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The ability to reliably detect enrofloxacin in animal-derived food products has important health implications. In the present study, a nanobody-horseradish peroxidase fusion specific for ENR was generated to enable a sensitive and rapid competitive ELISA suitable for detecting enrofloxacin in samples of milk and animal tissue. An enrofloxacin hapten generated via the glutaraldehyde method was initially used to immunize an adult Bactrian camel as a means of constructing a phage library. Enrofloxacin-specific nanobodies were then selected through three rounds of biopanning, and HRP-fused versions of these nanobodies were then expressed. Lastly, these nanobodies were used to develop a sensitive cELISA for enrofloxacin detection in milk and animal tissues, with the resultant assay exhibiting an IC 50 of 37.41 ng/mL and a linear detection range (IC 20 -IC 80 ) of 10.89 to 244.34 ng/mL. The limit of detection for this cELISA was 6.48 ng/mL, with 4.66 % cross-reactivity with ciprofloxacin, and recovery rates that ranged from84.99 % to 107.72 % together with an RSD below 10.70 %., 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.)

Invasive sandburs (Cenchrus spp.), tropical and subtropical plants, are preferred in grasslands and agricultural ecosystems worldwide, causing significant crop production losses and reducing native biodiversity. Integrating phylogenetic relatedness and potentially suitable habitats (PSHs) to identify areas at risk of invasion is critical for prioritizing management efforts and supporting decisions on early warning and surveillance for sandbur invasions. However, despite risk assessments for individual Cenchrus species, the combined analysis of suitable habitats and phylogenetic relationships remains unclear. Therefore, this study aims to assess the invasion risk regions-including PSHs, species richness (SR), and phylogenetic structure-of eight invasive and potentially invasive sandburs in China, to quantify their niche overlap and identify driving factors. Our results showed that the phylogenetic distance of potentially invasive sandburs was closely related to invasive sandburs. Especially, three potentially invasive sandburs, C. ciliaris, C. setigerus, and C. myosuroides, possessed invasion potential resulting from close phylogenetic relatedness and high climatic suitability compared with invasive sandburs. The PSHs for invasive sandburs were distributed in wider regions except northwest China and had higher suitability to different environmental conditions. Potentially invasive sandburs were primarily located in southwestern and southern China driven by precipitation, especially, being inspected in Guangdong, Hainan, and Yunnan on numerous occasions, or potentially introduced in Guangxi, Taiwan, and Fujian for sandburs invasion hotspots. The phylogenetic clustering for eight sandburs occurred in the eastern, center, and southern coastal China, where higher SR in distribution was correlated with invasion hotspots. The SR and phylogenetic relatedness metrics were related to temperature and topographic variables. Totally, the expansion and invasion risk could be increased toward higher latitudes under future global warming. These findings offer novel insights for the prevention and management of sandburs invasions., 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 genus Chrysanthemum has been widely used as both folk medicine and food in East Asia for thousands of years, serving as a significant source of nutritional and pharmacological value. According to the theory of traditional Chinese medicine, it clears heat and toxic materials and regulates liver function. Accumulating evidence has demonstrated that polysaccharides from the genus Chrysanthemum, especially Chrysanthemum morifolium, Chrysanthemum indicum, and Coreopsis tinctoria, are vital representative macromolecules with diverse biological activities, including antioxidant, immunomodulatory, anti-inflammatory, hypoglycemic, antitumor, and antiviral properties as well as the ability to regulate the gut microbiota. It is well-known that different extraction and purification methods may cause differences in the primary structures of chrysanthemum polysaccharides (CPs), which in turn lead to different polysaccharide biological activities. However, the lack of a review summarizing the recent advances in CPs may have hindered their development and utilization. The present review aims to review information on the extraction and purification, structural characterization, biological functions, toxicity, and applications of CPs. In addition, this review may deepen our understanding of CPs, and offers a theoretical basis for the further development of CPs into functional foods and therapeutic agents., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Reactive bromine species (RBS) such as bromine atom (Br • ) and dibromine radical (Br 2 •- ) are important oxidative species accounting for the transformation of organic compounds in bromide-containing water. This study developed quantitative structure-activity relationship (QSAR) models to predict second order rate constants (k) of RBS by machine learning (ML) and conducted knowledge transfer between RBS and reactive chlorine species (RCS, e.g., Cl • and Cl 2 •- ) to improve model performance. The ML-based models (RMSE test = 0.476 -0.712) outperformed the multiple linear regression-based models (RMSE test = 0.572 -3.68) for predicting k of RBS. In addition, the combination of molecular fingerprints (MFs) and quantum descriptors (QDs) as input features improved the performance of ML-based models (RMSE test = 0.476 -0.712) compared to those developed by MFs (RMSE test = 0.524 -0.834) or QDs (RMSE test = 0.572 -0.806) alone. E HOMO and E gap were identified to be the most important features affecting k of RBS based on SHAP analysis. A unified model integrating the datasets of four reactive halogen species (RHS, e.g., Br • , Br 2 •- , Cl • and Cl 2 •- ) was further developed (R 2 test = 0.802), which showed better predictive performance than the individual models (R 2 test = 0.521 -0.776). Meanwhile, the model performance changed differently by employing knowledge transfer among RHS, which was improved for Br • /Cl • , mixed for Br • /Br 2 •- and Cl • /Cl 2 •- , but worse for Br 2 •- /Cl 2 •- . This study provides useful tools for predicting k of RHS in aqueous 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.)

Background: PFAS pose a significant threat to cardiovascular health and increase the risk of atherosclerotic cardiovascular disease (ASCVD). However, there is limited research evidence regarding the mechanisms by which PFAS affect the risk of ASCVD and the exposure-risk (E-R) relationship. The effect of kidney function in the relationship between PFAS and ASCVD risk has not been adequately validated., Objective: This study aims to explore the mechanisms by which four PFAS (Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), Perfluorohexanesulfonic acid (PFHS), and Perfluorononanoic acid (PFNA)) affect the risk of ASCVD and to verify and discuss the mediating effect of kidney function in this impact., Methods: This study utilizes data from 14,607 participants in the NHANES 2005-2018 to conduct a cross-sectional study. Initially, Generalized Linear Model (GLM) and Restricted Cubic Splines models are used to assess the impact of four PFAS on ASCVD risk and the E-R relationship. Subsequently, the Weighted Quantile Sum regression (WQS) model is used to evaluate the relationship between mixed four PFAS exposure and ASCVD risk. Finally, Directed Acyclic Graphs (DAG) and causal mediation models are used to confirm and analyze whether the decline in kidney function mediates the impact of four PFAS on ASCVD risk., Results: The results from GLM and WQS models indicate that both singular and mixed four PFAS exposures are associated with an increased risk of ASCVD. The E-R curves between four PFAS singular and mixed exposures and ASCVD risk are all characterized by nonlinearity. The results from DAG and causal mediation models clearly indicate that the decline in kidney function plays a significant mediating role in the relationship between four PFAS and ASCVD risk., Conclusion: Exposure levels of four PFAS do not significantly increase the risk of ASCVD unless they reach a certain threshold, and the decline in kidney function exerts a significant mediating effect in the relationship between four PFAS exposure and ASCVD risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare early anatomic outcomes following treatment with faricimab vs. aflibercept in a pooled analysis of the head-to-head dosing phase of the TENAYA/LUCERNE trials in neovascular age-related macular degeneration (nAMD)., Design: TENAYA/LUCERNE (NCT03823287/NCT03823300) were identical, randomized, double-masked, active comparator-controlled phase 3 noninferiority trials., Participants: Aged ≥ 50 years with treatment-naïve nAMD., Methods: Patients were randomized (1:1) to intravitreal faricimab 6.0 mg up to every 16 weeks (Q16W) after 4 initial doses every 4 weeks (Q4W) or aflibercept 2.0 mg every 8 weeks (Q8W) after 3 initial doses given Q4W., Main Outcome Measures: Post hoc analyses comparing faricimab with aflibercept in terms of change in central subfield thickness (CST) from baseline and proportion of patients with an absence of subretinal (SRF) and intraretinal fluid (IRF) during initial 12-week head-to-head dosing phase, when both arms received 3 injections, and time to first absence of IRF and SRF., Results: 1329 patients were enrolled across TENAYA/LUCERNE (n = 665 faricimab; n = 664 aflibercept). There were greater (nominal P < 0.0001) reductions in adjusted mean CST from baseline with faricimab vs. aflibercept at weeks 4, 8, and 12, with comparable vision outcomes. At week 12, more patients (95% confidence interval) achieved an absence of SRF (87.9% [85.4%, 90.4%] vs. 79.0% [76.0%, 82.1%]) and both IRF and SRF (77.2% [74.0%, 80.4%] vs. 66.5% [62.9%, 70.0%]), but not IRF (88.4% [86.0%, 90.8%] vs. 85.0% [82.3%, 87.6%]), with faricimab vs. aflibercept, respectively. In patients with IRF and/or SRF at baseline (n = 581 faricimab; n = 591 aflibercept), the 75th percentile of time to first absence of IRF and SRF was reached at week 8 with faricimab and week 12 with aflibercept. At week 12, cumulative incidence of first-time absence of IRF and SRF was 85.5% (82.3%, 88.1%) with faricimab and 75.0% (71.3%, 78.3%) with aflibercept., Conclusions: Faricimab resulted in greater improvement in anatomic outcomes than aflibercept during the head-to-head dosing phase and a faster time to first absence of retinal fluid., (Copyright © 2024. Published by Elsevier Inc.)

We investigated the effect of individual, joint and fluctuating exposure to air pollution (PM 2.5 , BC, NO 3 - , NH 4 + , OM, SO 4 2- , PM 10 , NO 2 , SO 2 , O 3 ) on glucose metabolisms among prediabetes, and simultaneously explored the modifying effect of lifestyle. We conducted a longitudinal study among prediabetes during 2018-2022. Exposure windows within 60-days moving averages and their variabilities were calculated. FBG, insulin, HOMA-IR, HOMA-B, triglyceride glucose index (TyG), glucose insulin ratio (GI) and allostatic load of glucose homeostasis system (AL-GHS) was included. Linear mixed-effects model and BKMR were adopted to investigate the individual and overall effects, respectively. We also explored the preventive role of lifestyle. Individual air pollutant was associated with increased FBG, insulin, HOMA-IR, HOMA-B, TyG, and decreased GI. People with FBG ≥6.1 mmol/L were more susceptible. Air pollutants mixture were only associated with increased HOMA-B, and constituents have the highest group-PIP. Air pollutants variation also exert harmful effect. We observed similar diabetic effect on AL-GHS. Finally, the diabetic effect of air pollutants disappeared if participants adopt a favorable lifestyle. Our findings highlighted the importance of comprehensively assessing multiple air pollutants and their variations, focusing on metabolic health status in the early prevention of T2D, and adopting healthy lifestyle to mitigate such harmful effect., 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: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials., Design: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials., Participants: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes., Methods: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse., Main Outcome Measures: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses., Results: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (μm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 μm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average., Conclusions: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Percutaneous coronary intervention (PCI) can provide benefits for anatomically suitable left main coronary artery (LMCA) lesions. When compared to traditional coronary angiography (CAG) -guided PCI, the use of intravascular ultrasound (IVUS) guidance has shown significant long-term prognostic improvements in LMCA PCI. Optical coherence tomography (OCT) offers a higher axial resolution than IVUS. However, there is currently a lack of relevant randomized controlled trials investigating the use of OCT specifically for left main distal bifurcation lesions., Methods: The ISOLEDS trial is an ongoing multicenter study that aims to compare IVUS-guided PCI with OCT-guided PCI for patients with true LMCA distal bifurcation lesions. This prospective, randomized, controlled, non-inferiority trial will enroll a total of 664 patients with visually-defined Medina 1,1,1 or 0,1,1 classification of left main distal bifurcation lesions. The patients will be randomly assigned in a 1:1 ratio to either IVUS-guided or OCT-guided PCI. The primary endpoint is to assess the occurrence of target lesion failure (TLF) within 12 months after the procedure. After undergoing PCI, patients are required to visit the hospital for a 12-month clinical follow-up. During this clinical assessment, CAG can be performed to evaluate the status of target lesions., Discussion: The ISOLEDS trial represents the first attempt to compare two distinct intracoronary imaging techniques for guiding PCI in patients with true LMCA distal bifurcation lesions. By evaluating and comparing the outcomes of these two imaging techniques, the trial results will aid operators in selection of the most effective approach for guiding PCI in these patients., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

The livestock industry has long been a hotspot environment for antibiotic resistance genes, with smallholder farming still holding a significant position in pig farming. However, the microbial antibiotic resistance and pathogen risks in pigs under the smallholder farming model remain unclear. We systematically analyzed the antibiotic resistance and microbial composition of pig feces from smallholder and large-scale farming models in Sichuan. The results indicated a lower abundance of antibiotic resistance genes (ARGs) and similar microbial composition in smallholder farming compared to large-scale farming. Beneficial bacteria were more abundant in small-scale farming, whereas large-scale farming exhibited more ARGs, virulence genes, and human pathogenic bacteria (HPBs), including ESBL Escherichia coli strains closely related to human strains, indicating higher zoonotic risk. The findings suggest that smallholder farming presents a relatively better microbial composition and resistance profile, highlighting its advantages over large-scale farming in terms of pig and human health. It is noteworthy that a considerable proportion of HPBs carrying ARGs still exist in the feces from smallholder farming, and given the openness of fecal handling, there remains a high risk of transmitting ARGs and pathogens to humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Seaport infrastructure requires considerable resources and time for a full recovery from accidents caused by hazardous cargo. Despite their severity, the risk to seaport infrastructure from hazardous cargo operations has been insufficiently explored. This study aims to fill that gap by examining the risks to seaport infrastructure from the complex effects of hazardous cargo operations. It draws on literature, incident reports, and expert consultations to identify comprehensive risk factors and their interconnections. The study employs expert judgments alongside logistic regression to develop Conditional Probability Tables (CPTs) and conducts a risk analysis using Bayesian networks (BN). Our findings indicate that, under typical operating conditions, fire and explosion, corrosion, and improper handling are the most significant contributors to seaport infrastructure risk with probabilities of 8.73 %, 5.88 %, and 5.61 % respectively. Inverse propagation indicates that the contribution of improper handling and corrosion is enhanced by 153 % and 96 % respectively towards the increased risk. A sensitivity analysis was carried out to pinpoint critical risk factors. Based on these insights, the study suggests practical measures like the use of tracking and monitoring systems along with third-party audits for effective handling, augmented and virtual reality for advanced training, and automation technology for reduced human roles to subside risks to seaport infrastructure and promote uninterrupted operations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Treatment of triple-negative breast cancer (TNBC) poses significant challenges due to its propensity for metastasis. A key impediment lies in the suppressive immune microenvironment, which fosters tumor progression. This study introduces an approach employing a dual immune-stimulatory CD73 antibody-polymeric cytotoxic drug complex (αCD73-PLG-MMAE). This complex is designed for targeted eradication of TNBC while modulating tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. By enhancing antitumor immune responses, this strategy offers a highly effective means of treating TNBC and mitigating metastasis. The complex is synthesized by combining αCD73 with poly( L -glutamic acid) (PLG) grafted Fc binding peptides (Fc-III-4C) and Val-Cit-PAB-monomethyl auristatin E (MMAE), exploiting the affinity between αCD73 and Fc-III-4C. αCD73 selectively targets CD73 molecules on both tumor and immune suppressive cells, thereby inhibiting the adenosine pathway. Meanwhile, Val-Cit-PAB-MMAE, activated by cathepsin B, triggers selective release of MMAE, inducing ICD in tumor cells. In a 4T1 tumor model, αCD73-PLG-MMAE significantly enhances drug accumulation in tumors by 4.13-fold compared to IgG-PLG-MMAE, leading to suppression of tumor growth and metastasis. Furthermore, it synergistically augments the antitumor effects of αPD-1, resulting in a tumor inhibition rate of 92 % as compared to 21 % with αPD-1 alone. This study thus presents a pioneering therapeutic strategy for TNBC, emphasizing the potential of targeted immunomodulation in cancer treatment. STATEMENT OF SIGNIFICANCE: Antibody-drug conjugate (ADC) therapy holds promise for treating triple-negative breast cancer (TNBC). However, the current ADC, sacituzumab govitecan, fails to overcome the crucial role of adenosine in the suppressive immune microenvironment characteristic of this "cold tumor". Here, we present a dual immune-stimulatory complex, αCD73-PLG-MMAE, which targets TNBC specifically and modulates tumor immunity through mechanisms such as immunogenic cell death (ICD) and interference with the adenosine signaling pathway. Thus, it kills tumor cells with cytotoxic drugs, comprehensively regulates immunosuppression, and restores a durable immune response. This study proposes an antibody-polymeric drug complex with immunomodulatory and immunoagonist roles, offering new insights into TNBC treatment., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The clinical efficacy and safety between liver venous deprivation (LVD) and portal vein embolization (PVE) prior to major hepatectomy is still unclear., Methods: Studies comparing LVD and PVE were obtained by systemically searching PubMed, Embase, and Cochrane Library Central databases through 22 December 2023., Results: Ten studies including 588 patients were reviewed. Compared with PVE group, LVD group exhibited an increased liver resection rate (OR, 1.89; 95% CI, 1.13-3.15; P = 0.01), a faster KGR (MD, 1.37; 95% CI, 0.31-2.42; P = 0.01), and a shorter time to hepatectomy (MD, -6.66; 95% CI, -8.03 to -5.30; P < 0.0001). The pooled results showed that post-embolization complications (OR, 1.35; 95% CI, 0.66-2.74), overall postoperative complications (OR, 1.09; 95% CI, 0.68-1.75), severe complications (Clavien-Dindo ≥ III) (OR, 0.70; 95% CI, 0.43-1.14), and 90-day mortality (OR, 0.38; 95% CI, 0.13-1.09) were not significantly different in both groups. LVD group had significantly lower post-hepatectomy liver failure (PHLF) than PVE group (OR, 0.45; 95% CI, 0.22-0.91; P = 0.03)., Conclusion: LVD outperforms PVE regarding liver resection rate and future liver remnant (FLR) hypertrophy and shows comparable safety to PVE. In addition, LVD allowed for major hepatectomy with lower incidence of PHLF., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Cyclin-dependent kinase-like (CDKL) family proteins are serine/threonine protein kinases and is a specific branch of CMGC (including CDK, MAPK, GSK). Its name is due to the sequence similarity with CDK and it consists of 5 members. Their function in protein phosphorylation underpins their important role in cellular activities, including cell cycle, apoptosis, autophagy and microtubule dynamics. CDKL proteins have been demonstrated to regulate the length of primary cilium, which is a dynamic and diverse signaling hub and closely associated with multiple diseases. Furthermore, CDKL proteins have been shown to be involved in the development and progression of several diseases, including cancer, neurodegenerative diseases and kidney disease. In this review, we summarize the structural characteristics and discovered functions of CDKL proteins and their role in diseases, which might be helpful for the development of innovative therapeutic strategies for disease., Competing Interests: Declaration of competing interest All authors declare that the research was conducted in the absence of any commercial or financial relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lanthanide-doped upconversion nanoparticles (Ln-UCNPs) have been considered promising materials for various fields, such as biomedical and industrial applications. However, data and reports regarding its toxicity and environmental risks are scarce. Under these circumstances, data must be obtained to fully understand potential toxicity and adverse outcome pathways. In the present study, the toxicity of uncoated Ln-UCNP cores (NaYF 4 :Yb, Er) was systematically assessed in zebrafish embryos during early developmental stages. Ln-UCNPs were found to have multiple toxic effects, such as effects on survival rates, delayed hatching times, shorter body lengths, altered heart rates and blood circulation (significantly reduced), and neurobehavioral impairments in response to photoperiod stimulation. Bioimaging showed that Ln-UCNPs were distributed on the chorion, eyes, and skin at 72 hpf. However, it accumulates in the pharynx, esophagus, and intestine after oral administration. Ln-UCNPs disrupt the diversity and abundance of host-associated microorganisms (gut microbiota) leading to an increase in the prevalence of harmful bacteria in zebrafish. Transcriptomic and Ingenuity Pathway Analysis (IPA) predicted Interleukin-8 (IL-8) signaling, neuroinflammation, cardiac hypertrophy signaling pathways, immune and inflammation-related response interferon-gamma (ifnγ), and miR-155 as key mediators in regulatory effects. Based on this, a causal network was built showing the strong links between the induced gene expression of differentially expressed genes (DEGs), such as nitric oxide synthase 2 (nos2) and tumor necrosis factor (tnf) upon Ln-UCNPs treatment, and with the downstream adverse outcomes, in particular, the promotion of apoptosis, liver damage, and inflammatory response. Finally, RT-qPCR analysis confirmed the up-regulated expression of nos2 and tnf in the exposed larvae, consistent with the observation of an increased number of fluorescence-labelled neutrophils and macrophages in lyz: DsRed transgenic zebrafish until 120 hpf exposure, which together demonstrated the proinflammatory effects of Ln-UCNPs on organisms. In conclusion, we illustrated the developmental toxicity, disruption of gut-microbiome, and proinflammatory effects of Ln-UCNP cores on zebrafish, and the causal network from IPA analysis may help further elucidate the adverse outcome pathway of Ln-UCNPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Acinetobacter baumannii is currently one of the most important opportunistic pathogens causing severe nosocomial infections worldwide. Quorum Sensing (QS) system is a widespread mechanism in bacteria to coordinate group behavior by sensing the density of bacterial populations and affect eukaryotic host cell. In Acinetobacter baumannii, AbaI protein is used as QS molecule synthetase to synthesize N- acyl homoserine lactones (AHLs). Currently, QS has made great progress in the study of drug resistance, but there is still a lack of complete understanding of its damage to host cells after adhesion and invasion. Thus, in this study, we examined the effects of abaI mutant (ΔabaI) on the functions of adhesion and invasion, cell viability, inflammation, apoptosis in A. baumannii infected A549 cells, to evaluate the effects of ΔabaI in a zebrafish model. We found the group infected with ΔabaI increased cell viability, reduced adhesion and invasion, cell injury, inflammatory cytokine production and apoptosis. By RNA-Seq, we explored the possibility that abaI stimulated A549 cells inflammation by A. baumannii infection via TLR4/MAPK signaling pathway. In addition, the ΔabaI significantly reduced pathogenicity and recruitment to neutrophils in zebrafish. These observations suggest that abaI plays a major role in A. baumannii 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 B.V. All rights reserved.)

Neutropenia, a common side effect of chemotherapy for ovarian cancer, was observed in a 47-year-old female patient undergoing a six-cycle chemotherapy regimen. She experienced recurrent neutropenia and leukopenia but refused granulocyte colony-stimulating factor (G-CSF) due to severe bone pain and high costs. Moxibustion combined with guasha therapy (MGT) was administered each time neutropenia occurred. The treatment involved guasha therapy on the bladder meridian (BL) and the governor vessel (GV), followed by moxibustion at Zhongwan (CV 12), Guanyuan (CV 4), and Shenzhu (GV 12) points over 2-3 days. This approach led to the recovery of neutrophil and leukocyte counts, enabling the patient to complete six chemotherapy cycles without G-CSF. These findings suggest that MGT may enhance neutrophil and leukocyte counts in patients with chemotherapy-induced myelosuppression, presenting a potential alternative for those intolerant to G-CSF. However, further high-quality research is needed to confirm its efficacy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Psoriasis is an inflammatory skin disease with unclear pathogenesis and unmet therapeutic needs., Objective: To investigate the role of senescent CD4 + T cells in psoriatic lesion formation and explore the application of senolytics in treating psoriasis., Methods: We explored the expression levels of p16 INK4a and p21, classical markers of cellular senescence, in CD4 + T cells from human psoriatic lesions and imiquimod (IMQ)-induced psoriatic lesions. We prepared a senolytic gel using B-cell lymphoma 2 (BCL-2) inhibitor ABT-737 and evaluated its therapeutic efficacy in treating psoriasis., Results: Using multispectrum immunohistochemistry (mIHC) staining, we detected increased expression levels of p16 INK4a and p21 in CD4 + T cells from psoriatic lesions. After topical application of ABT-737 gel, significant alleviation of IMQ-induced psoriatic lesions was observed, with milder pathological alterations. Mechanistically, ABT-737 gel significantly decreased the percentage of senescent cells, expression of T cell receptor (TCR) α and β chains, and expression of Tet methylcytosine dioxygenase 2 (Tet2) in IMQ-induced psoriatic lesions, as determined by mIHC, high-throughput sequencing of the TCR repertoire, and RT-qPCR, respectively. Furthermore, the severity of psoriatic lesions in CD4 cre Tet2 f/f mice was milder than that in Tet2 f/f mice in the IMQ-induced psoriasis model., Conclusion: We revealed the roles of senescent CD4 + T cells in developing psoriasis and highlighted the therapeutic potential of topical ABT-737 gel in treating psoriasis through the elimination of senescent cells, modulation of the TCR αβ repertoire, and regulation of the TET2-Th17 cell pathway., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: Infantile hemangioma (IH) is a common vascular tumor in female infants, which can lead to aesthetic issues and facial scarring. This study aimed to investigate the inhibitory effects and underlying mechanisms of 755 nm long-pulsed alexandrite laser on IH., Methods: Hemangioma endothelial cells (HemECs) were exposed to 755 nm long-pulsed alexandrite laser to evaluate its impact on cell proliferation and apoptosis. A patient-derived xenograft model was established to assess the inhibitory effects of laser treatment on IH in vivo., Results: In vitro, 755 nm long-pulsed alexandrite laser effectively suppressed the proliferation of HemECs and induced cell apoptosis. Laser treatment significantly inhibited the volume and weight of tumors, accompanied by significant downregulation of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) expression levels in both hemangioma cells and tumors. Additionally, laser treatment resulted in the conversion of VEGFA 165a to VEGFA 165b . TUNEL staining demonstrated increased apoptosis in tumor cells after laser treatment, along with upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2., Conclusion: In addition to the principle of selective photothermal decomposition, modulation of the VEGF/PI3K/Akt axis may serve as a potential mechanism for IH treatment using a long pulse-width 755 nm laser. This sheds valuable light on the molecular mechanisms underlying IH pathogenesis and potential therapeutic targets while providing a theoretical basis for the safe and efficient management of proliferative IH using laser therapy., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Eucommia ulmoides Oliv. (tu-chung), as a famous nature medical and edible plant, has the effect of tonifying liver and kidney, strengthening the function of the muscles and bones, and miscarriage prevention. Accumulating evidence has demonstrated that the polysaccharides from Eucommia ulmoides Oliv. (EUPs) are a kind of vital and representative biologically active macromolecules and have various health-promoting biological activities in vivo and in vitro, such as antioxidant activity, immunomodulatory activity, hypolipidemic and hypoglycemic activities, anti-inflammatory activities, anti-tumor activity, and among others. The review aims to comprehensively and systematically collate the recent research progress on extraction and purification methods, structural characteristics, biological activities, mechanism of action, structural modification, and toxicity of EUPs to support their therapeutic potential and health-care functions. New valuable insights for future research with EUPs were also proposed in the areas of structural characterization and pharmacological activities to promoting the development of therapeutic agents and functional foods., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To investigate the therapeutic effect of toosendanin (TSN) against Eimeria tenella (E. tenella) in chicks. In this experiment, a chick model of artificially induced E. tenella infection was established. The anti-coccidial effect was investigated by treating different doses of TSN. A preliminary mechanism of action was conducted, using cecal cell apoptosis as a starting point. TSN at the concentration of 5 mg/kg BW showed the best effect against E. tenella with the ACI value of 164.35. In addition, TSN reduced pathological damage to cecal tissue, increased the secretion of glycogen and mucus in cecal mucosa, and enhanced the mucosal protective effect. It also elevated the levels of IFN-γ, IL-2, and IgG in serum, and raised the sIgA content in cecal tissue of infected chicks, thereby improving overall immune function. TSN was observed to promote the apoptosis of cecum tissue cells by TUNEL staining analysis. Immunohistochemistry analysis revealed that in TSN-treated groups, the expression of Caspase-3 and Bax was elevated, while the expression of Bcl-2 was reduced. TSN induced apoptosis in host cells by dose-dependently decreasing the Bcl-2/Bax ratio and upregulating Caspase-3 expression. In summary, TSN exhibited significant anticoccidial efficacy by facilitating apoptosis in host cecal cells, with the most pronounced effect observed at a dosage of 5 mg/kg body weight., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests, (Copyright © 2024. Published by Elsevier B.V.)

The total flavonoids of Desmodium styracifolium (TFDS) are flavonoid-rich extracts obtained from Desmodii Styracifolii Herba, which is approved for the treatment of urolithiasis in China. C-glycosylflavones including schaftoside, vicenin-1, vicenin-2, vicenin-3, and isovitexin are the main active constituents. In this study, the plasma protein binding of these compounds was determined for the first time in rat and human plasma by rapid equilibrium dialysis combined with HPLC-MS/MS method. The developed method was validated in terms of specificity, linearity, accuracy, precision, extraction effect, matrix effect, and stability. Schaftoside, vicenin-1, vicenin-2, and vicenin-3 exhibited moderate plasma protein binding, ranging from 56.6% to 61.5% in rat plasma and 55.0%-62.9% in human plasma. In comparison, isovitexin demonstrated a higher plasma protein binding in the range of 92.3-93.1% and 95.1-96.2% in rat and human plasma, respectively. Furthermore, the potential interactions mediated via plasma protein binding between isovitexin and nonsteroidal anti-inflammatory drugs (NSAIDs) were investigated by rapid equilibrium dialysis. No significant changes were observed, indicating a lower likelihood of interaction between TFDS and NSAIDs due to plasma protein binding in the treatment of urinary system disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Overt hepatic encephalopathy remains a serious complication after TIPS. Concomitant SPSS is associated with an increased risk of HE in patients treated with TIPS., Purpose: To perform a systematic review and meta-analysis on the effectiveness and safety of the prophylactic embolization of SPSS at the time of TIPS creation., Materials and Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to April 2023 to identify studies on the association between antegrade embolized SPSS before TIPS placement and the incidence of post-TIPS HE. Odds ratios (ORs) and their corresponding 95% CIs were used to identify significant differences in the outcomes., Results: Four studies enrolling 1243 patients with cirrhosis who received TIPS for variceal bleeding were included. A meta-analysis revealed that TIPS without simultaneous SPSS embolization was associated with an increased risk of overt HE (OR 2.41, 95% CI 1.32-4.38; p = 0.004). The risks of mortality (0.79, 95% CI 0.58-1.07; p = 0.13), variceal rebleeding (0.94, 95% CI 0.66-1.34; p = 0.74) and shunt dysfunction (1.40, 95% CI 0.51-3.83; p = 0.51) did not significantly differ among the groups., Conclusion: SPSS prevalence was associated with an increased risk of overt HE after TIPS. Concurrent antegrade SPSS embolization during TIPS creation reduced the risk for overt HE without increasing other complications., Competing Interests: Conflict of interest None., (Copyright © 2023. Published by Elsevier Ltd.)

This study employs a combination of bibliometric and epidemiological methodologies to investigate the relationship between metal exposure and glucose homeostasis. The bibliometric analysis quantitatively assessed this field, focusing on study design, predominant metals, analytical techniques, and citation trends. Furthermore, we analyzed cross-sectional data from Beijing, examining the associations between 14 blood metals and 6 glucose homeostasis markers using generalized linear models (GLM). Key metals were identified using LASSO-PIPs criteria, and Bayesian kernel machine regression (BKMR) was applied to assess metal mixtures, introducing an "Overall Positive/Negative Effect" concept for deeper analysis. Our findings reveal an increasing research interest, particularly in selenium, zinc, cadmium, lead, and manganese. Urine (27.6%), serum (19.0%), and whole blood (19.0%) were the primary sample types, with cross-sectional studies (49.5%) as the dominant design. Epidemiologically, significant associations were found between 9 metals-cobalt, copper, lithium, manganese, nickel, lead, selenium, vanadium, zinc-and glucose homeostasis. Notably, positive-metal mixtures exhibited a significant overall positive effect on insulin levels, and notable interactions involving nickel were identified. These finding not only map the knowledge landscape of research in this domain but also introduces a novel perspective on the analysis strategies for metal mixtures., 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.)

Gut microbiota is a complex microbial community with the ability of maintaining intestinal health. Intestinal homeostasis largely depends on the mucosal immune system to defense external pathogens and promote tissue repair. In recent years, growing evidence revealed the importance of gut microbiota in shaping intestinal mucosal immunity. Therefore, according to the existing findings, this review first provided an overview of intestinal mucosal immune system before summarizing the regulatory roles of gut microbiota in intestinal innate and adaptive immunity. Specifically, this review delved into the gut microbial interactions with the cells such as intestinal epithelial cells (IECs), macrophages, dendritic cells (DCs), neutrophils, and innate lymphoid cells (ILCs) in innate immunity, and T and B lymphocytes in adaptive immunity. Furthermore, this review discussed the main effects of gut microbiota dysbiosis in intestinal diseases and offered future research prospects. The review highlighted the key regulatory roles of gut microbiota in intestinal mucosal immunity via various host-microbe interactions, providing valuable references for the development of microbial therapy in intestinal diseases., Competing Interests: Declaration of competing interest All the authors claimed that there was no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Prostate cancer patients with visceral metastases often exhibited poor prognoses. Few researches had compared the prognostic impact and gene expression profiles among distinct visceral metastatic sites. Therefore, we conducted a comprehensive study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database and the Gene Expression Omnibus database., Patients and Methods: We analyzed the prostate cancer-specific mortality (PCSM) risk for 8,170 patients diagnosed with metastatic prostate cancer (mPCa) between 2000 and 2019, utilizing data from the SEER 17 registry database. Patients with metastatic disease in nonregional lymph nodes, bones, brains, livers, and lungs were identified. Competing risks regression was employed to evaluate the effect of visceral metastatic disease sites on PCSM. Differentially expressed genes (DEGs) between visceral metastases were assessed using data from the GSE6752 dataset. A relative protein-protein interaction (PPI) network was constructed based on STRING analysis. Furthermore, we explored the distribution of DEGs in various normal tissues and tumor tissues using the Human Protein Atlas and GEPIA., Results: Competing risks regression analysis revealed that liver and lung metastases had a substantial impact on PCSM (hazard ratio 2.24, 95% confidence interval 1.70-2.95, P < 0.001; hazard ratio 1.30, 95% confidence interval 1.06-1.59, P = 0.012, respectively). Seven significant DEGs were identified from samples of liver and lung metastases (HERV-FRD, NUDT12, FAM63A, SCGB3A1, CEACAM6, LOC440416, SFTPB) and were associated with respiratory gaseous exchange, pulmonary surfactant metabolism, and fibronectin matrix formation in PPI network analysis. Notably, the expression levels of the three DEGs significantly upregulated in lung metastases were also found to be higher in normal lung tissues compared to normal liver tissues., Conclusion: Patients diagnosed with mPCa and presenting with liver and/or lung metastases exhibit poorer prognoses. SCGB3A1, identified as a tumor suppressor gene, may contribute to the better survival prognosis observed in patients with prostate cancer lung metastases compared to those with liver metastases. The gene expression profiles in these two specific metastatic sites reveal a combination of both heterogeneity and homogeneity., Competing Interests: Declaration of competing interest The authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Network pharmacology is an interdisciplinary field that utilizes computer science, technology, and biological networks to investigate the intricate interplay among compounds/ingredients, targets, and diseases. Within the realm of traditional Chinese medicine (TCM), network pharmacology serves as a scientific approach to elucidate the compatibility relationships and underlying mechanisms of action in TCM formulas. It facilitates the identification of potential active ingredients within these formulas, providing a comprehensive understanding of their holistic and systematic nature, which aligns with the holistic principles inherent in TCM theory. TCM formulas exhibit complexity due to their multi-component characteristic, involving diverse targets and pathways. Consequently, investigating their material basis and mechanisms becomes challenging. Network pharmacology has emerged as a valuable approach in TCM formula research, leveraging its holistic and systematic advantages. The manuscript aims to provide an overview of the application of network pharmacology in studying TCM formula compatibility rules and explore future research directions. Specifically, we focus on how network pharmacology aids in interpreting TCM pharmacological theories and understanding formula compositions. Additionally, we elucidate the process of utilizing network pharmacology to identify active ingredients within TCM formulas. These findings not only offer novel research models and perspectives for integrating network pharmacology with TCM theory but also present new methodologies for investigating TCM formula compatibility. All in all, network pharmacology has become an indispensable and crucial tool in advancing TCM formula research., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

The oral bioavailability of poorly soluble drugs has always been the focus of pharmaceutical researchers. We innovatively combined nanocrystal technology and solid dispersion technology to prepare novel nanocrystalline solid dispersions (NCSDs), which enable both the solidification and redispersion of nanocrystals, offering a promising new pathway for oral delivery of insoluble Chinese medicine ingredients. The rubusoside (Rub) was first used as the multifunctional stabilizer of novel apigenin nanocrystal-based solid dispersions (AP-NSD), improving the in vitro solubilization rate of the insoluble drug apigenin(AP). AP-NSD has been produced using a combination of homogenisation and spray-drying technology. The effects of stabilizer type and concentration on AP nanosuspensions (AP-NS) particles, span, and zeta potential were studied. And the effects of different types of protective agents on the yield and redispersibility of AP-NSD were also studied. Furthermore, AP-NSD was characterized by infrared spectroscopy (IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Solubility was used to assess the in vitro dissolution of AP-NSD relative to APIs and amorphous solid dispersions (AP-ASD), and AP-ASD was prepared by the solvent method. The results showed that 20% Rub stabilized AP-NSD exhibited high drug-loading and good redispersibility and stability, and higher in vitro dissolution rate, which may be related to the presence of Rub on surface of drug. Therefore provides a natural and safe option for the development of formulations for insoluble drugs., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interests., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Background: Allopurinol, a xanthine inhibitor that lowers uric acid concentration, has been proven to reduce inflammation and oxidative stress in patients with cardiovascular disease. However, it is unknown whether these beneficial effects translate into favorable plaque modification in acute coronary syndromes (ACS). This study aimed to investigate whether allopurinol could improve coronary plaque stabilization using coronary computed tomography angiography (CCTA)., Methods: This was a prospective, single-center, randomized, double-blind clinical trial began in March 2019. A total of 162 ACS patients aged 18-80 years with a blood level of high-sensitivity C-reactive protein (hsCRP) ​> ​2 ​mg/L were included. The subjects were randomly assigned in a 1:1 ratio to receive either allopurinol sustained-release capsules (at a dose of 0.25 ​g once daily) or placebo for 12 months. The plaque analysis was performed at CCTA. The primary efficacy endpoint was the change in low-attenuation plaque volume (LAPV) from baseline to the 12-month follow-up., Results: Among 162 patients, 54 in allopurinol group and 51 in placebo group completed the study. The median follow-up duration was 14 months in both groups. Compared with placebo, allopurinol therapy did not significantly alter LAPV (-13.4 ​± ​3.7 ​% vs. -17.8 ​± ​3.6 ​%, p ​= ​0.390), intermediate attenuation plaque volume (-16.1 ​± ​3.0 ​% vs. -16.2 ​± ​2.9 ​%, p ​= ​0.992), dense calcified plaque volume (12.2 ​± ​13.7 ​% vs. 9.7 ​± ​13.0 ​%, p ​= ​0.894), total atheroma volume (-15.2 ​± ​3.2 ​% vs. -16.4 ​± ​3.1 ​%, p ​= ​0.785), remodeling index (2.0 ​± ​3.9 ​% vs. 5.4 ​± ​3.8 ​%, p ​= ​0.536) or hsCRP levels (-73.6 [-91.6-17.9] % vs. -81.2 [-95.4-47.7] %, p ​= ​0.286)., Conclusions: Our findings suggest that allopurinol does not improve atherosclerotic plaque stability or inflammation in ACS., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Ponazuril, a novel antiprotozoal drug in the class of triazine, has shown a promising application on apicomplexan infections in poultry and livestock. However, the effect and mechanism of action of ponazuril against Eimeria tenella (E. tenella) are unclear. The efficacy against E. tenella was initially studied by administering different doses of ponazuril in drinking water. The treated stage and site of ponazuril on E. tenella were observed through ultrastructural and histopathological analyses. Chicks were orally treated with a dose of 15 mg/kg body weight of ponazuril at different endogenous stages of E. tenella post-infection. According to the clinical study, the values of anticoccidial indices (ACI) were 157.0, 162.3, 196.9, 194.5, and 190.9, respectively, when the ponazuril was administered in drinking water at doses of 5, 10, 20, 40, and 50 mg/L for two consecutive days after infection. Among them, the 20 mg/L ponazuril group showed the best anticoccidial effect, which was superior to that of the toltrazuril treatment group, with an ACI value of 191.7. Histological analysis indicated that ponazuril effectively relieved cecal lesions, and decreased the number of merozoites. Transmission electron micrographs (TEM) observed that merozoites became irregular in shape, and some apparent protrusions of the outer membrane were presented especially the second-generation merozoites. Additionally, abnormalities in the development of WFBI and WFBII in the macrogametocyte were observed, which may affect the formation of the ovule wall. Moreover, merozoites in the treated group showed uneven and marginalized chromatin and mitochondrial swelling. These results suggested ponazuril is a potential anticoccidial drug, providing information on the mechanism of anticoccidial effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Aging is a key risk factor in cognitive diseases. Recently, metal exposures were found associated with both biological aging and cognitive function. Here, we aim to evaluate the associations of blood metals with cognitive function and the mediated effect of biological aging. Fourteen metals were detected and biological age was calculated through Klemera and Doubal method among 514 adults in Beijing, China. The generalized linear models indicated that the copper (Cu), molybdenum (Mo), and strontium (Sr) were positively associated with biological aging [β Cu (95% CI): 12.76 (9.26, 16.27); β Mo (95% CI): 1.50 (0.15, 2.85)], and β Sr (95% CI): 1.86 (0.68, 3.03)], while vanadium (V) was inversely related to biological aging [β V (95% CI): -0.76 (-1.48, -0.05)]. Subsequently, Cu, lead (Pb), selenium (Se), and biological aging were associated with cognitive function and further mediation analyses confirmed that biological aging partially mediated (33.98%, P = 0.019) the association of Cu and cognitive function. Additionally, we constructed a lifestyle index that implied the modifiable healthy lifestyle could slow aging to attenuate the detrimental effect of metals on cognition. Our findings provide insights into the potential pathways linking multiple metals exposure to aging and cognition and underscore the importance of adopting healthy lifestyles., 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 B.V. All rights reserved.)

Background: The progression of colorectal cancer (CRC) has been linked to metabolism alteration. Because insulin resistance (IR) is the basic mechanism of metabolism alteration, IR related indicators are considered to be associated with prognostic of CRC. In this study, we compared the prognostic values of common IR related indicators for CRC and selected the best one. Moreover, we explored the association between that indicator and CRC prognosis and possible interactive covariates., Methods: Medical records of patients with CRC (n = 1765) were retrieved from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. We compared the prognostic values of IR related indicators and select the best one using concordance index (C-index) and area under curve (AUC). Using Cox proportional hazard regression models, we evaluated the association between that indicator and CRC prognosis. Interaction tests were performed to evaluate possible interactions among covariates and the IR related indicator., Results: Results of C-index and AUC indicated that the ratio of low-density lipoprotein-to-high-density lipoprotein (LHR) showed the highest ability to predict the prognosis of patients with CRC. LHR independently predicted CRC prognosis [hazard ratio (HR) = 1.14; 95 % confidence interval (CI) = 1.05-1.22; P = 0.001]. The interactions between LHR, and age (<65 vs. ≥65; P for interaction = 0.001) or neutrocyte-to-lymphocyte ratio (NLR) (<3 vs. ≥3; P for interaction = 0.055) were also observed., Conclusion: LHR was found to be the best IR related indicators to predict prognosis of CRC, and it was negatively correlated with the prognosis of patients with CRC. NLR and aging might interact with LHR., 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.)

Indigo (IND) and indirubin (INB) have demonstrated a synergistic effect in treating ulcerative colitis at a ratio of 7.5:1. However, the colon mucus layer, a critical physiological barrier against external threats, is also a biological barrier, limiting the potential for effective drug delivery to the lamina propria for regulating inflammatory cells. Inspired by the potential of Hyaluronic acid (HA), to enhance cellular uptake by inflammatory cells, and Pluronic® F127 (F127), known for overcoming the mucus barrier, this study innovatively developed INB/IND nanosuspensions by co-modifying with F127 and HA. Moreover, inulin serves a dual purpose as a spray protective agent and a regulator of intestinal flora. Therefore, it was incorporated into INB/IND nanosuspensions for subsequent spray drying, resulting in the preparation of INB/IND nanocrystals (INB/IND-NC). The mucus penetration of INB/IND-NC was 24.30 times that of the control group. Besides, INB/IND-NC exhibited enhanced cellular uptake properties proximately twice that of Raw INB/IND. Importantly, INB/IND-NC exhibited improved therapeutic efficacy in DSS-induced mice by regulating the expression of cytokines, regulating immune responses via downregulating the expression of macrophages, neutrophils, and dendritic cells and maintaining intestinal flora homeostasis. Our study provides a new perspective for applying natural products for treating inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background & Aims: Myosteatosis, excess muscle fat infiltration, is a novel prognostic factor in cancer patients. To define myosteatosis, skeletal muscle radiodensity (SMD) is most commonly used, while intramuscular adipose tissue (IMAT) is newly introduced. We aimed to compare SMD-defined and IMAT-defined myosteatosis for predicting overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) and to explore whether patients with both low SMD and high IMAT had a shorter OS than patients with low SMD or high IMAT alone., Methods: We consecutively and prospectively recruited adult patients with stage IIIB or IV NSCLC at a teaching hospital. The mean SMD of all skeletal muscle areas and the area of IMAT on the unenhanced chest computed tomography (CT) images at the 12th thoracic vertebral level were segmented using Mimics version 21.0. Myosteatosis was defined by either low SMD (SMD-defined myosteatosis) or high IMAT (IMAT-defined myosteatosis). The optimal cutoffs for low SMD and high IMAT were also determined using the maximally selected rank statistics method. We calculated hazard ratios (HRs) and the corresponding confidence intervals (CIs) to evaluate the associations of OS with low SMD, high IMAT, and a combination of them., Results: We included 565 patients (345 men and 220 women; mean age 58.5 ± 9.0 years). Lower IMAT exhibited a tendency toward a favorable prognosis in men (p = 0.0015) and women (p < 0.0001); whereas higher SMD tended to have a favorable prognosis in men (p = 0.0006) and women (p < 0.0001). At baseline, 423 (74.9 %) participants had high IMAT, 432 (76.5 %) participants had low SMD and 370 (65.5 %) participants had both high IMAT and low SMD. Compared to those without either high IMAT or low SMD, the participants with either high IMAT or low SMD had a shorter OS, while the participants with both High IMAT and Low SMD had the shortest OS (log-rank p < 0.0001). After adjustment for the same confounders, high IMAT (HR, 1.44; 95 % CI, 1.10-1.87) and low SMD (HR, 1.92; 95 % CI, 1.36-2.43) were separately associated with poor prognosis. Moreover, the combination of high IMAT and low SMD indicated a higher risk of poor prognosis (HR, 2.43; 95 % CI, 1.62-3.66)., Conclusions: Both SMD-defined and IMAT-defined myosteatosis are highly prevalent in patients with advanced NSCLC and may serve as independent prognostic factors for OS. The diagnosis of myosteatosis might consider a combination of low SMD and high IMAT because this would help identify patients at a higher risk of mortality., Competing Interests: Conflicts of interest All authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: Choosing the optimal sarcopenia screening tool for a specific clinical scenario is challenging. We aimed to summarize all validated sarcopenia screening tools with diagnostic accuracy tested in one or more study populations., Design: Scoping review., Setting and Participants: Hospitals, nursing homes, communities, or health checkups., Methods: We systematically searched 3 databases in April 2022: MEDLINE, EMBASE, and CENTRAL. Two review authors independently performed the study selection and data extraction. The included tools' contents, characteristics, and number of citations were summarized and visualized., Results: We summarized 102 diagnostic accuracy studies involving 53 screening tools, classified into 7 groups: questionnaires (n = 13); serum biomarkers (n = 10); formulas, algorithms, and models (n = 9); physical ability tests (n = 9); integration tools (n = 7); anthropometric indices (n = 3); and ultrasound or bioimpedance analysis (n = 2). The most commonly used questionnaire was SARC-F (770 citations), followed by SARC-CalF (254 citations) and MSRA-7 (61 citations). Handgrip strength and Ishii score were the most widely used physical performance tests (331 citations) and formulas (294 citations), respectively. Sarcopenia index (based on serum cystatin C and creatinine) and calf circumference were the most commonly used serum biomarkers (123 citations) and anthropometric indexes (127 citations), respectively. Ultrasound was the most commonly used imaging tool for screening sarcopenia (57 citations). The included tools varied significantly in content. Various tools assessed some or all components of sarcopenia with different methods, and others assessed different domains, such as age, body mass index, falls, diet, and even mental health. We also summarized the screening tools that were validated in different clinical settings (hospitals, communities, nursing homes, and health checkups)., Conclusions and Implications: More than 50 validated tools are currently available for screening sarcopenia in different clinical settings. The results of this review may help clinicians and researchers in selecting optimal tools for sarcopenia in different clinical scenarios and in developing future tools., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Lung cancer has the highest mortality and morbidity rates among all cancers worldwide. Despite many complex treatment options, including radiotherapy, chemotherapy, targeted drugs, immunotherapy, and combinations of these treatments, efficacy is low in cases of resistance to therapy, metastasis, and advanced disease, contributing to low overall survival. There is a pressing need for the discovery of novel biomarkers and therapeutic targets for the early diagnosis of lung cancer and to determine the efficacy and outcomes of drug treatments. There is now substantial evidence for the diagnostic and prognostic value of long noncoding RNAs (lncRNAs). This review briefly discusses recent findings on the roles and mechanisms of action of lncRNAs in the responses to therapy in non-small cell lung cancer., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The heterogeneous morphologic and functional expression of hypertrophic obstructive cardiomyopathy (HOCM) is evidenced by established imaging, multimodality imaging is essential for a comprehensive assessment but may remain uncertain. This study aimed to develop a patient-specific hemodynamics assessment with cardiac computed tomography angiography (CCTA) based computational fluid dynamics (CFD) and prove its usability in cohorts of HOCM patients., Methods: A retrospective study was performed on eight HOCM patients with septal myectomy who had both preoperative and postoperative CCTA as well as transthoracic echocardiography (TTE). The three-dimensional models were reconstructed from CCTA data, following which patient-specific CFD simulations were performed to estimate the blood velocity, pressure gradient, and wall shear stress. The simulation output was compared with TTE. Based on CFD simulations, retrospective and blinded virtual myectomy was also performed, to predict the minimum resected volume for improving obstruction in patients., Result: The complex HOCM anatomy was successfully reconstructed for all 8 patients. The CFD simulation accurately assessed the pressure gradient, flow velocity. There was a good correlation between the peak pressure gradient measured by CFD and TTE in the pre- and post-operative assessments (r = 0.87 and 0.84, respectively), and the flow velocity (r = 0.87 and 0.90, respectively). The volumes of minimal resection myocardium predicted by CFD and virtual myectomy were consistent with the actual resection volumes., Conclusion: CCTA-based CFD for HOCM patients may play a unique role in the assessment of patient-specific morphology and hemodynamics. Combination with virtual myectomy might allow for optimizing therapy planning in septal myectomy., Clinical Perspective: CFD based CCTA may emerge as a complement to established imaging strategies, with accurate three-dimensional reconstruction and hemodynamic simulation of the left ventricle in this retrospective study. Combined with virtual myectomy, CFD simulation might allow for predicting the volume of resected myocardium for septal myectomy. Moving forward, this technology may be used by clinicians to better assess the conditions of HOCM patients, and guide the extent and depth of resection during septal myectomy. Therefore, further prospective clinical evaluation is clearly warranted., 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 B.V. All rights reserved.)

This study aimed to investigate the thyroid disrupting effects of multiple metals exposure with comprehensive investigation from the thyroid parenchyma to hormonal function. In this prospective cohort study of in-service staff of the Baoding Power Supply, we found that arsenic was negatively associated with total thyroxine (TT4) [β As = -0.075, 95% confidence interval (CI): -0.129, -0.020, P adj = 0.04]. Similarly, selenium was negatively correlated with TT4 (β Se = -0.134, 95% CI: -0.211, -0.058, P adj < 0.01) and peripheral deiodinase activity (GT) (β Se = -0.133, 95% CI: -0.210, -0.056, P adj = 0.01). With respect to strontium, there were positive associations of strontium with thyroid-stimulating hormone (β Sr = 0.263, 95% CI: 0.112, 0.414, P adj = 0.01), and negative associations of strontium with TT4 (β Sr = -0.099, 95% CI: -0.150, -0.048, P adj < 0.01) and GT (β Sr = -0.102, 95% CI: -0.153, -0.050, P adj < 0.01). We also observed negative associations of metal mixtures with TT4 and GT and potential interactions. Increased risks of thyroid nodule associated with aluminum, cobalt and nickel were also observed. Our findings suggest that multiple metals exposure leads to a multi-pronged assault to thyroid from the thyroid parenchyma to hormonal function. Future large-scale prospective cohort studies of general population and experimental studies were warranted., 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 B.V. All rights reserved.)

Aims: This study aimed to elucidate the role of Interleukin-11 (IL-11) in hepatic fibrosis (HF) and its potential as a therapeutic target for HF treatment., Materials and Methods: We investigated IL-11 expression in patients with varying degrees of liver injury through ELISA and immunohistochemistry. A CCl 4 -induced HF mouse model was constructed to study IL-11 expression and cell apoptosis using Western blotting (WB) and other techniques. The expression of IL-11 was silenced using rAAV8 in the mouse model. In vitro stimulation of hepatic stellate cells (LX-2) with TGF-β1, and of LO-2 cells with exogenous IL-11, were performed. Cell supernatants of TGF-β1-stimulated LX-2 were used to culture LO-2 cells, with apoptosis monitored via flow cytometry and WB., Key Findings: Increased IL-11 levels were observed in patients and the HF mouse model, with silencing reducing IL-11 expression. In vitro experiments revealed increased endogenous IL-11 in TGF-β1-stimulated LX-2 cells and an increase in apoptotic index, IL11RA, and gp130 in IL-11-stimulated LO-2 cells. Cell apoptosis was reduced in the siRNA/IL11, siRNA/IL11RA, and anti-IL11 groups. WB and immunohistochemistry results showed upregulated p-JNK, p-ERK, and p-P53 expressions in the CCl 4 -induced HF mouse model and IL-11-treated LO-2 cells., Significance: Our findings suggest IL-11 enhances LX-2 cell activation and proliferation, and promotes LO-2 cell apoptosis through JNK/ERK signaling pathways. This suggests that targeting IL-11 secretion may serve as a potential therapeutic strategy for HF, providing a foundation for its clinical application in HF treatment., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Etiology of hepatic steatosis and metabolic dysfunction-associated fatty liver disease (MAFLD) among acute coronary syndrome (ACS) remains unclear. Existing studies suggested the potential role of per- and polyfluoroalkyl substances (PFAS) in comorbidity of hepatic steatosis among ACS patients. Therefore, we conducted a cross-sectional study based on the ACS inpatients to assess the associations of plasma PFAS congeners and mixtures with hepatic steatosis and MAFLD. This study included 546 newly diagnosed ACS patients. Twelve PFAS were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry. Hepatic steatosis was defined by hepatic steatosis index (HSI). MAFLD was defined as the combination of hepatic steatosis based on the risk factor calculation with metabolic abnormalities. Generalized linear model was used to examine the associations of PFAS congeners with HSI and MAFLD. Adaptive elastic net (AENET) was further used for PFAS congeners selection. Mixture effects were also assessed with Bayesian kernel machine regression model (BKMR). Congeners analysis observed significant greater percent change of HSI for each doubling in PFOS (1.82%, 95% CI: 0.87%, 2.77%), PFHxS (1.17%, 95% CI: 0.46%, 1.89%) and total PFAS (1.84%, 95% CI: 0.56%, 3.14%). Moreover, each doubling in PFOS (OR=1.42, 95% CI: 1.13, 1.81), PFHxS (OR=1.31, 95% CI: 1.09, 1.59) and total PFAS (OR=1.43, 95% CI: 1.06, 1.94) was associated with increased risk of MAFLD. In AENET regression, only PFOS presented significant positive associations with HSI. Mixture analysis indicated significant positive associations between PFAS mixtures and HSI. This is the first study to demonstrate associations of PFAS congeners and mixtures with hepatic steatosis and MAFLD among ACS patients, which provides hypothesis into the mechanisms behind comorbidity of hepatic steatosis among ACS patients, as well as tertiary prevention of ACS., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Systemic inflammation is a key pathogenic criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Although cancer is commonly considered as a chronic inflammation-related disease, the inflammatory burden may vary depending on the type and stage of cancer. Therefore, a more precise definition of inflammation criteria could facilitate the identification of malnutrition in cancer., Methods: This prospective multicenter study included 1683 cancer patients screened via NRS2002 for malnutrition risk. The inflammatory burden index (IBI), C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and albumin (ALB) level were used to assess the inflammatory burden. Kaplan-Meier and Cox regression analyses were used to determine the relationship between the GLIM criteria and overall survival. Harrell's concordance index (C-index) was used to compare the discriminative performance of the original, IBI-based, CRP-based, NLR-based, and ALB-based GLIM criteria for survival. Logistic regression models were used to assess the association between GLIM criteria and short-term outcomes, length of hospital stay, and hospitalization costs., Results: Compared to the original GLIM criteria, the IBI/CRP/NLR/ALB-based GLIM criteria better predicted the long-term outcomes of patients with cancer (chi-square: 1.316 vs. 78.321 vs. 74.740 vs. 88.719 vs. 100.921). The C-index revealed that the inflammation marker-based GLIM criteria showed significantly better prognostic accuracy than the original GLIM criteria. The ALB-based GLIM criteria exhibited the best prognostic accuracy. The inflammation marker-based GLIM criteria were independent predictive factors for the long-term prognosis of cancer. Patients with malnutrition had a 45% higher risk of adverse long-term prognoses than those without malnutrition. The inflammation marker-based GLIM criteria had good prognostic ability to predict outcomes at 3, 6, and 12 months. The stepwise effect of the grading of severity via the IBI-based GLIM criteria and CRP-based GLIM criteria was notable. The inflammation marker-based GLIM criteria are useful for predicting short-term outcomes, length of hospitalization, and hospitalization costs., Conclusion: The inflammation marker-based GLIM criteria have a stronger predictive value than the original GLIM criteria in evaluating both the short- and long-term prognoses of cancer patients. It is recommended to use the inflammation marker-based GLIM criteria for nutritional evaluation of cancer patients., Competing Interests: Conflicts of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Phytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD 50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1., Competing Interests: Declaration of Competing Interest There are no conflicts of interest declared by the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tumor metastasis causes over 90% of cancer related death and no currently available therapies target it. However, there is limited understanding regarding the epigenetic regulation of genes during this complex process. Here by integrating single-cell ATAC-seq (scATAC-seq), single-cell RNA-seq (scRNA-seq), microarray, bulk RNA-seq, immunohistochemistry (IHC) staining, as well as proteomics datasets from paired primary and liver metastatic colorectal cancer (CRC) patient-derived xenograft (PDX) model and patients, we discovered that liver metastatic CRC cells lose their colon-specific chromatin accessible sites yet gain liver-specific ones. Importantly, we observed elevated accessibility of HNF4A, a liver-specific transcription factor, in liver metastatic CRC cells. Subsequently, we performed clustering analysis of liver metastatic CRC cells together with cells involved in liver development, revealing significant heterogeneity among the liver metastatic CRC cells. Over 50% of the liver metastatic CRC cells exhibited characteristics similar to those of erythroid progenitors and hepatocytes, showing increased expression of genes involved in oxidative phosphorylation and glycolysis. Moreover, our discovery further revealed that the MHC and IFN response genes in these cells exhibit moderate epigenetic activity, which is significantly associated with the low objective response rates in checkpoint blockade immunotherapy. Our findings uncovered the critical roles of HNF4A and the cell populations within liver metastatic CRC cells might serve as crucial therapeutic targets for addressing liver metastasis and improving the immunotherapy response in patients with CRC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bisphenol AF (BPAF) is an emerging endocrine-disrupting chemical (EDC) prevalent in the environment as one of the main substitutes for bisphenol A. Sex-specific effects of EDCs have been commonly reported and closely linked to sexually dimorphic patterns of hormone metabolism and related gene expression during different exposure windows, but our understanding of these mechanisms is still limited. Here, following 28-day exposure of adult zebrafish to an environmentally relevant concentration of BPAF at 10 μg/L, the global transcriptional networks applying RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) were respectively investigated in the male and female fish liver, connecting the sex-dependent toxicity of the long-term exposure of BPAF to molecular responses. As a result, more differentially expressed genes (DEGs) were detected in males (811) than in females (195), and spermatogenesis was the most enriched Gene Ontology (GO) functional classification in males, while circadian regulation of gene expression was the most enriched GO term in females. The expression levels of selected DEGs were routinely verified using qRT-PCR, which showed consistent alterations with the transcriptional changes in RNA-seq data. The causal network analysis by IPA suggested that the adverse outcomes of BPAF in males including liver damage, apoptosis, inflammation of organ, and liver carcinoma, associated with the regulation of several key DEGs detected in RNA-seq, could be linked to the activation of upstream regulatory molecules ifnα, yap1, and ptger2; while, the inhibition of upstream regulators hif1α, ifng, and igf1, leading to the down-regulated expression of several key DEGs, might be involved in BPAF's effects in females. Furthermore, BPAF exposure altered hepatic histological structure and inhibited antioxidant capability in both male and female livers. Overall, this study revealed different regulation networks involved in the sex-dependent effects of BPAF on the fish liver, and these detected DEGs upon BPAF exposure might be used as potential biomarkers for further assessing sex-specific hepatotoxicity following environmental EDC exposure., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Owing to volatility and poor water solubility, the medical application of Chimonanthus nitens Oliv. essential oil (CEO) in the fields of medicine was strictly limited. To tackle this problem, a novel CEO loaded rambutan-liked Pickering emulsion (CEO-RPE) with a spiky surface was effectively designed by coating with carboxymethyl cellulose sodium modified cellulose nanocrystals (CCN) as stabilizer. The effect of CCN concentration on the formation and stabilization of CEO-RPE was investigated. The results showed that CEO-RPE stabilized by 1 % CCN had a smaller droplet size and exhibited a rambutan-liked surface, and was stabilized against concentrated salt and high pH condition due to the steric barrier of CCN that covered in the droplet surface. Subsequently, the antibacterial performance of CEO-RPE was investigated against E. coli, S. aureus, P. aeruginosa, and S. pneumoniae by determining the minimum inhibitory concentration (MIC). The results showed that the CEO-RPE exhibited higher antibacterial activity compared to CEO, which could be attributed to its effective adhesion to the cell membrane of bacteria. In addition, the results of anti-inflammatory experiments showed that CEO-RPE also exhibited strong anti-inflammatory effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Therefore, the CCN stabilized rambutan-liked Pickering emulsion seemed to be a promising strategy to increase the antibacterial and anti-inflammatory activity of CEO., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) recently released the first international consensus on the diagnostic criteria for sarcopenic obesity (SO), which recommended skeletal muscle mass adjusted for body weight (SMM/W) to determine low muscle mass. SMM adjusted for body mass index (SMM/BMI) appeared to be better associated with physical performance than SMM/W. Thus, we modified the ESPEN/EASO criteria by using SMM/BMI. We aimed (1) to evaluate the agreement of the ESPEN/EASO-defined SO (SO ESPEN ) and the modified ESPEN/EASO-defined SO (SO ESPEN-M ) with other commonly used SO definitions, and (2) to compare different SO definitions for predicting mortality in a prospective cohort with advanced non-small cell lung cancer (NSCLC)., Methods: This prospective study included patients with advanced NSCLC. We defined SO according to five different diagnostic criteria: SO ESPEN , SO ESPEN-M , Asian Working Group for Sarcopenia (AWGS)-determined sarcopenia with BMI-determined obesity (SO AWGS ), computed tomography-derived sarcopenia with BMI-determined obesity (SO CT ), and fat mass to fat-free mass ratio >0.8 (SO FM ). The outcome was all-cause mortality., Results: Of the 639 participants (mean age 58.6 years, 229 women) we studied, 488 (76.4%) died during the median follow-up period of 25 months. SMM/BMI was significantly lower in the death group than in the survivor group (men: p = 0.001, women: p < 0.001), but SMM/W was not. Only 3 (0.47%) participants met all five SO diagnostic criteria. SO ESPEN showed an excellent agreement with SO ESPEN-M (Cohen's kappa = 0.896), a moderate agreement with SO AWGS (Cohen's kappa = 0.415), but poor agreements with SO CT and SO FM (Cohen's kappa = 0.078 and 0.092, respectively). After full adjustment for potential confounders, SO ESPEN (HR 1.54, 95% CI 1.26-1.89), SO ESPEN-M (HR 1.56, 95% CI 1.26-1.92), and SO AWGS (HR 1.43, 95% CI 1.14-1.78) were significantly associated with mortality. However, SO CT (HR 1.17, 95% CI 0.87-1.58) and SO FM (HR 1.15, 95% CI 0.90-1.46) showed no significant association with mortality., Conclusions: SO ESPEN showed an excellent agreement with SO ESPEN-M , a moderate agreement with SO AWGS , but poor agreements with SO CT and SO FM . SO ESPEN , SO ESPEN-M , and SO AWGS were independent prognostic factors for mortality in our study population, but SO CT and SO FM were not. Although SMM/BMI was better associated with survival than SMM/W, SO ESPEN-M did not show an advantage in predicting survival over SO ESPEN., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF- κ B) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)