Erosion of cultivated kelp facilitates dissolved organic carbon release.

Growing trend of interests for contributions of cultivation of kelp to carbon sequestration have been driven globally. Saccharina japonica is an important cultivated seaweed, with erosion phenomenon usually occurs at the distal part of the frond in S. japonica throughout the growth cycle. However, the dynamics of dissolved organic carbon (DOC) release induced by erosion of S. japonica are not well understood. This study revealed that erosion induced a substantial increase in DOC release, with a 14% increase under low light (LL) conditions and a 54% increase under high light (HL) conditions. A 10 cm of long slit cut into the distal part of S. japonica increased the rate of DOC release by 56% under LL conditions, and by 13% under HL conditions. Additionally, the epibiotic microorganisms facilitate the release of DOC, and the effects were even more pronounced in erosive S. japonica. Conversely, the proximal part of S. japonica exhibited a higher photosynthetic carbon fixation capacity, with a carbon-to-nitrogen (C/N) ratio approximately 1.76 times higher than that in distal part. During the growth of S. japonica, excess photosynthetic products were often transported from the proximal part into distal part, further facilitating DOC release. In summary, DOC released induced by erosion of S. japonica could make contributions to oceanic carbon sequestration.

Transcriptome analysis reveals the promoting effects of exogenous melatonin on the selenium uptake in grape under selenium stress.

Introduction: Exogenous melatonin (MT) can promote horticultural crops growth under stress conditions. Methods: In this study, the effects of exogenous MT on the accumulation of selenium (Se) in grape were studied under Se stress. Results and discussion: Under Se stress, exogenous MT increased the biomass, content of photosynthetic pigments and antioxidant enzyme activity of grapevines. Compared with Se treatment, MT increased the root biomass, shoot biomass, chlorophyll a content, chlorophyll b content, carotenoids, superoxide dismutase activity, and peroxidase activity by 18.11%, 7.71%, 25.70%, 25.00%, 25.93%, 5.73%, and 9.41%, respectively. Additionally, MT increased the contents of gibberellin, auxin, and MT in grapevines under Se stress, while it decreased the content of abscisic acid. MT increased the contents of total Se, organic Se and inorganic Se in grapevines. Compared with Se treatment, MT increased the contents of total Se in the roots and shoots by 48.82% and 135.66%, respectively. A transcriptome sequencing analysis revealed that MT primarily regulated the cellular, metabolic, and bioregulatory processes of grapevine under Se stress, and the differentially expressed genes (DEGs) were primarily enriched in pathways, such as aminoacyl-tRNA biosynthesis, spliceosome, and flavonoid biosynthesis. These involved nine DEGs and nine metabolic pathways in total. Moreover, a field experiment showed that MT increased the content of Se in grapes and improved their quality. Therefore, MT can alleviate the stress of Se in grapevines and promote their growth and the accumulation of Se.

Understanding the effect of adsorption sites of CO at cobalt surface on its reactivity with H2/H by DFT calculations.

Cobalt (Co) is widely used in Fischer-Tropsch synthesis (FTS), converting synthesis gas, carbon monoxide + hydrogen (CO + H2), to long-chain hydrocarbons. The adsorption of CO on the Co surface is the key step in FTS. In this work, the effect of CO adsorption sites on the reactions between CO and H2 was investigated by using density functional theory (DFT). The energetics and structures of the reactions between the adsorbed CO (CO*) and H2/adsorbed H2 (H2*)/adsorbed H atom (H*) were calculated. The results show that the reaction between CO* and H2 is initiated by the molecular adsorption of H2 on the Co surface. The reactions between CO* and H2*/H* are influenced by CO adsorption sites. For the reaction system of CO* + H2*, it has the lowest reaction barrier when CO is adsorbed at the hcp site, while for CO* + H*, it has the lowest reaction barrier when CO is adsorbed on the top site. Kinetic analysis indicates that to improve the reactivity of CO + H2 in FTS, the adsorption of CO should be controlled to favour the top and bridge sites. This article is part of the theme issue 'Celebrating the 15th anniversary of the Royal Society Newton International Fellowship'.

Identification of PI3K-AKT Pathway-Related Genes and Construction of Prognostic Prediction Model for ccRCC.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the predominate histological type of renal cell carcinoma (RCC), has been extensively studied, with poor prognosis as the stage increases. Research findings consistently indicated that the PI3K-Akt pathway is commonly dysregulated across various cancer types, including ccRCC. Targeting the PI3K-Akt pathway held promise as a potential therapeutic approach for treating ccRCC. Development and validation of PI3K-Akt pathway-related genes related biomarkers can enhance healthcare management of patients with ccRCC. PURPOSE: This study aimed to identify the key genes in the PI3K-Akt pathway associated with the diagnosis and prognosis of CCRCC using data mining from the Cancer Genome Atlas (TCGA) and Gene Expression Synthesis (GEO) datasets. METHODS: The purpose of this study is to use bioinformatics methods to screen data sets and clinicopathological characteristics associated with ccRCC patients. The exhibited significantly differential expressed genes (DEGs) associated with the PI3K-Akt pathway were examined by KEGG. In addition, Kaplan-Meier (KM) analysis used to estimate the survival function of the differential genes by using the UALCAN database and graphPad Prism 9.0. And exploring the association between the expression levels of the selected genes and the survival status and time of patients with ccRCC based on SPSS22.0. Finally, a multigene prognostic model was constructed to assess the prognostic risk of ccRCC patients. RESULTS: A total of 911 genes with common highly expressed were selected based on the GEO and TCGA databases. According to the KEGG pathway analysis, there were 42 genes enriched in PI3K-Akt signalling pathway. And seven of highly expressed genes were linked to a poor prognosis in ccRCC. And a multigene prognostic model was established based on IL2RG, EFNA3, and MTCP1 synergistic expression might be utilized to predict the survival of ccRCC patients. CONCLUSIONS: Three PI3K-Akt pathway-related genes may be helpful to identify the prognosis and molecular characteristics of ccRCC patients and to improve therapeutic regimens, and these risk characteristics might be further applied in the clinic.

Efficacy and safety of recombinant human thrombopoietin for the treatment of chronic primary immune thrombocytopenia in children and adolescents: A multicentre, randomized, double-blind, placebo-controlled phase III trial.

The efficacy and safety of recombinant human thrombopoietin (rhTPO) in children and adolescent patients with chronic primary immune thrombocytopenia (ITP) remains unclear. A multicentre, randomized, double-blind, placebo-controlled phase III trial was performed. Patients aged 6-17 years, diagnosed with ITP and resistant or relapsed to corticosteroid treatment were included. For the trial, part 1 was exploratory and part 2 was the main analysis, with part 1 determining whether part 2 was stratified by age. Patients in part 1 were treated with rhTPO (the 6- to 11-/12- to 17-year-old groups; 1:1). Patients in part 2 were randomized (3:1) to receive either rhTPO treatment or placebo. Patients received rhTPO or placebo at a dose of 300 U/kg once daily for up to 14 days. A total of 68 patients were included [part 1 (12 patients), part 2 (56 patients)]. The total response rate (TRR) in part 1 was 50.0% (95% CI: 21.09%-78.91%). For part 2, the TRR was 58.5% (95% CI: 42.11%-73.68%) and 13.3% (95% CI: 1.66%-40.46%) in the rhTPO and placebo groups (FAS) respectively. The difference in TRR between the rhTPO group and placebo group was 45.2% (95% CI: 22.33%-68.08%) and 44.6% (95% CI: 21.27%-67.85%) on the FAS and per-protocol set (PPS), respectively, which indicates the superiority of rhTPO treatment.

Physiological and Proteomic Analysis of Various Priming on Rice Seed under Chilling Stress.

Rice (Oryza sativa L.) cultivation using direct seeding is susceptible to chilling stress, particularly during seed germination and early seedling growth in the early season of a double cropping system. Alternatively, seed priming with various plant growth-promoting hormones is an effective technique to promote rapid and uniform emergence under chilling stress. Therefore, we evaluated the impact of gibberellin A3 (GA3) and brassinolide (BR) priming on rice seed emergence, examining their proteomic responses under low-temperature conditions. Results indicated that GA3 and BR increased the seed germination rate by 22.67% and 7.33% at 72 h and 35% and 15% at 96 h compared to the control (CK), respectively. Furthermore, proteomic analysis identified 2551, 2614, and 2592 differentially expressed proteins (DEPs) in GA, BR, and CK, respectively. Among them, GA exhibited 84 upregulated and 260 downregulated DEPs, while BR showed 112 upregulated and 102 downregulated DEPs, and CK had 123 upregulated and 81 downregulated DEPs. Notably, under chilling stress, both GA3 and BR are involved in peroxide metabolism, phenylpropanoid biosynthesis, and inositol phosphate metabolism, enhancing antioxidant capacity and providing energy substances for germination. In addition, GA3 triggers the specific regulation of stress responsive protein activation, GTP activation, and ascorbic acid biosynthesis and promotes the stability and integrity of cell membranes, as well as the synthesis of cell walls, providing physical defense for seeds to resist low temperatures. At the same time, BR triggers specific involvement in ribosome synthesis and amino acid synthesis, promoting biosynthetic ability and metabolic regulation to maintain plant life activities under low-temperature stress. Furthermore, the various genes' expression (OsJ_16716, OsPAL1, RINO1) confirmed GA3 and BR involved in peroxide metabolism, phenylpropanoid biosynthesis, and inositol phosphate metabolism, enhancing antioxidant capacity and providing energy substances for germination. This study provides valuable insights into how rice seed embryo responds to and tolerates chilling stress with GA3 seed priming.

SnO2-Based Interfacial Engineering towards Improved Perovskite Solar Cells.

Interfacial engineering is of great concern in photovoltaic devices. Metal halide perovskite solar cells (PSCs) have garnered much attention due to their impressive development in power conversion efficiencies (PCEs). Benefiting from high electron mobility and good energy-level alignment with perovskite, aqueous SnO2 as an electron transport layer has been widely used in n-i-p perovskite solar cells. However, the interfacial engineering of an aqueous SnO2 layer on PSCs is still an obscure and confusing process. Herein, we proposed the preparation of n-i-p perovskite solar cells with different concentrations of SnO2 as electron transport layers and achieved optimized PCE with an efficiency of 20.27%. I Interfacial engineering with regard to the SnO2 layer is investigated by observing the surface morphology, space charge-limited current (SCLC) with the use of an electron-only device, and time-resolved photoluminescence (TRPL) of perovskite films.

A Study of Classroom Behavior Recognition Incorporating Super-Resolution and Target Detection.

With the development of educational technology, machine learning and deep learning provide technical support for traditional classroom observation assessment. However, in real classroom scenarios, the technique faces challenges such as lack of clarity of raw images, complexity of datasets, multi-target detection errors, and complexity of character interactions. Based on the above problems, a student classroom behavior recognition network incorporating super-resolution and target detection is proposed. To cope with the problem of unclear original images in the classroom scenario, SRGAN (Super Resolution Generative Adversarial Network for Images) is used to improve the image resolution and thus the recognition accuracy. To address the dataset complexity and multi-targeting problems, feature extraction is optimized, and multi-scale feature recognition is enhanced by introducing AKConv and LASK attention mechanisms into the Backbone module of the YOLOv8s algorithm. To improve the character interaction complexity problem, the CBAM attention mechanism is integrated to enhance the recognition of important feature channels and spatial regions. Experiments show that it can detect six behaviors of students-raising their hands, reading, writing, playing on their cell phones, looking down, and leaning on the table-in high-definition images. And the accuracy and robustness of this network is verified. Compared with small-object detection algorithms such as Faster R-CNN, YOLOv5, and YOLOv8s, this network demonstrates good detection performance on low-resolution small objects, complex datasets with numerous targets, occlusion, and overlapping students.

Gut Microbiome variation in patients with early-stage mild-to-moderate intracerebral hemorrhage: A pilot study exploring therapeutic targets.

BACKGROUND: The significant morbidity and mortality rates of acute intracerebral hemorrhage (ICH) are well-known around the world. The link between gut microbiota and different types of strokes is becoming more studied. The goal of this study was to look at the relationships between intestinal flora and early-stage mild-to-moderate ICH (emICH), and to provide a new perspective for adjunctive treatment of emICH. METHODS: Fecal samples from 100 participants with emICH (n=50) and healthy individuals (n=50) in this study were collected as well as analyzed utilizing 16S rRNA gene amplicon sequencing in order to characterize the gut microbial community. RESULTS: Distinct microbial communities are present within each group, with emICH patients exhibiting a diminished diversity and uniformity in their microbial profiles. A notable shift in the gut microbiota composition of emICH patients has been observed, characterized by an upsurge in pro-inflammatory microbes belonging to the Euryarchaeota phylum and a concurrent decline in beneficial Bacteroidetes species. Concurrently, significant associations and patterns among operational taxonomic units (OTUs) were identified in emICH patients. A panel of biomarkers (WAL_1855D, Methanobrevibacter, Streptococcus, Bacteroides, Coprococcus, Lachnospira) has been effectively utilized to distinguish emICH patients from healthy individuals, with an area under the curve (AUC) of 0.845. Additionally, an analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation uncovered several perturbed pathways in emICH patients, predominantly those related to metabolic processes and the inflammatory response. Moreover, predictive profiling of the microbiome's phenotypic traits suggests that emICH patients are likely to harbor a higher prevalence of Gram-negative bacteria and potential opportunistic pathogens compared to healthy controls. CONCLUSIONS: The gut microbiota ecosystem of emICH patients is disrupted, characterized primarily by an increase in pro-inflammatory microbiota, elevated inflammatory signaling pathways, and metabolic dysregulation. Furthermore, microbiota modulation may be seen as a novel approach for the adjunctive treatment of emICH.

Development and validation of a nomogram for predicting intellectual disability in children with cerebral palsy.

Objective: Intellectual disability (ID) is a prevalent comorbidity in children with cerebral palsy (CP), presenting significant challenges to individuals, families and society. This study aims to develop a predictive model to assess the risk of ID in children with CP. Methods: We analyzed data from 885 children diagnosed with CP, among whom 377 had ID. Using least absolute shrinkage and selection operator regression, along with univariate and multivariate logistic regression, we identified key predictors for ID. Model performance was evaluated through receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Bootstrapping validation was also employed. Results: The predictive nomogram included variables such as preterm birth, CP subtypes, Gross Motor Function Classification System level, MRI classification category, epilepsy status and hearing loss. The model demonstrated strong discrimination with an area under the receiver operating characteristic curve (AUC) of 0.781 (95% CI: 0.7504-0.8116) and a bootstrapped AUC of 0.7624 (95% CI: 0.7216-0.8032). Calibration plots and the Hosmer-Lemeshow test indicated a good fit (χ2= 7.9061, p = 0.4427). DCA confirmed the model's clinical utility. The cases were randomly divided into test group and validation group at a 7:3 ratio, demonstrating strong discrimination, good fit and clinical utility; similar results were found when stratified by sex. Conclusions: This predictive model effectively identifies children with CP at a high risk for ID, facilitating early intervention strategies. Stratified risk categories provide precise guidance for clinical management, aiming to optimize outcomes for children with CP by leveraging neuroplasticity during early childhood.

Development and Validation of a Two-step Model to Predict Outcomes After Endovascular Treatment for Patients With Acute Ischemic Stroke.

BACKGROUND: Physicians and patients are eager to know likely functional outcomes at different stages of treatment after acute ischemic stroke (AIS). The aim of this study was to develop and validate a 2-step model to assess prognosis at different time points (pre- and posttreatment) in patients with AIS having endovascular thrombectomy (EVT). METHODS: The prediction model was developed using a prospective nationwide Chinese registry (ANGEL-ACT). A total of 1676 patients with AIS who underwent EVT were enrolled into the study and randomly divided into development (n=1351, 80%) and validation (n=325, 20%) cohorts. Multivariate logistic regression, least absolute shrinkage and selection operator regression, and the random forest recursive feature elimination algorithm were used to select predictors of 90-day functional independence. We constructed the model via discrimination, calibration, decision curve analysis, and feature importance. RESULTS: The incidence of 90-day functional independence was 46.3% and 40.6% in the development and validation cohorts, respectively. The area under the curve (AUC) for model 1 which included 5 pretreatment predictors (age, admission National Institutes for Health Stroke Scale score, admission glucose level, admission systolic blood pressure, and Alberta Stroke Program Early Computed Tomography score) was 0.699 (95% confidence interval [CI], 0.668-0.730) in the development cohort and 0.658 (95% CI, 0.592-0.723) in the validation cohort. Two treatment-related predictors (time from stroke onset to puncture and successful reperfusion) were added to model 2 which had an AUC of 0.719 (95% CI, 0.688-0.749) and 0.650 (95% CI, 0.585-0.716) in the development cohort and validation cohorts, respectively. CONCLUSIONS: The 2-step prediction model could be useful for predicting the functional independence in patients with AIS 90-days after EVT.

The electronic and magnetic properties modulated by ferroelectric polarization switching in two-dimensional VSeTe/Sc2CO2 van der Waals heterostructures.

Exploring multiferroic materials that combine magnetic and ferroelectric properties is scientifically interesting and has important technical implications for many functions of nanoscale devices. In this work, spintronics and magnetoelectric coupling devices are proposed in two-dimensional (2D) layered ferromagnetic (FM)/ferroelectric (FE) van de Waals (vdW) heterostructures, VSeTe/Sc2CO2, employing density functional theory (DFT) calculations. The results indicate that the VSeTe/Sc2CO2 vdW heterostructure changes from a metal to a semiconductor in Sc2CO2-P↑ and Sc2CO2-P↓ polarization states. At the same time, the charge at the interface of the VSeTe/Sc2CO2 heterostructure will also be redistributed with the transformation of the ferroelectric polarization state, resulting in the change of the distribution of the electronic states near the Fermi level, and thus the change in the magnetic anisotropy energy (EMAE) of the heterostructure. Interestingly, biaxial strain brings reversibility and non-volatile regulation to the heterostructure of semiconductors and metals. The results provide an effective way to fabricate magnetoelectric coupling devices with 2D multiferroic heterostructures.

Clinical value of macrogenome next-generation sequencing on infections.

Intracranial infection (ICI) is a frequent and serious complication after neurosurgery. Macrogenome next-generation sequencing (mNGS) technology can provide reference for clinical diagnosis and treatment of ICI. This work aimed to explore the application value of mNGS technology in analyzing the clinical characteristics of human immunodeficiency virus (HIV) infection and ICI after neurosurgery. A total of 60 patients with ICI were enrolled as the research objects, all patients underwent routine cerebrospinal fluid analysis and traditional pathogen detection, followed by mNGS genome analysis. Using clinical diagnosis of ICI as the gold standard, the sensitivity, specificity, positive predictive value, and negative predictive value for both detection methods were calculated. Receiver operating characteristic curves were constructed to assess the area under the curve (AUC) for evaluating the clinical value of mNGS in suspected intracranial infectious pathogen diagnosis. Results showed a positivity rate of 71.67% (43 cases) with mNGS compared to 28.33% (17 cases) with traditional pathogen detection methods, demonstrating a significant difference (P < 0.05). The sensitivity of mNGS for detecting ICIs was 83.7%, significantly higher than the 34.88% observed with traditional methods (P < 0.05). The pathogen detection rate of mNGS was higher than traditional methods (P = 0.002), with an AUC of 0.856 (95% CI: 0.638-0.967), significantly greater than the AUC of 0.572 (95% CI: 0.350-0.792) for traditional methods (P < 0.05). mNGS successfully identified microorganisms such as Cryptococcus, Propionibacterium, Staphylococcus, Corynebacterium, Micrococcus, and Candida associated with ICIs. These findings underscore the clinical applicability of mNGS technology in analyzing the characteristics of HIV infection and ICI post-neurosurgical procedures. This technology enables more accurate diagnosis and treatment of ICIs, providing valuable insights for developing effective therapeutic strategies.

Monocyte Chemoattractant Protein-1, Inflammatory Biomarkers, and Prognosis of Patients With Ischemic Stroke or Transient Ischemic Attack: Fndings From a Nationwide Registry Study.

BACKGROUND: Recent Mendelian randomization and meta-analysis highlight the relevance of MCP-1 (monocyte chemoattractant protein-1) in stroke. We aimed to investigate the associations between MCP-1 and clinical outcomes in patients with ischemic stroke or transient ischemic attack and test whether inflammation mediates or jointly contributes to the relationships. METHODS AND RESULTS: A total of 10 700 patients from the Third China National Stroke Registry study were included. Multivariable Cox regression was used for recurrent stroke and all-cause death, and logistic regression was used for poor functional outcome. Mediation analyses were performed to clarify whether inflammation mediates the associations. After adjusting for potential confounders, low MCP-1 level (<337.6 pg/mL) was associated with a reduced risk of all-cause death (hazard ratio [HR], 0.65 [95% CI, 0.51-0.82]) and poor functional outcome (odds ratio, 0.81 [95% CI, 0.70-0.94]) but was not associated with recurrent stroke (HR, 1.10 [95% CI, 0.95-1.27]), compared with high MCP-1 level (≥337.6 pg/mL). The association between MCP-1 and all-cause death was partially mediated by highly sensitive C-reactive protein, interleukin-6, and YKL-40 (Chitinase-3-like protein 1; mediated proportion: 7.4%, 10.5%, and 7.4%, respectively). The corresponding mediated proportion for poor functional outcome was 9.9%, 17.1%, and 7.1%, respectively. Patients with combined high levels of MCP-1 and inflammatory biomarkers had the highest risks of all-cause death and poor functional outcome. CONCLUSIONS: Low plasma MCP-1 level was associated with decreased risks of all-cause mortality and poor functional outcome after ischemic stroke or transient ischemic attack. Inflammation partially mediated and jointly contributed to the associations.

The function of the inter-alpha-trypsin inhibitors in the development of disease.

Through the formation of covalent connections with hyaluronic acid (HA), the inter-α-trypsin inhibitor (IαI) family collaborates to preserve the stability of the extracellular matrix (ECM). The five distinct homologous heavy chains (ITIH) and one type of light chain make up the IαI family. ITIH alone or in combination with bikunin (BK) has been proven to have important impacts in a number of earlier investigations. This implies that BK and ITIH might be crucial to both physiological and pathological processes. The functions of BK and ITIH in various pathophysiological processes are discussed independently in this paper. In the meanwhile, this study offers suggestions for further research on the roles of BK and ITIH in the course of disease and summarizes the plausible mechanisms of the previous studies.

The Impact of a Diet Rich in Omega-3 Fatty Acids on the Quality of Life of Patients with Squamous Cell Lung Cancer and Comorbid Depression: A Retrospective Study.

BACKGROUND: Lung cancer is a significant health concern, and is often accompanied by comorbid depression, leading to worsened prognosis and decreased quality of life for patients. This study aimed to investigate the potential influence of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and comorbid depression. METHODS: A retroactive analysis of clinical information from patients with squamous cell lung cancer and comorbid depression admitted to Hongqi Hospital Affiliated to Mudanjiang Medical University from June 2022 to June 2023 was conducted. The patients were classified into two groups on the basis of different dietary care approaches: the Routine Dietary Group and the Omega-3 Fatty Acids Group. Baseline characteristics, pulmonary function tests, dietary intake, depression scoring, and quality of life scores were compared between the two groups. RESULTS: 103 patients in total were included, with 51 in the Routine Dietary Group and 52 in the Omega-3 Fatty Acids Group. The Omega-3 Fatty Acids Group exhibited significantly higher ingestion of Omega-3 fatty acids in comparison with the Routine Dietary Group (3.15 ± 0.64 g/day vs. 2.93 ± 0.28 g/day, p = 0.022). Despite similar baseline pulmonary function tests, patients in the Omega-3 Fatty Acids Group showed significantly higher scores in physical (70.17 ± 4.81 vs. 68.18 ± 5.03, p = 0.043) and emotional (71.29 ± 4.58 vs. 69.38 ± 4.25, p = 0.030) functioning, as well as lower scores in insomnia (27.41 ± 4.51 vs. 29.34 ± 4.21, p = 0.027) and constipation (7.34 ± 1.66 vs. 8.43 ± 3.36, p = 0.040). CONCLUSION: The study provided insights into the potential impact of a diet rich in Omega-3 fatty acids on the quality of life of patients with squamous cell lung cancer and complicating depression, suggesting that dietary interventions emphasizing Omega-3 fatty acids may be conducive to improving physical and emotional functioning, as well as symptom management, in this patient population.

Causal Association of Arterial Stiffness With the Risk of Chronic Kidney Disease.

Background: Previous studies on the direction of the association between arterial stiffness (AS) and chronic kidney disease (CKD) were inconsistent, leaving a knowledge gap in understanding the temporal sequence of the association. Objectives: This study sought to assess the temporal and longitudinal relationship between AS and CKD. Methods: The temporal relationship between AS measured by brachial ankle pulse wave velocity and CKD measured by estimated glomerular filtration rate (eGFR) was analyzed among 7,753 participants with repeated examinations in the Kailuan study using cross-lagged panel analysis. The longitudinal associations of AS status and vascular aging (VA) phenotype with incident CKD were analyzed among 10,535 participants. Results: The adjusted cross-lagged path coefficient (ß 1 = -0.03; 95% CI: -0.06 to -0.01; P < 0.0001) from baseline brachial ankle pulse wave velocity to follow-up eGFR was significantly greater than the path coefficient (ß 2 = -0.01; 95% CI: -0.02 to 0.01; P = 0.6202) from baseline eGFR to follow-up brachial ankle pulse wave velocity (P < 0.0001 for the difference). During a median follow-up of 8.48 years, 953 cases of incident CKD (9.05%) occurred. After adjustment for confounders, borderline (HR: 1.17; 95% CI: 1.08-1.38) and elevated AS (HR: 1.39; 95% CI: 1.12-1.72) was associated a higher risk of CKD, compared with normal AS. Consistently, supernormal VA (HR: 0.76; 95% CI: 0.66-0.86) was associated with a decreased and early VA (HR: 1.36; 95% CI: 1.29-1.43) was associated with an increased risk of CKD, compared with normal VA. Conclusions: AS appeared to precede the decrease in eGFR. Additionally, increased AS and early VA were associated with an increased risk of incident CKD.

Repositioning fluphenazine as a cuproptosis-dependent anti-breast cancer drug candidate based on TCGA database.

Breast cancer is one of the most prevalent malignancies among women. Enhancing the prognosis is an effective approach to enhance the survival rate of breast cancer. Cuproptosis, a copper-dependent programmed cell death process, has been associated with patient prognosis. Inducing cuproptosis is a promising approach for therapy. However, there is currently no anti-breast cancer drug that induces cuproptosis. In this study, we repositioned the clinical drug fluphenazine as a potential agent for breast cancer treatment by inducing cuproptosis. Firstly, we utilized the Cancer Genome Atlas (TCGA) database and Connectivity Map (CMap) database to identify 22 potential compounds with anti-breast cancer activity through inducing cuproptosis. Subsequently, our findings demonstrated that fluphenazine effectively suppressed the viability of MCF-7 cells. Fluphenazine also significantly inhibited the viability of triple negative breast cancer cells MDA-MB-453 and MDA-MB-231. Furthermore, our study revealed that fluphenazine significantly down-regulated the expression of potential prognostic biomarkers associated with cuproptosis, increased copper ion levels, and reduced intracellular pyruvate accumulation. Additionally, it up-regulated the expression of FDX1 at both the mRNA and protein levels, which has been reported to play a crucial role in the induction of cuproptosis. These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

Hypoxia-initiated Cysteine-rich protein 61 secretion promotes chemoresistance of acute B lymphoblastic leukemia cells.

The drug resistance is a major obstacle in acute B-lymphoblastic leukemia (B-ALL) treatment. Our previous study has indicated that increased levels of Cysteine-rich protein 61 (Cyr61) in the bone marrow can mitigate the chemosensitivity of B-ALL cells, though the specific source of Cyr61 in the bone marrow remains unknown. In this study, we aimed to investigate whether hypoxia can induce Cyr61 production in B-ALL cells, delineates the underlying mechanisms, and evaluates the effect of Cyr61 on the chemosensitivity of B-ALL cells under hypoxia conditions. The results indicate that hypoxia promotes Cyr61 production in B-ALL cells by activating the NF-κB pathway. Increased Cyr61 expression appears to reduce the chemosensitivity of B-ALL cell to vincristine (VCR) and daunorubicin (DNR) through autophagy under hypoxia. Notably, inhibition of Cyr61 restores the chemosensitivity of B-ALL cells to both chemotherapeutic agents. This study is the first time to report that hypoxia decreases the chemosensitivity of B-ALL cells by inducing Cyr61 production, suggesting that targeting Cyr61 or its associated pathways could potentially improve the clinical response of B-ALL patients.

Rod-Shaped Au@Ce Nano-Platforms for Enhancing Photodynamic Tumor Collaborative Therapy.

Tumor photodynamic therapy (PDT) relies on intratumoral free radicals, while the limited oxygen source and the depletion of tissue oxygen may exacerbate the hypoxia. As the treatment progresses, there will eventually be a problem of insufficient free radicals. Here, it is found that Au@CeO2 nano-rods (Au@Ce NRs), assembled by gold nano-rods (Au NRs) and ceria nanoparticles (CeO2 NPs), can efficaciously absorb near-infrared light (NIR) to promote the release of oxygen and free radicals. Au@Ce NRs exhibit a higher proportion of Ce3+ (Ce2O3) after oxygen release, while Ce3+ is subsequently oxidized to Ce4+ (CeO2) by trace H2O2. Interestingly, Au@Ce NRs re-oxidized by trace H2O2 can re-releasing oxygen and free radicals again upon NIR treatment, achieving oxygenation/oxygen evolution, similar to charging/discharging. This loop maximizes the conversion of limited oxygen source into highly cytotoxic free radicals. As a result, when B16-F10 cells are treated by NIR/Au@Ce NRs, more tumor cells undergo apoptosis, consistent with the higher level of free radicals. Importantly, NIR/Au@Ce NRs successfully suppresses tumor growth and promotes the generation of epidermal collagen fibers in the transplanted tumor model. Therefore, the rod-shaped Au@Ce NRs provide an ideal platform for maximizing the utilization of intratumoral oxygen sources and improving the treatment of melanoma.