ANKRD1 aggravates renal ischaemia‒reperfusion injury via promoting TRIM25-mediated ubiquitination of ACSL3.

BACKGROUND: Renal ischaemia‒reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI). To date, effective therapies for delaying renal IRI and postponing patient survival remain absent. Ankyrin repeat domain 1 (ANKRD1) has been implicated in some pathophysiologic processes, but its role in renal IRI has not been explored. METHODS: The mouse model of IRI-AKI and in vitro model were utilised to investigate the role of ANKRD1. Immunoprecipitation-mass spectrometry was performed to identify potential ANKRD1-interacting proteins. Protein‒protein interactions and protein ubiquitination were examined using immunoprecipitation and proximity ligation assay and immunoblotting, respectively. Cell viability, damage and lipid peroxidation were evaluated using biochemical and cellular techniques. RESULTS: First, we unveiled that ANKRD1 were significantly elevated in renal IRI models. Global knockdown of ANKRD1 in all cell types of mouse kidney by recombinant adeno-associated virus (rAAV9)-mitigated ischaemia/reperfusion-induced renal damage and failure. Silencing ANKRD1 enhanced cell viability and alleviated cell damage in human renal proximal tubule cells exposed to hypoxia reoxygenation or hydrogen peroxide, while ANKRD1 overexpression had the opposite effect. Second, we discovered that ANKRD1's detrimental function during renal IRI involves promoting lipid peroxidation and ferroptosis by directly binding to and decreasing levels of acyl-coenzyme A synthetase long-chain family member 3 (ACSL3), a key protein in lipid metabolism. Furthermore, attenuating ACSL3 in vivo through pharmaceutical approach and in vitro via RNA interference mitigated the anti-ferroptotic effect of ANKRD1 knockdown. Finally, we showed ANKRD1 facilitated post-translational degradation of ACSL3 by modulating E3 ligase tripartite motif containing 25 (TRIM25) to catalyse K63-linked ubiquitination of ACSL3, thereby amplifying lipid peroxidation and ferroptosis, exacerbating renal injury. CONCLUSIONS: Our study revealed a previously unknown function of ANKRD1 in renal IRI. By driving ACSL3 ubiquitination and degradation, ANKRD1 aggravates ferroptosis and ultimately exacerbates IRI-AKI, underlining ANKRD1's potential as a therapeutic target for kidney IRI. KEY POINTS/HIGHLIGHTS: Ankyrin repeat domain 1 (ANKRD1) is rapidly activated in renal ischaemia‒reperfusion injury (IRI) models in vivo and in vitro. ANKRD1 knockdown mitigates kidney damage and preserves renal function. Ferroptosis contributes to the deteriorating function of ANKRD1 in renal IRI. ANKRD1 promotes acyl-coenzyme A synthetase long-chain family member 3 (ACSL3) degradation via the ubiquitin‒proteasome pathway. The E3 ligase tripartite motif containing 25 (TRIM25) is responsible for ANKRD1-mediated ubiquitination of ACSL3.

Sex-specific in the association between depressive symptoms and risk of cognitive impairment in Chinese older adults.

BACKGROUND: Many studies have focused on the relationship between depressive symptoms and cognitive impairment, but gender differences in this relationship are unclear, especially among Chinese older adults. Therefore, this study explores whether there are gender differences between depressive symptoms and risk of cognitive impairment based on a survey of a Chinese older adult population. STUDY DESIGN: This is a cross-sectional study. METHOD: We screened 9678 older adults aged 65 to 105 from the 2018 CLHLS database. The 10-item Center for Epidemiological Studies Depression Scale (CESD-10) and Mini-Mental State Examination (MMSE) were utilized for measuring depressive symptoms and cognitive performance, respectively. Logistic regressions and restricted cubic spline were applied to investigate the relationship between depressive symptoms and cognitive impairment. RESULTS: Of the 9678 participants, 4719 (48.8 %) were men. The association between severe depressive symptoms and cognitive impairment was more pronounced in older men (male × severe depressive symptoms: OR = 2.71, 95%CI = 1.07-6.92, p = 0.037). Compared with no depressive symptoms, severe depressive symptoms were associated with an almost five times greater risk of cognitive impairment in men (OR = 4.84, 95 % CI = 2.26-10.40, p < 0.001, compared to OR = 2.25, 95 % CI = 1.27-3.96, p = 0.005 in women). Gender differences were demonstrated in the association of individual ten depressive symptoms with cognitive impairment: men who felt lonely were more likely to have cognitive impairment (OR = 1.24, 95 % CI = 1.06-1.47, p = 0.010), while women who slept poorly were more likely to have cognitive impairment (OR = 1.42, 95 % CI = 1.16-1.74, p = 0.001). CONCLUSION: Results indicate a stronger association between severe depressive symptoms and cognitive impairment among older Chinese males. Our study suggests that reducing loneliness can help prevent cognitive impairment in older men, and improving sleep quality can help improve cognitive function in older women.

Patterned Ultraslippery Surfaces of Stainless Steel Prepared by Femtosecond Laser Ablation for Directional Manipulation of Liquid Droplets.

Slippery liquid-infused porous surfaces (SLIPS) have promising applications in chip laboratories, nanofriction power generation, and microfluidics due to their excellent properties such as good hydrophobicity and low adhesion. However, the self-driven stability of conventionally lubricated surfaces is not high, and the velocity of liquid droplets is difficult to regulate. This greatly limits the potential applications of SLIPS. A strategy is offered to prepare microporous structures of SLIPS directly on a stainless-steel substrate using femtosecond laser processing technology as the main means to realize exhibiting smoothness to liquids. At the same time, the principle of bionics is utilized, the porous structure of SLIPS is combined with the groove structure of rice leaves, or porous structures are combined with the wedge structure of shorebird beak to prepare the three-dimensional structure of SLIPS. Droplets exhibit significant individual anisotropy on three-dimensional (3D) SLIPS of leaf-like groove stripe structure in rice, enabling the precise control of droplet motion direction. When droplets are transported in wedge-shaped SLIPS with an asymmetric structure, the wedge edge can limit the direction of droplet motion while squeezing the droplet to generate Laplace pressure gradient, which achieves continuous self-driven transport of droplets. In addition, based on the above two processing strategies, an information transfer device is designed: the splicing of the self-driven transport surface with anisotropic topological channels enables the differential drive for liquid transport, which provides the conditions for the information transfer of the droplets. This strategy not only is simple and efficient but also provides new ideas for the effective development of multifunctional SLIPS as well as lab-on-a-chip and microfluidic domains.

Optical Tweezers Assembled Nanodiamond Quantum Sensors.

Here we show that gradient force optical tweezers can be used to mediate the self-assembly of nanodiamonds into superstructures, which can serve as optically trapped nanoscale quantum probes with superior magnetic resonance sensing capabilities. Enhanced fluorescence rates from nitrogen-vacancy NV- defect centers enable rapid acquisition of optically detected magnetic resonance (ODMR), and shape-induced forces can improve both positioning accuracy and orientation control. The use of confocal imaging can isolate the signal from individual nanodiamonds within the assembly, thereby retaining the desirable properties of a single crystal probe. The improvements afforded by the use nanodiamond assemblies has the potential to resolve dynamic changes through, for example, real-time monitoring of the ODMR contrast.

Dynamic changes in carbohydrate components and the bacterial community during the ensiling of wilted and unwilted sweet sorghum.

Sweet sorghum can be used to produce a substantial quantity of biofuel due to its high biological yield and high carbohydrate content. In this study, we investigated the dynamic changes in fermentation characteristics, carbohydrate components, and the bacterial community during the ensiling of wilted and unwilted sweet sorghum. The results revealed a rapid fermentation pattern and high-quality fermentation quality in wilted and unwilted sweet sorghum, wherein lactic acid, and acetic acid accumulated and stabilized during the initial 9 days of ensiling, with the pH values less than 4.2, until 60 days of ensiling. We found that the ensiling of sweet sorghum involved the degradation (5% ~ 10%) of neutral detergent fiber (NDF) and hemicellulose and that the degradation of NDF fit a first-order exponential decay model. A shift in dominance from Lactococcus to Lactobacillus occurred before the first 9 days of ensiling, and the abundance of Lactobacillus (r = -0.68, p < 0.001) was negatively correlated with the NDF content. The relative abundances of Lactobacillus in wilted and unwilted sweet sorghum after ensiling for 60 days were 76.30 and 93.49%, respectively, and relatively high fermentation quality was obtained. In summary, ensiling is proposed as a biological pretreatment for sweet sorghum for subsequent biofuel production, and unlike other materials, sweet sorghum quickly achieves good fermentation quality and has great potential for bioresource production.

Experiences and needs of family members following sudden cardiac death: A meta-synthesis.

OBJECTIVE: This meta-synthesis of qualitative studies aimed to explore the experiences and needs of family members of victims of sudden cardiac death. DESIGN: A meta-synthesis was conducted. DATA SOURCES: Five databases (PubMed, CINAHL, EMBASE, Web of Science, and China National Knowledge Infrastructure) were searched from establishment to May 2024. From initial searches with essential keywords (sudden cardiac death, family members, and qualitative studies), 3021 articles were retrieved. There were eight studies in the meta-synthesis, selected on the basis of inclusion and exclusion criteria. REVIEW METHODS: We evaluated the quality of the included studies using the Critical Appraisal Skills Programme-Qualitative Research Checklist. RESULTS: Eight studies from six countries reported on the experiences and needs of family members who had lost someone to sudden cardiac death, and five analytical themes were synthesized: negative emotional reaction, finding cause of death, rebuilding life, meaning reconstruction and need for support. These experiences and needs fuse with each other and are relevant to the health and future of the family members. CONCLUSION: Negative emotional reaction is a necessary process for family members dealing with sudden cardiac death, and rebuilding life is a challenge that family members must face. In the process of family members rebuilding normal life, finding the cause of death is the foundation, and meaning reconstruction is the core. Many of the needs faced by these family members are not well met, and policymakers and bereavement teams should provide comprehensive and personalized interventions for them.

The impact of donor diabetes on recipient postoperative complications, renal function, and survival rate in deceased donor kidney transplantation: a single-center analysis.

As the global incidence of diabetes rises and diagnoses among younger patients increase, transplant centers worldwide are encountering more organ donors with diabetes. This study examined 80 donors and 160 recipients, including 30 donors with diabetes (DD) and their 60 recipients (DDR). The control group comprised 50 non-diabetic donors (ND) and 100 recipients (NDR). We analyzed clinical, biochemical, and pathological data for both diabetic and control groups, using logistic regression to identify risk factors for delayed graft function (DGF) after kidney transplantation. Results showed that pre-procurement blood urea nitrogen levels were significantly higher in DD [18.20 ± 10.63 vs. 10.86 ± 6.92, p = 0.002] compared to ND. Renal pathological damage in DD was notably more severe, likely contributing to the higher DGF incidence in DDR compared to NDR. Although DDR had poorer renal function during the first three months post-transplant, both groups showed similar renal function thereafter. No significant differences were observed in 1-year or 3-year mortality rates or graft failure rates between DDR and NDR. Notably, according to the Renal Pathology Society (RPS) grading system, kidneys from diabetic donors with a grade > IIb are associated with significantly lower postoperative survival rates. Recipient gender [OR: 5.452 (1.330-22.353), p = 0.013] and pre-transplant PRA positivity [OR: 34.879 (7.698-158.030), p < 0.001] were identified as independent predictors of DGF in DDR. In conclusion, transplant centers may consider utilizing kidneys from diabetic donors, provided they are evaluated pathologically, without adversely impacting recipient survival and graft failure rates.

APOL6 predicts immunotherapy efficacy of bladder cancer by ferroptosis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are rapidly evolving in the management of bladder cancer (BLCA). Nevertheless, effective biomarkers for predicting immunotherapeutic outcomes in BLCA are still insufficient. Ferroptosis, a form of immunogenic cell death, has been found to enhance patient sensitivity to ICIs. However, the underlying mechanisms of ferroptosis in promoting immunotherapy efficacy in BLCA remain obscure. METHODS: Our analysis of The Cancer Genome Atlas (TCGA) mRNA data using single sample Gene Set Enrichment Analysis (ssGSEA) revealed two immunologically distinct subtypes. Based on these subtypes and various other public cohorts, we identified Apolipoprotein L6 (APOL6) as a biomarker predicting the efficacy of ICIs and explored its immunological correlation and predictive value for treatment. Furthermore, the role of APOL6 in promoting ferroptosis and its mechanism in regulating this process were experimentally validated. RESULTS: The results indicate that APOL6 has significant immunological relevance and is indicative of immunologically hot tumors in BLCA and many other cancers. APOL6, interacting with acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), mediates immunotherapy efficacy by ferroptosis. Additionally, APOL6 is regulated by signal transducer and activator of transcription 1 (STAT1). CONCLUSIONS: To conclude, our findings indicate APOL6 has potential as a predictive biomarker for immunotherapy treatment success estimation and reveal the STAT1/APOL6/GPX4 axis as a critical regulatory mechanism in BLCA.

Alternating electric fields transform the intricate network of tumour vasculature into orderly parallel capillaries and enhance the anti-angiogenesis effect of bevacizumab.

The search for effective strategies to target tumour angiogenesis remains a critical goal of cancer research. We present a pioneering approach using alternating electric fields to inhibit tumour angiogenesis and enhance the therapeutic efficacy of bevacizumab. Chicken chorioallantoic membrane, cell viability and in vitro endothelial tube formation assays revealed that electric fields with a frequency of 1000 kHz and an electric intensity of 0.6 V/cm inhibited the growth of vascular endothelial cells and suppressed tumour-induced angiogenesis. In an animal U87MG glioma model, 1000 kHz electric fields inhibited tumour angiogenesis and suppressed tumour growth. As demonstrated by 3D vessel analysis, tumour vasculature in the control group was a stout, interwoven network. However, electric fields transformed it into slim, parallel capillaries that were strictly perpendicular to the electric field direction. This architectural transformation was accompanied by apoptosis of vascular endothelial cells and a notable reduction in tumour vessel number. Additionally, we found that the anti-angiogenesis and tumour-suppression effects of electric fields synergised with bevacizumab. The anti-angiogenic mechanisms of electric fields include disrupting spindle formation during endothelial cell division and downregulating environmental angiogenesis-related cytokines, such as interleukin-6, CXCL-1, 2, 3, 5 and 8, and matrix metalloproteinases. In summary, our findings demonstrate the potential of alternating electric fields (AEFs) as a therapeutic modality to impede angiogenesis and restrain cancer growth.

Targeting MDM2-p53 interaction in Glioblastoma: Transcriptomic analysis and Peptide-Based inhibition strategy.

MDM2 is a gene that encodes a protein involved in cell survival, growth, and DNA repair. It has been implicated in the development and progression of glioblastoma (GBM). Inhibition of the MDM2-p53 interaction has emerged as a promising strategy for treating GBM. In this study, we performed comprehensive transcriptomic expression analysis from diverse datasets and observed MDM2 overexpression in a subset of GBM cases. MDM2 negatively regulates the major onco-suppressor p53. The interaction between MDM2 and p53 is a promising target for cancer therapy, as it can trigger p53-mediated cell death in response to different stress conditions, such as oncogene activation or DNA damage. In this study, we have identified a peptide-based inhibition of MDM2 as a therapeutic strategy for GBM. We have further validated the stability of the MDM2-peptide interaction using a molecular structural dynamics approach. The major trajectories, including root mean square of deviation (RMSD), root mean square of fluctuation (RMSF), and radius of gyration (RoG), indicate that the candidate peptides have a more stable binding compared to the native ligand and control drug. The stability of the binding interaction was further estimated by MMGBSA analysis, which also suggests that MDM2 has a stable binding with both peptide molecules. Based on these results, peptides P-1843 and P-3837 could be tested further for experimental validation to confirm their targeted inhibition of MDM-2. This approach could provide a highly selective and efficient inhibitor with potentially fewer side effects and less toxicity compared to small drug-based molecules.

Application progress of latent class growth models in dynamic prevention and control strategies for acquired immunodeficiency syndrome. / æ½œåˆ†ç±»å¢žé•¿æ¨¡åž‹åœ¨èŽ·å¾—æ€§å ç–«ç¼ºé™·ç»¼åˆå¾åŠ¨æ€é˜²æŽ§ç­–ç•¥ä¸­çš„åº”ç”¨è¿›å±•.

The prevention and control requirements for HIV/AIDS vary significantly among different populations, posing substantial challenges to the formulation and implementation of intervention strategies. Dynamically assessing the heterogeneity and disease progression trajectories of various groups is crucial. Latent class growth model (LCGM) serves as a statistical approach that fits a longitudinal data into N subgroups of individual development trajectories, identifying and analyzing the progression paths of different subgroups, thereby offering a novel perspective for disease control strategies. LCGM has shown significant advantages in the application of HIV/AIDS prevention and control, especially in gaining a deeper understanding and analysis of epidemiological characteristics, risk behaviors, psychological research, heterogeneity in testing, and dynamic changes. Summarizing the advantages and limitations of applying LCGM can provide a reliable basis for precise prevention and control of HIV/AIDS.

The Synergistic Effect of Graphene Oxide in Epoxy Resin on Photocured Coating Films with Anticorrosion and Antibacterial Properties.

In this work, graphene oxide (GO) and epoxy-functionalized graphene oxide (GOSi) are chosen as additives and incorporated into epoxy resin (EP) for nanocomposite photo-coating films (GO/EP and GOSi/EP series). Compared to GO/EP, the GOSi/EP nanocomposite demonstrates strong binding and excellent dispersibility, highlighting covalent bonding between GOSi and the epoxy coating. Furthermore, GOSi/EP-based films demonstrated superior thermal stability and adhesion performance on galvanized steel plates. The corrosion performance of the coated galvanized steel is investigated using electrochemical impedance spectroscopy (EIS) and polarization curve analysis (Tafel). The effectiveness of corrosion protection is evaluated based on a combination of photoreactivity, crosslinking density, dispersity, and adhesion properties. Out of all the treated films, the film based on 0.1GOSi/EP exhibited the highest percentage of inhibition (98.89%) and demonstrated superior long-term anticorrosion stability. In addition, the 0.1GOSi/EP based formulation showed remarkable antibacterial activity against S. aureus, resulting in a 92% reduction. This work demonstrates the development of a facile, environmentally friendly functionalized graphene oxide/epoxy photocured film with superior dual functionalities in both anticorrosion and antibacterial properties. These advancements hold promising potential for impactful practical applications.

The Efficacy and Safety of Complementary and Alternative Medicine for Depression: An Umbrella Review.

OBJECTIVE: Depression is a major public health problem. Many complementary and alternative medicine (CAM) interventions have been suggested as potential treatments. METHODS: We comprehensively searched for relevant systematic reviews and meta-analyses in the PubMed, EMBASE, Web of Science, and Cochrane Library databases. We assessed effectiveness based on efficiency and changes in Depression Assessment Scale scores and safety based on adverse events. RESULTS: This umbrella review included twenty-two eligible articles. Yueju antidepressant and Electro-acupuncture (EA) improved depression symptoms better than antidepressants. In addition, omega-3 fatty acids (n-3PUFAs), exercise, manual acupuncture (MA), Hypericum mono-preparations, relaxation, and Vitamin D showed better efficacy than placebo and control. GPD as adjunctive therapies have higher efficacy rates than antidepressant, and MA and Yueju antidepressants have a better safety profile than antidepressants. CONCLUSION: Our study demonstrated that 10 CAMs can effectively improve the condition of patients with clinical depression.

Genomic profiling of a multi-lineage and multi-passage patient-derived xenograft biobank reflects heterogeneity of ovarian cancer.

Ovarian cancer (OC) manifests as a complex disease characterized by inter- and intra-patient heterogeneity. Despite enhanced biological and genetic insights, OC remains a recalcitrant malignancy with minimal survival improvement. Based on multi-site sampling and a multi-lineage patient-derived xenograft (PDX) establishment strategy, we present herein the establishment of a comprehensive PDX biobank from histologically and molecularly heterogeneous OC patients. Comprehensive profiling of matched PDX and patient samples demonstrates that PDXs closely recapitulate parental tumors. By leveraging multi-lineage models, we reveal that the previously reported genomic disparities of PDX could be mainly attributed to intra-patient spatial heterogeneity instead of substantial model-independent genomic evolution. Moreover, DNA damage response pathway inhibitor (DDRi) screening uncovers heterogeneous responses across models. Prolonged iterative drug exposure recapitulates acquired drug resistance in initially sensitive models. Meanwhile, interrogation of induced drug-resistant (IDR) models reveals that suppressed interferon (IFN) response and activated Wnt/ß-catenin signaling contribute to acquired DDRi drug resistance.

VlMYB4 and VlCDF3 co-targeted the VlLOG11 promoter to regulate fruit setting in grape (Vitis vinifera L).

KEY MESSAGE: The VlLOG11 mediates the cytokinin signaling pathway to regulate grape fruit setting. Fruit set, as an accepted agronomic trait, is inextricably linked with fruit quality and yield. Previous studies have demonstrated that exogenous treatment with the synthetic cytokinin analog, forchlorfenuron (CPPU), significantly enhances fruit set. In this study, a significant reduction in endogenous cytokinins was found by measuring the content of cytokinins in young grape berries after CPPU treatment. LONELY GUYs (VlLOGs), a key cytokinin-activating enzyme working in the biosynthesis pathway of cytokinins, exhibited differential expression. Some differentially expressed VlLOGs genes were presented by RNA seq data and their functions and regulation patterns were further investigated. The results showed that VlLOG11 was differentially expressed in young grape berries after CPPU treatment. Overexpression of VlLOG11 in tomato increases the amount of fruit set, and upregulated the expression of genes associated with cytokinin signaling including SlHK4, SlHK5, SlHP3, SlHP4, SlPHP1, SlPHP2. VlMYB4 and VlCDF3 could regulate the expression of VlLOG11 by directly binding to its promoter in young grape berries during fruit set. These results strongly demonstrated that VlMYB4/VlCDF3-VlLOG11 regulatory module plays a key role in the process of fruit setting in grape. This provided a basis for the molecular mechanism of VlLOG11-mediated cytokinin biosynthesis in young grape fruit set.

Research progress on the role of mitochondria in the process of hepatic ischemia-reperfusion injury.

During liver ischemia-reperfusion injury, existing mechanisms involved oxidative stress, calcium overload, and the activation of inflammatory responses involve mitochondrial injury. Mitochondrial autophagy, a process that maintains the normal physiological activity of mitochondria, promotes cellular metabolism, improves cellular function, and facilitates organelle renewal. Mitochondrial autophagy is involved in oxidative stress and apoptosis, of which the PINK1-Parkin pathway is a major regulatory pathway, and the deletion of PINK1 and Parkin increases mitochondrial damage, reactive oxygen species production, and inflammatory response, playing an important role in mitochondrial quality regulation. In addition, proper mitochondrial permeability translational cycle regulation can help maintain mitochondrial stability and mitigate hepatocyte death during ischemia-reperfusion injury. This mechanism is also closely related to oxidative stress, calcium overload, and the aforementioned autophagy pathway, all of which leads to the augmentation of the mitochondrial membrane permeability transition pore opening and cause apoptosis. Moreover, the release of mitochondrial DNA (mtDNA) due to oxidative stress further aggravates mitochondrial function impairment. Mitochondrial fission and fusion are non-negligible processes required to maintain the dynamic renewal of mitochondria and are essential to the dynamic stability of these organelles. The Bcl-2 protein family also plays an important regulatory role in the mitochondrial apoptosis signaling pathway. A series of complex mechanisms work together to cause hepatic ischemia-reperfusion injury (HIRI). This article reviews the role of mitochondria in HIRI, hoping to provide new therapeutic clues for alleviating HIRI in clinical practice.

Preparation of high-affinity and high-specificity monoclonal antibody and development of ultra-sensitive immunoassay for the detection of 1-aminohydantoin, the metabolite of nitrofurantoin.

1-Aminohydantoin (AHD), the residual marker of nitrofurantoin, is usually detected after derivatisation using the derivatisation reagent 2-nitrobenzaldehyde. Avoiding the antibody recognition of the derivatisation reagent is essential for the accurate detection of AHD residues. In this paper, a novel hapten called hapten D was designed, and then, a monoclonal antibody that did not recognise 2-nitrobenzaldehyde was prepared based on this novel hapten. An ultra-sensitive indirect competitive enzyme linked-immunosorbent assay (icELISA) was established under optimal conditions. The 50% inhibition concentration and limit of detection of AHD were 0.056 and 0.0060 ng/mL, respectively, which improved the sensitivity by 9-37-fold compared with the previously reported icELISA methods. The average recovery rates were 88.1%-97.3%, and the coefficient of variation was <8.6%. The accuracy and reliability of the icELISA were verified using liquid chromatography-tandem mass spectrometry. These results demonstrated that the developed icELISA is a useful and reliable tool.

Pristimerin exhibits anti-cancer activity by inducing ER stress and AKT/GSK3ß pathway through increasing intracellular ROS production in human esophageal cancer cells.

Pristimerin (Pris), a bioactive triterpenoid compound extracted from the Celastraceae and Hippocrateaceae families, has been reported to exhibit an anti-cancer property on various cancers. However, the effects of Pris on esophageal cancer are poorly investigated. This current study sought to explore the activity and underlying mechanism of Pris against human esophageal squamous cell carcinoma (ESCC) cells. We demonstrated that Pris showed cytotoxicity in TE-1 and TE-10 ESCC cell lines, and significantly inhibited cell viability in a concentration dependent manner. Pris induced G0/G1 phase arrest and triggered apoptosis. It was also observed that the intracellular ROS level was remarkedly increased by Pris treatment. Besides, the function of Pris mediating the activation of ER stress and the inhibition of AKT/GSK3ß signaling pathway in TE-1 and TE-10 cells was further confirmed, which resulted in cell growth inhibition. And moreover, we revealed that all of the above pathways were regulated through ROS generation. In conclusion, our findings suggested that Pris might be considered as a novel natural compound for the developing anti-cancer drug candidate for human esophageal cancer.

Diagnostic Value of Nutritional Risk Index and Other Indices for Predicting Sarcopenia in the Middle-Aged and Elderly Population of China Without Cancer: A ROC Curve Analysis.

Background: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer. Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia. Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China's middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women. Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China's middle-aged and elderly male population without cancer.