Photocatalytic CO2 Reduction to Solar Fuels by a Chemically Stable Bimetallic Porphyrin-Based Framework.

Porphyrin-based photocatalysts have emerged as promising candidates for facilitating carbon dioxide (CO2) reduction due to their exceptional light-harvesting properties. However, their performance is hindered by complex synthesis procedures, limited structural stability, inadequate CO2 activation capabilities, and a lack of comprehensive structure-property relationships. This study investigates the performance of a porphyrin-based bimetallic framework, [Cu(TPP)Cu2Mo3O11] (TPP = tetrapyridylporphyrin), termed MoCu-1 for photocatalytic CO2 reduction. In addition to its straightforward one-pot synthesis method, the framework shows remarkable chemical stability, particularly notable in alkaline reaction conditions, making it a compelling option for sustainable catalytic applications. By harnessing the superior photoabsorption properties of the porphyrin linker and the abundance of catalytic sites provided by the bimetallic structure, this framework exhibits the potential for enhancing CO2 reduction efficiency. MoCu-1 demonstrates excellent activity in converting CO2 into CO, achieving a maximum yield of 3.21 mmol g-1 with a selectivity of ∼93%. We unravel the intricate interplay of structural features and catalytic activity through systematic characterization techniques and an in situ diffuse reflectance Fourier transform study, which provided insights into the mechanism governing CO2 conversion and was supported by density functional theory calculations. This work contributes to advancing our understanding of photocatalytic processes and offers guidance for designing robust materials for CO2 utilization in renewable energy applications.

A Versatile Method for Site-Specific Chemical Installation of Aromatic Posttranslational Modification Analogs into Proteins.

Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is the aromatic side chain of Tyr, which undergoes modifications such as phosphorylation and nitration. Despite the biological and physiological importance of Tyr-PTMs, our current understanding of the mechanisms by which these modifications contribute to human health and disease remains incomplete. This knowledge gap arises from the absence of natural amino acids that can mimic these PTMs and the lack of synthetic tools for the site-specific introduction of aromatic PTMs into proteins. Herein, we describe a facile method for the site-specific chemical installation of aromatic PTMs into proteins through palladium-mediated S-C(sp2) bond formation under ambient conditions. We demonstrate the incorporation of novel PTMs such as Tyr-nitration and phosphorylation analogs to synthetic and recombinantly expressed Cys-containing peptides and proteins within minutes and in good yields. To demonstrate the versatility of our approach, we employed it to prepare 10 site-specifically modified proteins, including nitrated and phosphorylated analogs of Myc and Max proteins. Furthermore, we prepared a focused library of site-specifically nitrated and phosphorylated α-synuclein (α-Syn) protein, which enabled, for the first time, deciphering the role of these competing modifications in regulating α-Syn conformation aggregation in vitro. Our strategy offers advantages over synthetic or semisynthetic approaches, as it enables rapid and selective transfer of rarely explored aromatic PTMs into recombinant proteins, thus facilitating the generation of novel libraries of homogeneous posttranslationally modified proteins for biomarker discovery, mechanistic studies, and drug discovery.

Enhanced drug delivery with nanocarriers: a comprehensive review of recent advances in breast cancer detection and treatment.

Breast cancer (BC) remains a leading cause of morbidity and mortality among women worldwide, with triple-negative breast cancer (TNBC) posing significant treatment challenges due to its aggressive phenotype and resistance to conventional therapies. Recent advancements in nanocarrier technology offer promising solutions for enhancing drug delivery, improving bioavailability, and increasing drug accumulation at tumor sites through targeted approaches. This review delves into the latest innovations in BC detection and treatment, highlighting the role of nanocarriers like polymeric micelles, liposomes, and magnetic nanoparticles in overcoming the limitations of traditional therapies. Additionally, the manuscript discusses the integration of cutting-edge diagnostic tools, such as multiplex PCR-Nested Next-Generation Sequencing (mPCR-NGS) and blood-based biomarkers, which are revolutionizing early detection and molecular profiling of BC. The convergence of these technologies not only enhances therapeutic outcomes but also paves the way for personalized medicine in BC management. This comprehensive review underscores the potential of nanocarriers in transforming BC treatment and emphasizes the critical importance of early detection in improving patient prognosis.

Solithromycin in Combination with Other Antimicrobial Agents Against the Carbapenem Resistant Klebsiella pneumoniae (CRKP).

Klebsiella pneumoniae is considered as the most common pathogen of hospital-acquired pneumonia. K. pneumoniae has emerged as the superbug which had shown multidrug resistance (MDR) as well as extensively drug resistance. Carbapenem resistant K. pneumoniae (CRKP) has become a menace for the treatment with monotherapy of the patients mainly admitted in intensive care units. Hence, in the present study we collected total 187 sputum isolates of K. pneumoniae and performed the antimicrobial susceptibility testing by using the automated Vitek-2 system and broth micro-dilution method (67 CRKP). The combination study of solithromycin with meropenem, colistin, cefotaxime, piperacillin and tazobactam, nitrofurantoin, tetracycline, levofloxacin, curcumin and nalidixic acid was performed by using checkerboard assay. We observed the high rate of resistance towards ampicillin, cefotaxime, ceftriaxone, cefuroxime and aztreonam. The colistin and tigecycline were the most sensitive drugs. The CRKP were 36%, maximum were from the patients of ICUs. The best synergistic effect of solithromycin was with meropenem and cefotaxime (100%), colistin and tetracycline (80%). So, these combinations can be a choice of treatment for the infections caused by MDR CRKP and other Gram-negative bacteria where the monotherapy could not work.

Site-Specific Acetylation of the Transcription Factor Protein Max Modulates Its DNA Binding Activity.

Chemical protein synthesis provides a powerful means to prepare novel modified proteins with precision down to the atomic level, enabling an unprecedented opportunity to understand fundamental biological processes. Of particular interest is the process of gene expression, orchestrated through the interactions between transcription factors (TFs) and DNA. Here, we combined chemical protein synthesis and high-throughput screening technology to decipher the role of post-translational modifications (PTMs), e.g., Lys-acetylation on the DNA binding activity of Max TF. We synthesized a focused library of singly, doubly, and triply modified Max variants including site-specifically acetylated and fluorescently tagged analogs. The resulting synthetic analogs were employed to decipher the molecular role of Lys-acetylation on the DNA binding activity and sequence specificity of Max. We provide evidence that the acetylation sites at Lys-31 and Lys-57 significantly inhibit the DNA binding activity of Max. Furthermore, by utilizing high-throughput binding measurements, we assessed the binding activities of the modified Max variants across diverse DNA sequences. Our results indicate that acetylation marks can alter the binding specificities of Max toward certain sequences flanking its consensus binding sites. Our work provides insight into the hidden molecular code of PTM-TFs and DNA interactions, paving the way to interpret gene expression regulation programs.

Trends in cannabis use in New Jersey: Effects of COVID-19 and cannabis legalization.

Objectives: With the legalization of cannabis in New Jersey on April 21, 2022, including the licensing of cannabis dispensaries, concerns have arisen about potential adverse events related to cannabis use. Here, we explore temporal trends and risk factors for cannabis-related harm in both adult and pediatric cannabis-related visits at a tertiary care academic institution. Methods: We performed a retrospective chart review and temporal trend analysis via the electronic health record from May 1, 2019 to October 31, 2022, covering 2 years before, and 6 months after, cannabis legalization in New Jersey. The pediatric charts identified were analyzed for root causes of adverse events, and changes in the frequency of specific unsafe practices since cannabis legalization were tracked. Results: We found that adult cannabis ED-related visits significantly increased during the COVID-19 pandemic and remained higher than pre-pandemic levels for the remainder of the study periods, without a significant change upon legalization. Pediatric rates of cannabis-related ED visits did not vary significantly during the study period. The vast majority of visits for children aged 0-12 years were related to accidental cannabis exposures-often a household member's edibles-whereas most visits for older children stemmed from intentional cannabis use. Conclusion: This project highlights the unintended consequences of wider cannabis access in New Jersey. Notably, cannabis use increased even before its legalization, presumably in response to the COVID-19 pandemic and its attendant mental health effects. Rates of cannabis use disorder and its highlight of other concurrent psychiatric disorders are important topics for both clinicians and lawmakers to consider.

Drug repurposing: A multi targetted approach to treat cardiac disease from existing classical drugs to modern drug discovery.

Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are several types of CVDs like stroke, endothelial dysfunction, thrombosis, atherosclerosis, plaque instability and heart failure. Identification of a new drug for heart disease takes longer duration and its safety efficacy test takes even longer duration of research and approval. This chapter explores drug repurposing, nano-therapy, and plant-based treatments for managing CVDs from existing drugs which saves time and safety issues with testing new drugs. Existing drugs like statins, ACE inhibitor, warfarin, beta blockers, aspirin and metformin have been found to be useful in treating cardiac disease. For better drug delivery, nano therapy is opening new avenues for cardiac research by targeting interleukin (IL), TNF and other proteins by proteome interactome analysis. Nanoparticles enable precise delivery to atherosclerotic plaques, inflammation areas, and damaged cardiac tissues. Advancements in nano therapeutic agents, such as drug-eluting stents and drug-loaded nanoparticles are transforming CVDs management. Plant-based treatments, containing phytochemicals from Botanical sources, have potential cardiovascular benefits. These phytochemicals can mitigate risk factors associated with CVDs. The integration of these strategies opens new avenues for personalized, effective, and minimally invasive cardiovascular care. Altogether, traditional drugs, phytochemicals along with nanoparticles can revolutionize the future cardiac health care by identifying their signaling pathway, mechanism and interactome analysis.

Reimagining old drugs with new tricks: Mechanisms, strategies and notable success stories in drug repurposing for neurological diseases.

Recent evolution in drug repurposing has brought new anticipation, especially in the conflict against neurodegenerative diseases (NDDs). The traditional approach to developing novel drugs for these complex disorders is laborious, time-consuming, and often abortive. However, drug reprofiling which is the implementation of illuminating novel therapeutic applications of existing approved drugs, has shown potential as a promising strategy to accelerate the hunt for therapeutics. The advancement of computational approaches and artificial intelligence has expedited drug repurposing. These progressive technologies have enabled scientists to analyse extensive datasets and predict potential drug-disease interactions. By prospecting into the existing pharmacological knowledge, scientists can recognise potential therapeutic candidates for reprofiling, saving precious time and resources. Preclinical models have also played a pivotal role in this field, confirming the effectiveness and mechanisms of action of repurposed drugs. Several studies have occurred in recent years, including the discovery of available drugs that demonstrate significant protective effects in NDDs, relieve debilitating symptoms, or slow down the progression of the disease. These findings highlight the potential of repurposed drugs to change the landscape of NDD treatment. Here, we present an overview of recent developments and major advances in drug repurposing intending to provide an in-depth analysis of traditional drug discovery and the strategies, approaches and technologies that have contributed to drug repositioning. In addition, this chapter attempts to highlight successful case studies of drug repositioning in various therapeutic areas related to NDDs and explore the clinical trials, challenges and limitations faced by researchers in the field. Finally, the importance of drug repositioning in drug discovery and development and its potential to address discontented medical needs is also highlighted.

Corneal stress-strain index in myopic Indian population.

AIM: The purpose is to study the corneal stress-strain index (SSI) in myopic refractive error among Indian subjects. METHODS: A retrospective study where young myopic subjects aged between 11 and 35 years who had undergone corneal biomechanics assessment using Corvis ST between January 2017 and December 2021 were enrolled. Subjects with central corneal thickness (CCT) <500 µ, intraocular pressure (IOP) >21 mmHg, history of any systemic and ocular disease or any previous ocular surgery, high astigmatism, corneal disease such as keratoconus were excluded. Subjects with missing data or having poor quality scan were excluded. Corneal biomechanical properties and corneal SSI were assessed using Corvis ST. For statistical purposes, eyes were divided into four different groups and were analyzed using one-way ANOVA. RESULTS: Nine hundred and sixty-six myopic eyes with mean ± standard deviation age, IOP, and CCT of 26.89 ± 4.92 years, 16.94 ± 2.00 mmHg, and 540.18 ± 25.23 microns, respectively, were included. There were 311, 388, 172, and 95 eyes that were low, moderate, severe, and extreme myopic. Deformation amplitude ratio at 1 mm and 2 mm were similar across different myopic groups. A significant increase in max inverse radius, ambrosia relational thickness, biomechanically corrected IOP, integrated radius was noted with an increase in myopic refractive error. Corvis biomechanical index, corneal SSI was found to be decreased significantly with an increase in myopic refractive error. We noted a significant positive association between myopic refractive error and SSI (P < 0.001). CONCLUSION: Corneal SSI was found to be reduced in extreme myopic eyes.

Therapeutic management of osteodystrophia fibrosa in early weaned Malabari male goat kids.

Osteodystrophia fibrosa is a metabolic disease of goats resulting from the insufficient mineralization of bones, excessive bone resorption, and improper bone development, leading to subsequent accumulation of the fibrous connective tissue. This report describes the successful therapeutic management of acute osteodystrophia fibrosa in early-weaned goat kids by following a medical protocol. Three Malabari male goat kids of forty days old from two different litters of the same farm were presented with spontaneous, bilaterally symmetrical, non-inflammatory facial swelling, protruded tongue, prominent eyeballs, frothy drooling saliva, diarrhoea, and inanition due to the inability in mastication or suckling for the last two weeks. As per the history, these kids were weaned and started feeding pelleted concentrate feed and jackfruit leaves along with the milk sucking three weeks back only. On clinical examination, the vital parameters were normal and the key phenotypic abnormalities noted were the abnormally developed maxilla/mandible, manifested as a swelling that was hard to touch, and the loosely attached teeth. In biochemical evaluation, the reduction in Ca:P ratio was evident and the serum creatinine level was within normal ranges. A therapeutic protocol was devised for three weeks by including calcium (calcium gluconate), phosphate-binder (Kaolin), vitamins (Vit. ADEH), and anabolic steroid (Nandrolone; a well-established drug promoting formation and mineralization of bone in mammals). Considerable improvement was observed after three weeks of therapy and the animals were having apparently normal facial appearance on the review after three months. The kids showed normal healthy growth and were slaughtered later for meat purpose after gaining adult body weight. This report accentuates the possibility of acute hypocalcemia-induced osteodystrophia fibrosa, rather than hyperphosphatemia-induced, and its management using anabolic steroids for better clinical recovery in growing goat kids.

Visual outcomes and higher-order aberrations in eyes implanted with hybrid extended depth of focus intraocular lens.

PURPOSE: To study the visual outcomes and higher order aberrations in eyes implanted with Hybrid EDOF IOL, particularly in Indian eyes. MATERIALS AND METHODS: This is retrospective case series where subjects aged between 40-65 years and were implanted with LUCIDIS IOL by single surgeon were included. Subjects with Pre surgery corneal astigmatism > 1.50 D, corneal guttae, IOP >22mmHg, any ocular Co morbidities, Intra or post operative complication were excluded. At 1 month follow up, uncorrected visual acuities at distance (UCDVA), intermediate (UCIVA) and near (UCNVA), refraction were recorded. Internal Higher order aberrations and strehl ratio for a fixed pupil of 4mm and 6mm were calculated using NIDEK OPD Scan. Monocular defocus curve was obtained at 4 meter logMAR chart. RESULTS: Total of 55 eyes of 35 patients with mean±SD age of 58.50±7.49 years were evaluated. 89.09% of the eyes achieved visual acuity of 6/6. 49.09% could read N10 font at intermediate distance without any correction and 85.45% of the eyes had uncorrected near visual acuity of N6. Around 67% of the eyes did not require any refractive correction whereas around 26% of the eyes required correction upto ±0.25D. The defocus curve showed that visual acuity also ranges from 0.05 logMAR to 0.2 logMAR for Plano to -3.00D respectively. Mean±SD Strehl ratio at 4 and 6 mm pupil size was 0.06±0.04 and 0.02±0.02 respectively. CONCLUSION: Hybrid EDOF IOL such as LUCIDIS provides excellent vision at all distances. This could be attributed to IOL design which is spherical aberration neutral lens.

Pore-Confined π-Chromophoric Tetracene as a Visible Light Harvester toward MOF-Based Photocatalytic CO2 Reduction in Water.

Integrating photoactive π-chromophoric guest molecules inside the MOF nanopore can result in the emergence of light-responsive features, which in turn can be utilized for developing photoactive materials with inherent properties of MOF. Herein, we report the confining of π-chromophoric tetracene (TET) molecules inside the nanospace of postmodified Zr-MOF-808 (Zr-MOF) with MBA molecules (MBA = 2-(5'-methyl-[2,2'-bipyridine]-5-yl)acetic acid) for effectively utilizing its light-harvesting properties toward photocatalytic CO2 reduction. The confinement of the TET molecules as a photosensitizer and the covalent grafting of a catalytically active [Re(MBA)(CO)3Cl] complex, postsynthetically, result in a single integrated catalytic system named Zr-MBA-TET-Re-MOF. Photoreduction of CO2 over Zr-MBA-TET-Re-MOF showed the evolution of 805 µmol g-1 CO with 99.9% selectivity after 10 h of continuous visible light irradiation in water without any additional sacrificial electron donor and having the apparent quantum efficiency of 1.3%. In addition, the catalyst demonstrated an appreciable activity even under direct sunlight irradiation in aqueous medium with a maximum production of 362.7 µmol g-1 CO, thereby mimicking artificial photosynthesis. Moreover, electron transfer from TET to the catalytic center was supported by the formation of photoinduced TET radical cation, as inferred from in situ UV-vis spectra, electron paramagnetic resonance (EPR) analysis, and transient absorption (TA) studies. Additionally, the in situ diffuse reflectance infrared Fourier transform (DRIFT) measurements support that the photoreduction of CO2 to CO proceeds via *COOH intermediate formation. The close proximity of the light-harvesting molecule and catalytic center facilitated facile electron transfer from the photosensitizer to the catalyst during the CO2 reduction.

Comparative meta-analysis of antimicrobial resistance from different food sources along with one health approach in the Egypt and UK.

BACKGROUND: Antimicrobial resistance (AMR) is a critical global issue that poses significant threats to human health, animal welfare, and the environment. With the increasing emergence of resistant microorganisms, the effectiveness of current antimicrobial medicines against common infections is diminishing. This study aims to conduct a competitive meta-analysis of surveillance data on resistant microorganisms and their antimicrobial resistance patterns in two countries, Egypt and the United Kingdom (UK). METHODS: Data for this study were obtained from published reports spanning the period from 2013 to 2022. In Egypt and the UK, a total of 9,751 and 10,602 food samples were analyzed, respectively. Among these samples, 3,205 (32.87%) in Egypt and 4,447 (41.94%) in the UK were found to contain AMR bacteria. RESULTS: In Egypt, the predominant resistance was observed against ß-lactam and aminoglycosides, while in the United Kingdom, most isolates exhibited resistance to tetracycline and ß-lactam. The findings from the analysis underscore the increasing prevalence of AMR in certain microorganisms, raising concerns about the development of multidrug resistance. CONCLUSION: This meta-analysis sheds light on the escalating AMR problem associated with certain microorganisms that pose a higher risk of multidrug resistance development. The significance of implementing One Health AMR surveillance is emphasized to bridge knowledge gaps and facilitate accurate AMR risk assessments, ensuring consumer safety. Urgent actions are needed on a global scale to combat AMR and preserve the effectiveness of antimicrobial treatments for the well-being of all living beings.

Nanobiotics and the One Health Approach: Boosting the Fight against Antimicrobial Resistance at the Nanoscale.

Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly and others factors including gene mutation, bacteria living in biofilms, and enzymatic degradation/hydrolyses help in the emergence and spread of AMR, which may lead to significant economic consequences such as reduced productivity and increased health care costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multi-drug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to obtain an understanding of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.

Deciphering the Role of the Ser-Phosphorylation Pattern on the DNA-Binding Activity of Max Transcription Factor Using Chemical Protein Synthesis.

The chemical synthesis of site-specifically modified transcription factors (TFs) is a powerful method to investigate how post-translational modifications (PTMs) influence TF-DNA interactions and impact gene expression. Among these TFs, Max plays a pivotal role in controlling the expression of 15 % of the genome. The activity of Max is regulated by PTMs; Ser-phosphorylation at the N-terminus is considered one of the key regulatory mechanisms. In this study, we developed a practical synthetic strategy to prepare homogeneous full-length Max for the first time, to explore the impact of Max phosphorylation. We prepared a focused library of eight Max variants, with distinct modification patterns, including mono-phosphorylated, and doubly phosphorylated analogues at Ser2/Ser11 as well as fluorescently labeled variants through native chemical ligation. Through comprehensive DNA binding analyses, we discovered that the phosphorylation position plays a crucial role in the DNA-binding activity of Max. Furthermore, in vitro high-throughput analysis using DNA microarrays revealed that the N-terminus phosphorylation pattern does not interfere with the DNA sequence specificity of Max. Our work provides insights into the regulatory role of Max's phosphorylation on the DNA interactions and sequence specificity, shedding light on how PTMs influence TF function.

Role of corneal epithelial mapping, Corvis biomechanical index, and artificial intelligence-based tomographic biomechanical index in diagnosing spectrum of keratoconus.

AIM: The aim of the study was to evaluate the utility of epithelial mapping, Corvis biomechanical index (CBI), and tomographic biomechanical index (TBI) in diagnosing the spectrum of keratoconus (KC). METHODS: This was a retrospective study where KC subjects with an age between 11 and 50 years were enrolled. Subjects with ocular diseases, history of previous corneal surgery, corneal scars or hydrops, ocular trauma, ocular surface disorder, systemic disease, and poor-quality scans were excluded. KC was classified using Belin ABCD classification system. Epithelial thickness, corneal tomography, and corneal biomechanical measurements were recorded using Fourier-domain optical coherence tomography Avanti with corneal adaptor module, Pentacam HR, and Corvis® ST, respectively. To understand the utility of various corneal parameters in diagnosing spectrum of keratoconus, cutoff values for epithelial thickness at the thinnest location and its standard deviation (SD) were considered 45 and 3 microns, respectively, CBI of 0.5 and TBI of 0.29 was considered. RESULTS: Sixty-five eyes (45 - KC, 10 - subclinical KC (SBKC), and 10 - forme fruste [FF]) of 34 patients with a mean ± SD age of 30.73 ± 5.71 were included. In our keratoconic sample, epithelial mapping alone helped diagnose the 77.77% of cases, however, when combined with CBI, it helped diagnose 95.5% cases and when combined with TBI, it was useful in diagnosing 100% of cases. In SBKC group, 40% of cases were detected by epithelial mapping alone, and when combined with CBI, it helped diagnose 70% of cases and TBI further helped diagnose 90% of cases. We did not see any role of epithelial mapping in detecting FFKC cases whereas CBI and TBI helped diagnose 60% and 90% of cases, respectively. CONCLUSION: The utility of epithelial mapping as a solitary tool is limited in detecting the spectrum of KC, especially SB and FFKC. However, combining it with corneal biomechanical parameters could help improve the efficacy of diagnosis of KC.

A Deep Learning Framework for the Characterization of Thyroid Nodules from Ultrasound Images Using Improved Inception Network and Multi-Level Transfer Learning.

In the past few years, deep learning has gained increasingly widespread attention and has been applied to diagnosing benign and malignant thyroid nodules. It is difficult to acquire sufficient medical images, resulting in insufficient data, which hinders the development of an efficient deep-learning model. In this paper, we developed a deep-learning-based characterization framework to differentiate malignant and benign nodules from the thyroid ultrasound images. This approach improves the recognition accuracy of the inception network by combining squeeze and excitation networks with the inception modules. We have also integrated the concept of multi-level transfer learning using breast ultrasound images as a bridge dataset. This transfer learning approach addresses the issues regarding domain differences between natural images and ultrasound images during transfer learning. This paper aimed to investigate how the entire framework could help radiologists improve diagnostic performance and avoid unnecessary fine-needle aspiration. The proposed approach based on multi-level transfer learning and improved inception blocks achieved higher precision (0.9057 for the benign class and 0.9667 for the malignant class), recall (0.9796 for the benign class and 0.8529 for malignant), and F1-score (0.9412 for benign class and 0.9062 for malignant class). It also obtained an AUC value of 0.9537, which is higher than that of the single-level transfer learning method. The experimental results show that this model can achieve satisfactory classification accuracy comparable to experienced radiologists. Using this model, we can save time and effort as well as deliver potential clinical application value.

Enabling Peptide Ligation at Aromatic Junction Mimics via Native Chemical Ligation and Palladium-Mediated S-Arylation.

Synthetic strategies to assemble peptide fragments are in high demand to access homogeneous proteins for various applications. Here, we combined native chemical ligation (NCL) and Pd-mediated Cys arylation to enable practical peptide ligation at aromatic junctions. The utility of one-pot NCL and S-arylation at the Phe and Tyr junctions was demonstrated and employed for the rapid chemical synthesis of the DNA-binding domains of the transcription factors Myc and Max. Organometallic palladium reagents coupled with NCL enabled a practical strategy to assemble peptides at aromatic junctions.

Age-related variations in corneal stress-strain index in the Indian population.

Purpose: To report age-related variations in corneal stress-strain index (SSI) in healthy Indians. Methods: It was a retrospective study where healthy Indian individuals aged between 11 and 70 years who had undergone corneal biomechanics assessment using Corvis ST between January 2017 and December 2021 were enrolled. Composite corneal biomechanical parameters and corneal SSI were abstracted from Corvis ST and compared across different age groups using one-way analysis of variance (ANOVA). Also, Pearson's correlation was used to evaluate the association between age and SSI. Results: Nine hundred and thirty-six eyes of 936 patients with ages between 11 and 77 years with mean ± SD intraocular pressure (IOP) and pachymetry of 16.52 ± 2.10 mmHg and 541.13 ± 26.39 µs, respectively. Composite corneal biomechanical parameters such as deformation amplitude ratio max at 1 mm (P < 0.001) and 2 mm (P < 0.001), biomechanically corrected IOP (P = 0.004), stiffness parameter at A1 (P < 0.001, Corvis biomechanical index (P < 0.018), and SSI (P < 0.001) were found to be significantly different as a function of age group. We noted a statistically significant positive association of SSI with age (P < 0.001), spherical equivalent refractive error (P < 0.001), and IOP (P < 0.001) and a significant negative association with anterior corneal astigmatism (P < 0.001) and Anterior chamber depth (ACD) (P < 0.001). Also, SSI was positively associated with SPA1 and bIOP, whereas negatively associated with integrated radius, max inverse radius, and Max Deformation amplitude (DA) ratio at 1 mm and 2 mm. Conclusion: We noted a positive association of corneal SSI with age in normal healthy Indian eyes. This information could be helpful for future corneal biomechanical research.