Advancements in PSMA ligand radiolabeling for diagnosis and treatment of prostate cancer: a systematic review.

Prostate cancer(PCa), a leading global health concern, profoundly impacts millions of men worldwide. Progressing through two stages, it initially develops within the prostate and subsequently extends to vital organs such as lymph nodes, bones, lungs, and the liver. In the early phases, castration therapy is often employed to mitigate androgen effects. However, when prostate cancer becomes resistant to this treatment, alternative strategies become imperative. As diagnostic and treatment methodologies for prostate cancer continually advance, radioligand therapy (RLT) has emerged as a promising avenue, yielding noteworthy outcomes. The fundamental principle of RLT involves delivering radionuclide drugs to cancerous lesions through specific carriers or technologies. Subsequently, these radionuclide drugs release radioactive energy, facilitating the destruction of cancer cell tissues. At present, the positron emission tomography (PET) targeting PSMA has been widely developed for the use of diagnosis and staging of PCa. Notably, FDA-approved prostate-specific membrane antigen (PSMA) targeting agents, such as 68Ga-PSMA-11 and 177Lu-PSMA-617, represent significant milestones in enhancing diagnostic precision and therapeutic efficacy. This review emphasizes the current research status and outcomes of various radionuclide-labeled PSMA ligands. The objective is to provide valuable insights for the continued advancement of diagnostic and therapeutic approaches in the realm of prostate cancer.

Compulsivity-related behavioral features of problematic usage of the internet: A scoping review of paradigms, progress, and perspectives.

Background and aims: Compulsivity contributes to the development and maintenance of multiple addictive disorders. However, the relationship between compulsivity-related cognitive features and problematic usage of the internet (PUI), an umbrella term for various internet use disorders/interfering behaviors, remains largely unclear, partly due to the multidimensional nature of compulsivity. This scoping review utilized a four-domain framework of compulsivity to consider this topic and aimed to summarize available evidence on compulsivity-related neuropsychological characteristics in PUI based on this framework. Methods: A systematic literature search was conducted by applying the combination of search term to the search engines of PubMed, PsycINFO and Web of Science. A four-domain framework of compulsivity, involving cognitive flexibility, set-shifting, attentional bias, and habit learning, was used to consider its complex structure and frequently used tasks. Main findings in related PUI studies were summarized based on this framework. Our secondary aim was to compare compulsivity-related features between different PUI subtypes. Results: Thirty-four empirical studies were retained, comprising 41 task-results and 35 independent data sets. Overall, individuals with PUI showed more consistent deficits in attentional biases and were relatively intact in set-shifting. Few studies have examined cognitive flexibility and habit learning, and more evidence is thus needed to establish reliable conclusions. Moreover, most studies focused on internet gaming disorder, whereas other PUI sub-types were not sufficiently examined. Conclusion: This systematic review highlights the use of the four-domain framework for advancing understanding of mechanisms underlying compulsivity in PUI. Related therapeutic implications and future directions are discussed.

Applications of FAPI PET/CT in the diagnosis and treatment of breast and the most common gynecologic malignancies: a literature review.

The fibroblast activating protein (FAP) is expressed by some fibroblasts found in healthy tissues. However, FAP is overexpressed in more than 90% of epithelial tumors, including breast and gynecological tumors. As a result, the FAP ligand could be used as a target for diagnosis and treatment purposes. Positron emission tomography/computed tomography (PET/CT) is a hybrid imaging technique commonly used to locate and assess the tumor's molecular and metabolic functions. PET imaging involves the injection of a radiotracer that tends to accumulate more in metabolically active lesions such as cancer. Several radiotracers have been developed to target FAP in PET/CT imaging, such as the fibroblast-activation protein inhibitor (FAPI). These tracers bind to FAP with high specificity and affinity, allowing for the non-invasive detection and quantification of FAP expression in tumors. In this review, we discussed the applications of FAPI PET/CT in the diagnosis and treatment of breast and the most common gynecologic malignancies. Radiolabeled FAPI can improve the detection, staging, and assessment of treatment response in breast and the most common gynecologic malignancies, but the problem with normal hormone-responsive organs remains insurmountable. Compared to the diagnostic applications of FAPI, further research is needed for future therapeutic applications.

Health diagnosis and recuperation of aged Li-ion batteries with data analytics and equivalent circuit modeling.

Battery health assessment and recuperation play crucial roles in the utilization of second-life Li-ion batteries. However, due to ambiguous aging mechanisms, it is challenging to estimate battery health and devise an effective strategy for cell rejuvenation. This paper presents aging and reconditioning experiments of 62 commercial lithium iron phosphate cells, which allow us to use machine learning models to predict cycle life and identify important indicators of recoverable capacity. An average test error of 16.84% ± 1.87% (mean absolute percentage error) for cycle life prediction is achieved by gradient boosting regressor. Some of the recoverable lost capacity is found to be attributed to the non-uniformity in electrodes. An experimentally validated equivalent circuit model is built to demonstrate how such non-uniformity can be accumulated, and how it can give rise to recoverable capacity loss. Furthermore, Shapley additive explanations (SHAP) analysis also reveals that battery operation history significantly affects the capacity recovery.

Hepatocellular carcinoma cells downregulate NADH:Ubiquinone Oxidoreductase Subunit B3 to maintain reactive oxygen species homeostasis.

BACKGROUND: HCC is a leading cause of cancer-related death. The role of reactive oxygen species (ROS) in HCC remains elusive. Since a primary ROS source is the mitochondrial electron transport chain complex Ι and the NADH:ubiquinone Oxidoreductase Subunit B3 (NDUFB3), a complex I subunit, is critical for complex I assembly and regulates the associated ROS production, we hypothesize that some HCCs progress by hijacking NDUFB3 to maintain ROS homeostasis. METHODS: NDUFB3 in human HCC lines was either knocked down or overexpressed. The cells were then analyzed in vitro for proliferation, migration, invasiveness, colony formation, complex I activity, ROS production, oxygen consumption, apoptosis, and cell cycle. In addition, the in vivo growth of the cells was evaluated in nude mice. Moreover, the role of ROS in the NDUFB3-mediated changes in the HCC lines was determined using cellular and mitochondrion-targeted ROS scavengers. RESULTS: HCC tissues showed reduced NDUFB3 protein expression compared to adjacent healthy tissues. In addition, NDUFB3 knockdown promoted, while its overexpression suppressed, HCC cells' growth, migration, and invasiveness. Moreover, NDUFB3 knockdown significantly decreased, whereas its overexpression increased complex I activity. Further studies revealed that NDUFB3 overexpression elevated mitochondrial ROS production, causing cell apoptosis, as manifested by the enhanced expressions of proapoptotic molecules and the suppressed expression of the antiapoptotic molecule B cell lymphoma 2. Finally, our data demonstrated that the apoptosis was due to the activation of the c-Jun N-terminal kinase (JNK) signaling pathway and cell cycle arrest at G0/G1 phase. CONCLUSIONS: Because ROS plays essential roles in many biological processes, such as aging and cancers, our findings suggest that NDFUB3 can be targeted for treating HCC and other human diseases.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Extraction of Tooth Cusps based on DBSCAN Density Clustering and Neighborhood Search Algorithm.

A good tooth cusp extraction is helpful in evaluating the effect of cosmetic dental work in virtual tooth surgery. We propose a new tooth cusp extraction, which integrates the DBSCAN (density-based spatial clustering of applications with noise) clustering algorithm with the neighborhood search algorithm to extract tooth cusp from a three-dimensional cloud-point tooth model. This method used the point cloud height and curvature to screen out the dented point set. Then we employ the DBSCAN clustering algorithm to segment different feature regions of the tooth surface and generate the candidate point set. Finally, the candidate point set was accurately located at the tooth apex through the neighborhood search algorithm and the traversal search method of non-maximum suppression. The experimental results show that the proposed method is superior to the traditional watershed algorithm-based methods by calculating the recall rate and accuracy rate, and also has higher extraction speed and extraction precision than manual extraction methods.

Biomarker Changes during 20 Years Preceding Alzheimer's Disease.

BACKGROUND: Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer's disease have not been extensively investigated in longitudinal studies. METHODS: We conducted a multicenter, nested case-control study of Alzheimer's disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year-to-3-year intervals. A total of 648 participants in whom Alzheimer's disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups. RESULTS: The median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer's disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aß)42, 18 years; the ratio of Aß42 to Aß40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer's disease group initially accelerated and then slowed. CONCLUSIONS: In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer's disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal. (Funded by the Key Project of the National Natural Science Foundation of China and others; ClinicalTrials.gov number, NCT03653156.).

Profiling of T cell repertoire in peripheral blood of patients from type 2 diabetes with complication.

PURPOSE: More than 90% of patients with diabetes worldwide are type 2 diabetes (T2D), which is caused by insulin resistance or impaired producing insulin by pancreatic ß cells. T2D and its complications, mainly large cardiovascular (LCV) and kidney (Ne) complications, are the major cause of death in diabetes patients. Recently, the dysregulation of peripheral T cell immune homeostasis was found in most T2D patients. However, the characteristics of T-cell receptors (TCR) remain largely unexplored in T2D patients. PATIENTS AND METHODS: Here we investigated the TCR repertoire using high-throughput sequencing in peripheral blood collected from T2D patient with (8 LCV and 7 Ne) or without complications. RESULTS: Our analysis of TCR repertoires in peripheral blood samples showed that TCR profiles in T2D patients with complications tended to be single and specific compared to controls, according to the characteristics of TCR repertoire in V-J combination number, diversity, principal component analysis (PCA) and differential genes. And we identified some differentially expressed V-J gene segments and amino acid clonotypes, which had the potential to contribute to distinguishing T2D patient with or without complications. As the progression of the disease, we found that the profiling of TCR repertoire was also differential between T2D patients with LVD and Ne complications base on this pilot analysis. CONCLUSION: This study demonstrated the protentional unique property of TCR repertoire in peripheral blood of T2D patient with and without complications, or T2D patients with LVD and Ne complications, which provided the possibility for future improvements in immune-related diagnosis and therapy for T2D complications.

GLUD1 inhibits hepatocellular carcinoma progression via ROS-mediated p38/JNK MAPK pathway activation and mitochondrial apoptosis.

Glutamate dehydrogenase 1 (GLUD1) is an important enzyme in glutamine metabolism. Previously, we found GLUD1 was down-regulated in tumor tissues of hepatocellular carcinoma (HCC) patients by proteomics study. To explore its role in the progression of HCC, the expressional level of GLUD1 was firstly examined and presented as that both the protein and mRNA levels were down-regulated in tumor tissues compared to the normal liver tissues. GLUD1 overexpression significantly inhibited HCC cells proliferation, migration, invasion and tumor growth both in vitro and in vivo, while GLUD1 knocking-down promoted HCC progression. Metabolomics study of GLUD1 overexpressing and control HCC cells showed that 129 differentially expressed metabolites were identified, which mainly included amino acids, bases, and phospholipids. Moreover, metabolites in mitochondrial oxidative phosphorylation system (OXPHOS) were differentially expressed in GLUD1 overexpressing cells. Mechanistic studies showed that GLUD1 overexpression enhanced mitochondrial respiration activity and reactive oxygen species (ROS) production. Excessive ROS lead to mitochondrial apoptosis that was characterized by increased expression levels of p53, Cytochrome C, Bax, Caspase 3 and decreased expression level of Bcl-2. Furthermore, we found that the p38/JNK MAPK pathway was activated in GLUD1 overexpressing cells. N-acetylcysteine (NAC) treatment eliminated cellular ROS and blocked p38/JNK MAPK pathway activation, as well as cell apoptosis induced by GLUD1 overexpression. Taken together, our findings suggest that GLUD1 inhibits HCC progression through regulating cellular metabolism and oxidative stress state, and provide that ROS generation and p38/JNK MAPK pathway activation as promising methods for HCC treatment.

Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFß1/Smad2 in Chronic Asthma.

PURPOSE: Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. METHODS: We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor ß1 (TGFß1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. RESULTS: We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = -0.485, P < 0.01) and FEV1 (%predicted) (r = -0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFß1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFß1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFß1/Smad2 pathway. CONCLUSIONS: Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFß1/Smad2 pathway.

Feline infectious peritonitis virus ORF7a is a virulence factor involved in inflammatory pathology in cats.

A hyperinflammatory response is a prominent feature of feline infectious peritonitis (FIP), but the mechanisms behind the feline infectious peritonitis virus (FIPV)-induced cytokine storm in the host have not been clarified. Studies have shown that coronaviruses encode accessory proteins that are involved in viral replication and associated with viral virulence, the inflammatory response and immune regulation. Here, we found that FIPV ORF7a gene plays a key role in viral infection and host proinflammatory responses. The recombinant FIPV strains lacking ORF7a (rQS-79Δ7a) exhibit low replication rates in macrophages and do not induce dramatic upregulation of inflammatory factors. Furthermore, through animal experiments, we found that the rQS-79Δ7a strain is nonpathogenic and do not cause symptoms of FIP in cats. Unexpectedly, after three vaccinations with rQS-79Δ7a strain, humoral and cellular immunity was increased and provided protection against virulent strains in cats, and the protection rate reaches 40%. Importantly, our results demonstrated that ORF7a is a key virulence factor that exacerbates FIPV infection and inflammatory responses. Besides, our findings will provide novel implications for future development of live attenuated FIPV vaccines.

Bimetal-bridging Nitrogen Coordination in Carbon-based Electrocatalysts for pH-universal Oxygen Reduction.

Electrocatalysts with atomically dispersed metal sites (e.g., metal-nitrogen-carbon) have been deemed as promising alternatives for noble-metal catalysts in couples of electrocatalytic reactions. However, the modulation of such atomic sites and the understanding of their interactions are still highly challenging. Herein, we propose a unique supermolecule assembly-profile coating strategy to prepare a series of diatomic electrocatalysts by profile coating of eight Prussian blue analogues (PBAs) on supramolecular supports respectively as bimetallic sources. The detailed microstructure analysis revealed that the metal-nitrogen-carbon sites with four- (Zn-N4 ) and five-coordination (Fe-N5 ) via the nitrogen coordination are similar to the cytochrome c oxidases. For promising electrocatalysis, such unique microstructure is able to activate oxygen molecules due to nitrogen-bonding coordination with bimetal sites, thus leading to efficient four-electron oxygen reduction in alkaline, neutral, and acid electrolytes. Especially, zinc group elements (e.g., Zn and Cd) with d10 electron configuration would significantly boost the nitrogen-bonding coordination with bimetal sites to enhance electrocatalytic activity. The proof-of-concept for the general synthesis of advanced electrocatalysts with controllable bimetal active sites and the mechanistic understanding will promote the promising electrocatalysis by applying the similar principles.

Strong p-d Orbital Hybridization on Bismuth Nanosheets for High Performing CO2 Electroreduction.

Single-atom alloys (SAAs) show great potential for a variety of electrocatalytic reactions. However, the atomic orbital hybridization effect of SAAs on the electrochemical reactions is unclear yet. Herein, the in situ confinement of vanadium/molybdenum/tungsten atoms on bismuth nanosheet is shown to create SAAs with rich grain boundaries, respectively. With the detailed analysis of microstructure and composition, the strong p-d orbital hybridization between bismuth and vanadium enables the exceptional electrocatalytic performance for carbon dioxide (CO2 ) reduction with the Faradaic efficiency nearly 100% for C1 products in a wide potential range from -0.6 to -1.4 V, and a long-term electrolysis stability for 90 h. In-depth in situ investigations with theoretical computations reveal that the electron delocalization toward vanadium atoms via the p-d orbital hybridization evokes the bismuth active centers for efficient CO2 activation via the σ-donation of O-to-Bi, thus reduces protonation energy barriers for formate production. With such fundamental understanding, SAA electrocatalyst is employed to fabricated the solar-driven electrolytic cell of CO2 reduction and 5-hydroxymethylfurfural oxidation, achieving an outstanding 2,5-furandicarboxylic acid yield of 90.5%. This study demonstrates a feasible strategy to rationally design advanced SAA electrocatalysts via the basic principles of p-d orbital hybridization.

Bisphenol A Regulates the TNFR1 Pathway and Excessive ROS Mediated by miR-26a-5p/ADAM17 Axis to Aggravate Selenium Deficiency-Induced Necroptosis in Broiler Veins.

Selenium (Se) deficiency can affect the expression of microRNA (miRNA) and induce necroptosis, apoptosis, etc., resulting in damage to various tissues and organs. Bisphenol A (BPA) exposure can cause adverse consequences such as oxidative stress, endothelial dysfunction, and atherosclerosis. The toxic effects of combined treatment with Se-deficiency and BPA exposure may have a synergistic effect. We replicated the BPA exposure and Se-deficiency model in broiler to investigate whether the combined treatment of Se-deficiency and BPA exposure induced necroptosis and inflammation of chicken vascular tissue via the miR-26A-5p/ADAM17 axis. We found that Se deficiency and BPA exposure significantly inhibited the expression of miR-26a-5p and increased the expression of ADAM17, thereby increasing reactive oxygen species (ROS) production. Subsequently, we discovered that the tumor necrosis factor receptor (TNFR1), which was highly expressed, activated the necroptosis pathway through receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed-lineage kinase domain-like (MLKL), and regulated the heat shock proteins-related genes expressions and inflammation-related genes expressions after exposure to BPA and selenium deficiency. In vitro, we found that miR-26a-5p knockdown and increased ADAM17 can induce necroptosis by activating the TNFR1 pathway. Similarly, both N-Acetyl-L-cysteine (NAC), Necrostatin-1 (Nec-1), and miR-26a-5p mimic prevented necroptosis and inflammation caused by BPA exposure and Se deficiency. These results suggest that BPA exposure activates the miR-26a-5p/ADAM17 axis and exacerbates Se deficient-induced necroptosis and inflammation through the TNFR1 pathway and excess ROS. This study lays a data foundation for future ecological and health risk assessments of nutrient deficiencies and environmental toxic pollution.

Association of Pulse Pressure Fluctuation During Hospitalization With Adverse Outcomes Within 3 Months After Ischemic Stroke.

BACKGROUND: Pulse pressure (PP) depends on heart function and arterial wall elasticity, which is closely related to the incidence of ischemic stroke. However, the association of PP fluctuation during hospitalization with adverse outcomes after ischemic stroke remains unclear. METHODS: The present study included 3,971 patients with ischemic stroke. The primary outcome was the composite outcome of death or vascular events within 3 months after ischemic stroke. PP fluctuation was reflected by successive variation of PP (PP-SV). RESULTS: The cumulative incidence rates of the primary outcome were the highest in the patients in the highest quartiles of PP-SV (P < 0.05). The multivariable-adjusted hazard ratios (95% confidence intervals) of the primary outcome in the highest quartiles were 1.86 (1.03-3.38) for death or vascular events, and 2.15 (1.06-4.37) for vascular events (all Ptrend < 0.05). Multivariable-adjusted restricted cubic spline analyses showed linear associations of PP-SV during hospitalization with the primary outcome (P for linearity <0.05). CONCLUSIONS: Large PP fluctuation during hospitalization was associated with increased risks of adverse outcomes within 3 months after ischemic stroke, which provided valuable new insight for blood pressure management in the acute phase of ischemic stroke. Controlling PP fluctuation may be contributing to improving prognosis after ischemic stroke.

Diffusion-weighted, intravoxel incoherent motion, and diffusion kurtosis tensor MR imaging in chronic kidney diseases: Correlations with histology.

OBJECTIVES: To probe the correlations of parameters derived from standard DWI and its extending models including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DKI) with the pathological and functional alterations in CKD. MATERIAL AND METHODS: Seventy-nine CKD patients with renal biopsy and 10 volunteers were performed with DWI, IVIM, diffusion kurtosis tensor imaging (DKTI) scanning. Correlations between imaging results and the pathological damage [glomerulosclerosis index (GSI) and tubulointerstitial fibrosis index (TBI)], as well as eGFR, 24 h urinary protein and Scr) were evaluated.CKD patients were divided into 2 groups: group 1: both GSI and TBI scores <2 points (61 cases); group 2: both GSI and TBI scores ≥2 points (18 cases). RESULTS: There were significant difference in cortical and medullary MD, and cortical D among 3 groups and between group 1 and 2. Cortical and medullary MD, cortical D, and medullary FA were negatively correlated with GSI score (r = -0.322 to -0.386, P < 0.05). Cortical and medullary MD and D, medullary FA were also negatively correlated with TBI score (r = -0.257 to -0.395, P < 0.05). These parameters were all correlated with eGFR and Scr. Cortical MD and D showed the highest AUC of 0.790 and 0.745 in discriminating mild and moderate-severe glomerulosclerosis and tubular interstitial fibrosis, respectively. CONCLUSIONS: The corrected diffusion-related indices, including cortical and medullary D and MD, as well as medullary FA were superior to ADC, perfusion-related and kurtosis indices for evaluating the severity of renal pathology and function in CKD patients.

Role of the RIP3-PGAM5-Drp1 pathway in aluminum-induced PC12 cells necroptosis.

Epidemiological studies from diverse global regions suggest a correlation between the accumulation of aluminum in the brain and the onset of various neurodegenerative diseases, including Alzheimer's disease, of which, neuronal cells death happen. Our previous research has found the potential of aluminum to induce neuronal cell death. A comprehensive exploration of the regulatory pathways influenced by aluminum in neuronal cell death could contribute to the development of strategies aimed at preventing the detrimental impact of aluminum on neuronal cells. This study is dedicated to exploring the impact of aluminum on mitochondrial homeostasis through the RIP3-PGAM5-Drp1 pathway, with a specific focus on its potential role in necroptosis. We observed that the inhibition of RIP3 function and the reduction in PGAM5 protein expression both mitigate aluminum-induced necroptosis in PC12 cells and enhance mitochondrial function. However, the inhibition of PGAM5 protein expression does not exert an impact on the expression of RIP3 and MLKL proteins. In summary, our study posits that aluminum can induce necroptosis in PC12 cells through the RIP3-PGAM5-Drp1 pathway.