during PEDV infection. These findings highlight SAP18's role in activating the type I interferon pathway and inhibiting viral replication by promoting RIG-I dephosphorylation through its interaction with PPP1CA., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dieulafoy's lesion (DL) is a rare and important cause of acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), however, there is a lack of clear guidelines focus on the endoscopic hemostasis treatment for DL. Sclerotherapy, as the ANVUGIB guideline recommended endoscopic hemostasis method, is widely used in clinical practice. The aim of this study is to investigate the efficacy of sclerotherapy as the initial treatment for Dieulafoy's lesion of the upper gastrointestinal tract (UDL)., Methods: Patients with UDL who underwent the ANVUGIB standard endoscopic hemostasis between April 2007 and January 2023 were enrolled. The endoscopic therapy method was left to the discretion of the endoscopist., Results: In total, 219 patients were finally obtained, with 74 (33.8%) receiving sclerotherapy and 145 (66.2%) receiving other standard endoscopic therapy. The rebleeding within 30 days was significantly lower in the sclerotherapy group compared to the other standard group (5.8% vs. 16.8%, p = 0.047). There were no significant differences between the two groups in terms of successful hemostasis rate (93.2% vs. 94.5%, p = 0.713), median number of red blood cell transfusions (3.5 vs. 4.0 units, p = 0.257), median hospital stay (8.0 vs. 8.0 days, p = 0.103), transferred to ICU rate (8.1% vs. 6.2%, p = 0.598), the need for embolization or surgery rate (12.2% vs. 9.7%, p = 0.567) and 30-day mortality (0 vs. 2.1%, p = 0.553). In addition, we found no difference in efficacy between sclerotherapy alone and combination (3.1% vs. 8.1%, p = 0.714). Further analysis revealed that thermocoagulation for hemostasis was associated with a higher rate of rebleeding (28.6% vs. 3.1%, p = 0.042) and longer hospital stay (11.5 vs. 7.5 days, p = 0.005) compared to sclerotherapy alone., Conclusion: Sclerotherapy represents an effective endoscopic therapy for both alone and combined use in patients with upper gastrointestinal Dieulafoy's lesion. Therefore, sclerotherapy could be considered as initial treatment in patients with bleeding of UDL., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/β-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro , HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of β-catenin arrested cell migration and reduced the expression levels of Wnt/β-catenin signaling-related molecules (Wnt4, p-GSK3β and β-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of β-catenin. Furthermore, the combination of Ori treatment and β-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/β-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.

Microplastic records from lake cores can reconstruct the plastic pollution history. However, the associations between anthropogenic activities and microplastic accumulation are not well understood. Huguangyan Maar Lake (HML) is a deep-enclosed lake without inlets and outlets, where the sedimentary environment is ideal for preserving a stable and historical microplastic record. Microplastic (size: 10-500 μm) characteristics in the HML core were identified using the Laser Direct Infrared Imaging system. The earliest detectable microplastics appeared unit in 1955 (1.1 items g -1 ). The microplastic abundance ranged from n.d. to 615.2 items g -1 in 1955-2019 with an average of 134.9 items g -1 . The abundance declined slightly during the 1970s and then increased rapidly after China's Reform and Opening Up in 1978. Sixteen polymer types were detectable, with polyethylene and polypropylene dominating, accounting for 23.5 and 23.3% of the total abundance, and the size at 10-100 μm accounted for 80%. Socioeconomic factors dominated the microplastic accumulation based on the random forest modeling, and the contributions of GDP per capita, plastic-related industry yield, and total crop yield were, respectively, 13.9, 35.1, and 9.3% between 1955-2019. The total crop yield contribution further increased by 1.7% after 1978. Coarse sediment particles increased with soil erosion exacerbated microplastics discharging into the sediment.

Leaf senescence is essential for the growth and development of deciduous trees in the next season. Larix gmelinii , a deciduous coniferous tree, exhibits its most distinctive feature by turning yellow in the autumn and eventually shedding its leaves, resulting in significant changes in its appearance during the fall. Lysine acetylation plays an important role in diverse cellular processes; however, limited knowledge is available regarding acetylations in the needle senescence of L. gmelinii. In this study, the proteomics and acetylated modification omics of two phenotypic leaves, yellow and green (senescent and non-senescent) needles, were analyzed before autumn defoliation. In total, 5022 proteins and 4469 unique acetylation sites in 2414 lysine acylated proteins were identified, and this resulted in the discovery of 1335 differentially expressed proteins (DEPs) and 605 differentially expressed acetylated proteins (DAPs) in yellow versus green needles. There are significant differences between the proteome and acetylome; only 269 proteins were found to be DEP and DAP, of which 136 proteins were consistently expressed in both the DEP and DAP, 91 proteins were upregulated, and 45 proteins were down-regulated. The DEPs participate in the metabolism of starch and sucrose, while the DAPs are involved in glycolysis and the tricarboxylic acid cycle. Among them, DEPs underwent significant changes in glycolysis and citric acid cycling. Most of the enzymes involved in glycolysis and the citrate cycle were acetylated. DAPs were down-regulated in glycolysis and up-regulated in the citrate cycle. In all, the results of this study reveal the important role of lysine acetylation in the senescence of L. gmelinii needles and provide a new perspective for understanding the molecular mechanism of leaf senescence and tree seasonal growth.

There is evidence to support the links between lead and cadmium exposure with hypertension and also with leukocyte telomere length (LTL). The objective of this study is to investigate the role that LTL may play in the relationship between lead and cadmium exposure and hypertension. This study consisted of 3718 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Logistic regression was used to analyze the relationship between blood metals with hypertension, and the mediating model was used to evaluate the mediating effect of LTL. In the fully adjusted model, both blood lead and cadmium ln-transformed concentrations were significantly positively associated with hypertension risk, as were all quartiles of blood lead. Additionally, we observed positive linear dose-response relationships with hypertension by restricted cubic spline analysis (both p overall < 0.001, p non-linear = 0.3008 for lead and p non-linear = 0.7611 for cadmium). The ln-transformed blood lead and cadmium concentrations were associated with shorter LTL. LTL was inversely related to hypertension and the OR was 0.65 (95% CI: 0.47 to 0.89). Furthermore, LTL had mediating effects on the associations of blood lead and cadmium with hypertension risk, and the mediation proportions were 2.25% and 4.20%, respectively. Our findings suggested that exposure to lead and cadmium raised the risk of hypertension, while LTL played as a mediating factor.

The biotic nitrate reduction rate in freshwater ecosystems is typically constrained by the scarcity of carbon sources. In this study, 'two-chambers' - 'two-electrodes' photoautotrophic biofilm-soil microbial fuel cells (P-SMFC) was developed to accelerate nitrate reduction by activating in situ electron donors that originated from the soil organic carbon (SOC). The nitrate reduction rate of P-SMFC (0.1341 d -1 ) improved by ∼ 1.6 times on the 28th day compared to the control photoautotrophic biofilm. The relative abundance of electroactive bacterium increased in the P-SMFC and this bacterium contributed to obtain electrons from SOC. Biochar amendment decreased the resistivity of P-SMFC, increased the electron transferring efficiency, and mitigated anodic acidification, which continuously facilitated the thriving of putative electroactive bacterium and promoted current generation. The results from physiological and ecological tests revealed that the cathodic photoautotrophic biofilm produced more extracellular protein, increased the relative abundance of Lachnospiraceae, Magnetospirillaceae, Pseudomonadaceae, and Sphingomonadaceae, and improved the activity of nitrate reductase and ATPase. Correspondingly, P-SMFC in the presence of biochar achieved the highest reaction rate constant for nitrate reduction (k obs ) (0.2092 d -1 ) which was 2.4 times higher than the control photoautotrophic biofilm. This study provided a new strategy to vitalize in situ carbon sources in paddy soil for nitrate reduction by the construction of P-SMFC., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Sedimentary records of polycyclic aromatic hydrocarbons (PAHs) and phthalates could reflect energy consumption and industrial production adjustment. However, there is limited knowledge about their effects on variations of PAH and phthalate compositions in the sediment core. The PAH and phthalate sedimentary records in Huguangyan Maar Lake in Guangdong, China were constructed, and random forest models were adopted to quantify the associated impact factors. Sums of sixteen PAH (∑ 16 PAH) and seven phthalate (∑ 7 PAE) concentrations in the sediment ranged from 28.8 to 1110 and 246-4290 μg/kg dry weight in 1900-2020. Proportions of 5-6 ring PAHs to the ∑ 16 PAHs increased from 32.0 %-40.7 % in 1900-2020 with increased coal and petroleum consumption, especially after 1980. However, those of 2-3 ring PAHs decreased from 30.7 % to 23.6 % due to the biomass substitution with natural gas. The proportions of bis (2-ethylhexyl) phthalate to the ∑ 7 PAEs decreased from 52.3 %-29.1 % in 1900-2020, while those of di-isobutyl phthalate increased (13.7 % to 42.3 %). The shift from traditional plasticizers to non-phthalates drove this transformation, though the primary plastic production is increasing. Our findings underscore the effectiveness of optimizing energy structures and updating chemical products in reducing organic pollution in aquatic environments., 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.)

Purpose: Cardiovascular disease is one of the leading causes of mortality in patients with obesity. Metabolically healthy obesity (MHO), in which people do not have metabolic disorders, is a transient state of obesity. However, over the long term, a proportion of individuals with MHO develop metabolic syndrome (MetS). We aimed to investigate the effect of substantial weight loss following bariatric surgery in MHO on carotid intima-media thickness (CIMT) and pulse-wave velocity (PWV), which are independent predictors of subclinical atherosclerosis., Methods: This prospective study included 38 patients (34 women, four men) undergoing bariatric surgery who had severe obesity but without comorbidities (hypertension, diabetes, and hyperlipidemia), and 28 control individuals who were matched for age and sex. CIMT and PWV of the left common carotid artery were measured. At 12-month follow-up after bariatric surgery, measurements were repeated in the 38 patients with obesity., Results: Mean baseline body mass index (BMI) in the MHO group was 40.55 ± 3.59 kg/m 2 , which decreased by 33.1% after bariatric surgery. Compared with controls, CIMT and PWV were increased in MHO (543.53 ± 55.29 vs. 407.82 ± 53.09 μm, 6.70 ± 1.22 vs. 5.45 ± 0.74 m/s, respectively; all P < 0.001). At 12 months post-bariatric surgery, CIMT in MHO was lower than baseline (466.79 ± 53.74 vs. 543.53 ± 55.29 μm, P = 0.009), but PWV was not significantly different from baseline (6.27 ± 0.86 vs. 6.70 ± 1.22 m/s, P = 0.132). Multivariate regression showed that BMI was an independent predictor of CIMT (β = 0.531, P < 0.001)., Conclusion: Carotid artery structure and function were impaired in MHO, and improved carotid artery structure was associated with weight loss in MHO after bariatric surgery., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Fungi possess well-developed secondary metabolism pathways that are worthy of in-depth exploration. The One Strain Many Compounds (OSMAC) strategy is a useful method for exploring chemically diverse secondary metabolites. In this study, continued chemical investigations of the marine red algae-derived endophytic fungus Penicillium oxalicum 2021CDF-3 cultured in PDB media yielded six structurally diverse indole derivatives, including two new prenylated indole alkaloids asperinamide B ( 1 ) and peniochroloid B ( 5 ), as well as four related derivatives (compounds 2 - 4 and 6 ). The chemical structures of these compounds, including the absolute configurations of 1 and 5 , were determined by extensive analyses of HRESIMS, 1D and 2D NMR spectroscopic data, and TDDFT-ECD calculations. Compound 1 was found to possess an unusual 3-pyrrolidone dimethylbenzopyran fused to the bicyclo[2.2.2]diazaoctane moiety, which was rare in previously reported prenylated indole alkaloids. In vitro cytotoxic experiments against four human tumor cell lines (HeLa, HepG2, FADU, and A549) indicated that 1 strongly inhibited the FADU cell line, with an IC 50 value of 0.43 ± 0.03 μM. This study suggested that the new prenylated indole alkaloid 1 is a potential lead compound for anti-FADU drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Ji, Zhang and Cao.)

Background: Pharmacist clinics offer professional pharmaceutical services that can improve public health outcomes. However, primary healthcare staff in China face various barriers and challenges in implementing such clinics. To identify existing problems and provide recommendations for the implementation of pharmacist clinics, this study aims to assess the knowledge, attitudes, and practices of pharmacist clinics among primary healthcare providers., Methods: A cross-sectional survey based on the Knowledge-Attitude-Practice (KAP) model, was conducted in community health centers (CHCs) and private hospitals in Shanghai, China in May, 2023. Descriptive analytics and the Pareto principle were used to multiple-answer questions. Chi-square test, Fisher's exact test, and binary logistic regression models were employed to identify factors associated with the knowledge, attitudes, and practices of pharmacist clinics., Results: A total of 223 primary practitioners participated in the survey. Our study revealed that most of them had limited knowledge (60.1%, n = 134) but a positive attitude (82.9%, n = 185) towards pharmacist clinics, with only 17.0% (n = 38) having implemented them. The primary goal of pharmacist clinics was to provide comprehensive medication guidance (31.5%, n = 200), with medication education (26.3%, n = 202) being the primary service, and special populations (24.5%, n = 153) identified as key recipients. Logistic regression analysis revealed that education, age, occupation, position, work seniority, and institution significantly influenced their perceptions. Practitioners with bachelor's degrees, for instance, were more likely than those with less education to recognize the importance of pharmacist clinics in medication guidance (aOR: 7.130, 95%CI: 1.809-28.099, p-value = 0.005) and prescription reviews (aOR: 4.675, 95% CI: 1.548-14.112, p-value = 0.006). Additionally, practitioners expressed positive attitudes but low confidence, with only 33.3% (n = 74) feeling confident in implementation. The confidence levels of male practitioners surpassed those of female practitioners (p-value = 0.037), and practitioners from community health centers (CHCs) exhibited higher confidence compared to their counterparts in private hospitals (p-value = 0.008). Joint physician-pharmacist clinics (36.8%, n = 82) through collaboration with medical institutions (52.0%, n = 116) emerged as the favored modality. Daily sessions were preferred (38.5%, n = 86), and both registration and pharmacy service fees were considered appropriate for payment (42.2%, n = 94). The primary challenge identified was high outpatient workload (30.9%, n = 69)., Conclusions: Although primary healthcare practitioners held positive attitudes towards pharmacist clinics, limited knowledge, low confidence, and high workload contributed to the scarcity of their implementation. Practitioners with diverse sociodemographic characteristics, such as education, age, and institution, showed varying perceptions and practices regarding pharmacist clinics., (© 2024. The Author(s).)

Myocardial infarction (MI) is associated with inflammatory reaction, which is a pivotal component in MI pathogenesis. Moreover, excessive inflammation post-MI can lead to cardiac dysfunction and adverse remodeling, emphasizing the critical need for an effective inflammation-regulating treatment for cardiac repair. Macrophage polarization is crucial in the inflammation process, indicating its potential as an adjunct therapy for MI. In this study, we developed an injectable alginate hydrogel loaded with annexin A1 (AnxA1, an endogenous anti-inflammatory and pro-resolving mediator) for MI treatment. In vitro results showed that the composite hydrogel had good biocompatibility and consistently released AnxA1 for several days. Additionally, this hydrogel led to a reduced number of pro-inflammatory macrophages and an increased proportion of pro-healing macrophages via the adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mammalian target of the rapamycin (mTOR) axis. Furthermore, the intramyocardial injection of this composite hydrogel into a mouse MI model effectively modulated macrophage transition to pro-healing phenotypes. This transition mitigated early inflammatory responses and cardiac fibrosis, promoted angiogenesis, and improved cardiac function. Therefore, our study findings suggest that combining biomaterials and endogenous proteins for MI treatment is a promising approach for limiting adverse cardiac remodeling, preventing cardiac damage, and preserving the function of infarcted hearts.

Hybrid rice (Oryza sativa) generally outperforms its inbred parents in yield and stress tolerance, a phenomenon termed heterosis, but the underlying mechanism is not completely understood. Here, we combined transcriptome, proteome, physiological, and heterosis analyses to examine the salt response of super hybrid rice Chaoyou1000 (CY1000). In addition to surpassing the mean values for its two parents (mid-parent heterosis), CY1000 exhibited a higher reactive oxygen species scavenging ability than both its parents (over-parent heterosis or heterobeltiosis). Nonadditive expression and allele-specific gene expression assays showed that the glutathione S-transferase gene OsGSTU26 and the amino acid transporter gene OsAAT30 may have major roles in heterosis for salt tolerance, acting in an overdominant fashion in CY1000. Furthermore, we identified OsWRKY72 as a common transcription factor that binds and regulates OsGSTU26 and OsAAT30. The salt-sensitive phenotypes were associated with the OsWRKY72 paternal genotype or the OsAAT30 maternal genotype in core rice germplasm varieties. OsWRKY72 paternal specifically repressed the expression of OsGSTU26 under salt stress, leading to salinity sensitivity, while OsWRKY72 maternal specifically repressed OsAAT30, resulting in salinity tolerance. These results suggest that the OsWRKY72-OsAAT30/OsGSTU26 module may play an important role in heterosis for salt tolerance in an overdominant fashion in CY1000 hybrid rice, providing valuable clues to elucidate the mechanism of heterosis for salinity tolerance in hybrid rice., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Background: Progressive loss of peripheral muscle strength is highly pronounced in patients receiving maintenance hemodialysis (MHD), of which the pathological mechanism tends to be multifactorial. Plasma nickel was reportedly correlated with muscular strength in non-dialysis patients. However, scarce is known regarding the association between blood nickel level and handgrip strength among the patients undergoing MHD., Methods: This cross-sectional study included patients undergoing MHD at our center in October 2021. Blood samples were collected before the hemodialysis sessions. Nickel level was measured using inductively coupled plasma mass spectrometry. Eligible patients were stratified into three groups by the blood nickel level: tertile 1 (≥ 5.2 ug/L); tertile 2 (< 5.2 ug/L and ≥ 4.5 ug/L); and tertile 3 (< 4.5 ug/L). Handgrip strength measurement was used to evaluate the muscle status. Spearman's analyses and multivariable linear regression analyses were performed to study the relationship between blood nickel level and handgrip strength., Results: A total of 236 patients were enrolled, with an average age of 55.51 ± 14.27 years and a median dialysis vintage of 83 (IQR: 48-125) months. Patients in group with a higher blood nickel level (tertile 1) tended to be female, had longer dialysis vintage and higher Kt/V, but lower BMI, serum creatinine, hemoglobin, and handgrip strength level (all p < 0.05). After adjustment for confounding factors in multivariable models, for every 1ug/L increase in nickel level, the patient's handgrip strength decreases by 2.81 kg (β: - 2.810, 95% confidence interval: - 5.036 to - 0.584, p = 0.014). Restricted cubic spline confirmed the relationship was nearly linear., Conclusions: Our study highlighted that blood nickel level was related to handgrip strength in patients undergoing MHD. Prospective studies with larger sample sizes are still needed to confirm the result., (© 2023. The Author(s).)

Salinity stress constrains lateral root (LR) growth and severely affects plant growth. Auxin signaling regulates LR formation, but the molecular mechanism by which salinity affects root auxin signaling and whether salt induces other pathways that regulate LR development remains unknown. In Arabidopsis thaliana, the auxin-regulated transcription factor LATERAL ORGAN BOUNDARY DOMAIN 16 (LBD16) is an essential player in LR development under control conditions. Here, we show that under high-salt conditions, an alternative pathway regulates LBD16 expression. Salt represses auxin signaling but, in parallel, activates ZINC FINGER OF ARABIDOPSIS THALIANA 6 (ZAT6), a transcriptional activator of LBD16. ZAT6 activates LBD16 expression, thus contributing to downstream cell wall remodeling and promoting LR development under high-salt conditions. Our study thus shows that the integration of auxin-dependent repressive and salt-activated auxin-independent pathways converging on LBD16 modulates root branching under high-salt conditions., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Biofilms formed by pathogenic bacteria present a persistent risk to human health. While the eradication of matured biofilms remains a formidable challenge, delaying or preventing their formation, which is coordinately regulated by quorum sensing (QS), presents a simpler and more advantageous strategy. Quercetin, a naturally occurring compound with anti-QS properties, has the potential to act as an antibiofilm agent. However, it is plagued by certain inherent drawbacks, including poor water solubility and limited bioavailability. Furthermore, solely blocking QS is not enough to prevent biofilm formation because it lacks bactericidal properties. To address these difficulties, we fabricated bi-functional nanoparticles through the co-assembly of quercetin and copper ions in a facile manner. The resulting quercetin/copper nanoparticles (QC NPs) demonstrated minimal cytotoxicity and hemolysis in vitro . In response to the low pH of microenvironments that were populated by bacterial colonies, the QC NPs underwent disassembly to release copper ions and quercetin. The former exterminated bacteria by disrupting the integrity of the cell membrane, while the latter disrupted the processes involved in QS that are responsible for the biofilm by downregulating the expression of specific genes, effectively preventing the formation of biofilms by both Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus . In addition, the QC NPs were integrated into a bacterial cellulose membrane. The composite membrane proved to be highly effective at inhibiting biofilm formation in vitro and demonstrated the ability to reduce inflammatory responses and accelerate the healing of bacteria-infected wounds in vivo . Overall, the bi-functional QC NPs hold great potential for use in addressing the challenges associated with the management of bacterial biofilms.

Biofilm contamination presents a significant threat to public health, the food industry, and aquatic/marine-related applications. In recent decades, although various methods have emerged to combat biofilm contamination, the intricate and persistent nature of biofilms makes complete eradication challenging. Therefore, innovative alternative solutions are imperative for addressing biofilm formation. Instead of solely focusing on the eradication of mature biofilms, strategically advantageous measures involve the delay or prevention of biofilm formation on surfaces. Quorum sensing, a communication system enabling bacteria to coordinate their behavior based on population density, plays a pivotal role in biofilm formation for numerous microbial species. Materials possessing antibiofilm properties that target quorum sensing have gained considerable attention for their potential to prevent biofilm formation. This Review consolidates recent research progress on the utilization of materials with antiquorum sensing properties for combating biofilm formation. These materials can be categorized into three distinct types: (i) antibiofilm nanomaterials, (ii) antibiofilm surfaces, and (iii) antibiofilm hydrogels with antiquorum sensing capabilities. Finally, the Review concludes with a brief discussion of current challenges and outlines potential avenues for future research.

Saturated bicyclic amines are increasingly targeted to the pharmaceutical industry as sp 3 -rich bioisosteres of anilines. Numerous strategies have been established for the preparation of bridgehead aminobicyclics. However, methods to assemble the bridge-amino hydrocarbon skeleton, which serves as a meta -substituted arene bioisostere, are limited. Herein, a general approach to access 2-aminobicyclo[2.1.1]hexanes (aminoBCHs) by titanium-catalyzed formal [2π + 2σ] cycloaddition of bicyclo[1.1.0]butanes and 2-azadienes was developed. Simple derivatization of aminoBCHs leads to various medicinally and agrochemically important analogues.

Exposure to benzo[a]pyrene (B[a]P) has been linked to lung injury and carcinogenesis. Airway epithelial cells express the B[a]P receptor AHR, so B[a]P is considered to mainly target airway epithelial cells, whereas its potential impact on alveolar cells remains inadequately explored. Metformin, a first-line drug for diabetes, has been shown to exert anti-inflammatory and tissue repair-promoting effects under various injurious conditions. Here, we explored the effect of chronic B[a]P exposure on alveolar cells and the impact of metformin on B[a]P-induced lung injury by examining the various parameters including lung histopathology, inflammation, fibrosis, and related signal pathway activation. MLKL knockout (Mlkl -/- ) and AT2-lineage tracing mice (Sftpc Cre-ERT2 ;LSL-tdTomato flox+/- ) were used to delineate the role of necroptosis in B[a]P-induced alveolar epithelial injury and repair. Mice receiving weekly administration of B[a]P for 6 weeks developed a significant alveolar damaging phenotype associated with pulmonary inflammation, fibrosis, and activation of the necroptotic cell death pathway. These effects were significantly relieved in MLKL null mice. Furthermore, metformin treatment, which were found to promote AMPK phosphorylation and inhibit RIPK3, as well as MLKL phosphorylation, also significantly alleviated B[a]P-induced necroptosis and lung injury phenotype. However, the protective efficacy of metformin was rendered much less effective in Mlkl null mice or by blocking the necroptotic pathway with RIPK3 inhibitor. Our findings unravel a potential protective efficacy of metformin in mitigating the detrimental effects of B[a]P exposure on lung health by inhibiting necroptosis and protecting AT2 cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The storage period of tea is a major factor affecting tea quality. However, the effect of storage years on the non-volatile major functional components and quality of green tea remains largely unknown. In this study, a comparative analysis of organic green teas with varying storage years (1-16 years) was conducted by quantifying 47 functional components, using electronic tongue and chromatic aberration technology, alongside an evaluation of antioxidative capacity. The results indicated a significant negative correlation between the storage years and levels of tea polyphenols, total amino acids, soluble sugars, two phenolic acids, four flavonols, three tea pigments, umami amino acids, and sweet amino acids. The multivariate statistical analysis revealed that 10 functional components were identified as effective in distinguishing organic green teas with different storage years. Electronic tongue technology categorized organic green teas with different storage years into three classes. The backpropagation neural network (BPNN) analysis demonstrated that the classification predictive ability of the model based on the electronic tongue was superior to the one based on color difference values and 10 functional components. The combined analysis of antioxidative activity and functional components suggested that organic green teas with shorter storage periods exhibited stronger abilities to suppress superoxide anion radicals and hydroxyl radicals and reduce iron ions due to the higher content of eight components. Long-term-stored organic green teas, with a higher content of substances like L-serine and theabrownins, demonstrated stronger antioxidative capabilities in clearing both lipid-soluble and water-soluble free radicals. Therefore, this study provided a theoretical basis for the quality assessment of green tea and prediction of green tea storage periods.

Porcine epidemic diarrhea virus (PEDV) requires complete dependence on the metabolic system of the host cell to complete its life cycle. There is a strong link between efficient viral replication and cellular lipid synthesis. However, the mechanism by which PEDV interacts with host cells to hijack cellular lipid metabolism to promote its replication remains unclear. In this study, PEDV infection significantly enhanced the expression of lipid synthesis-related genes and increased cellular lipid accumulation. Furthermore, using liquid chromatography-tandem mass spectrometry, we identified heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) as the interacting molecule of PEDV NSP9. We demonstrated that the expression of HNRNPA3 was downregulated by PEDV-induced miR-218-5p through targeting its 3' untranslated region. Interestingly, knocking down HNRNPA3 facilitated the PEDV replication by promoting cellular lipid synthesis. We next found that the knockdown of HNRNPA3 potentiated the transcriptional activity of sterol regulatory element-binding transcription factor 1 (SREBF1) through zinc finger protein 135 (ZNF135) as well as PI3K/AKT and JNK signaling pathways. In summary, we propose a model in which PEDV downregulates HNRNPA3 expression to promote the expression and activation of SREBF1 and increase cellular lipid accumulation, providing a novel mechanism by which PEDV interacts with the host to utilize cellular lipid metabolism to promote its replication.IMPORTANCEAs the major components and structural basis of the viral replication complexes of positive-stranded RNA viruses, lipids play an essential role in viral replication. However, how PEDV manipulates host cell lipid metabolism to promote viral replication by interacting with cell proteins remains poorly understood. Here, we found that SREBF1 promotes cellular lipid synthesis, which is essential for PEDV replication. Moreover, HNRNPA3 negatively regulates SREBF1 activation and specifically reduces lipid accumulation, ultimately inhibiting PEDV dsRNA synthesis. Our study provides new insight into the mechanisms by which PEDV hijacks cell lipid metabolism to benefit viral replication, which can offer a potential target for therapeutics against PEDV infection., Competing Interests: The authors declare no conflict of interest.

Therapeutic resistance is a major obstacle to successful treatment or effective containment of cancer. Peroxisome proliferator-activated receptors (PPARs) play an essential role in regulating energy homeostasis and determining cell fate. Despite of the pleiotropic roles of PPARs in cancer, numerous studies have suggested their intricate relationship with therapeutic resistance in cancer. In this review, we provided an overview of the roles of excessively activated PPARs in promoting resistance to modern anti-cancer treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The mechanisms through which activated PPARs contribute to therapeutic resistance in most cases include metabolic reprogramming, anti-oxidant defense, anti-apoptosis signaling, proliferation-promoting pathways, and induction of an immunosuppressive tumor microenvironment. In addition, we discussed the mechanisms through which activated PPARs lead to multidrug resistance in cancer, including drug efflux, epithelial-to-mesenchymal transition, and acquisition and maintenance of the cancer stem cell phenotype. Preliminary studies investigating the effect of combination therapies with PPAR antagonists have suggested the potential of these antagonists in reversing resistance and facilitating sustained cancer management. These findings will provide a valuable reference for further research on and clinical translation of PPAR-targeting treatment strategies., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Ascending aortic aneurysm is a serious health risk. In order to study ascending aortic aneurysms, elastase and calcium ion treatment for aneurysm formation are mainly used, but their aneurysm formation time is long, the aneurysm formation rate is low. Thus, this study aimed to construct a rat model of ascending aorta aneurysm with a short modeling time and high aneurysm formation rate, which may mimic the pathological processes of human ascending aorta aneurysm., Methods: Cushion needles with different pipe diameters (1.0, 1.2, 1.4 and 1.6 mm) were used to establish a human-like rat model of ascending aortic aneurysm by narrowing the ascending aorta of rats and increasing the force of blood flow on the vessel wall. The vascular diameters were evaluated using color Doppler ultrasonography after two weeks. The characteristics of ascending aortic aneurysm in rats were detected by Masson's trichrome staining, Verhoeff's Van Gieson staining and hematoxylin and eosin staining while RT-PCR were utilized to assess the total RNA of cytokine interleukin-1β, interleukin 6, transforming growth factor-beta1 and metalloproteinase 2., Results: Two weeks after surgery, the ultrasound images and the statistical analysis demonstrated that the diameter of the ascending aorta in rats increased more than 1.5 times, similar to that in humans, indicating the success of animal modeling of ascending aortic aneurysm. Moreover, the optimal constriction diameter of the ascending aortic aneurysm model is 1.4 mm by the statistical analysis of the rate of ascending aortic aneurysm and mortality rate in rats with different constriction diameters., Conclusions: The human-like ascending aortic aneurysm model developed in this study can be used for the studies of the pathological processes and mechanisms in ascending aortic aneurysm in a more clinically relevant fashion., (S. Karger AG, Basel.)

Kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) promotes the progression of bladder cancer and lung adenocarcinoma. However, its expression and biological function in breast cancer remain largely unknown. Therefore, this study aimed to analyze KNSTRN expression, prognoses, correlation with immune infiltration, expression-associated genes, and regulated signaling pathways to characterize its role in regulating the cell cycle using both bioinformatics and in vitro functional experiments. Analyses of The Cancer Genome Atlas, Gene Expression Omnibus, TIMER, and The Human Protein Atlas databases revealed a significant upregulation of KNSTRN transcript and protein levels in breast cancer. Kaplan-Meier survival analyses demonstrated a significant association between high expression of KNSTRN and poor overall survival, relapse-free survival, post-progression survival, and distant metastases-free survival in patients with breast cancer. Furthermore, multivariate Cox regression analyses confirmed that KNSTRN is an independent prognostic factor for breast cancer. Immune infiltration analysis indicated a positive correlation between KNSTRN expression and T regulatory cell infiltration while showing a negative correlation with Tgd and natural killer cell infiltration. Gene set enrichment analysis along with single-cell transcriptome data analysis suggested that KNSTRN promoted cell cycle progression by regulating the expression of key cell cycle proteins. The overexpression and silencing of KNSTRN in vitro, respectively, promoted and inhibited the proliferation of breast cancer cells. The overexpression of KNSTRN enhanced the expression of key cell cycle regulators, including CDK4, CDK6, and cyclin D3, thereby accelerating the G1/S phase transition and leading to aberrant proliferation of breast cancer cells. In conclusion, our study demonstrates that KNSTRN functions as an oncogene in breast cancer by regulating immune response, promoting G1/S transition, and facilitating breast cancer cell proliferation. Moreover, KNSTRN has potential as a molecular biomarker for diagnostic and prognostic prediction in breast cancer., (© 2024. The Author(s).)

To analyze the clinical value of echocardiography combined with serum lacuna protein-1 (Cav-1), activated T cell nuclear factor C1 (NFATc1), and plasminogen activator inhibitor-1 (PAI-1) in the diagnosis of Kawasaki disease (KD) complicated with coronary artery lesions (CAL). A total of 200 children with KD treated in our hospital from January 2019 to October 2021 were grouped as the KD alone group (n = 56) and the KD complicated with CAL group (n = 144) according to the results of coronary angiography. The levels of Cav-1, NFATc1, and PAI-1 were detected by enzyme-linked immunosorbent assay. Echocardiography was performed and the internal diameters of left and right coronary arteries were compared between the two groups. The area under the curve (AUC), sensitivity, and specificity of echocardiography combined with serum Cav-1, NFATc1, and PAI-1 in the diagnosis of KD complicated with CAL were analyzed with receiver operating characteristic (ROC) curve. Coronary angiography, as the gold standard, showed that the sensitivity of echocardiography in diagnosing KD with CAL was 88.19% (127/144), the specificity was 66.07% (37/56), and the accuracy was 82.00% (164/200). ROC curve analysis revealed that the AUC of KD complicated with CAL diagnosed by echocardiography, Cav-1, NFATc1, and PAI-1 was 0.819, 0.715, 0.688, and 0.663, respectively, and the AUC of combined diagnosis of the four was 0.896. The combination of echocardiography, Cav-1, NFATc1, and PAI-1 has high value in diagnosing KD complicated with CAL, which can be widely used in clinical practice., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Potassium Calcium-Activated Channel Subfamily N1 (KCNN1), an integral membrane protein, is thought to regulate neuronal excitability by contributing to the slow component of synaptic after hyperpolarization. However, the role of KCNN1 in tumorigenesis has been rarely reported, and the underlying molecular mechanism remains unclear. Here, we report that KCNN1 functions as an oncogene in promoting breast cancer cell proliferation and metastasis. KCNN1 was overexpressed in breast cancer tissues and cells. The pro-proliferative and pro-metastatic effects of KCNN1 were demonstrated by CCK8, clone formation, Edu assay, wound healing assay and transwell experiments. Transcriptomic analysis using KCNN1 overexpressing cells revealed that KCNN1 could regulate key signaling pathways affecting the survival of breast cancer cells. KCNN1 interacts with ERLIN2 and enhances the effect of ERLIN2 on Cyclin B1 stability. Overexpression of KCNN1 promoted the protein expression of Cyclin B1, enhanced its stability and promoted its K63 dependent ubiquitination, while knockdown of KCNN1 had the opposite effects on Cyclin B1. Knockdown (or overexpression) ERLNI2 partially restored Cyclin B1 stability and K63 dependent ubiquitination induced by overexpression (or knockdown) of KCNN1. Knockdown (or overexpression) ERLIN2 also partially neutralizes the effects of overexpression (or knockdown) KCNN1-induced breast cancer cell proliferation, migration and invasion. In paired breast cancer clinical samples, we found a positive expression correlations between KCNN1 and ERLIN2, KCNN1 and Cyclin B1, as well as ERLIN2 and Cyclin B1. In conclusion, this study reveals, for the first time, the role of KCNN1 in tumorigenesis and emphasizes the importance of KCNN1/ERLIN2/Cyclin B1 axis in the development and metastasis of breast cancer., (© The Author(s) 2023. Published by Oxford University Press.)

3-Alkyl-2-methoxypyrazines (MPs) could be considered as off-flavor for red wine if the concentration exceeds a certain threshold. It is unknown whether the vine water status has an influence on MP metabolism in grape berries and, therefore, in wines. This study aimed to evaluate the effect of vine water status on MP content and on the expression level of VvOMTs ; moreover, the exact functions of VvOMT2/3 were investigated. In this study, the grapevines were subjected over two years (2020 and 2021) to different levels of water constraints and the treatments were (i) light water constraint (LW); (ii) moderate water constraint (MW); and (iii) severe water constraint (SW) in comparison with well-irrigated vines used as control (CK). The results showed that six MPs, including ETMP, MEMP, MOMP, SBMP, IPMP, and IBMP, were negatively and significantly affected by water constraints. Meanwhile, the levels of VvOMT1 , VvOMT2 , VvOMT3 , and VvOMT4 were 0.17-fold, 0.13-fold, 0.35-fold, and 0.75-fold, respectively, at 40 DAA or 60 DAA under MW treatment relative to CK in 2020. In 2021, the trend was similar to that in 2020. When VvOMT2 and VvOMT3 genes were transiently overexpressed in grape berries and callus, both their expression level and protein level were induced; in addition, IPMP, SBMP, and IBMP contents were significantly increased. Moreover, heterologous expression of VvOMT3 in tomato led to IPMP, SBMP, and IBMP accumulation, whereas VvOMT2 could only promote the accumulation of IPMP. Altogether, moderate water constraint not only improved the quality of "Marselan" grape berries but also reduced the MP content per berry. This study showed for the first time, according to our knowledge, the effect of vine water constraint on the metabolism of MPs by way of allowing the reduction of the precursors of this aromatic compound, which could be perceived as an off-flavor impacting negatively wine aromatic profiles with notes of asparagus and green pepper.

Determinants of thrombotic events remain uncertain in patients with atrial fibrillation treated with direct oral anticoagulants (DOACs). Our aim was to identify risk factors associated with thromboembolism in patients with at atrial fibrillation on DOACs and to construct and externally validate a predictive model that would provide a validated tool for clinical assessment of thromboembolism. In the development cohort, prediction model was built by logistic regression, the area under the curve (AUC), and Nomogram. External validation and calibration of the model using AUC and Hosmer-Lemeshow test. This national multicenter retrospective study included 3263 patients with atrial fibrillation treated with DOACs. The development cohort consisted of 2390 patients from three centers and the external validation cohort consisted of 873 patients from 13 centers. Multifactorial analysis showed that heavy drinking, hypertension, prior stroke/transient ischemic attack (TIA), cerebral infarction during hospitalization were independent risk factors for thromboembolism. The Alfalfa-TE risk score was constructed using these four factors (AUC = 0.84), and in the external validation cohort, the model showed good discriminatory power (AUC = 0.74) and good calibration (Hosmer-Lemeshow test P value of 0.649). Based on four factors, we derived and externally validated a predictive model for thromboembolism with DOACs in patients with atrial fibrillation (Alfalfa-TE risk score). The model has good predictive value and may be an effective tool to help reduce the occurrence of thromboembolism in patients with DOACs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Water stress can affect plant ecological distribution, crop growth and carbohydrate distribution, impacting berry quality. However, previous studies mainly focused on short-term water stress or osmotic stress and few studies paid attention to the responses of grape to long-term water stresses. Grapevines were subjected to no water stress (CK), mild water stress (T1) and moderate water stress (T2). Hundred-berry weight and malic acid content were reduced under T1 and T2; however, glucose and fructose content showed the opposite trend. Endogenous hormones and polyamines (PAs) can regulate plant growth and development as well as physiological metabolic processes. T1 and T2 could increase abscisic acid content, however, indole-3-acetic acid, jasmonate, gibberellins 3 and 4, cytokinin and trans -zeatin contents were slightly decreased. Three species of PAs (putrescine, spermidine and spermine) were detected, presenting obvious tissue specificity. Furthermore, there was a statistically positive correlation relating spermidine content in the pulp with glucose and fructose contents of grape berries; and a negative correlation with organic acid. In summary, water stress had a profound influence on hormonally-driven changes in physiology and berry quality, indicating that endogenous hormones and the PAs play a critical role in the development and ripening of grape berries under water stress.

Increasing food demand has led to more intensive farming, which threatens our ecosystem and human health due to toxic elements accumulation. This study aimed to estimate the vulnerability of different agricultural systems with unequal high fertilizer input practices regarding toxic element pollution in the greenhouse, kiwifruit orchard, cereal field, and forest/grassland. Soil samples were collected from 181 sites across Shaanxi Province, China, and analyzed for selected characteristics and toxic elements (As, Cd, Cr, Cu, Hg, Pb, and Zn). The contamination factor (CF x ) represents the ratio of the measured value of the toxic element in the soil over the soil background values. The CF x values of all the toxic elements were above background values, while Cd and Hg contamination levels were more severe than those of Zn, Cu, As, Cr, and Pb. Kiwifruit orchards and greenhouse soils were contaminated with Cd, Hg, Cu, and Zn, but cereal fields and forest/grassland soils were contaminated with As, Cd, Hg, and Hg. Overall, the cumulative pollution load (PLI) of toxic elements indicated moderate contamination. The cumulative ecological risk (RI) results indicated that greenhouse (178.81) and forest/grassland (156.25) soils were at moderate ecological risks, whereas kiwifruit orchards (120.97) and cereal field (139.72) soils were at low ecological risks. According to a Pearson correlation analysis, Cd, Hg, Cu, and Zn were substantially linked with soil organic matter (SOM), total nitrogen (TN), total phosphorous (TP), and total potassium (TK). The primary sources of toxic elements were phosphate and potash fertilizers, manure, composts, and pesticides in a greenhouse, kiwifruit orchards, and cereal fields, whereas, in forest/grassland soils parent material and atmospheric deposition were the sources identified by positive matrix factorization (PMF). Furthermore, the partial least square structural equation model (PLS-SEM) demonstrated that agriculture inputs largely influenced toxic elements accumulation. We conclude that high fertilizer inputs in greenhouse soils should be considered carefully so that toxic element pollution may be minimized., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background: The glucose-to-lymphocyte ratio (GLR), a glucose metabolism and systemic inflammatory response parameter, is associated with an adverse prognosis for various diseases. However, the association between serum GLR and prognosis in patients undergoing peritoneal dialysis (PD) is poorly understood., Methods: In this multi-center cohort study, 3236 PD patients were consecutively enrolled between 1 January 2009 and 31 December 2018. Patients were divided into four groups according to the quartiles of baseline GLR levels (Q1: GLR ≤ 2.91, Q2:2.91 < GLR ≤ 3.91, Q3:3.91 < GLR < 5.59 and Q4: GLR ≥ 5.59). The primary endpoint was all-cause and cardiovascular disease (CVD) related mortality. The correlation between GLR and mortality was examined using Kaplan-Meier and multivariable Cox proportional analyses., Results: During the follow-up period of 45.93 ± 29.01 months, 25.53% (826/3236) patients died, of whom 31% (254/826) were in Q4 (GLR ≥ 5.59). Multivariable analysis revealed that GLR was significantly associated with all-cause mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p  = .019) and CVD mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p  = .04). Compared with the Q1 (GLR ≤ 2.91), placement in Q4 was associated with an increased risk of all-cause mortality (adjusted HR: 1.26, 95% CI: 1.02 ∼ 1.56, p  = .03) and CVD mortality (adjusted HR 1.76; CI 1.31 ∼ 2.38, p  < .001). A nonlinear relationship was found between GLR and all-cause or CVD mortality in patients undergoing PD ( p  = .032)., Conclusion: A higher serum GLR level is an independent prognostic factor for all-cause and CVD mortality in patients undergoing PD, suggesting that more attention should be paid to GLR.

Background: There are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia., Methods: This is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 10 9 /L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 10 9 /L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 10 9 /L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis., Results: Higher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12-2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19-2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14-4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66-5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46-6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23-13.54, P = 0.577)., Conclusions: Higher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia., (© 2023. The Author(s).)

Malic acid is the predominant organic acid in grape berries, and its content is affected by abiotic factors such as temperature (fruit zone microclimate) and water (vine water status). The objectives of this study were to explore the potential mechanisms behind the effects of vine water status on the biosynthesis and degradation of berry malic acid and the potential downstream effects on berry metabolism. This study was conducted over two growing seasons in 2021 and 2022, comprising three watering regimes: no water stress (CK), light water stress (LWS), and moderate water stress (MWS). Compared to CK, a significantly higher level of malic acid was found in berries from the MWS treatment when the berry was still hard and green (E-L 33) in both years. However, water stress reduced the malic acid content at the ripe berry harvest (E-L 38) stage. The activities of NAD-malate dehydrogenase (NAD-MDH) and pyruvate kinase (PK) were enhanced by water stress. Except for the E-L 33 stage, the activity of phosphoenolpyruvate carboxylase (PEPC) was reduced by water stress. The highest phosphoenolpyruvate carboxykinase (PEPCK) activity was observed at the berry veraison (E-L 35) stage and coincided with the onset of a decrease in the malate content. Meanwhile, the expression of VvPEPCK was consistent with its enzyme activity. This study showed that water stress changed the content of some free amino acids (GABA, proline, leucine, aspartate, and glutamate), two of which (glutamate and GABA) are primary metabolites of the GABA pathway.

Functional coatings with desired bioactivities are required for various biomedical applications. Candle soot (CS) composed of carbon nanoparticles has attracted significant attention as a versatile component of functional coatings because of its unique physical and structural characteristics. However, the application of CS-based coatings in the biomedical field is still limited due to the lack of modification methods that can endow them with specific biofunctionality. Herein, a facile and widely applicable approach to fabricate multifunctional CS-based coatings is developed by grafting functional polymer brushes on the silica-stabilized CS. The resulting coatings not only exhibited excellent near-infrared-activated biocidal ability (the killing efficiency was over 99.99 %) due to the inherent photothermal property of CS but also showed desired biofunctions (such as antifouling property or controllable bioadhesion; the repelling efficiency and bacterial release ratio were nearly 90 %) originated from the grafted polymers. Moreover, these biofunctions were enhanced by the nanoscale structure of CS. Because the deposition of CS is a simple substrate-independent process while the grafting of polymer brushes via surface-initiated polymerization is applicable to a wide range of vinyl monomers, the proposed approach can be potentially used for the fabrication of multifunctional coatings and would extend the applications of CS in the biomedical field., 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 © 2023 Elsevier Inc. All rights reserved.)

Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its lifecycle under multiple environmental stresses, including high salinity. Yet, the key physiological and structural traits underlying its stress-adapted lifestyle are unknown along with trade-offs when surviving salt stress at the expense of growth and reproduction. We aimed to identify the influential adaptive trait responses that lead to stress-resilient and uncompromised growth across developmental stages when treated with salt at levels known to inhibit growth in Arabidopsis and most crops. Its resilient growth was promoted by traits that synergistically allowed primary root growth in seedlings, the expansion of xylem vessels across the root-shoot continuum, and a high capacity to maintain tissue water levels by developing thicker succulent leaves while enabling photosynthesis during salt stress. A successful transition from vegetative to reproductive phase was initiated by salt-induced early flowering, resulting in viable seeds. Self-fertilization in salt-induced early flowering was dependent upon filament elongation in flowers otherwise aborted in the absence of salt during comparable plant ages. The maintenance of leaf water status promoting growth, and early flowering to ensure reproductive success in a changing environment, were among the most influential traits that contributed to the extremophytic lifestyle of S. parvula., (© 2023 Society for Experimental Biology and John Wiley & Sons Ltd.)

Bacterial adhesion and subsequent biofilm formation on the surfaces of synthetic materials imposes a significant burden in various fields, which can lead to infections in patients or reduce the service life of industrial devices. Therefore, there is increasing interest in imbuing surfaces with antibacterial properties. Bioinspired superhydrophobic surfaces with high water contact angles (>150°) exhibit excellent surface repellency against contaminations, thereby preventing initial bacterial adhesion and inhibiting biofilm formation. However, conventional superhydrophobic surfaces typically lack long-term durability and are incapable of achieving persistent efficacy against bacterial adhesion. To overcome these limitations, in recent decades, dual-function superhydrophobic antibacterial surfaces with both bacteria-repelling and bacteria-killing properties have been developed by introducing bactericidal components. These surfaces have demonstrated improved long-term antibacterial performance in addressing the issues associated with surface-attached bacteria. This review summarizes the recent advancements of these dual-function superhydrophobic antibacterial surfaces. First, a brief overview of the fabrication strategies and bacteria-repelling mechanism of superhydrophobic surfaces is provided and then the dual-function superhydrophobic antibacterial surfaces are classified into three types based on the bacteria-killing mechanism: i) mechanotherapy, ii) chemotherapy, and iii) phototherapy. Finally, the limitations and challenges of current research are discussed and future perspectives in this promising area are proposed., (© 2023 Wiley-VCH GmbH.)

Introduction: Pathogen spectrum of Hand, foot and mouth disease (HFMD) has substantially changed in the past decade in China. Growing evidence has indicated that anti-COVID-19 nonpharmaceutical interventions (NPIs) can support control of various infectious diseases, including intestinal diseases., Methods: In this study, HFMD cases were enrolled from sentinel hospitals of Nanchang, Jiangxi province, and enteroviruses were genotyped using specific real time RT-PCR. We systematically characterized the epidemiology of HFMD based on the continuous molecular surveillance and estimated the impact of COVID-19 intervention on HFMD incidence using seasonal autoregressive integrated moving average (ARIMA) models., Results: A total of 10247 HFMD cases were included during 2010-2022, of which 6121 enterovirus (EV)-positive cases (59.7%) were identified by real-time RT-PCR. Over 80% cases were associated with EV-A71 and coxsackievirus A16 (CVA16) during 2010-2012, while the type distribution significantly changed as CVA6 emerged to be dominant, accounting for 22.6%-59.6% during 2013-2022. It was observed that the prevalence patterns of EV-A71 and CVA16 were similar and both of them peaked in the second quarter and then leveled off. However, CVA6 was generally prevalent around the fourth quarter, demonstrating a staggered prevalence during 2010-2019. During the COVID-19 epidemic, the seasonal HFMD epidemic peak was restrained, and the ARIMA analysis indicated that the COVID-19 intervention had mitigated EV transmission during the first COVID-19 outbreak in early 2020. In addition, bivariate Spearman's cross-correlation coefficients were estimated for the major types CVA6, CVA16 and EV-A71. Our analyses indicated the possible existence of correlations among CVA6, CVA16 and EV-A71 prevalence in the epidemiological level., Discussion: Taken together, the type distribution of HFMD has substantially changed over the last decade and CVA6 and CVA16 are currently the most predominant types co-circulating in Nanchang. The anti-COVID-19 NPIs significantly reduced the incidence of EV infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Qian, Zhu, Yi, Tu, Yang, Zhang, Zhang, Xia, Ni, Xu, He and Li.)

Lake sediment is a natural sink for polycyclic aromatic hydrocarbons (PAHs). PAH sedimentation characteristics and their impact factors of Chinese lakes have mainly been qualitative assessed. However, quantitative impacts of PAH sedimentation from different factors have not been well analyzed. To fill this gap, we screened PAH sedimentation records from the literature, for 51 lakes in China and other regions of the world, to identify historical concentration variation and the impact factors of PAHs in different regions, in lake sediment. The results show that PAH concentrations in the sediment core in the selected Chinese lakes (478 ± 812 ng/g dry weight (dw)) were significantly lower than those in North America (5518 ± 6572 ng/g dw) and Europe (3817 ± 4033 ng/g dw). From 1900 to 2015, most of the lakes in China showed an increasing trend of PAH sedimentation concentrations, with the lakes in Southeastern China showed a decreasing trend of PAH concentration in the period of 2001-2015, which was later than the peak times shown in Western countries (1941-1970). The 2-3-ring PAHs were the main components in the sediment core of Chinese lakes, but the proportion to the total PAHs decreased from 72% in 1900-1940 to 55% in 2001-2015. Generalized additive modeling (GAM) was adopted to simulate the associations between PAH sedimentation records and the impact factors. There are large regional variations of economic and industrial development in China. The impact factors of PAH accumulation in the lake sediments differ in different regions. However, population and the consumption of coal, pesticides, and fertilizer were identified to be the most important impact factors influencing PAH sedimentation. The Chinese government needs to strengthen control measures on pollutant discharge to reduce the anthropogenic impact of PAH sedimentation in lakes., 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 © 2023 Elsevier Inc. All rights reserved.)

One of the serious threats to global public health is the bacterial biofilm, which results in numerous persistent and recurrent infections. Herein, we proposed a near-infrared (NIR) light-triggered "nano-domino" system with "dispersing and killing" functionality for biofilm eradication. The nanoplatform was fabricated by the self-assembly of chitosan conjugated with L-arginine (L-Arg, a natural nitric oxide (NO) donor) and indocyanine green (ICG, a phototherapy agent). Using an NIR irradiation "trigger", a series of reactive oxygen species (ROS) including singlet oxygen ( 1 O 2 ), hydrogen peroxide (H 2 O 2 ), and superoxide anions (·O 2 - ), as well as heat were generated from ICG aggregates. Subsequently, 1 O 2 and H 2 O 2 catalyzed L-Arg to produce NO, which dispersed the biofilm and reacted with ·O 2 - to form peroxynitrite to kill bacteria with ROS collaboratively. Meanwhile, the generated heat increased the permeability of bacterial membranes, aggravating the damage to biofilm bacteria. The experiments on biofilm eradication demonstrated that this "nano-domino" system was capable to eradicate over 99.99% of biofilms formed by Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa under 5-min NIR irradiation. Notably, these integrated benefits allowed the system to promote the healing of MRSA biofilm-infected wounds in vivo with negligible toxicity. Overall, this reported NIR-triggered "nano-domino" system holds great promise for addressing the difficulties associated with bacterial biofilm eradication. STATEMENT OF SIGNIFICANCE: Novel agents for biofilm eradication are urgently needed due to the alarming rise in antimicrobial resistance to conventional antibiotics and the critical shortage of new drugs. In this study, we created a nano-domino system that uses near-infrared (NIR) light as a trigger to eradicate mature biofilms. In response to a short-term NIR irradiation, the proposed nanoplatform could generate nitric oxide and peroxynitrite to disperse the biofilm and kill the bacteria inside, respectively, leading to efficient eradication of Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa biofilms with minimal cytotoxicity. The findings, therefore, indicate that this nanoplatform with enhanced antibiofilm performance might provide a reliable and promising solution to biofilm-related problems., 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 © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)