Ultra-Tough Graphene Oxide/DNA 2D Hydrogel with Intrinsic Sensing and Actuation Functions.

Hydrogel devices with mechanical toughness and tunable functionalities are highly desirable for practical long-term applications such as sensing and actuation elements for soft robotics. However, existing hydrogels have poor mechanical properties, slow rates of response, and low functionality. In this work, two-dimensional hydrogel actuators are proposed and formed on the self-assembly of graphene oxide (GO) and deoxynucleic acid (DNA). The self-assembly process is driven by the GO-induced transition of double stranded DNA (dsDNA) into single stranded DNA (ssDNA). Thus, the hydrogel's structural unit consists of two layers of GO covered by ssDNA and a layer of dsDNA in between. Such heterogeneous architectures stabilized by multiple hydrogen bondings have Young's modulus of up to 10 GPa and rapid swelling rates of 4.0 × 10-3 to 1.1 × 10-2 s-1, which surpasses most types of conventional hydrogels. It is demonstrated that the GO/DNA hydrogel actuators leverage the unique properties of these two materials, making them excellent candidates for various applications requiring sensing and actuation functions, such as artificial skin, wearable electronics, bioelectronics, and drug delivery systems.

Graphene oxide-DNA/graphene oxide-PDDA sandwiched membranes with neuromorphic function.

The behavior of polyelectrolytes in confined spaces has direct relevance to the protein mediated ion transport in living organisms. In this paper, we govern lithium chloride transport by the interface provided by polyelectrolytes, polycation, poly(diallyldimethylammonium chloride) (PDDA) and, polyanion, double stranded deoxyribonucleic acid (dsDNA), in confined graphene oxide (GO) membranes. Polyelectrolyte-GO interfaces demonstrate neuromorphic functions that were successfully applied with nanochannel ion interactions contributed, resulting in ion memory effects. Excitatory and inhibitory post-synaptic currents were tuned continuously as the number of pulses applied increased accordingly, increasing decay times. Furthermore, we demonstrated the short-term memory of a trained vs untrained device in computation. On account of its simple and safe production along with its robustness and stability, we anticipate our device to be a low dimensional building block for arrays to embed artificial neural networks in hardware for neuromorphic computing. Additionally, incorporating such devices with sensing and actuating parts for a complete feedback loop produces robotics with its own ability to learn by modifying actuation based on sensing data.

Thiadiazole-, selenadiazole- and triazole-fused anthraquinones as G-quadruplex targeting anticancer compounds.

G-quadruplex (G4) ligands attract considerable attention as potential anticancer therapeutics. In this study we proposed an original scheme for synthesis of azole-fused anthraquinones and prepared a series of G4 ligands carrying amino- or guanidinoalkylamino side chains. The heterocyclic core and structure of the terminal groups strongly affect on binding to G4-forming oligonucleotides, cellular accumulation and antitumor potency of compounds. In particular, thiadiazole- and selenadiazole- but not triazole-based ligands inhibit the proliferation of tumor cells (e.g. K562 leukemia) and stabilize primarily telomeric and c-MYC G4s. Anthraselenadiazole derivative 11a showed a good affinity to c-MYC G4 in vitro and down-regulated expression of c-MYC oncogene in cellular conditions. Further studies revealed that anthraselenadiazole 11a provoked cell cycle arrest and apoptosis in a dose- and time-dependent manner inhibiting K562 cells growth. Taken together, this work gives a valuable example that the closely related heterocycles may cause a significant difference in biological properties of G4 ligands.

Interventions in preconception and pregnant women at risk of gestational diabetes; a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. OBJECTIVE: To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. METHODS: Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. RESULTS: Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference - 0.03, 95% CI 0.06, - 0.01; I2 58.69%), inositol (risk difference - 0.19, 95% CI 0.33, - 0.06; I2 92.19%), and vitamin D supplements (risk difference - 0.16, 95% CI 0.25, - 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference - 0.16, 95% CI 0.25, - 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference - 0.17, 95% CI 0.22, - 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. CONCLUSIONS: This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted.

Graphene oxide-polyamine preprogrammable nanoreactors with sensing capability for corrosion protection of materials.

Corrosion is one of the major issues for sustainable manufacturing globally. The annual global cost of corrosion is US$2.5 trillion (approximately 3.4% of the world's GDP). The traditional ways of corrosion protection (such as barriers or inhibiting) are either not very effective (in the case of barrier protection) or excessively expensive (inhibiting). Here, we demonstrate a concept of nanoreactors, which are able to controllably release or adsorb protons or hydroxides directly on corrosion sites, hence, selectively regulating the corrosion reactions. A single nanoreactor comprises a nanocompartment wrapped around by a pH-sensing membrane represented, respectively, by a halloysite nanotube and a graphene oxide/polyamine envelope. A nanoreactor response is determined by the change of a signaling pH on a given corrosion site. The nanoreactors are self-assembled and suitable for mass-line production. The concept creates sustainable technology for developing smart anticorrosion coatings, which are nontoxic, selective, and inexpensive.

A nanofluidic sensing platform based on robust and flexible graphene oxide/chitosan nanochannel membranes for glucose and urea detection.

We present the development of a health-monitoring nanofluidic membrane utilizing biocompatible and biodegradable graphene oxide, chitosan, and graphene quantum dots. The nanoconfinement provided by graphene oxide nanolayers encapsulates chitosan molecules, allowing for their conformational changes and switchable hydrophobic-hydrophilic behavior in response to pH variations. This low-dimensional membrane operates as an array of nanofluidic channels that can release quantum dots upon pH change. The photoluminescence emission from quantum dots enables rapid and reliable optical visualization of pH changes, facilitating efficient human health monitoring. To ensure fouling prevention and enable multiple usages, we adopt a design approach that avoids direct contact between biomarkers and the nanochannels. This design strategy, coupled with good mechanical properties (Young's modulus of 5.5 ± 0.7 GPa), preserves the integrity and functionality of the sensors for repeated sensing cycles. Furthermore, leveraging the memory effect, our sensors can be reloaded with graphene quantum dots multiple times without significant loss of selectivity, achieving reusability. The wide-ranging capabilities of 2D materials and stimuli-responsive polymers empower our sustainable approach to designing low-dimensional, robust, and flexible sensing materials. This approach allows for the integration of various biorecognition elements and signal transduction modes, expanding the versatility and applications of the designed materials.

Trends in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and vaccine antibody prevalence in a multi-ethnic inner-city antenatal population: A cross-sectional surveillance study.

OBJECTIVE: To determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in pregnancy in an inner-city setting and assess associations with demographic factors and vaccination timing. DESIGN: Repeated cross-sectional surveillance study. SETTING: London maternity centre. SAMPLE: A total of 906 pregnant women attending nuchal scans, July 2020-January 2022. METHODS: Blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid (N) and spike (S) proteins. Self-reported vaccination status and coronavirus disease 2019 (COVID-19) infection were recorded. Multivariable regression models determined demographic factors associated with seroprevalence and antibody titres. MAIN OUTCOME MEASURES: Immunoglobulin G N- and S-protein antibody titres. RESULTS: Of the 960 women, 196 (20.4%) were SARS-CoV-2 seropositive from previous infection. Of these, 70 (35.7%) self-reported previous infection. Among unvaccinated women, women of black ethnic backgrounds were most likely to be SARS-CoV-2 seropositive (versus white adjusted risk ratio [aRR] 1.88, 95% CI 1.35-2.61, p < 0.001). Women from black and mixed ethnic backgrounds were least likely to have a history of vaccination with seropositivity to S-protein (versus white aRR 0.58, 95% CI 0.40-0.84, p = 0.004; aRR 0.56, 95% CI 0.34-0.92, p = 0.021, respectively). Double vaccinated, previously infected women had higher IgG S-protein antibody titres than unvaccinated, previously infected women (mean difference 4.76 fold-change, 95% CI 2.65-6.86, p < 0.001). Vaccination timing before versus during pregnancy did not affect IgG S-antibody titres (mean difference -0.28 fold-change, 95% CI -2.61 to 2.04, p = 0.785). CONCLUSIONS: This cross-sectional study demonstrates high rates of asymptomatic SARS-CoV-2 infection with women of black ethnic backgrounds having higher infection risk and lower vaccine uptake. SARS-CoV-2 antibody titres were highest among double-vaccinated, infected women.

Angstrom-Confined Electrochemical Synthesis of Sub-Unit-Cell Non-Van Der Waals 2D Metal Oxides.

Bottom-up electrochemical synthesis of atomically thin materials is desirable yet challenging, especially for non-van der Waals (non-vdW) materials. Thicknesses below a few nanometers have not been reported yet, posing the question how thin can non-vdW materials be electrochemically synthesized. This is important as materials with (sub-)unit-cell thickness often show remarkably different properties compared to their bulk form or thin films of several nanometers thickness. Here, a straightforward electrochemical method utilizing the angstrom-confinement of laminar reduced graphene oxide (rGO) nanochannels is introduced to obtain a centimeter-scale network of atomically thin (<4.3 Å) 2D-transition metal oxides (2D-TMO). The angstrom-confinement provides a thickness limitation, forcing sub-unit-cell growth of 2D-TMO with oxygen and metal vacancies. It is showcased that Cr2 O3 , a material without significant catalytic activity for the oxygen evolution reaction (OER) in bulk form, can be activated as a high-performing catalyst if synthesized in the 2D sub-unit-cell form. This method displays the high activity of sub-unit-cell form while retaining the stability of bulk form, promising to yield unexplored fundamental science and applications. It is shown that while retaining the advantages of bottom-up electrochemical synthesis, like simplicity, high yield, and mild conditions, the thickness of TMO can be limited to sub-unit-cell dimensions.

Inpatient COVID-19 vaccination rollout: Improving access to vaccination.

BACKGROUND: We were aware of high numbers of inpatients unvaccinated against COVID-19 at Guy's and St Thomas' NHS Foundation Trust (GSTT). Due to this, an inpatient vaccination protocol was set up in July 2021, with initially limited uptake. METHODS: From October 2021, a multidisciplinary team worked to improve the protocol for inpatient vaccination, with the development of a system that gave ownership to clinical teams. RESULTS: In 4 months (July 2021 to November 2021), 20 inpatients had been vaccinated at GSTT. Following our intervention, rates of uptake increased, and 34 patients were vaccinated in less than 2 months (November 2021 to January 2022). Forty-five patients who had been referred were discharged without vaccination; attempts were made to invite them to receive a vaccine. CONCLUSION: An improved pathway and referral process increased the number of inpatient vaccinations delivered. Further work is required in order to ensure that more patients who have been referred are vaccinated.

Design, Synthesis and In Vitro Investigation of Cabozantinib-Based PROTACs to Target c-Met Kinase.

(1) Background: This investigation aimed at developing a series of c-Met-targeting cabozantinib-based PROTACs. (2) Methods: Purification of intermediate and target compounds was performed using column chromatography, in vitro antiproliferation activity was measured using a standard MTT assay and a c-Met degradation assay was performed via the immunoblotting technique. (3) Results: Several compounds exhibited antiproliferative activity towards different cell lines of breast cancer (T47D, MDA-MB-231, SKBR3, HCC1954 and MCF7) at the same level as parent cabozantinib and 7-demethyl cabozantinib. Two target conjugates, bearing a VHL-ligand as an E3-ligase binding moiety and glycol-based linkers, exhibited the effective inhibition of c-Met phosphorylation and an ability to decrease the level of c-Met in HCC1954 cells at micromolar concentrations. (4) Conclusions: Two compounds exhibit c-Met inhibition activity in the nanomolar range and can be considered as PROTAC molecules due to their ability to decrease the total level of c-Met in HCC1954 cells. The structures of the offered compounds can be used as starting points for further evaluation of cabozantinib-based PROTACs.

Satellite Glial Cells: Morphology, functional heterogeneity, and role in pain.

Neurons in the somatic, sympathetic, and parasympathetic ganglia are surrounded by envelopes consisting of satellite glial cells (SGCs). Recently, it has become clear that SGCs are highly altered after nerve injury, which influences neuronal excitability and, consequently, the development and maintenance of pain in different animal models of chronic pain. However, the exact mechanism underlying chronic pain is not fully understood yet because it is assumed that SGCs in different ganglia share many common peculiarities, making the process complex. Here, we review recent data on morphological and functional heterogeneity and changes in SGCs in various pain conditions and their role in response to injury. More research is required to decipher the role of SGCs in diseases, such as chronic pain, neuropathology, and neurodegenerative diseases.

Heterocyclic ring expansion yields anthraquinone derivatives potent against multidrug resistant tumor cells.

Chemical modifications of anthraquiones are aimed at novel derivatives with improved antitumor properties. Emergence of multidrug resistance (MDR) due to overexpression of transmembrane ATP binding cassette transporters, in particular, MDR1/P-glycoprotein (Pgp), can limit the use of anthraquinone based drugs. Previously we have demonstrated that annelation of modified five-membered heterocyclic rings with the anthraquinone core yielded a series of compounds with optimized antitumor properties. In the present study we synthesized a series of anthraquinone derivatives with six-membered heterocycles. Selected new compounds showed the ability to kill parental and MDR tumor cell lines at low micromolar concentrations. Molecular docking into the human Pgp model revealed a stronger interaction of 2-methylnaphtho[2,3-g]quinoline-3-carboxamide 17 compared to naphtho[2,3-f]indole-3-carboxamide 3. The time course of intracellular accumulation of compound 17 in parental K562 leukemia cells and in Pgp-positive K562/4 subline was similar. In contrast, compound 3 was readily effluxed from K562/4 cells and was significantly less potent for this subline than for K562 cells. Together with reported strategies of drug optimization of the anthracycline core, these results add ring expansion to the list of perspective modifications of heteroarene-fused anthraquinones.

Heterogeneity and Potency of Peripheral Glial Cells in Embryonic Development and Adults.

This review describes the heterogeneity of peripheral glial cell populations, from the emergence of Schwann cells (SCs) in early development, to their involvement, and that of their derivatives in adult glial populations. We focus on the origin of the first glial precursors from neural crest cells (NCCs), and their ability to differentiate into several cell types during development. We also discuss the heterogeneity of embryonic glia in light of the latest data from genetic tracing and transcriptome analysis. Special attention has been paid to the biology of glial populations in adult animals, by highlighting common features of different glial cell types and molecular differences that modulate their functions. Finally, we consider the communication of glial cells with axons of neurons in normal and pathological conditions. In conclusion, the present review details how information available on glial cell types and their functions in normal and pathological conditions may be utilized in the development of novel therapeutic strategies for the treatment of patients with neurodiseases.

Soft Hydrogel Actuator for Fast Machine-Learning-Assisted Bacteria Detection.

We demonstrate that our bio-electrochemical platform facilitates the reduction of detection time from the 3-day period of the existing tests to 15 min. Machine learning and robotized bioanalytical platforms require the principles such as hydrogel-based actuators for fast and easy analysis of bioactive analytes. Bacteria are fragile and environmentally sensitive microorganisms that require a special environment to support their lifecycles during analytical tests. Here, we develop a bio-electrochemical platform based on the soft hydrogel/eutectic gallium-indium alloy interface for the detection of Streptococcus thermophilus and Bacillus coagulans bacteria in various mediums. The soft hydrogel-based device is capable to support bacteria' viability during detection time. Current-voltage data are used for multilayer perceptron algorithm training. The multilayer perceptron model is capable of detecting bacterial concentrations in the 104 to 108 cfu/mL range of the culture medium or in the dairy products with high accuracy (94%). Such a fast and easy biodetection is extremely important for food and agriculture industries and biomedical and environmental science.

A UK based two-centre review of multifocality and its role in the treatment of papillary thyroid cancer.

INTRODUCTION: Multifocality is increasingly observed in papillary thyroid carcinoma (PTC) due to improvements in imaging and histopathological analysis. However, its significance in management, particularly as a sole risk-factor, remains controversial. This study aimed to investigate the prognostic value of multifocality in predicting recurrence following thyroid lobectomy in a contemporary group of PTC patients managed in the UK. METHODS: Patients with PTC in NHS Lothian (2009-19) and Guys and St Thomas NHS Foundation Trust (2012-19) were identified. Categorical variables were compared using Chi-squared or Fisher's exact test. Five-year recurrence free survival (RFS) were analysed using Kaplan-Meier method and compared using log-rank. RESULTS: Of 828 patients; 492 (59%) had unifocal and 336 (41%) multifocal disease on final pathology. A higher rate of pathological nodal disease (22%v36%,p < 0.001), total thyroidectomy (TT) (78%v92%,p < 0.001) and radioactive iodine (RAI) (57%v75%,p < 0.001) was demonstrated in patients with multifocality. With a median follow-up of 50 months, overall 5-year RFS was 96.5%; 96.5% for unifocal versus 96.6% for multifocal disease (p = 0.695). Recurrence was not shown to be associated with multifocality on either univariate or multivariate analysis. Amongst patients with T1/2N0M0 disease (n = 341), more patients were treated with TT and RAI with multifocal compared to unifocal disease (<0.001). Only two patients within this group recurred during follow up, both of whom had multifocal disease and were treated with TT and RAI (5yRFS100%v98.1%,p = 0.051). CONCLUSION: Multifocality is a common feature of PTC but does not appear to be an independent predictor of outcome. Therefore, treatment intensification on the basis of multifocality alone seems unwarranted.

Modeling Doxorubicin-Induced Cardiomyopathy With Fibrotic Myocardial Damage in Wistar Rats.

Background: Cardiovascular complications, arising after anthracycline chemotherapy, cause a significant deterioration in the life quality and expectancy of those patients who were previously successfully treated for malignant neoplasms. A number of clinical studies have demonstrated that patients with cardiotoxicity manifested during anthracyclines therapy also have extensive fibrotic changes in the cardiac muscle in the long term. Given the lack of an unambiguous understanding of the mechanisms of fibrotic changes formation under doxorubicin treatment in the myocardium, there is the obvious necessity to create a relevant experimental model of chronic doxorubicin-induced cardiomyopathy with fibrotic myocardial lesions and delayed development of diastolic dysfunction. Methods: The study was divided into two stages: first stage (creation of acute doxorubicin cardiomyopathy) - 35 male Wistar rats; second stage (creation of chronic doxorubicin cardiomyopathy) - 40 male Wistar rats. The animals were split into eight groups (two control ones and six experimental ones), which determined the doxorubicin dose (first stage: 25, 20.4, 15 mg/kg; second stage: 5, 10, 15 mg/kg, intraperitoneally) and the frequency of injection. Echocardiographic, hematological, histological, and molecular methods were used to confirm the successful modeling of acute and chronic doxorubicin-induced cardiomyopathy with fibrotic lesions. Results: A model of administration six times every other day with a cumulative dose of doxorubicin 20 mg/kg is suitable for evaluation of acute cardiotoxicity. The 15 mg/kg doxorubicin dose is highly cardiotoxic; what's more, it correlates with progressive deterioration of the clinical condition of the animals after 2 months. The optimal cumulative dose of doxorubicin leads to clinical manifestations confirmed by echocardiographic, histological, molecular changes associated with the development of chronic doxorubicin-induced cardiomyopathy with fibrotic lesions of the left ventricular of the cardiac muscle and ensure long-term survival of animals is 10 mg/kg doxorubicin. A dose of 5 mg/kg of the doxorubicin does not ensure the development of fibrous changes formation. Conclusion: We assume that cumulative dose of 10 mg/kg with a frequency of administration of six times in 2 days can be used to study the mechanisms of anthracycline cardiomyopathy development.

Periodic Self-Assembly of Poly(ethyleneimine)-poly(4-styrenesulfonate) Complex Coacervate Membranes.

Coacervation is a self-assembly strategy based on the complexation of polyelectrolytes, which is utilized in biomedicine and agriculture, as well as automotive and textile industries. In this paper, we developed a new approach to the on-demand periodic formation of polyelectrolyte complexes through a Liesegang-type hierarchical organization. Adjustment of reaction conditions allows us to assemble materials with a tunable spatiotemporal geometry and establish materials' production cycles with a regulated periodicity. The proposed methodology allows the membrane to self-assemble when striving to reach balance and self-heal after exposure to external stimuli, such as potential difference and high pH. Using chronopotentiometry, K+ ion permeability behavior of the PEI-PSS coacervate membranes was demonstrated. The periodically self-assembled polyelectrolyte nanomembranes could further be integrated into novel energy storage devices and intelligent biocompatible membranes for bionics, soft nanorobotics, biosensing, and biocomputing.

Graphene-Based Technologies for Tackling COVID-19 and Future Pandemics.

The COVID-19 pandemic highlighted the need for rapid tools and technologies to combat highly infectious viruses. The excellent electrical, mechanical and other functional properties of graphene and graphene-like 2D materials (2DM) can be utilized to develop novel and innovative devices to tackle COVID-19 and future pandemics. Here, the authors outline how graphene and other 2DM-based technologies can be used for the detection, protection, and continuous monitoring of infectious diseases including COVID-19. The authors highlight the potential of 2DM-based biosensors in rapid testing and tracing of viruses to enable isolation of infected patients, and stop the spread of viruses. The possibilities of graphene-based wearable devices are discussed for continuous monitoring of COVID-19 symptoms. The authors also provide an overview of the personal protective equipment, and potential filtration mechanisms to separate, destroy or degrade highly infectious viruses, and the potential of graphene and other 2DM to increase their efficiency, and enhance functional and mechanical properties. Graphene and other 2DM could not only play a vital role for tackling the ongoing COVID-19 pandemic but also provide technology platforms and tools for the protection, detection and monitoring of future viral diseases.

Protein-Bound Uremic Toxins Induce Reactive Oxygen Species-Dependent and Inflammasome-Mediated IL-1ß Production in Kidney Proximal Tubule Cells.

Protein bound-uremic toxins (PBUTs) are not efficiently removed by hemodialysis in chronic kidney disease (CKD) patients and their accumulation leads to various co-morbidities via cellular dysfunction, inflammation and oxidative stress. Moreover, it has been shown that increased intrarenal expression of the NLRP3 receptor and IL-1ß are associated with reduced kidney function, suggesting a critical role for the NLRP3 inflammasome in CKD progression. Here, we evaluated the effect of PBUTs on inflammasome-mediated IL-1ß production in vitro and in vivo. Exposure of human conditionally immortalized proximal tubule epithelial cells to indoxyl sulfate (IS) and a mixture of anionic PBUTs (UT mix) increased expression levels of NLRP3, caspase-1 and IL-1ß, accompanied by a significant increase in IL-1ß secretion and caspase-1 activity. Furthermore, IS and UT mix induced the production of intracellular reactive oxygen species, and caspase-1 activity and IL-1ß secretion were reduced in the presence of antioxidant N-acetylcysteine. IS and UT mix also induced NF-κB activation as evidenced by p65 nuclear translocation and IL-1ß production, which was counteracted by an IKK inhibitor. In vivo, using subtotal nephrectomy CKD rats, a significant increase in total plasma levels of IS and the PBUTs, kynurenic acid and hippuric acid, was found, as well as enhanced urinary malondialdehyde levels. CKD kidney tissue showed an increasing trend in expression of NLRP3 inflammasome components, and a decreasing trend in superoxide dismutase-1 levels. In conclusion, we showed that PBUTs induce inflammasome-mediated IL-1ß production in proximal tubule cells via oxidative stress and NF-κB signaling, suggesting their involvement in disease-associated inflammatory processes.