Non-enzymatic glycation and diabetic kidney disease.

Chronic diabetes leads to various complications including diabetic kidney disease (DKD). DKD is a major microvascular complication and the leading cause of morbidity and mortality in diabetic patients. Varying degrees of proteinuria and reduced glomerular filtration rate are the cardinal clinical manifestations of DKD that eventually progress into end-stage renal disease. Histopathologically, DKD is characterized by renal hypertrophy, mesangial expansion, podocyte injury, glomerulosclerosis, and tubulointerstitial fibrosis, ultimately leading to renal replacement therapy. Amongst the many mechanisms, hyperglycemia contributes to the pathogenesis of DKD via a mechanism known as non-enzymatic glycation (NEG). NEG is the irreversible conjugation of reducing sugars onto a free amino group of proteins by a series of events, resulting in the formation of initial Schiff's base and an Amadori product and to a variety of advanced glycation end products (AGEs). AGEs interact with cognate receptors and evoke aberrant signaling cascades that execute adverse events such as oxidative stress, inflammation, phenotypic switch, complement activation, and cell death in different kidney cells. Elevated levels of AGEs and their receptors were associated with clinical and morphological manifestations of DKD. In this chapter, we discussed the mechanism of AGEs accumulation, AGEs-induced cellular and molecular events in the kidney and their impact on the pathogenesis of DKD. We have also reflected upon the possible options to curtail the AGEs accumulation and approaches to prevent AGEs mediated adverse renal outcomes.

New arsenals for old armour: Biogenic nanoparticles in the battle against drug-resistant Candida albicans.

Candida albicans is a common commensal fungus and fourth most frequent causative agent of nosocomial infections including life-threatening invasive candidiasis in humans. The effectiveness of present antifungal therapies using azoles, polyenes, flucytosine and echinocandins has plateaued in managing fungal infections. The limitations of these drugs are related to polymorphic morphology, biofilm formation, emergence of drug-resistant strains and production of several virulence factors. Development of new antifungal agents, which can particularly targeting multiple cellular targets and limiting evolving resistant strains are needed. Recently, metal nanoparticles have emerged as a source of new antifungal agents for antifungal formulations. Furthermore, green nanotechnology deals with the use of biosynthetic routes that offer new avenue for synthesizing antifungal nanoparticles coupled with less toxic chemical inventory and environmental sustainability. This article reviews the recent developments on C. albicans pathogenesis, biofilm formation, drug resistance, mode of action of antifungal drugs and antifungal activities of metal nanoparticles. The antifungal efficacy and mode of action of metal nanoparticles are described in the context of prospective therapeutic applications.

Retraction notice to "Performance and exergy analysis of an inclined solar still with baffle arrangements" [Heliyon 9 (2023) e14807].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e14807.].

Biosynthesis, classification, properties, and applications of Weissella bacteriocins.

This review aims to comprehensively chronicle the biosynthesis, classification, properties, and applications of bacteriocins produced by Weissella genus strains, particularly emphasizing their potential benefits in food preservation, human health, and animal productivity. Lactic Acid Bacteria (LAB) are a class of microorganisms well-known for their beneficial role in food fermentation, probiotics, and human health. A notable property of LAB is that they can synthesize antimicrobial peptides known as bacteriocins that exhibit antimicrobial action against both closely related and other bacteria as well. Bacteriocins produced by Weissella spp. are known to exhibit antimicrobial activity against several pathogenic bacteria including food spoilage species, making them highly invaluable for potential application in food preservation and food safety. Importantly, they provide significant health benefits to humans, including combating infections, reducing inflammation, and modulating the gut microbiota. In addition to their applications in food fermentation and probiotics, Weissella bacteriocins show promising prospects in poultry production, processing, and improving animal productivity. Future research should explore the utilization of Weissella bacteriocins in innovative food safety measures and medical applications, emphasizing their potential to combat antibiotic-resistant pathogens, enhance gut microbiota composition and function, and synergize with existing antimicrobial therapies.

Two-dimensional perovskite templates for durable, efficient formamidinium perovskite solar cells.

We present a design strategy for fabricating ultrastable phase-pure films of formamidinium lead iodide (FAPbI3) by lattice templating using specific two-dimensional (2D) perovskites with FA as the cage cation. When a pure FAPbI3 precursor solution is brought in contact with the 2D perovskite, the black phase forms preferentially at 100°C, much lower than the standard FAPbI3 annealing temperature of 150°C. X-ray diffraction and optical spectroscopy suggest that the resulting FAPbI3 film compresses slightly to acquire the (011) interplanar distances of the 2D perovskite seed. The 2D-templated bulk FAPbI3 films exhibited an efficiency of 24.1% in a p-i-n architecture with 0.5-square centimeter active area and an exceptional durability, retaining 97% of their initial efficiency after 1000 hours under 85°C and maximum power point tracking.

Structural Evolution and Photoluminescence Quenching across the FASnI3-xBrx (x = 0-3) Perovskites.

One of the primary methods for band gap tuning in metal halide perovskites has been halide (I/Br) mixing. Despite widespread usage of this type of chemical substitution in perovskite photovoltaics, there is still little understanding of the structural impacts of halide alloying, with the assumption being the formation of ideal solid solutions. The FASnI3-xBrx (x = 0-3) family of compounds provides the first example where the assumption breaks down, as the composition space is broken into two unique regimes (x = 0-2.9; x = 2.9-3) based on their average structure with the former having a 3D and the latter having an extended 3D (pseudo 0D) structure. Pair distribution function (PDF) analyses further suggest a dynamic 5s2 lone pair expression resulting in increasing levels of off-centering of the central Sn as the Br concentration is increased. These antiferroelectric distortions indicate that even the x = 0-2.9 phase space behaves as a nonideal solid-solution on a more local scale. Solid-state NMR confirms the difference in local structure yielding greater insight into the chemical nature and local distributions of the FA+ cation. In contrast to the FAPbI3-xBrx series, a drastic photoluminescence (PL) quenching is observed with x ≥ 1.9 compounds having no observable PL. Our detailed studies attribute this quenching to structural transitions induced by the distortions of the [SnBr6] octahedra in response to stereochemically expressed lone pairs of electrons. This is confirmed through density functional theory, having a direct impact on the electronic structure.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. METHODS: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. RESULTS: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). CONCLUSION: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. STUDY REGISTRATION: Clinical Trials Registry-India (CTRI/2020/08/027000).

The Patient Population at Homeopathic Outpatient Clinics across India: A Clinical Data Collection Study.

BACKGROUND: Even though several initiatives have been undertaken in different locations worldwide to collect clinical data in homeopathy, it is important to further investigate these aspects in the context of health care in India. OBJECTIVE: The study aimed to gather and analyze patients' clinical data and to derive insights into homeopathic treatment using an internet-based software program for data storage, retrieval and repertorization. METHODS: A multi-center observational study was conducted across 14 homeopathy outpatient clinics in India that are affiliated with the Central Council for Research in Homoeopathy (CCRH). Patient symptoms and demographic details were documented anonymously, and prescriptions were guided by repertorial suggestions from the Vithoulkas Compass software. During follow-up visits, treatment outcome was also recorded using an online assessment form. A retrospective analysis of data on patients' demographics, follow-up visits, morbidity (International Classification of Diseases 11th Revision), rubrics used, prescribed medicines and the level of improvement was achieved using Microsoft Excel-generated pivot tables. RESULTS: Throughout the study duration of one year a total of 2,811 patients attended the 14 outpatient clinics, of whom 2,468 were new patients with a total of 2,172 initial homeopathic prescription entries. Across the study, there were 3,491 prescriptions and 1,628 follow-up consultations for 868 follow-up patients, all of which data were thoroughly analyzed. The highest frequency of patients was in the 20-49 age group, and a higher proportion of the patients overall was female. Musculoskeletal, dermatological and respiratory complaints were the most frequently reported. The rubrics "Desire for sweets" and "Desire for spices" emerged as the most commonly used in the repertorizations. Further, Sulphur stood out as the most commonly prescribed medicine overall. With homeopathic treatment, some degree of clinical improvement was reported in 86% of the follow-up cases. CONCLUSION: Homeopathy is prescribed in CCRH outpatient clinics for a wide range of ailments in people across India, with at least some clinical improvement noted in a high proportion of those patients. The large-scale systematic data collection in these clinics has provided clear insights into the use and clinical value of homeopathy in India, with the potential to build a substantive nationwide data inventory over time.

Heavy metal association with chronic kidney disease of unknown cause in central India-results from a case-control study.

BACKGROUND: Chronic Kidney Disease of unknown cause (CKDu) a disease of exclusion, and remains unexplained in various parts of the world, including India. Previous studies have reported mixed findings about the role of heavy metals or agrochemicals in CKDu. These studies compared CKDu with healthy controls but lacked subjects with CKD as controls. The purpose of this study was to test the hypothesis whether heavy metals, i.e. Arsenic (As), Cadmium (Cd), Lead (Pb), and Chromium (Cr) are associated with CKDu, in central India. METHODS: The study was conducted in a case-control manner at a tertiary care hospital. CKDu cases (n = 60) were compared with CKD (n = 62) and healthy subjects (n = 54). Blood and urine levels of As, Cd, Pb, and Cr were measured by Inductively Coupled Plasma- Optical Emission Spectrometry. Pesticide use, painkillers, smoking, and alcohol addiction were also evaluated. The median blood and urine metal levels were compared among the groups by the Kruskal-Wallis rank sum test. RESULTS: CKDu had significantly higher pesticide and surface water usage as a source of drinking water. Blood As levels (median, IQR) were significantly higher in CKDu 91.97 (1.3-132.7) µg/L compared to CKD 4.5 (0.0-58.8) µg/L and healthy subjects 39.01 (4.8-67.4) µg/L (p < 0.001) On multinominal regression age and sex adjusted blood As was independently associated with CKDu[ OR 1.013 (95%CI 1.003-1.024) P < .05].Blood and urinary Cd, Pb, and Cr were higher in CKD compared to CKDu (p > .05). Urinary Cd, Pb and Cr were undetectable in healthy subjects and were significantly higher in CKDu and CKD compared to healthy subjects (P = < 0.001). There was a significant correlation of Cd, Pb and Cr in blood and urine with each other in CKDu and CKD subjects as compared to healthy subjects. Surface water use also associated with CKDu [OR 3.178 (95%CI 1.029-9.818) p < .05). CONCLUSION: The study showed an independent association of age and sex adjusted blood As with CKDu in this Indian cohort. Subjects with renal dysfunction (CKDu and CKD) were found to have significantly higher metal burden of Pb, Cd, As, and Cr as compared to healthy controls. CKDu subjects had significantly higher pesticide and surface water usage, which may be the source of differential As exposure in these subjects.

Growth-dependent cr(VI) reduction by Alteromonas sp. ORB2 under haloalkaline conditions: toxicity, removal mechanism and effect of heavy metals.

Bacterial reduction of hexavalent chromium (VI) to chromium (III) is a sustainable bioremediation approach. However, the Cr(VI) containing wastewaters are often characterized with complex conditions such as high salt, alkaline pH and heavy metals which severely impact the growth and Cr(VI) reduction potential of microorganisms. This study investigated Cr(VI) reduction under complex haloalkaline conditions by an Alteromonas sp. ORB2 isolated from aerobic granular sludge cultivated from the seawater-microbiome. Optimum growth of Alteromonas sp. ORB2 was observed under haloalkaline conditions at 3.5-9.5% NaCl and pH 7-11. The bacterial growth in normal culture conditions (3.5% NaCl; pH 7.6) was not inhibited by 100 mg/l Cr(VI)/ As(V)/ Pb(II), 50 mg/l Cu(II) or 5 mg/l Cd(II). Near complete reduction of 100 mg/l Cr(VI) was achieved within 24 h at 3.5-7.5% NaCl and pH 8-11. Cr(VI) reduction by Alteromonas sp. ORB2 was not inhibited by 100 mg/L As(V), 100 mg/L Pb(II), 50 mg/L Cu(II) or 5 mg/L Cd(II). The bacterial cells grew in the medium with 100 mg/l Cr(VI) contained lower esterase activity and higher reactive oxygen species levels indicating toxicity and oxidative stress. In-spite of toxicity, the cells grew and reduced 100 mg/l Cr(VI) completely within 24 h. Cr(VI) removal from the medium was driven by bacterial reduction to Cr(III) which remained in the complex medium. Cr(VI) reduction was strongly linked to aerobic growth of Alteromonas sp. The Cr(VI) reductase activity of cytosolic protein fraction was pronounced by supplementing with NADPH in vitro assays. This study demonstrated a growth-dependent aerobic Cr(VI) reduction by Alteromonas sp. ORB2 under complex haloalkaline conditions akin to wastewaters.

Determinants of Poison-related Mortality in Tertiary Care Hospital, South India.

Aims and background: Acute poisoning is one of the most common emergencies in India and around the world. Understanding the factors associated with mortality can aid us in devising appropriate preventive strategies to curtail deaths due to poisoning. Purpose of this study is to find various factors that determine the mortality among acute poisoning cases admitted in a tertiary care center. Materials and methods: A retrospective hospital records-based study was conducted at Chengalpattu Medical College Hospital. The study included 2,123 cases of various poisoning cases admitted for a year from January to December 2022. Cases of bites, stings, drowning, and hanging were excluded. Information on sociodemographic profile, type of poison, time since ingestion and admission, and treatment outcome were collected using a structured pro forma. Results: The mean age of the study population was 29.90 ± 14.98 years. Poisoning was found to be predominantly among males (56.42%) and residents of rural areas (58%). Insecticide consumption (27.0%) was the most common modality, followed by oleander poisoning (20%), corrosive poison (17%), rat poison (15%), tablet poison (13%), and other poisons. The overall case fatality rate (CFR) was 5.2%, with the highest CFR of 12.25% with insecticide poisoning. In multivariate analysis, Glasgow coma scale (GCS) score at admission is the only parameter showing a statistically significant association with mortality (adjusted odds-ratio 0.271(0.2-0.38, p-value < 0.01). Conclusion: Acute poisoning primarily affects the young and economically productive population. In the south Indian population, pesticides are still the major contributor though corrosives are a major contributor among children. Mortality is still significant, and GCS status admission is the only predictor of mortality. How to cite this article: Krishnasamy N, Narmadhalakshmi R, Parameshwari P, Jayalakshmi R, Lokesh R, Jayanthi R, et al. Determinants of Poison-related Mortality in Tertiary Care Hospital, South India. Indian J Crit Care Med 2024;28(4):329-335.

Comparison of Janani Suraksha Yojana (JSY) and augmented Arogya Laxmi scheme (ALS) in improving maternal and child health outcomes in urban settlements of Hyderabad, South India.

BACKGROUND: India accounts for the largest number of global neonatal deaths with around 20 per 1000 live births. To improve the utilization of government services for institutional deliveries, Augmented Arogya Laxmi Scheme (ALS) was launched in Telangana state of southern India. This study assessed the effectiveness of the Janani Suraksha Yojana (JSY), which combines cash assistance with delivery and post-delivery care, in comparison to ALS in improving the outcomes related to antenatal, natal, and postnatal care in urban settlements of Hyderabad, Telangana, southern India. METHODS: This was a two-year cross-sectional study conducted in 14 urban settlements of Hyderabad city from September 2017- August 2019. All mothers delivered during the 18 months preceding the survey were enrolled after a written informed consent. Field investigators collected data on variables related to socio-demographic characteristics, awareness, and utilization of JSY and ALS programs. Variables related to antenatal history, antenatal care, complications during birth, delivery outcomes, newborn care, and postnatal care till 28 days were assessed. We used multivariable logistic regression model to examine the association between the different maternal, child, and socio-demographic characteristics of the two study groups. RESULTS: A total of 926 mothers were beneficiaries of Janani Suraksha Yojana (JSY) program while 933 mothers were beneficiaries of augmented Arogya Laxmi Scheme (ALS). Mothers in ALS group (AOR 1.71; 95% CI 1.21-2.43) were at increased odds of having more than eight antenatal care (ANC) visits compared to the mothers availing JSY. Mothers in ALS group were at decreased odds of having complications like severe pain in the abdomen (AOR 0.43; 95% CI 0.22-0.86), swelling of legs or feet (AOR 0.59; 95% CI 0.44-0.80) compared to mothers in JSY group. Children of mothers in the ALS group had increased odds of receiving breastfeeding within 30 minutes of birth (AOR 1.46; 95% CI 1.13-1.88) compared to children of mothers in JSY group. CONCLUSIONS: The newly launched augmented ALS led to the increased utilization of the government health facilities and improved the maternal and child health outcomes.

Reinvestigation of diphenylmethylpiperazine analogues of pyrazine as new class of Plasmodial cysteine protease inhibitors for the treatment of malaria.

Malaria eradication is still a global challenge due to the lack of a broadly effective vaccine and the emergence of drug resistance to most of the currently available drugs as part of the mainline artemisinin-based combination therapy. A variety of experimental approaches are quite successful in identifying and synthesizing new promising pharmacophore hybrids with distinct mechanisms of action. Based on our recent findings, the current study demonstrates the reinvestigation of a series of diphenylmethylpiperazine and pyrazine-derived molecular hybrids. Pyrazine-derived molecular hybrids were screened to investigate the antiplasmodial activity on drug-susceptible Pf3D7 and drug-resistant PfW2 strains. The selected compounds were shown to be potent dual inhibitors of cysteine protease PfFP2 and PfFP3. Time-course parasitic development study demonstrated that compounds were able to arrest the growth of the parasite at the early trophozoite stage. The compounds did not show hemolysis of red blood cells and showed selectivity to the parasite compared with the mammalian Vero and A5489 cell lines. The study underlined HR5 and HR15 as a new class of Plasmodial falcipain inhibitors with an IC50 of 6.2 µM and 5.9 µM for PfFP2 and 6.8 µM and 6.4 µM for PfFP3, respectively. Both compounds have antimalarial efficacy with IC50 values of 3.05 µM and 2.80 µM for the Pf3D7 strain, and 4.35 µM and 3.39 µM for the PfW2 strain, respectively. Further structural optimization may turn them into potential Plasmodial falcipain inhibitors for malaria therapeutics.

Obesity-related glomerulopathy is associated with elevated WT1 expression in podocytes.

BACKGROUND: The prevalence of obesity is increasing worldwide at an alarming rate. In addition to the increased incidence of cardiovascular and metabolic diseases, obesity is the most potent risk factor for developing chronic kidney disease (CKD). Although systemic events such as hemodynamic factors, metabolic effects, and lipotoxicity were implicated in the pathophysiology of obesity-related glomerulopathy (ORG) and kidney dysfunction, the precise mechanisms underlying the association between obesity and CKD remain unexplored. METHODS: In this study, we employed spontaneous WNIN/Ob rats to investigate the molecular events that promote ORG. Further, we fed a high-fat diet to mice and analyzed the incidence of ORG. Kidney functional parameters, micro-anatomical manifestations, and podocyte morphology were investigated in both experimental animal models. Gene expression analysis in the rodents was compared with human subjects by data mining using Nephroseq and Kidney Precision Medicine Project database. RESULTS: WNIN/Ob rats were presented with proteinuria and several glomerular deformities, such as adaptive glomerulosclerosis, decreased expression of podocyte-specific markers, and effacement of podocyte foot process. Similarly, high-fat-fed mice also showed glomerular injury and proteinuria. Both experimental animal models showed increased expression of podocyte-specific transcription factor WT1. The altered expression of putative targets of WT1 such as E-cadherin, podocin (reduced), and α-SMA (increased) suggests elevated expression of WT1 in podocytes elicits mesenchymal phenotype. Curated data from CKD patients revealed increased expression of WT1 in the podocytes and its precursors, parietal epithelial cells. CONCLUSION: WT1 is crucial during nephron development and has minimal expression in adult podocytes. Our study discovered elevated expression of WT1 in podocytes in obesity settings. Our analysis suggests a novel function for WT1 in the pathogenesis of ORG; however, the precise mechanism of WT1 induction and its involvement in podocyte pathobiology needs further investigation.

Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study.

BACKGROUND AND AIM: Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. METHODS: A hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman's rank correlation was used to evaluate the relationship between the categorical variables. RESULTS: The median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= -0.486, p<0.001). CONCLUSION: Plasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.

An enumerative pre-processing approach for retinopathy severity grading using an interpretable classifier: a comparative study.

BACKGROUND: Diabetic retinopathy (DR) is a serious eye complication that results in permanent vision damage. As the number of patients suffering from DR increases, so does the delay in treatment for DR diagnosis. To bridge this gap, an efficient DR screening system that assists clinicians is required. Although many artificial intelligence (AI) screening systems have been deployed in recent years, accuracy remains a metric that can be improved. METHODS: An enumerative pre-processing approach is implemented in the deep learning model to attain better accuracies for DR severity grading. The proposed approach is compared with various pre-trained models, and the necessary performance metrics were tabulated. This paper also presents the comparative analysis of various optimization algorithms that are utilized in the deep network model, and the results were outlined. RESULTS: The experimental results are carried out on the MESSIDOR dataset to assess the performance. The experimental results show that an enumerative pipeline combination K1-K2-K3-DFNN-LOA shows better results when compared with other combinations. When compared with various optimization algorithms and pre-trained models, the proposed model has better performance with maximum accuracy, precision, recall, F1 score, and macro-averaged metric of 97.60%, 94.60%, 98.40%, 94.60%, and 0.97, respectively. CONCLUSION: This study focussed on developing and implementing a DR screening system on color fundus photographs. This artificial intelligence-based system offers the possibility to enhance the efficacy and approachability of DR diagnosis.

Investigations on anticancer activity of Eu3+ doped hydroxyapatite nanocomposites against MCF7 and 4T1 breast cancer cell lines: A structural and luminescence Perspective.

Breast cancer remains a significant global health concern, necessitating the development of novel therapeutic approaches. In this study, we investigate the role of Eu3+ doped hydroxyapatite nanocomposites (Han: Eu3+) in the treatment of MCF7 and 4T1 breast cancer cell lines. Furthermore, we explored the structural and luminescent properties of these nanocomposites. Han: Eu3+ were synthesized using a modified co-precipitation method, and their morphology and crystal structure were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD) in which the average crystalline size of Han: Eu3+ was found to be 25 nm, rendering them suitable for cellular uptake and targeted therapy. To gain insights into the luminescent properties of Han: Eu3+, their excitation and emission spectra were recorded using photoluminescence spectrometer. The characteristic red emission of Eu3+ ions was observed upon excitation, validating the successful doping of Eu3+ into the Han lattice, which was confirmed by the CIE chromaticity coordinate study. These luminescent properties of Han: Eu3+ hold promise for potential applications in bioimaging. To evaluate the efficacy of Han: Eu3+ in breast cancer treatment, MCF7 and 4T1 cell lines were exposed to varying concentrations of the nanocomposites. Cell viability assays revealed a concentration-dependent reduction in cell viability, indicating the potential anticancer activity of Han: Eu3+. The findings of this study contribute to the expanding field of nanomedicine, bringing targeted breast cancer treatments and us closer to more effective.

Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrity.

Protein ubiquitination is essential for cellular homeostasis and regulation of several processes, including cell division and genome integrity. Ubiquitin E3 ligases determine substrate specificity for ubiquitination, and Cullin-RING E3 ubiquitin ligases (CRLs) make the largest group among the ubiquitin E3 ligases. Although conserved and most studied in model eukaryotes, CRLs remain underappreciated in Plasmodium and related parasites. To investigate the CRLs of human malaria parasite Plasmodium falciparum, we generated parasites expressing tagged P. falciparum cullin-1 (PfCullin-1), cullin-2 (PfCullin-2), Rbx1 (PfRbx1) and Skp1 (PfSkp1). PfCullin-1 and PfCullin-2 were predominantly expressed in erythrocytic trophozoite and schizont stages, with nucleocytoplasmic localization and chromatin association, suggesting their roles in different cellular compartments and DNA-associated processes. Immunoprecipitation, in vitro protein-protein interaction, and ubiquitination assay confirmed the presence of a functional Skp1-Cullin-1-Fbox (PfSCF) complex, comprising of PfCullin-1, PfRbx1, PfSkp1, PfFBXO1, and calcyclin binding protein. Immunoprecipitation, sequence analysis, and ubiquitination assay indicated that PfCullin-2 forms a functional human CRL4-like complex (PfCRL4), consisting of PfRbx1, cleavage and polyadenylation specificity factor subunit_A and WD40 repeat proteins. PfCullin-2 knock-down at the protein level, which would hinder PfCRL4 assembly, significantly decreased asexual and sexual erythrocytic stage development. The protein levels of several pathways, including protein translation and folding, lipid biosynthesis and transport, DNA replication, and protein degradation were significantly altered upon PfCullin-2 depletion, which likely reflects association of PfCRL4 with multiple pathways. PfCullin-2-depleted schizonts had poorly delimited merozoites and internal membraned structures, suggesting a role of PfCRL4 in maintaining membrane integrity. PfCullin-2-depleted parasites had a significantly lower number of nuclei/parasite than the normal parasites, indicating a crucial role of PfCRL4 in cell division. We demonstrate the presence of functional CRLs in P. falciparum, with crucial roles for PfCRL4 in cell division and maintaining membrane integrity.

Specific and Strong Acceleration of Nitrosation by Nitrosyl Sulfonates Using the Bis-Coordinating Lewis Acid TiCl4 or SnCl4.

Nitrosyl triflate is an excellent donor of NO+ to C═C and very unreactive benzenoids, in contrast to the much less reactive nitrosyl mesylate. However, both of these reagents are strongly activated by the bis-coordinating Lewis acids TiCl4 and SnCl4 and become super reactive NO+ donors. Strong catalysis and activation are even observed with the inherently less electrophilic nitrosyl trifluoroacetate. Monocoordinating strong Lewis acids, e.g., MeAlCl2, are relatively ineffective.

Production, purification, and functional characterization of glucan exopolysaccharide produced by Enterococcus hirae strain OL616073 of fermented food origin.

Microbial exopolysaccharides (EPS) are high molecular weight polymeric substances with great diversity and variety of applications in the food and pharma industry. In this study, we report the extraction of an EPS from Enterococcus hirae OL616073 strain originally isolated from Indian fermented food and its purification by ion exchange and size exclusion chromatography for physical-functional analyses. The EPS showed two prominent fractions (EPS F1 and EPS F2) with molecular mass 7.7 × 104 and 6.5 × 104 Da respectively by gel permeation chromatography. These fractions were further characterized by FTIR, HPTLC, GC-MS, and NMR as a homopolysaccharide of glucose linked with α-(1 â†’ 6) and α-(1 â†’ 3) glycosidic linkages. The porous, spongy, granular morphology of EPS was observed under scanning electron microscopy. EPS has revealed strong physico-functional properties like water solubility index (76.75 %), water contact angle (65.74°), water activity (0.35), hygroscopicity (3.05 %), water holding capacity (296.19 %), oil holding capacity (379.91 %), foaming capacity (19.58 %), and emulsifying activity (EA1-72.22 %). Rheological analysis showed that aqueous solution of EPS exhibited a non-Newtonian fluid behavior and shear-thinning characteristics. Overall, EPS exhibits techno functional properties with potential applications as a functional biopolymer in food and pharma industry.