Mechanisms and therapeutic potential of disulphidptosis in cancer.

SLC7A11 plays a pivotal role in tumour development by facilitating cystine import to enhance glutathione synthesis and counteract oxidative stress. Disulphidptosis, an emerging form of cell death observed in cells with high expression of SLC7A11 under glucose deprivation, is regulated through reduction-oxidation reactions and disulphide bond formation. This process leads to contraction and collapse of the F-actin cytoskeleton from the plasma membrane, ultimately resulting in cellular demise. Compared to other forms of cell death, disulphidptosis exhibits distinctive characteristics and regulatory mechanisms. This mechanism provides novel insights and innovative strategies for cancer treatment while also inspiring potential therapeutic approaches for other diseases. Our review focuses on elucidating the molecular mechanism underlying disulphidptosis and its connection with the actin cytoskeleton, identifying alternative metabolic forms of cell death, as well as offering insights into disulphidptosis-based cancer therapy. A comprehensive understanding of disulphidptosis will contribute to our knowledge about fundamental cellular homeostasis and facilitate the development of groundbreaking therapies for disease treatment.

Plasma EGFR mutation ctDNA dynamics in patients with advanced EGFR-mutated NSCLC treated with Icotinib: phase 2 multicenter trial result.

Plasma epidermal growth factor receptor mutation (EGFRm) circulating tumor DNA (ctDNA) dynamics exhibit promise in predicting outcomes in patients with EGFRm-advanced non-small cell lung cancer (NSCLC). However, there remains limited trial-level data on integrating ctDNA monitoring into clinical practice. We performed a prospective, multicenter trial to investigate the relationship between EGFRm ctDNA dynamic changes and clinical outcomes in NSCLC patients with EGFRm. Ninety-eight treatment-naive EGFRm-advanced NSCLC patients were recruited and administered icotinib until disease progression. Plasma samples were collected at baseline and four weeks after icotinib administration. ctDNA was analyzed using a droplet-digital polymerase chain reaction. At baseline, 71.4% of patients had detectable EGFRm ctDNA. Among them, 45.9% of patients' ctDNA became undetectable within four weeks of treatment. These patients demonstrated significantly longer progression-free survival (PFS) and overall survival (OS) than those with detectable ctDNA after treatment (P = 0.004 and < 0.001, respectively) and were comparable to those with undetectable ctDNA at both baseline and four weeks. ctDNA detectable at four weeks emerged as a poor independent risk factor for PFS and OS. Patients whose ctDNA became undetectable after treatment had outcomes similar to those with initially undetectable ctDNA, underscoring the predictive value of ctDNA dynamics in treatment efficacy.Registry and the Registration No. of the study/trial: ChiCTR-DDD-17013131. Date of registration: 2017-10-27.

Enhancing thermal transport of epoxy composites with vertically aligned graphene in situ grown on the thermal interface.

The escalating demands for miniaturization, integration, and portability in electronic devices have underscored the criticality of efficient heat dissipation. The utilization of high-performance thermal interface materials (TIMs) to fill the gaps between contacting surfaces holds significant potential for enhancing heat transfer efficiency. Herein, we successfully enhance the thermal properties of the epoxy composite TIM by integrating in situ grown vertically aligned graphene on the metal surface using radio frequency plasma-enhanced chemical vapor deposition (RF-PECVD). To investigate the effect of vertical graphene on epoxy, the sandwich structure of copper/vertical graphene-epoxy/copper (Cu/VG-EP/Cu) is fabricated by incorporating epoxy resin. The experimental results demonstrate that the thermal conductivity of VG-EP reaches 2.06 W m-1 K-1 and achieves an impressive 1215% maximum enhancement. Furthermore, the numerical simulation findings show that vertical graphene consistent with the temperature gradient exhibits the highest heat transfer efficiency. This work presents an in-depth study of vertically aligned graphene within the epoxy resin, highlighting the advantages of vertically aligned fillers and offering novel perspectives for the advancement of TIMs.

Integration and competition between space and time in the hippocampus.

Episodic memory is organized in both spatial and temporal contexts. The hippocampus is crucial for episodic memory and has been demonstrated to encode spatial and temporal information. However, how the representations of space and time interact in the hippocampal memory system is still unclear. Here, we recorded the activity of hippocampal CA1 neurons in mice in a variety of one-dimensional navigation tasks while systematically varying the speed of the animals. For all tasks, we found neurons simultaneously represented space and elapsed time. There was a negative correlation between the preferred space and lap duration, e.g., the preferred spatial position shifted more toward the origin when the lap duration became longer. A similar relationship between the preferred time and traveled distance was also observed. The results strongly suggest a competitive and integrated representation of space-time by single hippocampal neurons, which may provide the neural basis for spatiotemporal contexts.

Efficacy analysis of immunotherapy­based combinations for patients with EGFR­mutant advanced non­small cell lung cancer after TKI failure.

Treatment options for epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC) following tyrosine kinase inhibitor (TKI) failure are limited, and platinum-based chemotherapy remains the main treatment. The development of effective immunotherapy for this disease has been challenging. In the present study, 37 patients with EGFR-mutant advanced NSCLC who were treated with programmed cell death-1 (PD-1) inhibitor-based combinations after TKI failure were reviewed. The total cohort had a median progression-free survival (mPFS) of 5.2 months (95% CI, 4.077-6.323 months) and a median overall survival (mOS) of 18.3 months (95% CI, 12.932-23.668 months). Patients with Eastern Cooperative Oncology Group performance-status (ECOG-PS) scores of 0 or 1 had longer mPFS than those with ECOG-PS scores of 2 (5.4 vs. 2.4 months; P=0.006). In addition, a PFS benefit was observed in patients with EGFR T790M-negative compared with EGFR T790M-positive tumors (mPFS 6.2 vs. 4.4 months; P=0.041). Patients treated with immunotherapy-based combinations as a front-line therapy had a longer mPFS than those in which the combinations were used as a late-line therapy (6.2 vs. 2.4 months; P<0.001). PD-1 inhibitor combined with chemotherapy and bevacizumab did not show a clear advantage over PD-1 inhibitor combined with chemotherapy alone (mPFS, 6.2 vs. 4.4 months; P=0.681), although it resulted in an improved overall response rate (ORR) and disease control rate. Notably, the 7 patients with a programmed cell death ligand-1 (PD-L1) tumor proportion score of ≥50% had an ORR of 100% and an mPFS of 8.3 months. Therefore, it is suggested that PD-1 inhibitor-based combinations should be a priority treatment option in selective populations, such as those with low ECOG-PS scores, T790M-negative status or high PD-L1 expression in EGFR-mutant NSCLC after TKI failure. The use of immunotherapy and chemotherapy in combination with antiangiogenic agents appears to be a promising combination therapy for such patients.

Associations of Patient Activation with Outcomes Among Patients on Chronic Hemodialysis: A Retrospective, Longitudinal, Observational Study.

BACKGROUND: Patient activation, defined as an individual's readiness, willingness, and ability to manage their own health and health care, is associated with healthy behaviors and improved outcomes. Patients undergoing in-center hemodialysis (HD) have low activation, but the association of patient activation with clinical outcomes among dialysis patients is unclear. We investigated the association between patient activation and outcomes in HD patients. METHODS: This cohort included 925 prevalent, in-center HD patients among 10 facilities in a mid-sized dialysis provider. All patients who completed the Patient Activation Measure 13-item (PAM-13) survey during a previous study were included, and their records were cross-referenced with data from the electronic heath system. Patients were followed for 180 days after completion of the survey for the primary outcomes of time to (1) death and (2) time to hospitalization. Markers of non-adherence during the month before and the month after completion of the PAM survey were examined as secondary outcomes, including (1) serum potassium >5.0 mEq/L; (2) serum phosphorus >5.5 mg/dL; (3) missed dialysis treatment due to absence (not hospitalization); and (4) interdialytic weight gain >4.0%. Univariate and adjusted regression models were fit to estimate associations of a 3-point increment in PAM-13 score with the outcomes of interest; adjustment factors comprised age, sex, dialysis vintage, serum albumin, diabetes, and hospitalization history. RESULTS: A 3-point increment in PAM score was associated with lower hazard of death (univariate HR=0.89, 95% CI: 0.84-0.94; adjusted HR=0.90, 95% CI: 0.85-0.96), but not with hospitalization (univariate HR=0.99, 95% CI: 0.96-1.02; adjusted HR=0.99, 95% CI: 0.96-1.02). Higher scores were associated with increased odds of having high phosphorus levels in the unadjusted analysis, but this was attenuated and not significant in adjusted models. There were no significant relationships between a 3-point increment in PAM score and any of the other secondary outcomes in univariate and adjusted analyses. CONCLUSION: In a cohort of prevalent, in-center HD patients, low activation was associated with mortality but not with hospitalization or measures of non-adherence.

Structure-Dependent Distribution, Metabolism, and Toxicity Effects of Alkyl Organophosphate Esters in Lettuce (Lactuca sativa L.).

This study provides a comprehensive investigation into the structure-dependent uptake, distribution, biotransformation, and potential toxicity effects of alkyl organophosphate esters (OPEs) in hydroponic lettuce (Lactuca sativa L.). Trimethyl, triethyl, and tripropyl phosphates were readily absorbed and acropetally translocated, while tributyl, tripentyl, and trihexyl phosphates accumulated mainly in lateral roots. The acropetal translocation potential was negatively associated with log Kow values. Trimethyl and triethyl phosphates are less prone to biotransformation, while a total of 14 novel hydrolysis, hydroxylated, and conjugated metabolites were identified for other OPEs using nontarget analysis. The extent of hydroxylation decreases from tripropyl phosphate to trihexyl phosphate, but multiple hydroxylations occurred more frequently on longer chain OPEs. Further comparative toxicity test revealed that hydrolyzed and hydroxylated metabolites have stronger toxic effects on Ca2+-dependent protein kinases (CDPK) than their parent OPEs. Dibutyl 3-hydroxybutyl phosphate particularly induces upregulation of CDPK in lateral roots of lettuce, probably associated with adenine reduction that may play an important role in the self-defense and detoxification processes. This study contributes to understanding the uptake and transformation behaviors of alkyl OPEs as well as their associations with a toxic effect on lettuce. This emphasizes the necessary evaluation of the environmental risk of the use of OPEs, particularly focusing on their hydroxylated metabolites.

Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. / Anoikiså’Œè‚¿ç˜¤å ç–«å¾®çŽ¯å¢ƒç›¸å ³åŸºå› åœ¨éª¨è‚‰ç˜¤æ²»ç–—ä¸­çš„é¢„åŽä»·å€¼ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents, with a poor prognosis. Anchorage-dependent cell death (anoikis) has been proven to be indispensable in tumor metastasis, regulating the migration and adhesion of tumor cells at the primary site. However, as a type of programmed cell death, anoikis is rarely studied in osteosarcoma, especially in the tumor immune microenvironment. This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. METHODS: Anoikis-related genes (ANRGs) were obtained from GeneCards. Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus (GEO) databases. ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis (WGCNA) algorithm. Machine learning algorithms were performed to construct long-term survival predictive strategy, each sample was divided into high-risk and low-risk subgroups, which was further verified in the GEO cohort. Finally, based on single-cell RNA-seq from the GEO database, analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment. RESULTS: A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified, from which 3 genes (MERTK, BNIP3, S100A8) were selected to construct the prognostic model. Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis (all P<0.05). Additionally, characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway. CONCLUSIONS: The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.

SPRank─A Knowledge-Based Scoring Function for RNA-Ligand Pose Prediction and Virtual Screening.

The growing interest in RNA-targeted drugs underscores the need for computational modeling of interactions between RNA molecules and small compounds. Having a reliable scoring function for RNA-ligand interactions is essential for effective computational drug screening. An ideal scoring function should not only predict the native pose for ligand binding but also rank the affinity of the binding for different ligands. However, existing scoring functions are primarily designed to predict the native binding modes for a given RNA-ligand pair and have not been thoroughly assessed for virtual screening purposes. In this paper, we introduce SPRank, a combination of machine-learning and knowledge-based scoring functions developed through a weighted iterative approach, specifically designed to tackle both binding mode prediction and virtual screening challenges. Our approach incorporates third-party docking software, such as rDock and AutoDock Vina, to sample flexible ligands against an ensemble of RNA structures, capturing the conformational flexibility of both the RNA and the ligand. Through rigorous testing, SPRank demonstrates improved performance compared to the tested scoring functions across four test sets comprising 122, 42, 55, and 71 nucleic acid-ligand complexes. Furthermore, SPRank exhibits improved performance in virtual screening tests targeting the HIV-1 TAR ensemble, which highlights its advantage in drug discovery. These results underscore the advantages of SPRank as a potentially promising tool for the RNA-targeted drug design. The source code of SPRank and the data sets are freely accessible at https://github.com/Vfold-RNA/SPRank.

Multi-Quantifying Maxillofacial Traits via a Demographic Parity-Based AI Model.

Objective and Impact Statement: The multi-quantification of the distinct individualized maxillofacial traits, that is, quantifying multiple indices, is vital for diagnosis, decision-making, and prognosis of the maxillofacial surgery. Introduction: While the discrete and demographically disproportionate distributions of the multiple indices restrict the generalization ability of artificial intelligence (AI)-based automatic analysis, this study presents a demographic-parity strategy for AI-based multi-quantification. Methods: In the aesthetic-concerning maxillary alveolar basal bone, which requires quantifying a total of 9 indices from length and width dimensional, this study collected a total of 4,000 cone-beam computed tomography (CBCT) sagittal images, and developed a deep learning model composed of a backbone and multiple regression heads with fully shared parameters to intelligently predict these quantitative metrics. Through auditing of the primary generalization result, the sensitive attribute was identified and the dataset was subdivided to train new submodels. Then, submodels trained from respective subsets were ensembled for final generalization. Results: The primary generalization result showed that the AI model underperformed in quantifying major basal bone indices. The sex factor was proved to be the sensitive attribute. The final model was ensembled by the male and female submodels, which yielded equal performance between genders, low error, high consistency, satisfying correlation coefficient, and highly focused attention. The ensemble model exhibited high similarity to clinicians with minor processing time. Conclusion: This work validates that the demographic parity strategy enables the AI algorithm with greater model generalization ability, even for the highly variable traits, which benefits for the appearance-concerning maxillofacial surgery.

Differences in the Quantitative HRCT Characteristics of Patients with Asthma, COPD and Asthma-COPD Overlap and Their Relationships with Pulmonary Function.

Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structure‒function relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.

Ultrasound Elastography Assessment of Knee Intra-Articular Adhesions at Varying Knee Angles.

We aimed to verify the feasibility of using shear wave elastography (SWE) to quantify knee scars and the elastic modulus of scar tissues. Overall, 16 participants underwent SWE assessments and range-of-motion measurement and completed the Knee Injury and Osteoarthritis Outcome Score. The inter-rater reliability for SWE in the suprapatellar bursa, below the patellar tendon, and in the medial and lateral trochlear groove remained within 0.861-0.907. The SWE values in the four regions increased with increasing knee angle, and significant differences were observed between the values for below the patellar tendon and the suprapatellar bursa at knee flexion angles of 60° and 90°. The SWE values of the medial and lateral trochlear groove at 30°, 60°, and 90° knee flexion were higher on the affected side. A negative correlation was observed between the SWE values for the lateral trochlear groove at 0°, 30°, and 60° and those for below the patellar tendon at 0° and the suprapatellar bursa at 30° with both active and passive knee extension. The suprapatellar bursa value at 60° exhibited a positive correlation with both knee flexion and passive knee flexion, whereas that of the suprapatellar bursa at 90° exhibited a positive correlation with both the range of motion and passive range of motion. SWE is a replicable and effective method for detecting scar strength in the knee joint.

A multi-scale feature selection module based architecture for the diagnosis of Alzheimer's disease on [18F]FDG PET.

OBJECTIVE: Alzheimer's disease (AD) is a prevalent form of dementia worldwide as a cryptic neurodegenerative disease. The symptoms of AD will last for several years, which brings great mental and economic burden to patients and their families. Unfortunately, the complete cure of AD still faces great challenges. Therefore, it is crucial to diagnose the disease in the early stage. MATERIALS AND METHODS: The Visual Geometry Group (VGG) network serves as the backbone for feature extraction, which could reduce the time cost of network training to a certain extent. In order to better extract image information and pay attention to the association information in the images, the group convolutional module and the multi-scale RNN-based feature selection module are proposed. The dataset employed in the study are drawn from [18F]FDG-PET images within the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. RESULTS: Comprehensive experimental results show that the proposed model outperforms several competing approaches in AD-related diagnostic tasks. In addition, the model reduces the number of parameters of the model compared to the backbone model, from 134.27 M to 17.36 M. Furthermore, the ablation reaserch is conducted to confirm the effectiveness of the proposed module. CONCLUSIONS: The paper introduces a lightweight network architecture for the early diagnosis of AD. In contrast to analogous methodologies, the proposed method yields acceptable results.

Efficacy and safety of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer: a retrospective analysis.

OBJECTIVE: This retrospective analysis aimed to evaluate the efficacy and adverse reactions of metronomic oral vinorelbine and its combination therapy as second- and later-line regimens for advanced non-small-cell lung cancer (NSCLC). METHODS: NSCLC patients undergoing metronomic oral vinorelbine as second- and later-line regimens in Fujian Cancer Hospital from October 2018 to October 2022 were enrolled, and patients' demographic and clinical characteristics were collected. The efficacy and safety of metronomic oral vinorelbine monotherapy and its combination therapy regimens were compared. RESULTS: Of 57 study subjects, 63.2% received third- and later-line therapy, with median progression-free survival (mPFS) of 4 months, overall response rate (ORR) of 10.5%, and disease control rate (DCR) of 80.7%. The incidence of therapy-related adverse events was 42.1%, and there was only one case presenting grades 3 and 4 adverse events (1.8%). Among driver gene-negative participants, vinorelbine combination therapy regimens achieved longer mPFS (4.6 vs. 1.2 months, hazards ratio = 0.11, P < 0.0001) and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine combined with immune checkpoint inhibitors showed the highest response, with mPFS of 5.6 months (95% CI 4.8 to 6.4 months), ORR of 25%, and DCR of 81.3%. Among participants with gradual resistance to osimertinib, continuing osimertinib in combination with metronomic oral vinorelbine achieved mPFS of 6.3 months (95% CI 0.1 to 12.5 months) and DCR of 86.7%. CONCLUSION: Metronomic oral vinorelbine and its combination therapy regimens are favorable options as second- and later-line therapy for advanced NSCLC patients, with acceptable efficacy and tolerable toxicity. Vinorelbine combination therapy regimens show higher efficacy and comparable toxicity in relative to metronomic oral vinorelbine, and metronomic oral vinorelbine may have a synergistic effect with immunotherapy and EGFR-TKI targeted therapy.

Description and outcomes of a staff-assisted peritoneal dialysis program in the United States.

BACKGROUND: Staff-assisted peritoneal dialysis (PD) can help overcome barriers to self-care but is not yet available in the United States (US). We developed and implemented a staff-assisted PD program that fits within current regulatory and cost restraints in the US healthcare environment. METHODS: Patient care technicians (PCTs) were trained on PD procedures and troubleshooting common problems. The program expanded from two centers in August 2020 to sixteen by October 2022. We described the logistic elements of program delivery, and patient and treatment outcomes for patients discharged by end of April 2023, with a cohort follow up until October 2023. RESULTS: A total of 121 patients were referred to the program. The most common indications for referral were physical function limitations, cognitive impairment, and psychosocial challenges. Staff assistance was provided for 73 patients. Mean age was 72 (standard deviation 14) years. A total of 604 visits were delivered, with a median 5 (interquartile range [IQR] 3-10, range: 1-49) visits per patient. Median duration of assistance was 8 (IQR: 2-21, range: 1-84) days. Assistance was most frequently needed for PD treatment setup and for observing and directing the technique. No peritonitis events or exit-site infections were reported. Sixty-eight patients (93%) were discharged on PD without staff assistance. The 6- and 12-month survival of PD without assistance was 71% and 57%, respectively. CONCLUSIONS: Staff-assisted PD for limited time periods is operationally feasible with PCTs in the US and can support transitioning and maintaining patients on PD.ClinicalTrials.gov Identifier: NCT04319185.

Modeling the reactive oxygen species (ROS) wave in Chlamydomonas reinhardtii colonies.

Reactive oxygen species (ROS) play a crucial role as signaling molecules in both plant and animal cells, enabling rapid responses to various stimuli. Among the many cellular mechanisms used to generate and transduce ROS signals, ROS-induced-ROS release (RIRR) is emerging as an important pathway involved in the responses of various multicellular and unicellular organisms to environmental stresses. In RIRR, one cellular compartment, organelle, or cell generates or releases ROS, triggering an increased ROS production and release by another compartment, organelle, or cell, thereby giving rise to a fast propagating ROS wave. This RIRR-based signal relay has been demonstrated to facilitate mitochondria-to-mitochondria communication in animal cells and long-distance systemic signaling in plants in response to biotic and abiotic stresses. More recently, it has been discovered that different unicellular microorganism communities also exhibit a RIRR cell-to-cell signaling process triggered by a localized stress treatment. However, the precise mechanism underlying the propagation of the ROS signal among cells within these unicellular communities remained elusive. In this study, we employed a reaction-diffusion model incorporating the RIRR mechanism to analyze the propagation of ROS-mediated signals. By effectively balancing production and scavenging processes, our model successfully reproduces the experimental ROS signal velocities observed in unicellular green algae (Chlamydomonas reinhardtii) colonies grown on agar plates, furthering our understanding of intercellular ROS communication.

Cracking the Code: Enhancing Molecular Tools for Progress in Nanobiotechnology.

Nature continually refines its processes for optimal efficiency, especially within biological systems. This article explores the collaborative efforts of researchers worldwide, aiming to mimic nature's efficiency by developing smarter and more effective nanoscale technologies and biomaterials. Recent advancements highlight progress and prospects in leveraging engineered nucleic acids and proteins for specific tasks, drawing inspiration from natural functions. The focus is developing improved methods for characterizing, understanding, and reprogramming these materials to perform user-defined functions, including personalized therapeutics, targeted drug delivery approaches, engineered scaffolds, and reconfigurable nanodevices. Contributions from academia, government agencies, biotech, and medical settings offer diverse perspectives, promising a comprehensive approach to broad nanobiotechnology objectives. Encompassing topics from mRNA vaccine design to programmable protein-based nanocomputing agents, this work provides insightful perspectives on the trajectory of nanobiotechnology toward a future of enhanced biomimicry and technological innovation.

POSTN promotes nucleus pulposus cell senescence and extracellular matrix metabolism via activing Wnt/ß-catenin and NF-κB signal pathway in intervertebral disc degeneration.

BACKGROUND: Intervertebral disc (IVD) degeneration (IVDD) is a prevalent condition contributing to back pain and disability. Periostin (POSTN) has emerged as a potential molecular marker and therapeutic target in IVDD, prompting further investigation into its role and mechanisms. METHODS: This study employs bioinformatics analysis combined with experimental validation to explore the role of POSTN in IVDD. Gene expression datasets from the GEO database were analyzed to identify genes associated with IVDD, and the effects of POSTN on rat nucleus pulposus (NP) cells senescence and extracellular matrix (ECM) metabolism were assessed both in vitro and in vivo. RESULTS: Elevated POSTN expression was observed in degenerated discs from IVDD patients, correlating with disease severity. In vitro experiments demonstrated that POSTN promotes NP cells senescence and ECM metabolism in a dose- and time-dependent manner. In vivo studies confirmed that POSTN inhibition can ameliorate the progression of IVDD. Further mechanistic insights revealed that POSTN may exert its effects by activating the NF-κB and Wnt/ß-catenin signaling pathways. CONCLUSION: POSTN plays a significant role in the pathogenesis of IVDD, with its upregulated expression closely linked to NP cells senescence and ECM metabolism. Targeting POSTN could offer a novel therapeutic strategy for IVDD. Additionally, the study predicts small molecules that may inhibit POSTN expression, providing potential candidates for the development of new drug treatments.

Design of a Transformer Oil Viscosity, Density, and Dielectric Constant Simultaneous Measurement System Based on a Quartz Tuning Fork.

Transformer oil, crucial for transformer and power system safety, demands effective monitoring. Aiming to address the problems of expensive and bulky equipment, poor real-time performance, and single parameter detection of traditional measurement methods, this study proposes a quartz tuning fork-based simultaneous measurement system for online monitoring of the density, viscosity, and dielectric constant of transformer oil. Based on the Butterworth-Van Dyke quartz tuning fork equivalent circuit model, a working mechanism of transformer oil density, viscosity, and dielectric constant was analyzed, and a measurement model for oil samples was obtained. A miniaturized simultaneous measurement system was designed based on a dedicated chip for vector current-voltage impedance analysis for data acquisition and a Savitzky-Golay filter for data filtering. A transformer oil test platform was built to verify the simultaneous measurement system. The results showed that the system has good repeatability, and the measurement errors of density, viscosity, and dielectric constant are lower than 2.00%, 5.50%, and 3.20%, respectively. The online and offline results showed that the system meets the requirements of the condition maintenance system for online monitoring accuracy and real-time detection.