Search

Machine learning (ML) and deep learning (DL) techniques can considerably enhance the process of making a precise diagnosis of Alzheimer’s disease (AD). Recently, DL techniques have had considerable success in processing medical data. They still have drawbacks, like large data requirements and a protracted training phase. With this concern, we have developed a novel strategy with the four stages. In the initial stage, the input data is subjected to data imbalance processing, which is crucial for enhancing the accuracy of disease detection. Subsequently, entropy-based, correlation-based, and improved mutual information-based features will be extracted from these pre-processed data. However, the curse of dimensionality will be a serious issue in this work, and hence we have sorted it out via optimization strategy. Particularly, the tunicate updated golden eagle optimization (TUGEO) algorithm is proposed to pick out the optimal features from the extracted features. Finally, the ensemble classifier, which integrates models like CNN, DBN, and improved RNN is modeled to diagnose the diseases by training the selected optimal features from the previous stage. The suggested model achieves the maximum F-measure as 97.67, which is better than the extant methods like TSO = 72.39%, BMO = 78, SSA = 84.15%, GEO = 70.39%, and FFLY = 73.13%, respectively. The suggested TUGEO-based AD detection is then compared to the traditional models like various performance matrices including accuracy, sensitivity, specificity, and precision. [ABSTRACT FROM AUTHOR]

Cyclophilin A (CypA) binds to the HIV-1 capsid to facilitate reverse transcription and nuclear entry and counter the antiviral activity of TRIM5α. Interestingly, recent studies suggest that the capsid enters the nucleus of an infected cell and uncoats prior to integration. We have previously reported that the capsid protein regulates HIV-1 integration. Therefore, we probed whether CypA-capsid interaction also regulates this post-nuclear entry step. First, we challenged CypA-expressing (CypA +/+ ) and CypA-depleted (CypA -/- ) cells with HIV-1 and quantified the levels of provirus. CypA-depletion significantly reduced integration, an effect that was independent of CypA's effect on reverse transcription, nuclear entry, and the presence or absence of TRIM5α. In addition, cyclosporin A, an inhibitor that disrupts CypA-capsid binding, inhibited proviral integration in CypA +/+ cells but not in CypA -/- cells. HIV-1 capsid mutants (G89V and P90A) deficient in CypA binding were also blocked at the integration step in CypA +/+ cells but not in CypA -/- cells. Then, to understand the mechanism, we assessed the integration activity of the HIV-1 preintegration complexes (PICs) extracted from acutely infected cells. PICs from CypA -/- cells retained lower integration activity in vitro compared to those from CypA +/+ cells. PICs from cells depleted of both CypA and TRIM5α also had lower activity, suggesting that CypA's effect on PIC was independent of TRIM5α. Finally, CypA protein specifically stimulated PIC activity, as this effect was significantly blocked by CsA. Collectively, these results provide strong evidence that CypA directly promotes HIV-1 integration, a previously unknown role of this host factor in the nucleus of an infected cell., Importance: Interaction between the HIV-1 capsid and host cellular factors is essential for infection. However, the molecular details and functional consequences of viral-host factor interactions during HIV-1 infection are not fully understood. Over 30 years ago, Cyclophilin A (CypA) was identified as the first host protein to bind to the HIV-1 capsid. Now it is established that CypA-capsid interaction promotes reverse transcription and nuclear entry of HIV-1. In addition, CypA blocks TRIM5α-mediated restriction of HIV-1. In this report, we show that CypA promotes the post-nuclear entry step of HIV-1 integration by binding to the viral capsid. Notably, we show that CypA stimulates the viral DNA integration activity of the HIV-1 preintegration complex. Collectively, our studies identify a novel role of CypA during the early steps of HIV-1 infection. This new knowledge is important because recent reports suggest that an operationally intact HIV-1 capsid enters the nucleus of an infected cell., Competing Interests: The authors declare no conflict of interest.

Diabetic kidney disease (DKD) is the leading cause of end stage kidney failure worldwide, of which cellular insulin resistance is a major driver. Here, we study key human kidney cell types implicated in DKD (podocytes, glomerular endothelial, mesangial and proximal tubular cells) in insulin sensitive and resistant conditions, and perform simultaneous transcriptomics and proteomics for integrated analysis. Our data is further compared with bulk- and single-cell transcriptomic kidney biopsy data from early- and advanced-stage DKD patient cohorts. We identify several consistent changes (individual genes, proteins, and molecular pathways) occurring across all insulin-resistant kidney cell types, together with cell-line-specific changes occurring in response to insulin resistance, which are replicated in DKD biopsies. This study provides a rich data resource to direct future studies in elucidating underlying kidney signalling pathways and potential therapeutic targets in DKD., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Histidine phosphorylation (pHis) is a non-canonical post-translational modification (PTM) that is historically understudied due to a lack of robust reagents that are required for its investigation, such as high affinity pHis-specific antibodies. Engineering pHis-specific antibodies is very challenging due to the labile nature of the phosphoramidate (P-N) bond and the stringent requirements for selective recognition of the two isoforms, 1-phosphohistidine (1-pHis) and 3-phosphohistidine (3-pHis). Here, we present a strategy for in vitro engineering of antibodies for detection of native 3-pHis targets. Specifically, we humanized the rabbit SC44-8 anti-3-pTza (a stable 3-pHis mimetic) mAb into a scaffold (herein referred to as hSC44) that was suitable for phage display. We then constructed six unique Fab phage-displayed libraries using the hSC44 scaffold and selected high affinity 3-pHis binders. Our selection strategy was carefully designed to enrich antibodies that bound 3-pHis with high affinity and had specificity for 3-pHis versus 3-pTza. hSC44.20N32F L , the best engineered antibody, has an ~10-fold higher affinity for 3-pHis than the parental hSC44. Eleven new Fab structures, including the first reported antibody-pHis peptide structures were solved by X-ray crystallography. Structural and quantum mechanical calculations provided molecular insights into 3-pHis and 3-pTza discrimination by different hSC44 variants and their affinity increase obtained through in vitro engineering. Furthermore, we demonstrate the utility of these newly developed high-affinity 3-pHis-specific antibodies for recognition of pHis proteins in mammalian cells by immunoblotting and immunofluorescence staining. Overall, our work describes a general method for engineering PTM-specific antibodies and provides a set of novel antibodies for further investigations of the role of 3-pHis in cell biology., Competing Interests: Competing Interest Statement: Authors declare no competing interests.

The utilization of bio-oil derived from biomass presents a promising alternative to fossil fuels, though it faces challenges when directly applied in diesel engines. Microemulsification has emerged as a viable strategy to enhance bio-oil properties, facilitating its use in hybrid fuels. This study explores the microemulsification of Jatropha bio-oil with ethanol, aided by a surfactant, to formulate a hybrid liquid fuel. Additionally, a bio-nano CaO heterogeneous catalyst synthesized from eggshells is employed to catalyse the production of Jatropha biodiesel from the microemulsified fuel using microwave irradiation. The catalyst is characterized through UV-Vis, XRD, and SEM analysis. The investigation reveals a significant reduction in CO, CO 2 , and NO X emissions with the utilization of microemulsion-based biodiesel blends. Various blends of conventional diesel, Jatropha biodiesel, and ethanol are prepared with different ethanol concentrations (5, 10, and 20 wt%). Engine performance parameters, including fuel consumption, NOX emission, and brake specific fuel consumption, are analyzed. Results indicate that the conventional diesel/Jatropha biodiesel/ethanol (10 wt%) blend exhibits superior performance compared to conventional diesel, Jatropha biodiesel, and other blends. The fuel consumption of the conventional diesel/Jatropha biodiesel/ethanol (10 wt%) blend is measured at 554.6 g/h, surpassing that of conventional diesel and other biodiesel blends. The presence of water (0.14 %) in the blend reduces the heating value, consequently increasing the energy requirement. CO and CO 2 emissions for the conventional diesel/Jatropha biodiesel/ethanol (10 wt%) blend are notably lower compared to conventional C-18 hydrocarbons and various biodiesel blends. These findings accentuate the efficacy of the microemulsion process in enhancing fuel characteristics and reducing emissions. Further investigations could explore optimizing the emulsifying agents and their impact on engine performance and emission characteristics, contributing to the advancement of sustainable fuel technologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study examines catalytic ability of various zeolite materials in converting discarded tire pyrolyzed oil by employing a moderate sized pyrolysis plant of a 10 L working volume. The study revealed that the yield of liquid fractions using γ-Al 2 O 3 was greater than that of HZSM-5 and HY, while the yield of condensates were limited in the absence of catalyst. The tire waste pyrolysis oil catalytcially enhanced by alumina catalyst analyzed using Fourier transform infrared spectroscopy exhibited the stretching bands corresponding to aromatic and non-aromatic compounds. The GC MS analysis revealed that the cyclic unsaturated fragment percentages in liquids were decreased by the catalysts to 53.9% with HY, 59.0% with γ-Al 2 O 3 , and 62.2% with HZSM-5, which in turn was converted into aromatic chemicals. Nitrogen adsorption desorption analysis revealed that γ-Al 2 O 3 has an enhanced surface area of 635 m 2 /g which improved its catalytic performance. The cracked liquid oil had viscosity (10.36 cSt), values of pour and flash temperatures of -2.2 °C and 41 °C respectively, analogous to petroleum diesel. The upgraded pyrolysis oil (10%) is blended with gasoline (90%), and emission analysis was performed. Moreover, liquid oil needs post treatment (refining) for its use as energy source in transportation application. The novelty of this research is in its comparative analysis of multiple catalysts under controlled conditions using a small pilot-scale pyrolysis reactor, which provides insights into optimizing the pyrolysis process for industrial applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, we studied the hydrocracking of waste chicken oil (WCO) catalyzed by mesoporous SO 4 2- /KIT-6. The study included WCO extraction, SO 4 2- /KIT-6 catalyst synthesis, hydrocracking, and catalytic characterization. XRD patterns revealed intense peaks in the low-angle region, with shoulder peaks showing an increase in sulphate loading from 10% to 30%. The BET-specific surface area for the pure KIT-6 supports measured at 1003 m 2 /g, indicative of a well-defined mesoporous structure. Thermogravimetric analysis (TGA) showed a two-stage weight loss, attributed to the elimination of hydrated water (about 200 °C) and decomposition of sulphate ions (400-450 °C). SEM analysis highlighted the surface morphology of the active SK-2 catalyst. Hydrocatalytic and catalytic cracking reactions were performed, and about 99.8% conversion was achieved with 20 mL/H H 2 flow, whereas higher production of bioliquids was observed at a flow of 15 mL/h. The hydrocracking mechanism was also studied to understand the formation of lower hydrocarbons. GC analyses of simulated distilled gasoline, kerosene, and diesel showed diverse hydrocarbon compositions. For engine testing, non-hydrocracked fuel rose to 28 kW at 3000 rpm and declined to 21 kW at 3500 rpm. Emission analysis revealed decreasing trends in NOX emissions of hydrogen-rich blends, with values of 65 ppm, 54 ppm, and 48 ppm for petrol, NHBL, and HBL, respectively. Similarly, SO 2 emissions reduced from petrol to NHBL and HBL at 910 ppm, 800 ppm, and 600 ppm, respectively, suggesting reduced environmental impact. CO emissions exhibited a substantial reduction in NHBL (0.90%) and HBL (0.54%) compared to petrol (2.70%), emphasizing the cleaner combustion characteristics. Our results provide a comprehensive exploration of waste chicken oil hydrocracking, emphasizing catalyst synthesis, fuel characterization, engine performance, and environmental impact, thereby contributing valuable insights to the field of sustainable bioenergy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, we studied the conversion of Jatropha curcas oil to biodiesel by using three distinct reactor systems: microchannel, fixed bed, and microwave reactors. ZSM-5 was used as the catalyst for this conversion and was thoroughly characterized. X-ray diffraction was used to identify the crystalline structure, Brunauer-Emmett-Teller analysis to determine surface area, and temperature-programmed desorption to evaluate thermal stability and acidic properties. These characterizations provided crucial insights into the catalyst's structural integrity and performance under reaction conditions. The microchannel reactor exhibited superior biodiesel yield compared to the fixed bed and microwave reactors, and achieved peak efficiency at 60 °C, delivering high FAEE yield (99.7%) and conversion rates (99.92%). Ethanol catalyst volume at 1% was optimal, while varying flow rates exhibited trade-offs, emphasizing the need for nuanced control. Comparative studies against microwave and fixed-bed reactors consistently favored the microchannel reactor, emphasizing its remarkable FAME percentages, high conversion rates, and adaptability to diverse operating conditions. The zig-zag configuration enhances its efficiency, making it the optimal choice for biodiesel production and showcasing promising prospects for advancing sustainable biofuel synthesis technologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The most recent advancement in food packaging research involves improving the shelf life of perishable foods by utilising bio-based resources that are edible, eco-friendly, and biodegradable. The current study investigated the effect of edible pectin coating on mature green tomatoes to improve shelf life and storage properties. Zucchini pectin was used to make edible coating. The antimicrobial and antioxidant properties of extracted pectin were investigated. The findings indicated that the extracted pectin had antimicrobial (Staphylococcus aureus, Escherichia coli, and Aspergillus niger) and antioxidant (34.32% at 1 mg/mL) properties.Tomatoes were immersed in pectin solutions of varying concentrations, 1, 3, and 5% (w/v). Physiological evaluations of weight loss, total sugar content, titratable acidity pH, and ascorbic acid were performed on tomatoes during their maturing stages of mature green, light red, pure red, and breaking. Coating the tomatoes with pectin (5%) resulted in minimal weight loss while increasing the retention of total sugar, ascorbic acid, and titratable acidity. The shelf life of the pectin-coated tomatoes was extended to 11 days, while the uncoated control tomatoes lasted 9 days. Thus, a 5% edible pectin solution was found to be effective in coating tomatoes. The current study suggests that using 5% pectin as an edible coating on tomatoes can delay/slow the ripening/maturing process while also extending the shelf-life of tomatoes without affecting their physiochemical properties, which is scalable on a large scale for commercial purposes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

This present study enlightens the eco-friendly green synthesis of ZSM-5 from natural clay montmorillonite, and its proper incorporation with 'Ni'. Nickle (Ni) was wet impregnated onto HZSM-5 and the resulting catalyst was characterized by various techniques including XRD, BET, N2 Sorption Studies, TPD, SEM and TEM techniques. The SEM images revealed the uniform distribution of Ni over HZSM-5 zeolite catalyst and the XRD results indicated the undistorted crystalline structure of HZSM-5 even after impregnation of Ni. The latter part of the work concentrates on the strength of the catalyst in cracking oil derived from discarded fish parts. Discarded fish waste was pyrolyzed to obtain the fish oil, which was then used for cracking studies. The fish oil was efficiently converted (99% conversion) by Ni/ZSM5 (50 wt %) and yielded 70% liquid fractions, which formed gasoline (78.6%), kerosene (12.3%) and diesel (9.1%). The research is a complete parcel to examine the working potential of the produced biofuel in pre-existing engines. The quality of gasoline fraction was tested according to ASTM standards, which showed that the heating value was slightly lower compared to fossil gasoline. The torque and brake fuel consumption were also examined and it indicated that the fish oil derived gasoline fuel may need to be mixed with the commercial gasoline to optimize its performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) provide valuable insights into the cellular states of kidney cells. However, the annotation of cell types often requires extensive domain expertise and time-consuming manual curation, limiting scalability and generalizability. To facilitate this process, we tested the performance of five supervised classification methods for automatic cell type annotation., Results: We analyzed publicly available sc/snRNA-seq datasets from five expert-annotated studies, comprising 62,120 cells from 79 kidney biopsy samples. Datasets were integrated by harmonizing cell type annotations across studies. Five different supervised machine learning algorithms (support vector machines, random forests, multilayer perceptrons, k-nearest neighbors, and extreme gradient boosting) were applied to automatically annotate cell types using four training datasets and one testing dataset. Performance metrics, including accuracy (F1 score) and rejection rates, were evaluated. All five machine learning algorithms demonstrated high accuracies, with a median F1 score of 0.94 and a median rejection rate of 1.8 %. The algorithms performed equally well across different datasets and successfully rejected cell types that were not present in the training data. However, F1 scores were lower when models trained primarily on scRNA-seq data were tested on snRNA-seq data., Conclusions: Despite limitations including the number of biopsy samples, our findings demonstrate that machine learning algorithms can accurately annotate a wide range of adult kidney cell types in scRNA-seq/snRNA-seq data. This approach has the potential to standardize cell type annotation and facilitate further research on cellular mechanisms underlying kidney disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

In this study, bimetallic Cu-Fe nanoparticles were synthesized using the green approach with Piper betle leaves, and the removal efficiency of one of the pharmaceutical compounds, Atorvastatin, was investigated. UV, SEM, FTIR, EDAX, particle size, and zeta potential measurements were used to confirm nanoparticle fabrication. The removal efficiency of Atorvastatin (10 mg/L) by bimetallic Cu-Fe nanoparticles was 67% with a contact time of 30 min at pH 4, the adsorbent dosage of 0.2 g/L, and stirring at 100 rpm. Piper betle bimetallic Cu-Fe nanoparticles have demonstrated excellent stability, reusability, and durability, even after being reused five times. Furthermore, the synthesized bimetallic Cu-Fe nanoparticles demonstrated remarkable antimicrobial properties against gram-negative strains such as Escherichia coli and Klebsiella pneumoniae, gram-positive strains such as Staphylococcus aureus and Bacillus subtilis, and fungi such as Aspergillus niger. In addition, the antioxidant properties of the synthesized bimetallic Cu-Fe nanoparticles were assessed using the DPPH radical scavenging assay. The results indicated that the nanoparticles had good antioxidant activity. Thus, using Piper betle extract to make Cu-Fe nanoparticles made the procedure less expensive, chemical-free, and environmentally friendly, and the synthesized bimetallic Cu-Fe nanoparticles helped remove the pharmaceutical compound Atorvastatin from wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Phosphohistidine (pHis) is a reversible protein post-translational modification (PTM) that is currently poorly understood. The P-N bond in pHis is heat and acid-sensitive, making it more challenging to study than the canonical phosphoamino acids pSer, pThr, and pTyr. As advancements in the development of tools to study pHis have been made, the roles of pHis in cells are slowly being revealed. To date, a handful of enzymes responsible for controlling this modification have been identified, including the histidine kinases NME1 and NME2, as well as the phosphohistidine phosphatases PHPT1, LHPP, and PGAM5. These tools have also identified the substrates of these enzymes, granting new insights into previously unknown regulatory mechanisms. Here, we discuss the cellular function of pHis and how it is regulated on known pHis-containing proteins, as well as cellular mechanisms that regulate the activity of the pHis kinases and phosphatases themselves. We further discuss the role of the pHis kinases and phosphatases as potential tumor promoters or suppressors. Finally, we give an overview of various tools and methods currently used to study pHis biology. Given their breadth of functions, unraveling the role of pHis in mammalian systems promises radical new insights into existing and unexplored areas of cell biology.

Cyclophilin A (CypA) promotes HIV-1 infection by facilitating reverse transcription, nuclear entry and by countering the antiviral activity of TRIM5α. These multifunctional roles of CypA are driven by its binding to the viral capsid. Interestingly, recent studies suggest that the HIV-1 capsid lattice enters the nucleus of an infected cell and uncoats just before integration. Therefore, we tested whether CypA-capsid interaction regulates post-nuclear entry steps of infection, particularly integration. First, we challenged CypA-expressing (CypA +/+ ) and CypA-depleted (CypA -/- ) cells with HIV-1 particles and quantified the resulting levels of provirus. Surprisingly, CypA-depletion significantly reduced integration, an effect that was independent of CypA's effect on reverse transcription, nuclear entry, and the presence or absence of TRIM5α. Additionally, cyclosporin A, an inhibitor that disrupts CypA-capsid binding, inhibited HIV-1 integration in CypA +/+ cells but not in CypA -/- cells. Accordingly, HIV-1 capsid mutants (G89V and P90A) deficient in CypA binding were also blocked at integration in CypA +/+ cells but not in CypA -/- cells. Then, to understand the mechanism, we assessed the integration activity of HIV-1 preintegration complexes (PICs) extracted from infected cells. The PICs from CypA -/- cells had lower activity in vitro compared to those from CypA +/+ cells. PICs from cells depleted for CypA and TRIM5α also had lower activity, suggesting that CypA's effect on PIC activity is independent of TRIM5α. Finally, addition of CypA protein significantly stimulated the integration activity of PICs extracted from both CypA +/+ and CypA -/- cells. Collectively, these results suggest that CypA promotes HIV-1 integration, a previously unknown role of this host factor., Importance: HIV-1 capsid interaction with host cellular factors is essential for establishing a productive infection. However, the molecular details of such virus-host interactions are not fully understood. Cyclophilin A (CypA) is the first host protein identified to specifically bind to the HIV-1 capsid. Now it is established that CypA promotes reverse transcription and nuclear entry steps of HIV-1 infection. In this report, we show that CypA promotes HIV-1 integration by binding to the viral capsid. Specifically, our results demonstrate that CypA promotes HIV-1 integration by stimulating the activity of the viral preintegration complex and identifies a novel role of CypA during HIV-1 infection. This new knowledge is important because recent reports suggest that an operationally intact HIV-1 capsid enters the nucleus of an infected cell.

Central roles of Mn 2+ ions in immunity, brain function, and photosynthesis necessitate probes for tracking this essential metal ion in living systems. However, developing a cell-permeable, fluorescent sensor for selective imaging of Mn 2+ ions in the aqueous cellular milieu has remained a challenge. This is because Mn 2+ is a weak binder to ligand-scaffolds and Mn 2+ ions quench fluorescent dyes leading to turn-off sensors that are not applicable for in vivo imaging. Sensors with a unique combination of Mn 2+ selectivity, μM sensitivity, and response in aqueous media are necessary for not only visualizing labile cellular Mn 2+ ions live, but also for measuring Mn 2+ concentrations in living cells. No sensor has achieved this combination thus far. Here we report a novel, completely water-soluble, reversible, fluorescent turn-on, Mn 2+ selective sensor, M4, with a K d of 1.4 μM for Mn 2+ ions. M4 entered cells within 15 min of direct incubation and was applied to image Mn 2+ ions in living mammalian cells in both confocal fluorescence intensity and lifetime-based set-ups. The probe was able to visualize Mn 2+ dynamics in live cells revealing differential Mn 2+ localization and uptake dynamics under pathophysiological versus physiological conditions. In a key experiment, we generated an in-cell Mn 2+ response curve for the sensor which allowed the measurement of the endogenous labile Mn 2+ concentration in HeLa cells as 1.14 ± 0.15 μM. Thus, our computationally designed, selective, sensitive, and cell-permeable sensor with a 620 nM limit of detection for Mn 2+ in water provides the first estimate of endogenous labile Mn 2+ levels in mammalian cells., Competing Interests: The authors declare no competing interest., (This journal is © The Royal Society of Chemistry.)

Background: Adult kidney transplant recipients (KTRs) fully vaccinated against COVID-19 have substantial morbidity and mortality related to SARS-CoV-2 infection compared with the general population. However, little is known regarding the safety and efficacy of the COVID-19 vaccination series in pediatric KTRs., Methods: A multicenter, retrospective observational study was performed across nine pediatric transplantation centers. Eligible KTRs fully vaccinated against COVID-19 were enrolled and data were collected pertaining to SARS-CoV-2 infection incidence and severity, graft outcomes and post-vaccination safety profile, as well as overall patient survival., Results: A total of 247 patients were included in this investigation with a median age at transplantation of 11 years (IQR 5-15). SARS-CoV-2 infection was observed in 30/110 (27.27%) of fully vaccinated patients, tested post-transplant, within the defined follow-up period. Of these patients, 6/30 (18.18%) required hospitalization and 3/30 (12.12%) required reduction in immunosuppression, with no reported deaths. De novo donor-specific antibodies (DSAs) were found in 8/86 (9.30%) of DSA-tested patients with two experiencing rejection and subsequent graft loss. The overall incidence of rejection and graft loss among the total cohort was 11/247 (4.45%) and 6/247 (3.64%), respectively. A 100% patient survival was observed., Conclusions: Observationally, infectious outcomes of SARS-CoV-2 in fully vaccinated pediatric KTRs are excellent, with a low incidence of infection requiring hospitalization and no associated deaths. Though de novo DSAs were observed, there was minimal graft rejection and graft loss reported in the total cohort., (© 2024 Wiley Periodicals LLC.)

HIV type 1 (HIV-1) is the causative agent of AIDS. Since the start of the epidemic, HIV/AIDS has been responsible for ≈40 million deaths. Additionally, an estimated 39 million people are currently infected with the virus. HIV-1 primarily infects immune cells, such as CD 4+ (cluster of differentiation 4 + ) T lymphocytes (T cells), and as a consequence, the number of CD 4+ T cells progressively declines in people living with HIV. Within a span of ≈10 years, HIV-1 infection leads to the systemic failure of the immune system and progression to AIDS. Fortunately, potent antiviral therapy effectively controls HIV-1 infection and prevents AIDS-related deaths. The efficacy of the current antiviral therapy regimens has transformed the outcome of HIV/AIDS from a death sentence to a chronic disease with a prolonged lifespan of people living with HIV. However, antiviral therapy is not curative, is challenged by virus resistance, can be toxic, and, most importantly, requires lifelong adherence. Furthermore, the improved lifespan has resulted in an increased incidence of non-AIDS-related morbidities in people living with HIV including cardiovascular diseases, renal disease, liver disease, bone disease, cancer, and neurological conditions. In this review, we summarize the current state of knowledge of the cardiovascular comorbidities associated with HIV-1 infection, with a particular focus on hypertension. We also discuss the potential mechanisms known to drive HIV-1-associated hypertension and the knowledge gaps in our understanding of this comorbid condition. Finally, we suggest several directions of future research to better understand the factors, pathways, and mechanisms underlying HIV-1-associated hypertension in the post-antiviral therapy era., Competing Interests: Disclosures None.

We describe a patient diagnosed with a metastatic adenocarcinoma of Müllerian origin, harboring a BRAF V600E mutation, ten years after being treated for a serous borderline tumor (SBOT). While BRAF mutations in the setting of SBOTs are common, they have been typically associated with a low chance of transformation or recurrence. The therapeutic approach, which combined hormone inhibition with receptor tyrosine kinase inhibitors (dabrafenib and trametinib), has demonstrated notable and enduring efficacy. This is clinically evidenced through serial PET-CT scans with sustained responses and extended progression-free survival, and serologically confirmed by monitoring CA-125 levels. This case demonstrates the critical role of early next-generation sequencing in detecting actionable molecular changes in rare cancers and possible metastases. It provides valuable insights into treating uncommon Müllerian adenocarcinomas and underscores the importance of targeted therapies in achieving long-lasting treatment outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Inc.)

The antimicrobial, antidiabetic, and anti-inflammatory activities efficiency of Aerva lanata plant extracts (aqueous (Aqu-E), acetone (Ace-E), and ethanol (Eth-E)) were investigated in this study. Furthermore, the active molecules exist in the crude extract were characterized by UV-Visible spectrophotometer, Fourier transform infrared (FTIR), High-performance liquid chromatography (HPLC), and Gas Chromatography-Mass Spectrometry (GC-MS) analyses. The preliminary phytochemical study revealed that the Ace-E restrain more phytochemicals like alkaloids, saponins, anthraquinone, tannins, phenolics, flavonoids, glycosides, terpenoids, amino acid, steroids, protein, coumarin, as well as quinine than Aqu-E and Eth-E. Accordingly to this Ace-E showed considerable antimicrobial activity as the follows: for bacteria S. aureus > E. coli > K. pneumoniae > P. aeruginosa > B. subtilis and for fungi T. viride > A.flavus > C. albicans > A.niger at 30 mg ml concentration. Similarly, Ace-E showed considerable antidiabetic (α-amylase: 71.7 % and α-glucosidase: 70.1 %) and moderate anti-inflammatory (59 % and 49.8 %) activities. The spectral and chromatogram studies confirmed that the Ace-E have pharmaceutically valuable bioactive molecules such as (Nbutyl)-octadecane, propynoic acid, neophytadiene, and 5,14-di (N-butyl)-octadecane. These findings suggest that Ace-E from A. lanata can be used to purify additional bioactive substances and conduct individual compound-based biomedical application research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

COVID-19 has been a significant public health concern for the last four years; however, little is known about the mechanisms that lead to severe COVID-associated kidney injury. In this multicenter study, we combined quantitative deep urinary proteomics and machine learning to predict severe acute outcomes in hospitalized COVID-19 patients. Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrated predictive power for both discovery and validation set with 87% and 79% accuracy, respectively. These predictive urinary biomarkers were recapitulated in non-COVID acute kidney injury revealing overlapping injury mechanisms. We further combined orthogonal multiomics datasets to understand the mechanisms that drive severe COVID-associated kidney injury. Functional overlap and network analysis of urinary proteomics, plasma proteomics and urine sediment single-cell RNA sequencing showed that extracellular matrix and autophagy-associated pathways were uniquely impacted in severe COVID-19. Differentially abundant proteins associated with these pathways exhibited high expression in cells in the juxtamedullary nephron, endothelial cells, and podocytes, indicating that these kidney cell types could be potential targets. Further, single-cell transcriptomic analysis of kidney organoids infected with SARS-CoV-2 revealed dysregulation of extracellular matrix organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters showed significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. Collectively, these data suggest that extracellular matrix degradation and adhesion-associated mechanisms could be a main driver of COVID-associated kidney injury and severe outcomes.

Phosphoinositides, phospholipids that are key cell-signal mediators, are present at very low levels in cellular membranes and within nuclei. Phosphatidylinositol-(3,4,5)-trisphosphate (PIP3), a phosphoinositide barely present in resting cell membranes, is produced when cells receive either growth, proliferation, or movement signals. Aberrant PIP3 levels are associated with the formation of cancers. PIP3 pools are also present in the nucleus, specifically in the nucleolus. However, questions related to the organization and function of this lipid in such membraneless intranuclear structures remain unanswered. Therefore, chemical sensors for tracking cellular PIP3 are invaluable not only for timing signal initiation in membranes but also for identifying the organization and function of membraneless nuclear PIP3 pools. Because PIP3 is present in the inner leaflet of cell membranes and in the nucleus, cell-permeable, rapid-response fluorescent sensors would be ideal. We have designed two peptide-based, water-soluble, cell-permeable, ratiometric PIP3 sensors named as MFR-K17H and DAN-NG-H12G . MFR-K17H rapidly entered into the cell cytoplasm, distinctly reporting rapid (<1 min) time scales of growth factor-stimulated PIP3 generation and depletion within cell membranes in living cells. Importantly, MFR-K17H lighted up inherently high levels of PIP3 in triple-negative breast cancer cell membranes, implying future applications in the detection of enhanced PIP3 levels in cancerous cells. On the other hand, DAN-NG-H12G targeted intranuclear PIP3 pools, revealing that within membraneless structures, PIP3 resided in a hydrophobic environment. Together, both probes form a unique orthogonally targeted combination of cell-permeable, ratiometric probes that, unlike previous cell-impermeable protein-based sensors, are easy to apply and provide an unprecedented handle into PIP3-mediated cellular processes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part, this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Identifying the molecular and genetic regulators unique to nephron segments that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI. Here, we examined the role of Pax2 and Pax8 in recovery from ischemic AKI and found them upregulated after severe AKI and correlated with chronic injury. Surprisingly, proximal-tubule-selective deletion of Pax2 and Pax8 resulted in a less severe chronic injury phenotype. This effect was mediated by protection against the acute insult, similar to pre-conditioning. Prior to injury, Pax2 and Pax8 mutant mice develop a unique subpopulation of proximal tubule cells in the S3 segment that displayed features usually seen only in acute or chronic injury. The expression signature of these cells was strongly enriched with genes associated with other mechanisms of protection against ischemic AKI including caloric restriction, hypoxic pre-conditioning, and female sex. Thus, our results identified a novel role for Pax2 and Pax8 in mature proximal tubules that regulates critical genes and pathways involved in both the injury response and protection from ischemic AKI., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Diabetic kidney disease (DKD) is a common cause of chronic kidney disease with around 25-40% of patients with diabetes being affected. The course of DKD is variable, and estimated glomerular filtration rate (eGFR) and albuminuria, the currently used clinical markers, are not able to accurately predict the individual disease trajectory, in particular in early stages of the disease. The aim of this study was to assess the association of urine levels of selected protein biomarkers with the progression of DKD at an early stage of disease., Methods: We measured 22 protein biomarkers using the Mesoscale Discovery platform in 461 urine samples of the PROVALID cohort, an observational study of patients with type 2 diabetes mellitus followed at the primary health care level for a minimum of 4 years. Odds ratios (ORs) were estimated for the effect of marker values above median on fast progression using unadjusted and adjusted logistic regression models. RNA expression at the single-cell level in kidney biopsy samples obtained from a cohort of young persons with type 2 diabetes mellitus was in addition determined for markers showing significant associations with disease progression., Results: Increased urinary levels of epidermal growth factor (EGF) were linked to lower odds of fast progression (defined as annual eGFR decline greater than 2.58 mL/min per 1.73 m2) with an OR of 0.60 (95% CI: 0.46, 0.78). The association with outcome was even stronger when adjusting for a set of 14 baseline clinical parameters including age, biological sex, eGFR, body mass index, albuminuria, and HbA1c. Elevated urinary levels of fatty acid-binding protein 3 (FABP3) and vascular cell adhesion molecule 1 (VCAM1) were each significantly associated with fast progression with an OR of 1.44 (95% CI: 1.11, 1.87) and an OR of 1.41 (95% CI: 1.08, 1.83), respectively. Enriched expression of EGF and FABP3 was observed in distal convoluted tubular cells and VCAM1 in parietal epithelial cells at single-cell level from biopsies of patients with early DKD., Conclusion: In summary, we show that lower urinary levels of EGF and higher urinary levels of FABP3 and VCAM1 are significantly associated with DKD progression in early-stage disease., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

In recent years, g-C 3 N 4 -Ag nanocomposite synthesis has gained considerable attention for its potential to treat polycyclic aromatic hydrocarbons (PAHs) and to act against bacteria and fungi. In this study, we present a novel approach to the synthesis of g-C 3 N 4 -Ag nanocomposite and evaluate its efficiency in both PAH removal and antimicrobial activity. The synthesis process involved the preparation of g-C 3 N 4 by thermal polycondensation of melamine. The factors that affect the adsorption process of PAHs, like time, pH, irradiation type, and adsorbent dosage, were also evaluated. Isotherm models like Langmuir and Freundlich determined the adsorption capability of g-C 3 N 4 -Ag. In simulated models, phenanthrene was degraded to a maximum of 85% at lower concentrations of catalyst. The adsorption profile of phenanthrene obeys the pseudo-second-order and Freundlich isotherms pattern. The g-C 3 N 4 -Ag nanocomposite also exhibited antimicrobial activity against bacteria (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae) and fungi (Candida albicans). The present study is the first report stating the dual application of g-C 3 N 4 -Ag nanocomposite in reducing the concentration of PAH and killing bacterial and fungal pathogens. The higher adsorption capability proclaimed by g-C 3 N 4 -Ag nanocomposite shows the fabricated nanomaterial with great potential to remediate organic pollutants from the ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A sol-gel method was used to synthesize the cerium dioxide nanoparticles. The nanoparticles formed were then characterized with UV-visible spectrophotometry, Fourier Transform Infrared Spectrophotometer (FTIR), SEM-EDAX, XRD, and Dynamic Light Scattering (DLS). The UV-visible absorbance at 282 nm and characteristic peak at 600-4000 cm -1 provided insight into the formation of cerium dioxide nanoparticles using a chemical method. SEM analysis and EDAX analysis confirmed nanoparticle formation and elements within the nanoparticles based on their irregular morphology. The hydrodynamic size obtained from the DLS analysis was 178.4 nm and the polydispersity was 0.275 nm. Furthermore, XRD results confirmed the crystalline nature of cerium dioxide nanoparticles. Using batch adsorption as a method, the effect of concentration of Polycyclic Aromatic Hydrocarbons (PAH), adsorbent concentration, pH, and irradiation source was investigated. Under UV light conditions, 10 μg/mL cerium dioxide nanoparticle at pH 5 degraded 2 μg/mL of PAH (anthracene and fluorene). Consequently, the synthesized cerium dioxide nanoparticles were effective photocatalysts. For anthracene and fluorene, kinetic studies showed the degradation process followed pseudo-second-order kinetics and Freundlich isotherms. Cerium oxide also exhibited significant antimicrobial and antibiofilm activity against bacteria and fungi. As a result, the cerium dioxide nanoparticle has proved to be a highly effective photocatalytic tool for the degradation of PAHs and exhibits strong antimicrobial activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are omnipresent, persistent, and carcinogenic pollutants continuously released in the atmosphere due to the rapid increase in population and industrialization worldwide. Hence, there is an ultimate rise in concern about eliminating the toxic PAHs and their related aromatic hydrocarbons from the air, water, and soil environment by employing efficient removal technologies using nanoparticles as a catalyst. Here, the degradation of selective PAHs viz., anthracene and benzene using laboratory synthesized rGO-Ag-Cu-Ni nanocomposite (catalyst) was studied. Characterization studies revealed the nanocomposites exhibited surface plasma resonance at 350 - 450 nm, confirming the presence of Ag, Cu, and Ni metal ions embedded on the reduced graphene substrate. It was found that the nanocomposites synthesized were spherical, amorphous in nature, and aggregated together with measurements ranging from 423 to 477 nm. An SEM-EDX analysis of the nanocomposite demonstrated that it contained 25.13% O, 14.24% Ni, 27.79% Cu, and 32.84% Ag, which confirms the synthesis of the nanocomposite. Crystalline, sharp nanocomposites of average size 17-41 nm with an average diameter of 118.5 nm (X-ray diffraction and DLS) were observed. FTIR spectra showed that the nanocomposites had the functional groups alkanes, alkenes, alkynes, carboxylic acids, and halogen derivatives. Batch adsorption studies revealed that the maximum degradation achieved at optimum nano-composite concentration of 10 μg/mL, pH value of 5, PAHs concentration of 2 μg/mL and effective irradiation source being UV radiations in the case of both benzene and anthracene pollutants. The degradation of benzene and anthracene followed Freundlich & Langmuir isotherm with the highest R 2 value of 0.9894 & 0.9885, respectively. Adsorption kinetic studies under optimum conditions revealed that the adsorption of both benzene and anthracene followed Pseudo-second order kinetics. Antimicrobial studies revealed that the synthesized nano-composite exhibited potential antimicrobial activity against Gram positive bacterium (Bacillus subtilis, Staphylococcus aureus), Gram negative bacterium (Klebsiella pneumonia, Escherichia coli) and fungal strain (Aspergillus niger) respectively. Thus, the synthesized rGO-Ag-Cu-Ni nano-composite acts as an effective antimicrobial agent as well as a PAHs degrading agent, helping to overcome antibiotics resistance and to mitigate the overgrowing PAHs pollution in the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To degrade anthracene, magnetite nanoparticles were produced using a simple co-precipitation process. The fabricated nanoparticles have been analyzed for structural and optical properties. XRD examination revealed that the produced Fe 3 O 4 nanoparticles were cubic phase, having a mean crystallite dimension of 18.84 nm. DLS determined the hydrodynamic diameter of Fe 3 O 4 nanoparticles to be 182 nm. UV-Vis research revealed that Fe 3 O 4 nanoparticles absorb at 390 nm. A peak at 895 cm -1 in the FT-IR study indicated the metal-oxygen connection. The synthesized Fe 3 O 4 nanoparticles demonstrated an effective photocatalytic performance towards anthracene degradation and was found to be 86.55%. Furthermore, Fe 3 O 4 nanoparticles showed the highest antimicrobial activity against Bacillus subtilis was 19.43 mm. The present study is the first and foremost study determining the dual role of Fe 3 O 4 nanoparticles towards bioremediation and biomedical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the present study, cobalt oxide nanoparticles have been synthesized using the root extract of Curcuma longa in a manner that is both environmentally friendly and economical. Initially, the synthesized nanoparticles were characterized using a UV-Vis spectroscopy analysis, in which plasma resonance at 345 nm was observed, which confirmed that CL-Cobalt oxide nanoparticles were synthesized. While FTIR analysis showed a peak at 597.37 cm -1 indicating Co-O stretching vibration. In addition, DLS, SEM and XRD analyses confirmed the synthesis of polydispersed (average size distribution of 97.5 ± 35.1 nm), cubic phase structure, and spherical-shaped CL-Cobalt oxide nanoparticles. CL-Cobalt oxide nanoparticles synthesized from green materials showed antioxidant and antimicrobial properties. CL-Cobalt oxide nanoparticles exhibited antibacterial activity against Gram negative (Klebsiella pneumoniae and Escherichia coli) and Gram positive bacteria (Bacillus subtilis, Staphylococcus aureus), while CL-Cobalt oxide nanoparticles additionally displayed significant antifungal activity against Aspergillus niger. CL-Cobalt oxide also showed application in a bioremediation perspective by showing strong photocatalytic degradation of methyl red, methyl orange and methyl blue dye. In addition, CL-Cobalt oxide also demonstrated anticancer activity against MDA-MB-468 cancer cell lines with an IC 50 value of 150.8 μg/ml. Therefore, this is the first and foremost report on CL-Cobalt oxide nanoparticles synthesized using Curcuma longa showing antioxidant, antibacterial, antifungal, dye degradation and anticancer applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In ancient times, herbal plants were considered one of the greatest gifts from nature that human beings could receive, and about 80% of these plants have medicinal uses. In traditional medicine, Mentha arvensis, commonly known as mint, has many applications, and in the present study, the mint leaf extract has been used to synthesis nanoparticles using the mint leaf extract as a biosource for the extraction of nanoparticles. In addition to having a wide range of applications in various fields, calcium oxide (CaO) nanoparticles are also considered to be safe for human use. In order to assess the characteristics of the abstracted CaO nanoparticles, UV-visible absorption spectrophotometers, Fourier Transform Infrared spectrophotometers (FTIR), Scanning Electron Microscopes (SEMs), Dynamic Light Scattering (DLS), and X-ray Diffraction Spectrophotometers (XRDs) were used. By conducting a protein denaturation assay and nitric oxide scavenging assay, mint leaf mediated CaO nanoparticles were evaluated for their therapeutic applications. MTT assays were used to prove that the CaO nanoparticles mediated by mint leaf had anti-cancer properties. By examining the ability of mint leaf mediated CaO nanoparticles to degrade various dyes such as methyl red, methyl orange, and methylene blue, which are the most used azo dyes in textile industries resulting in water contamination, the ability of these nanoparticles to act as a photocatalytic agent was examined., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.

Acute kidney injury (AKI) is a common condition that lacks effective treatments. In part this shortcoming is due to an incomplete understanding of the genetic mechanisms that control pathogenesis and recovery. Pax2 and Pax8 are homologous transcription factors with overlapping functions that are critical for kidney development and are re-activated in AKI. In this report, we examined the role of Pax2 and Pax8 in recovery from ischemic AKI. We found that Pax2 and Pax8 are upregulated after severe AKI and correlate with chronic injury. Surprisingly, we then discovered that proximal-tubule-selective deletion of Pax2 and Pax8 resulted in a less severe chronic injury phenotype. This effect was mediated by protection against the acute insult, similar to preconditioning. Prior to injury, Pax2 and Pax8 mutant mice develop a unique subpopulation of S3 proximal tubule cells that display features usually seen only in acute or chronic injury. The expression signature of these cells was strongly enriched with genes associated with other mechanisms of protection against ischemic AKI including caloric restriction, hypoxic preconditioning, and female sex. Taken together, our results identify a novel role for Pax2 and Pax8 in mature proximal tubules that regulates critical genes and pathways involved in both injury response and protection from ischemic AKI., Translational Statement: Identifying the molecular and genetic regulators unique to the nephron that dictate vulnerability to injury and regenerative potential could lead to new therapeutic targets to treat ischemic kidney injury. Pax2 and Pax8 are two homologous nephron-specific transcription factors that are critical for kidney development and physiology. Here we report that proximal-tubule-selective depletion of Pax2 and Pax8 protects against both acute and chronic injury and induces an expression profile in the S3 proximal tubule with common features shared among diverse conditions that protect against ischemia. These findings highlight a new role for Pax proteins as potential therapeutic targets to treat AKI.

Underlying molecular mechanisms of the kidney protective effects of sodium glucose co-transporter 2 (SGLT2) inhibitors are not fully elucidated. Therefore, we studied the association between urinary epidermal growth factor (uEGF), a mitogenic factor involved in kidney repair, and kidney outcomes in patients with type 2 diabetes (T2D). The underlying molecular mechanisms of the SGLT2 inhibitor canagliflozin on EGF using single-cell RNA sequencing from kidney tissue were examined. Urinary EGF-to-creatinine ratio (uEGF/Cr) was measured in 3521 CANagliflozin cardioVascular Assessment Study (CANVAS) participants at baseline and week 52. Associations of uEGF/Cr with kidney outcome were assessed using multivariable-adjusted Cox regression models. Single-cell RNA sequencing was performed using protocol kidney biopsy tissue from ten young patients with T2D on SGLT2i, six patients with T2D on standard care only, and six healthy controls (HCs). In CANVAS, each doubling in baseline uEGF/Cr was associated with a 12% (95% confidence interval 1-22) decreased risk of kidney outcome. uEGF/Cr decreased after 52 weeks with placebo and remained stable with canagliflozin (between-group difference +7.3% (2.0-12.8). In young persons with T2D, EGF mRNA was primarily expressed in the thick ascending loop of Henle. Expression in biopsies from T2D without SGLT2i was significantly lower compared to HCs, whereas treatment with SGLT2i increased EGF levels closer to the healthy state. In young persons with T2D without SGLT2i, endothelin-1 emerged as a key regulator of the EGF co-expression network. SGLT2i treatment was associated with a shift towards normal EGF expression. Thus, decreased uEGF represents increased risk of kidney disease progression in patients with T2D. Canagliflozin increased kidney tissue expression of EGF and was associated with a downstream signaling cascade linked to tubular repair and reversal of tubular injury., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: In India, the awareness about the psycho-social dimension of chronic pain is minimal among physicians and patients. The research with community-based group therapies (like mindfulness) to address the psycho-social aspects in chronic pain patients remains limited. The aim of this randomized controlled trial was to see the effects of mindfulness on pain intensity, pain catastrophizing, chronic pain acceptance, perceived stress, well-being, and mindfulness characteristics., Materials and Methods: In this two-site, parallel group, clinical trial, 170 patients attending pain outdoors of two government hospitals in West Bengal, India, were randomized to attend five weekly in-person mindfulness sessions (cases) or usual care sessions (controls) within the hospital premises. Pre-program and post-program data were collected and analyzed using statistical methods like repeated measures analysis of variance., Results: In participants of the mindfulness group, significant changes post session were noted in pain intensity [F(1,326) = 15.0122; P = 0.0001291], pain acceptance [F(1,326) = 4.5311; P = 0.03403], and perceived stress score [F(1,326) = 13.2788; P = 0.0003122] compared to pre-session. The changes in pain catastrophizing, World Health Organization well-being and Freiburg mindfulness inventory scores were non-specific., Conclusion: Mindfulness had a positive influence on pain intensity, pain acceptance, and perceived stress of Indian chronic pain patients. The effects on pain catastrophizing, mindfulness characteristics, and well-being (non-specific) were also encouraging. Further studies will be required to substantiate these results., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Psychiatry.)

This study explores the challenges facing microalgae biofuel production, specifically low lipid content and difficulties with algal cell harvesting. The purpose of the research is to investigate the effect of seawater content and nanoparticle concentration on freshwater microalgae growth and biofuel production. The principal results of the study show that increasing the proportion of seawater and nanoparticles enhances the lipid content and cell diameter of microalgae, while excessive concentrations of nanoparticles and low seawater content lead to reduced microalgae growth. Furthermore, an optimal cell diameter was identified at a nanoparticle concentration of 150 mg/L. The study also reveals that increasing seawater content can decrease zeta potential and increase chlorophyll a content due to the concentration of dissolved organic matter. Increasing the seawater content from 0% to 25% decreased zeta potential by 1% owing to the instability and aggregation of the cells. Chlorophyll a for the 0% seawater was 0.55 which is increased to 1.32 only due to the increase in the seawater content. This significant increase is due to the concentration of dissolved organic matter in seawater. Additionally, the presence of seawater positively affects microalgae metabolic activity and biochar yield. The findings of this study offer valuable insights into the potential for optimizing microalgae biofuel production. The use of seawater and nanoparticles has shown promise in enhancing microalgae growth and biofuel yield, and the results of this study underscore the scientific value of exploring the role of seawater and nanoparticles in microalgae biofuel production. Further research in this area has the potential to significantly contribute to the development of sustainable energy solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Microalgae is one the promising source of energy for the production of biofuel and other value-added products to replace the existing conventional fossil fuels. However, low lipid content and poor cell harvesting are the key challenges. Based on the growth conditions the lipid productivity will be affected. The current study examines the mixtures of both wastewater and NaCl on the microalgae growth was studied. The microalgae used for conducting the tests were Chlorella vulgaris microalgae. Mixtures of the wastewater was prepared under the different concentrations of the seawater, classified as S0%, S20%, and S40%. The growth of microalgae was studied in the presence of these mixtures, and the addition of Fe 2 O 3 nanoparticles was included to stimulate the growth. The results showed that increasing the salinity in the wastewater resulted in decreased biomass production, but significantly increased lipid content compared to S0%. The highest lipid content was recorded at S40%N with 21.2%. The Highest lipid productivity was also witnessed for S40% with 45.6 mg/Ld. The cell diameter was also found to increase with increasing salinity content in the wastewater. The addition of Fe 2 O 3 nanoparticles in the seawater was found to enhance the productivity of the microalgae extensively, resulting in 9.2% and 6.15% increased lipid content and lipid productivity respectively compared to conventional cases. However, the inclusion of the nanoparticles slightly increased the zeta potential of microalgal colloids, with no noticeable effects on the cell diameter or bio-oil yields. Based on these findings, Chlorella vulgaris was identified as a suitable candidate for treating wastewater with high salinity exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Arteriolar hyalinosis in kidneys is an independent predictor of cardiovascular disease, the main cause of mortality in chronic kidney disease (CKD). The underlying molecular mechanisms of protein accumulation in the subendothelial space are not well understood. Using single cell transcriptomic data and whole slide images from kidney biopsies of patients with CKD and acute kidney injury in the Kidney Precision Medicine Project, the molecular signals associated with arteriolar hyalinosis were evaluated. Co-expression network analysis of the endothelial genes yielded three gene set modules as significantly associated with arteriolar hyalinosis. Pathway analysis of these modules showed enrichment of transforming growth factor beta / bone morphogenetic protein (TGFβ / BMP) and vascular endothelial growth factor (VEGF) signaling pathways in the endothelial cell signatures. Ligand-receptor analysis identified multiple integrins and cell adhesion receptors as over-expressed in arteriolar hyalinosis, suggesting a potential role of integrin-mediated TGFβ signaling. Further analysis of arteriolar hyalinosis associated endothelial module genes identified focal segmental glomerular sclerosis as an enriched term. On validation in gene expression profiles from the Nephrotic Syndrome Study Network cohort, one of the three modules was significantly associated with the composite endpoint (> 40% reduction in estimated glomerular filtration rate (eGFR) or kidney failure) independent of age, sex, race, and baseline eGFR, suggesting poor prognosis with elevated expression of genes in this module. Thus, integration of structural and single cell molecular features yielded biologically relevant gene sets, signaling pathways and ligand-receptor interactions, underlying arteriolar hyalinosis and putative targets for therapeutic intervention.

The goal of this study was to extract saponins from the tuberous root of Decalepis hamiltonii and assess their potential clinical applications, which included antioxidant, antibacterial, antithrombotic, and anticancer properties. Surprisingly, the results of this study revealed that the extracted saponins have excellent antioxidant activities, as demonstrated by 2,2-diphenylpicrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Hydrogen peroxide (H 2 O 2 ), and Nitric oxide (NO) scavenging assays. Nonetheless, at a concentration of 100 g/mL, crude saponin had excellent antibacterial activity, particularly against gramme positive bacteria (Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, and Micrococcus luteus), followed by gramme negative bacteria (Escherichia coli, Salmonella typhi, Proteus mirabilis, and Klebsiella pneumonia). Despite this, the crude saponin had no effect on Aspergillus niger and Candida albicans. The crude saponin also possesses outstanding in vitro antithrombotic activity on blood clot. Interestingly, the crude saponins have an outstanding anticancer activity of 89.26%, with an IC 50 value of 58.41 μg/mL. Overall, the findings conclude that crude saponin derived from D. hamiltonii tuberous root could be used in pharmaceutical formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The physicochemical attributes of textile effluents collected from secondary treatment stage was investigated in this study and also assess the biosorption potential of membrane immobilized Bacillus cereus and free form of Bacillus cereus on textile effluent through bioreactor model study to find a sustainable solution to manage the textile effluent as vital need. Furthermore, the phytotoxicity and cytotoxicity nature of treated and untreated textile effluents on Vigna mungo and Artemia franciscana larvae under laboratory conditions as a novel approach. The textile effluent physicochemical parameter analysis results showed that the properties such as colour (Hazen unit), pH, turbidity, As, Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Cd, Cl, Cr, Cu, Hg, Ni, Pb, SO 4 2- , and Zn were beyond the acceptable limits. Bacillus cereus immobilized on a polyethylene membrane eliminated greater amounts of dye (25.0 ± 1.3, 56.5 ± 1.8, 57.18 ± 1.5, and 54.34 ± 1.7 Hazen unit from An1, Ae2, Ve3, and So4 respectively) and pollutants (As: 0.9-2.0, Cd: 6-8, Cr: 300-450, Cu: 5-7, Hg: 0.1-0.7, Ni: 8-14, Pb: 4-5, and Zn: 4-8 mg L -1 ) from textile effluent in a week of biosorption investigation using a bioreactor model (batch type) compared to a free form of B. cereus on textile effluent. The phytotoxicity and cytotoxicity study results revealed that the membrane immobilized B. cereus treated textile effluent exposure showed reduced phytotoxicity and minimal cytotoxicity (including mortality) percentage compared with free form B. cereus treated and untreated textile effluents. These entire results conclude that the membrane immobilized B. cereus may considerably minimize/detoxify the harmful pollutants from the textile effluents. A large scale level biosorption approach need to be performed to validate the maximum pollutants removing potential of this membrane immobilized bacteria species and optimal conditions for effective remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease., (© 2023. Springer Nature Limited.)

Presence of emerging pollutants (EPs), aka Micropollutants (MPs) in the freshwater environments is a severe threat to the environment and human beings. They include pharmaceuticals, insecticides, industrial chemicals, natural hormones, and personal care items and the pollutants are mostly present in wastewater generated from urbanization and increased industrial growth. Even concentrations as low as ngL -1 or mgL -1 have proven ecologically lethal to aquatic biota. For several years, the biodegradation of various Micropollutants (MPs) in aquatic ecosystems has been a significant area of research worldwide, with many chemical compounds being discovered in various water bodies. As aquatic biota spends most of their formative phases in polluted water, the impacts on aquatic biota are obvious, indicating that the environmental danger is substantial. In contrast, the impact of these contaminants on aquatic creatures and freshwater consumption is more subtle and manifests directly when disrupting the endocrine system. Research and development activities are expected to enable the development of ecologically sustainable, cost-effective, and efficient treatments for practical systems in the near future. Therefore, this review aims to understand recent emerging pollutants discovered and the available treatment technologies and suggest an innovative and cost-effective method to treat these EPs, which is sustainable and follows the circular bioeconomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

According to the World Health Organization and the Food and Agricultural Organization of the United Nations, T-2 is one of the most harmful food-toxic chemicals, penetrates intact skin. The current study examined the protective benefits of menthol topical treatment on T-2 toxin-induced cutaneous toxicity in mice. Lesions were observed on the skin of the T-2 toxin-treated groups at 72 and 120 h. The T-2 toxin (2.97 mg/kg/bw)-treated group developed skin lesions, skin inflammation, erythema, and necrosis of skin tissue in contrast to the control group. Our findings reveal that topical application of 0.25% and 0.5% MN treated groups resulted in no erythema or inflammation, and normal skin was observed with growing hairs. The 0.5% MN administered group demonstrated an 80% blister and erythema healing effect in in vitro tests. In addition, MN dose-dependently suppressed ROS and lipid peroxidation mediated by the T-2 toxin up to 120%. Histology discoveries and the immunoblotting investigations with the downregulation of i-NOS gene expression confirmed the validity of menthol activity. Further molecular docking experiments of menthol against the i-NOS protein demonstrated stable binding efficacy with conventional hydrogen bond interactions, indicating compelling evidence of menthol's anti-inflammatory effects on the T-2 toxin-induced skin inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)