Significance of interactions of low molecular weight crystallin fragments in lens aging and cataract formation

Analysis of aged and cataract lenses shows the presence of increased amounts of crystallin fragments in the high molecular weight aggregates of water-soluble and water-insoluble fractions. However, the significance of accumulation and interaction of low molecular weight crystallin fragments in aging and cataract development is not clearly understood. In this study, 23 low molecular mass (<3.5-kDa) peptides in the urea-soluble fractions of young, aged, and aged cataract human lenses were identified by mass spectroscopy. Two peptides, B-(1-18) (MDIAIHHPWIRRPFFPFH) and A3/A1-(59-74)(SD(N)AYHIERLMSFRPIC), present in aged and cataract lens but not young lens, and a third peptide, S-(167-178) (SPAVQSFRRIVE) present in all three lens groups were synthesized to study the effects of interaction of these peptides with intact -, -, and -crystallins and alcohol dehydrogenase, a protein used in aggregation studies. Interaction of B-(1-18) and A3/A1-(59-74) peptides increased the scattering of light by - and -crystallin and alcohol dehydrogenase. The ability of -crystallin subunits to function as molecular chaperones was significantly reduced by interaction with B-(1-18) and A3/A1-(59-74) peptides, whereas S peptide had no effect on chaperone-like activity of -crystallin. The A3/A1-(59-74 peptide caused a 5.64-fold increase in B-crystallin oligomeric mass and partial precipitation. Replacing hydrophobic residues in B-(1-18) and A3/A1-(59-74) peptides abolished their ability to induce crystallin aggregation and light scattering. Our study suggests that interaction of crystallin-derived peptides with intact crystallins could be a key event in age-related protein aggregation in lens and cataractogenesis

Unveiling the Hidden Agony: Exploring Neuropathic Pain in the Younger Generation: A Narrative Review

Pain is described as “an unpleasant sensory and emotional experience associated with, or resembling that associated with actual or potential tissue damage.” Neuropathic Pain (NP), a common condition, is characterised by subjective negative and positive sensations that range from numbness to debilitating agony. The prevalence of chronic pain and nerve pain in young individuals is estimated to be around 30%-50% and 6%-11%, respectively. The exact cause of NP is unknown, but research suggests that factors such as allodynia, external sensitisation, neuronal swelling, free radical damage, activation of microglia, and physiological state play a significant role in its development and progression. While there have been recent suggestions for medications, neurostimulation techniques, and interventional management, comprehensive guidelines covering all these treatments are yet to be released. Both peripheral and Central Nervous System (CNS) mechanisms contribute to the persistence of most NP types. The initial approach to treating NP in young individuals often involves pharmacotherapy. The types of drugs prescribed for general and specific types of NP in young individuals, including antidepressants and anticonvulsants, align with guidelines and consensus statements from various organisations worldwide. However, many individuals may not experience complete relief from their pain despite using these first-line treatments. Neuralgia, affecting 7 to 10% of the general population, is caused by dysfunction in the sensory organs of the body, which comprise A, A, and C fibers, as well as the brainstem and spinal cord

Exploratory Data Analysis on Blueberry yield through Bayes and Function Models

Agricultural researchers are using machine learning to predict crop yield. Many machine learning algorithms need lots of data. One of the major challenges in training and experimenting with machine learning algorithms is the availability of training data in sufficient quality and quantity remains a limiting factor. The Linear Discriminant Analysis produces 95.88% of accuracy which is most efficient of selected models; The Nave Bayes Multinomial has 69.88% accuracy, while the Linear Discriminant Analysis has 0.96 precision. The NBM has 0.71 precision, while Linear Discriminant Analysis has 0.95 recall. The Linear Discriminant Analysis produces 0.99 of ROC, which is the most efficient outcome of selected models. The NBM gives least ROC, which is 0.80. The Linear Discriminant Analysis produces 0.99 of PRC, which is the most efficient outcome of selected models. The NBM gives least PRC, which is 0.72. The LDA explores efficient outcome with low deviations. Four machine-learning-based predictive models were then built using the simulated dataset. This simulated data provides researchers with actual field observation data and those who want to test machine learning algorithms' response to real data with crop yield prediction models

Construction of Heteroatom-Doped Porous Carbon Architectures for Energy and Sensing Applications

In this chapter, we have concentrated on the main electrocatalytic oxygen processes, oxygen reduction reaction (ORR) and water splitting oxygen evolution reaction (OER), and biosensors based on porous carbon architectures, which are more important areas of research because of the rise in demand for energy management, supply, and disease diagnosis. Heteroatom-doped carbon hollow spheres are very useful because they have a large surface area, mesoporosity, spherical wall thicknesses, edge plane defect sites, catalytic active sites, and fast heterogeneous electron-transfer rates. These properties are very important for making commercial devices. This chapter provides an overview of hollow carbon nanospheres that are doped with single and double heteroatoms, as well as cobalt oxide. These carbon compounds function as dual catalysts for OER and ORR, as well as an effective electrocatalyst for the oxygen reduction process in both acidic and alkaline media. Electrocatalytically, heteroatom-doped carbon sphere-modified electrodes can simultaneously and specifically identify and determine the analytes, while also validating the target species in real samples. N-doped hollow carbon spheres coated-Co3O4 functioned as an efficient dual-function oxygen electrocatalyst for oxygen evolution and oxygen reduction processes and also as a biosensor for highly effective electrochemical sensing of acetaminophen. A symmetric supercapacitor using dual heteroatom-doped and SBA-15 templated porous carbon was also discussed

Toward Fairness in Speech Recognition: Discovery and mitigation of performance disparities

As for other forms of AI, speech recognition has recently been examined with respect to performance disparities across different user cohorts. One approach to achieve fairness in speech recognition is to (1) identify speaker cohorts that suffer from subpar performance and (2) apply fairness mitigation measures targeting the cohorts discovered. In this paper, we report on initial findings with both discovery and mitigation of performance disparities using data from a product-scale AI assistant speech recognition system. We compare cohort discovery based on geographic and demographic information to a more scalable method that groups speakers without human labels, using speaker embedding technology. For fairness mitigation, we find that oversampling of underrepresented cohorts, as well as modeling speaker cohort membership by additional input variables, reduces the gap between top- and bottom-performing cohorts, without deteriorating overall recognition accuracy.Comment: Proc. Interspeech 202

Silver Complexes as Anticancer Agents: A Perspective Review

Metal complexes gained more attention in the medical field, particularly cancer treatment, due to their enhanced potential and redox ability. These complexes exhibited more significant antiproliferation potential by triggering the generation of reactive oxygen species (ROS), altering cell membrane, changing cell redox potential and by DNA replication inhibition. Platinum-based metal complex Cisplatin was prepared. It was widely used in treating lung, breast, ovarian and testicular cancers; however, these complexes showed many adverse effects such as renal insufficiency and electrolyte abnormalities, neurotoxicity, ototoxicity, nausea, vomiting and drug resistance. To overcome these side effects and drug resistance mechanisms, silver metal is highly employed as a cytotoxic agent by DNA binding through the formation of disulphide bonds. Moreover, silver complexes exhibited more significant cytotoxicity with the lowest toxicity. This review highlighted silver complexes' anticancer and cytotoxic potential with various bioactive ligands

Targeting AKR1B10 by drug repurposing with epalrestat overcomes chemoresistance in non-small cell lung cancer patient-derived tumor organoids

PURPOSE: Systemic treatments given to patients with non-small cell lung cancer (NSCLC) are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTO) and matched tumor tissues from surgically treated patients with NSCLC to identify drug repurposing targets to overcome resistance toward standard-of-care platinum-based doublet chemotherapy. EXPERIMENTAL DESIGN: PDTOs were established from 10 prospectively enrolled patients with non-metastatic NSCLC from resected tumors. PDTOs were compared with matched tumor tissues by histopathology/immunohistochemistry, whole exome sequencing, and transcriptome sequencing. PDTO growths and drug responses were determined by measuring 3D tumoroid volumes, cell viability, and proliferation/apoptosis. Differential gene expression analysis identified drug-repurposing targets. Validations were performed with internal/external data sets of patients with NSCLC. NSCLC cell lines were used for aldo-keto reductase 1B10 (AKR1B10) knockdown studies and xenograft models to determine the intratumoral bioavailability of epalrestat. RESULTS: PDTOs retained histomorphology and pathological biomarker expression, mutational/transcriptomic signatures, and cellular heterogeneity of the matched tumor tissues. Five (50%) PDTOs were chemoresistant toward carboplatin/paclitaxel. Chemoresistant PDTOs and matched tumor tissues demonstrated overexpression of AKR1B10. Epalrestat, an orally available AKR1B10 inhibitor in clinical use for diabetic polyneuropathy, was repurposed to overcome chemoresistance of PDTOs. In vivo efficacy of epalrestat to overcome drug resistance corresponded to intratumoral epalrestat levels. CONCLUSIONS: PDTOs are efficient preclinical models recapitulating the tumor characteristics and are suitable for drug testing. AKR1B10 can be targeted by repurposing epalrestat to overcome chemoresistance in NSCLC. Epalrestat has the potential to advance to clinical trials in patients with drug-resistant NSCLC due to favorable toxicity, pharmacological profile, and bioavailability

Knowledge, attitude, and practice towards face mask use among residents of Greater Chennai Corporation, India, March 2021

BackgroundWearing a mask is one of the simplest ways to reduce the spread of COVID-19. Studies reported poor mask compliance in Greater Chennai Corporation, India. Hence, we described the knowledge, attitude, and practice regarding mask use among adults (≥18 years) in Greater Chennai Corporation, Tamil Nadu, India.MethodsWe conducted a cross-sectional survey among residents of Greater Chennai Corporation in March 2021. We estimated the sample size to be 203 per strata (slum and non-slum). We used a simple random sampling technique to select 20 locations using a digital map in the slum and non-slum areas. After reaching the location chosen, we selected 10 consecutive households and one adult (≥18 years of age) from each household. We used a validated, semi-structured questionnaire for collecting data regarding knowledge, attitudes, and practices for mask use. We estimated proportions and 95% CI for key variables and compared the variables between slums and non-slums.ResultsOf 430 participants included in the study, 51.4% were males. The mean (S.D.) age of the participants is 41.1 (14.6) years. The majority (86.7%) of the participants felt that wearing a mask helped in reducing the spread of coronavirus and the knowledge differed (p-value &lt; 0.05) between the slum (81.4%) and non-slum (92.3%). Nearly half (46.5%) of the participants did not like being forced to wear the mask. About 63.9% of the participants reported the practice of mask use while going out which was similar across slums and non-slums.ConclusionAlthough the knowledge regarding mask use was good among the public, the attitude was unfavorable. We suggest continuous reinforcement by spreading awareness and educating the community on the appropriate use of the mask

αA-Crystallin Peptide 66SDRDKFVIFLDVKHF80 Accumulating in Aging Lens Impairs the Function of α-Crystallin and Induces Lens Protein Aggregation

The eye lens is composed of fiber cells that are filled with α-, β- and γ-crystallins. The primary function of crystallins is to maintain the clarity of the lens through ordered interactions as well as through the chaperone-like function of α-crystallin. With aging, the chaperone function of α-crystallin decreases, with the concomitant accumulation of water-insoluble, light-scattering oligomers and crystallin-derived peptides. The role of crystallin-derived peptides in age-related lens protein aggregation and insolubilization is not understood.We found that αA-crystallin-derived peptide, (66)SDRDKFVIFLDVKHF(80), which accumulates in the aging lens, can inhibit the chaperone activity of α-crystallin and cause aggregation and precipitation of lens crystallins. Age-related change in the concentration of αA-(66-80) peptide was estimated by mass spectrometry. The interaction of the peptide with native crystallin was studied by multi-angle light scattering and fluorescence methods. High molar ratios of peptide-to-crystallin were favourable for aggregation and precipitation. Time-lapse recordings showed that, in the presence of αA-(66-80) peptide, α-crystallin aggregates and functions as a nucleus for protein aggregation, attracting aggregation of additional α-, β- and γ-crystallins. Additionally, the αA-(66-80) peptide shares the principal properties of amyloid peptides, such as β-sheet structure and fibril formation.These results suggest that crystallin-derived peptides such as αA-(66-80), generated in vivo, can induce age-related lens changes by disrupting the structure and organization of crystallins, leading to their insolubilization. The accumulation of such peptides in aging lenses may explain a novel mechanism for age-related crystallin aggregation and cataractogenesis