Customizable polarization-selective narrowband meta-filters using a printable UV-curing nanocomposite.

Low-cost nanocomposite metasurfaces have demonstrated attractive potential to replace the equivalent dielectric metasurfaces for light engineering. However, the resonance characteristics of embedded structures in nanocomposite metasurfaces have not been further analyzed beyond the effective refractive index. Herein, we have proposed customizable polarization-selective narrowband meta-filters using ultraviolet-curable (UV) nanocomposites. As an additional degree of freedom, near-field effects between highly concentrated doped nanoparticles can enhance the Mie resonance of the low aspect ratio (AR = 0.2) meta-units. The surface lattice resonances (SLRs) of meta-filters can be coupled with enhanced Mie resonances of individual meta-units to realize tunable narrowband (FWHM ∼0.007λ) reflections with intensities near unity. Meanwhile, the polarization-selective properties of the reflection peaks can be tuned by optimizing the asymmetric lattice. Such proposed new-generation customizable meta-filters will offer, to our knowledge, novel strategies for filtering specific near-infrared polarized fluorescence in the integrated imaging systems.

Exploring Si-centered phthalocyanine as a single atom catalyst for N2O reduction: a DFT study.

To remove the greenhouse gas N2O from the environment, recently, researchers have taken great interest in single-atom catalysts (SACs). In this study, we investigated various reaction pathways and barrier energies for the N2O reduction process onto Si-coordinated phthalocyanine (Si@PthC) employing density functional theory. The outcomes validate that Si decoration in PthC is energetically stable while the corresponding electronic properties show that the Si atom acts as the reactive site for catalytic activity. The N2O molecule exhibits spontaneous dissociation over the catalyst surface from the O-end with -4.01 eV dissociation energy. Meanwhile, N2O dissociation via the N-end involves chemisorption onto the Si@PthC surface with an adsorption energy (Ead) of -1.16 eV, and the dissociation needs an energy barrier of 0.51 eV. The bond distances and negative adsorption energies (-1.11 and -2.40 eV) evince that CO and O2 species chemisorbed onto the Si@PthC surface. However, these energies are smaller than the N2O dissociation energy, which demonstrates that the presence of CO and O2 molecules cannot interrupt the N2O reduction process. Additionally, the CO + O* → CO2 reaction was executed for catalyst recovery, and the reaction proceeds very quickly on the Si@PthC catalyst, with a very small energy barrier (0.37 eV), indicating the excellent catalytic reactivity of the studied catalyst. These results propose that the designed catalyst can be valuable in the progress of novel noble metal-free catalysts for the elimination of harmful N2O from the environment.

Utilization of social franchising in family planning services: a Pakistan perspective.

Introduction: Pakistan's private sector caters to around 65% of family planning users. Private sector family planning was promoted in the Delivering Accelerated Family Planning in Pakistan (DAFPAK) program by UK's Foreign, Commonwealth & Development Office (FCDO) in 2019. We use data from DAFPAK to analyze the clientele and products distributed by two major NGOs, Marie Stopes Society (MSS) and DKT Pakistan, that support private providers in Pakistan. We also examined the effect of COVID-19 on client visits and contraceptives uptake at private facilities in Pakistan. Methods: DAFPAK used field validation surveys to analyze the volume of clients and products of 639 private facilities across three provinces (Punjab, KPK and Balochistan) of Pakistan. The data was collected in two phases (February 2020 and 2021) using multi-stage cluster sampling at 95% confidence level. Using a generalized negative binomial regression, facility-level characteristics and impact of COVID-19 was analyzed with the volume of clients and products given out at 95% confidence interval alongside descriptive analysis. Results: DKT facilities covered 53% of the sample while MSS covered 47%, with 72% facilities in the rural areas. Average facility existence duration is 87 months (7.25 years). While the average experience of the facility staff is 52 months (4.33 years). MSS is serving more clients as compared to DKT during both phase 1 (IRR: 3.15; 95% CI: 2.74, 3.61) and phase 2 (IRR: 2.11; 95% CI: 1.79, 2.49). Similarly, MSS had a greater volume of products given out in both phases 1 (IRR: 1.89; 95% CI: 1.51, 2.38) and phase 2 (IRR: 2.57; 95% CI: 2.09, 3.14). In both phases, client visits and product distribution decreased when client privacy is invaded (IRR: 0.74; 95% CI: 0.67, 0.82 - phase 1) and (IRR: 0.83; 95% CI: 0.72, 0.97 - phase 2). Lastly, during COVID-19, products distribution decreased by a factor of 0.84 (IRR: 0.84; 95% CI: 0.72, 0.97) but client visits remain unaffected. Conclusion: Overall, clientele is low for all facilities. At a facility, privacy is a determinant of client visits and products given out per visit. Transiently, during COVID-19, client volumes decreased, with a shift from oral pills to condoms and emergency contraceptive pills.

Achieving optimal balance: tuning electrical and optical characteristics of carbon electrodes for emerging photovoltaics.

Transparent and conductive electrodes (TCEs) are essential for various optoelectronic and photovoltaic applications, but they often require expensive and complex fabrication methods. In this paper, a unique low-cost, eco-friendly, and scalable method of fabricating TCEs using spray-coated carbon ink is investigated. Firstly the carbon particles used for this process underwent a size reduction from 20 microns to 0.96 microns via ball milling. Then ink was prepared by mixing graphite powder (for conductivity), ethyl cellulose (for viscosity), and toluene (for solubility) with different weight-per-volume ratios (w/v) of 5%, 10%, and 15%. The TCEs were fabricated by spray coating the ink onto glass substrates using an airbrush. The sheet resistance (Ω sq-1) and transparency (%) of the TCEs were measured by a digital multimeter (DMM) probe method and a UV-vis spectrophotometer, respectively. The sheet resistance of the TCEs decreased linearly from 60 to 20 Ω sq-1, while the transparency decreased exponentially from 37.18% to 18.88% as the ink concentration increased from 5% to 15% w/v. This paper also reports the reflectance and absorbance values for each ink concentration. The results demonstrate that spray-coated carbon ink TCEs achieve sheet resistance and transparency values of 20 Ω sq-1 and 18.88%, respectively, with low-cost and eco-friendly materials and methods, which are desirable for optoelectronic and photovoltaic applications. These TCEs can play an important role as electrodes in semi-transparent perovskite cells enhancing their stability and overall efficiency.

Central Serous Chorioretinopathy: Epidemiology, Genetics and Clinical Features.

Central serous chorioretinopathy (CSCR) is the fourth most common medical retinal disease. Moderate vision loss occurs in approximately one-third of patients who have the chronic form of the disease. CSCR has a multifactorial etiology, with acquired risk factors and increasing evidence of genetic susceptibility factors. The detection of new gene variants in CSCR and association of these variants with age-related macular degeneration provide insights into possible disease mechanisms. The contribution of multimodal ocular imaging and associated research studies to the modern-day clinical investigation of CSCR has been significant. This review aims to provide an overview of the most significant epidemiological and genetic studies of CSCR, in addition to describing its clinical and multimodal imaging features. The review also provides an update of the latest evidence from studies investigating pathophysiological mechanisms in CSCR and current opinions on multimodal imaging to better classify this complex retinal disease.

Improvements in Wear and Corrosion Resistance of Ti-W-Alloyed Gray Cast Iron by Tailoring Its Microstructural Properties.

The improved wear and corrosion resistance of gray cast iron (GCI) with enhanced mechanical properties is a proven stepping stone towards the longevity of its versatile industrial applications. In this article, we have tailored the microstructural properties of GCI by alloying it with titanium (Ti) and tungsten (W) additives, which resulted in improved mechanical, wear, and corrosion resistance. The results also show the nucleation of the B-, D-, and E-type graphite flakes with the A-type graphite flake in the alloyed GCI microstructure. Additionally, the alloyed microstructure demonstrated that the ratio of the pearlite volume percentage to the ferrite volume percentage was improved from 67/33 to 87/13, whereas a reduction in the maximum graphite length and average grain size from 356 ± 31 µm to 297 ± 16 µm and 378 ± 18 µm to 349 ± 19 µm was detected. Consequently, it improved the mechanical properties and wear and corrosion resistance of alloyed GCI. A significant improvement in Brinell hardness, yield strength, and tensile strength of the modified microstructure from 213 ± 7 BHN to 272 ± 8 BHN, 260 ± 3 MPa to 310 ± 2 MPa, and 346 ± 12 MPa to 375 ± 7 MPa was achieved, respectively. The substantial reduction in the wear rate of alloyed GCI from 8.49 × 10-3 mm3/N.m to 1.59 × 10-3 mm3/N.m resulted in the upgradation of the surface roughness quality from 297.625 nm to 192.553 nm. Due to the increase in the corrosion potential from -0.5832 V to -0.4813 V, the impedance of the alloyed GCI was increased from 1545 Ohm·cm2 to 2290 Ohm·cm2. On the basis of the achieved experimental results, it is suggested that the reliability of alloyed GCI based on experimentally validated microstructural compositions can be ensured during the operation of plants and components in a severe wear and corrosive environment. It can be predicted that the proposed alloyed GCI components are capable of preventing the premature failure of high-tech components susceptible to a wear and corrosion environment.

Assessment of textile effluent treatment by immobilized Trametes pubescens MB 89 for plant growth promotion.

Industrialization and the ever-increasing world population have diminished high-quality water resources for sustainable agriculture. It is imperative to effectively treat industrial effluent to render the treated water available for crop cultivation. This study aimed to assess the effectiveness of textile effluent treated with Trametes pubescens MB 89 in supporting maize cultivation. The fungal treatment reduced the amounts of Co, Pb and As in the textile effluent. The biological oxygen demand, total dissolved solids and total suspended solids were within the permissible limits in the treated effluent. The data indicated that the irrigation of maize with fungal-treated textile effluent improved the growth parameters of the plant including root, shoot length, leaf area and chlorophyll content. Moreover, better antioxidant activity, total phenol content and protein content in roots, stems and leaves of maize plants were obtained. Photosynthetic parameters (potential quantum yield, electron transport rate and fluorescence yield of non-photochemical losses other than heat) were also improved in the plants irrigated with treated effluent as compared to the control groups. In conclusion, the treatment of textile effluent with the immobilized T. pubescens presents a sustainable solution to minimize chemical pollution and effectively utilize water resources.

Efficient detection of nitric oxide a biomarker associated with COVID19 via N, P co-doped C60 fullerene: a computational study.

CONTEXT: Coronavirus (COVID-19) is a novel respiratory viral infection, causing a relatively large number of deaths especially in people who underly lung diseases such as chronic obstructive pulmonary and asthma, and humans are still suffering from the limited testing capacity. In this article, a solution is proposed for the detection of COVID-19 viral infections through the analysis of exhaled breath gasses, i.e., nitric oxide, a prominent biomarker released by respiratory epithelial, as a non-invasive and time-saving approach. Here, we designed a novel and low-cost N and P co-doped C60 fullerene-based breathalyzer for the detection of NO gas exhaled from the respiratory epithelial cells. This breathalyzer shows a quick response to the detection of NO gas by directly converting NO to NO2 without passing any energy barrier (0 kcal/mol activation energy). The recovery time of breathalyzer is very short (0.98 × 103 s), whereas it is highly selective for NO sensing in the mixture of CO2 and H2O gasses. The study provides an idea for the synthesis of low-cost (compared to previously reported Au atom decorated nanostructure and metal-based breathalyzer), efficient, and highly selective N and P co-doped C60 fullerene-based breathalyzer for COVID-19 detection. METHODS: The geometries of N and P-doped systems and gas molecules are simulated using spin-polarized density functional theory calculations.

Robust polymer hybrid and assembly materials from structure tailoring to efficient catalytic remediation of emerging pollutants.

A massive amount of toxic substances and harmful chemicals are released every day into the outer environment, imposing serious environmental impacts on both land and aquatic animals. To date, research is constantly in progress to determine the best catalytic material for the effective remediation of these harmful pollutants. Hybrid nanomaterials prepared by combining functional polymers with inorganic nanostructures got attention as a promising area of research owing to their remarkable multifunctional properties deriving from their entire nanocomposite structure. The versatility of the existing nanomaterials' design in polymer-inorganic hybrids, with respect to their structure, composition, and architecture, opens new prospects for catalytic applications in environmental remediation. This review article provides comprehensive detail on catalytic polymer nanocomposites and highlights how they might act as a catalyst in the remediation of toxic pollutants. Additionally, it provides a detailed clarification of the processing of design and synthetic ways for manufacturing polymer nanocomposites and explores further into the concepts of precise design methodologies. Polymer nanocomposites are used for treating pollutants (electrocatalytic, biocatalytic, catalytic, and redox degradation). The three catalytic techniques that are frequently used are thoroughly illustrated. Furthermore, significant improvements in the method through which the aforementioned catalytic process and pollutants are extensively discussed. The final section summarizes challenges in research and the potential of catalytic polymer nanocomposites for environmental remediation.

Surface roughness influence on extracellular electron microbiologically influenced corrosion of C1018 carbon steel by Desulfovibrio ferrophilus IS5 biofilm.

Carbon steel microbiologically influenced corrosion (MIC) by sulfate reducing bacteria (SRB) is known to occur via extracellular electron transfer (EET). A higher biofilm sessile cell count leads to more electrons being harvested for sulfate reduction by SRB in energy production. Metal surface roughness can impact the severity of MIC by SRB because of varied biofilm attachment. C1018 carbon steel coupons (1.2 cm2 top working surface) polished to 36 grit (4.06 µm roughness which is relatively rough) and 600 grit (0.13 µm) were incubated in enriched artificial seawater inoculated with highly corrosive Desulfovibrio ferrophilus IS5 at 28 â„ƒ for 7 d and 30 d. It was found that after 7 d of SRB incubation, 36 grit coupons had a 11% higher sessile cell count at (2.0 ± 0.17) × 108 cells/cm2, 52% higher weight loss at 22.4 ± 5.9 mg/cm2 (1.48 ± 0.39 mm/a uniform corrosion rate), and 18% higher maximum pit depth at 53 µm compared with 600 grit coupons. However, after 30 d, the differences diminished. Electrochemical tests with transient information supported the weight loss data trends. This work suggests that a rougher surface facilitates initial biofilm establishment but provides no long-term advantage for increased biofilm growth.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency.

Synthesis of hydrazone-based polyhydroquinoline derivatives - antibacterial activities, α-glucosidase inhibitory capability, and DFT study.

In recent years, polyhydroquinolines have gained much attention due to their widespread applications in medicine, agriculture, industry, etc. Here, we synthesized a series of novel hydrazone-based polyhydroquinoline derivatives via multi-step reactions. These molecules were characterized by modern spectroscopic techniques (1H-NMR, 13C NMR, and LC-HRMS) and their antibacterial and in vitro α-glucosidase inhibitory activities were assessed. Compound 8 was found to be the most active inhibitor against Listeria monocytogenes NCTC 5348, Bacillus subtilis IM 622, Brevibacillus brevis, and Bacillus subtilis ATCC 6337 with a zone of inhibition of 15.3 ± 0.01, 13.2 ± 0.2, 13.1 ± 0.1, and 12.6 ± 0.3 mm, respectively. Likewise, compound 8 also exhibited the most potent inhibitory potential for α-glucosidase (IC50 = 5.31 ± 0.25 µM) in vitro, followed by compounds 10 (IC50 = 6.70 ± 0.38 µM), and 12 (IC50 = 6.51 ± 0.37 µM). Furthermore, molecular docking and DFT analysis of these compounds showed good agreement with experimental work and the nonlinear optical properties calculated here indicate that these compounds are good candidates for nonlinear optics.

Misidentification of the True Aortic Annulus With 2-dimensional Echocardiography: A Critical Appraisal Using 3-Dimensional Imaging.

OBJECTIVES: This study aimed to evaluate the accuracy of identifying the true aortic valve (AV) annulus using 2-dimensional (2D) echocardiography, with the goal of highlighting potential misidentification issues in clinical practice. DESIGN: An observational study employing 3-dimensional (3D) datasets to generate 2D images of the AV annulus for analysis. SETTING: The study was conducted in an academic medical center. PARTICIPANTS: Three-dimensional transesophageal echocardiography datasets were obtained from 11 patients with normal AV and aortic root anatomies undergoing coronary artery bypass surgery. Attending anesthesiologists certified by the National Board of Echocardiography (NBE) were approached subsequently to participate in this study. INTERVENTIONS: Two images per patient were generated from 3D datasets, reflecting the mid-esophageal long-axis view of the AV, a true AV annulus image, and an off-axis image. A survey was distributed to NBE-certified perioperative echocardiographers across 12 academic institutions to identify the true AV annulus from these images. MEASUREMENTS AND MAIN RESULTS: The survey, completed by 45 qualified respondents, revealed a significant misidentification rate of the true AV annulus, with only 36.8% of responses correctly identifying it. The rate of correct identification varied across image sets, with 44.4% of participants unable to correctly identify any true AV annulus image. CONCLUSIONS: The study highlighted the limitations of 2D echocardiography in accurately identifying the true AV annulus in complex 3D structures like the aortic root. The findings suggest a need for greater reliance on advanced imaging modalities, such as 3D echocardiography, to improve accuracy in clinical practice.

Effects of Regulating Hippo and Wnt on the Development and Fate Differentiation of Bovine Embryo.

The improvement of in vitro embryo development is a gateway to enhance the output of assisted reproductive technologies. The Wnt and Hippo signaling pathways are crucial for the early development of bovine embryos. This study investigated the development of bovine embryos under the influence of a Hippo signaling agonist (LPA) and a Wnt signaling inhibitor (DKK1). In this current study, embryos produced in vitro were cultured in media supplemented with LPA and DKK1. We comprehensively analyzed the impact of LPA and DKK1 on various developmental parameters of the bovine embryo, such as blastocyst formation, differential cell counts, YAP fluorescence intensity and apoptosis rate. Furthermore, single-cell RNA sequencing (scRNA-seq) was employed to elucidate the in vitro embryonic development. Our results revealed that LPA and DKK1 improved the blastocyst developmental potential, total cells, trophectoderm (TE) cells and YAP fluorescence intensity and decreased the apoptosis rate of bovine embryos. A total of 1203 genes exhibited differential expression between the control and LPA/DKK1-treated (LD) groups, with 577 genes upregulated and 626 genes downregulated. KEGG pathway analysis revealed significant enrichment of differentially expressed genes (DEGs) associated with TGF-beta signaling, Wnt signaling, apoptosis, Hippo signaling and other critical developmental pathways. Our study shows the role of LPA and DKK1 in embryonic differentiation and embryo establishment of pregnancy. These findings should be helpful for further unraveling the precise contributions of the Hippo and Wnt pathways in bovine trophoblast formation, thus advancing our comprehension of early bovine embryo development.

Systematic surface bowing in 2D III-nitride monolayers.

In this article we report novel composite materials of bucky ball (C60 fullerene) and III-nitrides (BN, AlN, GaN, InN). The experimental feasibility of the novel composite materials is confirmed through negative binding energies and molecular dynamics simulations performed at 500 K. The structural properties of the novel composites are explored through density functional theory. An unusual phenomenon of surface bowing is observed in the 2D structure of the III-nitride monolayers due to the C60 sticking. This surface bowing systematically increases as one proceeds from BN → AlN → GaN → InN. The electron density difference and Hirshfeld charge density analysis show smaller charge transfer during the complexation, which is probably due to weak van der Waal's forces. The presence of van der Waal's forces is also confirmed by the Atom in Molecule analysis, Reduced Density Gradient Technique and Non-covalent Interaction analysis. This work provides a foundation for further theoretical and experimental studies of the novel phenomenon of systematic bowing in the 2D structure of III-nitride monolayers.

Correction: Biogenic synthesis of silver nanoparticles using Rubus fruticosus extract and their antibacterial efficacy against Erwinia caratovora and Ralstonia solanacearum phytopathogens.

[This corrects the article DOI: 10.1039/D3RA06723H.].

Advancements in Genetic Biomarkers and Exogenous Antioxidant Supplementation for Safeguarding Mammalian Cells against Heat-Induced Oxidative Stress and Apoptosis.

Heat stress represents a pervasive global concern with far-reaching implications for the reproductive efficiency of both animal and human populations. An extensive body of published research on heat stress effects utilizes controlled experimental environments to expose cells and tissues to heat stress and its disruptive influence on the physiological aspects of reproductive phenotypic traits, encompassing parameters such as sperm quality, sperm motility, viability, and overall competence. Beyond these immediate effects, heat stress has been linked to embryo losses, compromised oocyte development, and even infertility across diverse species. One of the primary mechanisms underlying these adverse reproductive outcomes is the elevation of reactive oxygen species (ROS) levels precipitating oxidative stress and apoptosis within mammalian reproductive cells. Oxidative stress and apoptosis are recognized as pivotal biological factors through which heat stress exerts its disruptive impact on both male and female reproductive cells. In a concerted effort to mitigate the detrimental consequences of heat stress, supplementation with antioxidants, both in natural and synthetic forms, has been explored as a potential intervention strategy. Furthermore, reproductive cells possess inherent self-protective mechanisms that come into play during episodes of heat stress, aiding in their survival. This comprehensive review delves into the multifaceted effects of heat stress on reproductive phenotypic traits and elucidates the intricate molecular mechanisms underpinning oxidative stress and apoptosis in reproductive cells, which compromise their normal function. Additionally, we provide a succinct overview of potential antioxidant interventions and highlight the genetic biomarkers within reproductive cells that possess self-protective capabilities, collectively offering promising avenues for ameliorating the negative impact of heat stress by restraining apoptosis and oxidative stress.

The complex landscape of intracellular signalling in protein modification under hyperglycaemic stress leading to metabolic disorders.

Hyperglycaemia is a life-threatening risk factor that occurs in both chronic and acute phases and has been linked to causing injury to many organs. Protein modification was triggered by hyperglycaemic stress, which resulted in pathogenic alterations such as impaired cellular function and tissue damage. Dysregulation in cellular function increases the condition associated with metabolic disorders, including cardiovascular diseases, nephropathy, retinopathy, and neuropathy. Hyperglycaemic stress also increases the proliferation of cancer cells. The major areas of experimental biomedical research have focused on the underlying mechanisms involved in the cellular signalling systems involved in diabetes-associated chronic hyperglycaemia. Reactive oxygen species and oxidative stress generated by hyperglycaemia modify many intracellular signalling pathways that result in insulin resistance and ß-cell function degradation. The dysregulation of post translational modification in ß cells is clinically associated with the development of diabetes mellitus and its associated diseases. This review will discuss the effect of hyperglycaemic stress on protein modification and the cellular signalling involved in it. The focus will be on the significant molecular changes associated with severe metabolic disorders.

Thioredoxin is a metabolic rheostat controlling regulatory B cells.

Metabolic programming is important for B cell fate, but the bioenergetic requirement for regulatory B (Breg) cell differentiation and function is unknown. Here we show that Breg cell differentiation, unlike non-Breg cells, relies on mitochondrial electron transport and homeostatic levels of reactive oxygen species (ROS). Single-cell RNA sequencing analysis revealed that TXN, encoding the metabolic redox protein thioredoxin (Trx), is highly expressed by Breg cells, unlike Trx inhibitor TXNIP which was downregulated. Pharmacological inhibition or gene silencing of TXN resulted in mitochondrial membrane depolarization and increased ROS levels, selectively suppressing Breg cell differentiation and function while favoring pro-inflammatory B cell differentiation. Patients with systemic lupus erythematosus (SLE), characterized by Breg cell deficiencies, present with B cell mitochondrial membrane depolarization, elevated ROS and fewer Trx+ B cells. Exogenous Trx stimulation restored Breg cells and mitochondrial membrane polarization in SLE B cells to healthy B cell levels, indicating Trx insufficiency underlies Breg cell impairment in patients with SLE.