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Several genetic disorders are associated with either a permanent deficit or a delay in central nervous system myelination. We investigated 24 unrelated families (25 individuals) with deficient myelination after clinical and radiological evaluation. A combinatorial approach of targeting and/or genomic testing was employed. Molecular diagnosis was achieved in 22 out of 24 families (92%). Four families (4/9, 44%) were diagnosed with targeted testing and 18 families (18/23, 78%) were diagnosed using broad genomic testing. Overall, 14 monogenic disorders were identified. Twenty disease-causing variants were identified in 14 genes including PLP1, GJC2, POLR1C, TUBB4A, UFM1, NKX6-2, DEGS1, RNASEH2C, HEXA, ATP7A, SETBP1, GRIN2B, OCLN, and ZBTB18. Among these, nine (45%) variants are novel. Fourteen families (82%, 14/17) were diagnosed using proband-only exome sequencing (ES) complemented with deep phenotyping, thus highlighting the utility of singleton ES as a valuable diagnostic tool for identifying these disorders in resource-limited settings., (© 2024 Wiley Periodicals LLC.)

The pro-inflammatory enzyme cyclooxygenase 2 (COX-2) has been known to impart metastatic property to cancer cells. However, blocking of COX-2 with nonsteroidal anti-inflammatory drugs or COX-2-specific inhibitors has failed in clinical trials due to adverse effects associated with their prolonged use. We have previously shown that extracellular ATP (eATP), a major component of the tumor microenvironment, enhances COX-2 expression several-fold, both in macrophages and in various cancer cells, by acting on purinergic (P2) receptors. In this study, we show that blocking of P2 receptors significantly reduced tumor growth in a mouse model of lymphoma. Tumors were induced in mice through subcutaneous injection of syngeneic EL4 lymphoma cells. Various P2 receptor antagonists were injected within the tumors after they were palpable. The broad-spectrum P2 receptor antagonist, suramin, P2X7 receptor-specific antagonist, oATP, P2Y6 receptor-specific antagonist, MRS 2578, and P2Y12 receptor-specific antagonist, AR-C 69931, all showed significant arrest in tumor growth. Both suramin and AR-C 69931-treated tumors showed strong reduction in COX-2 expression and modulation of various metastatic markers. Disaggregated cells from AR-C 69931-treated tumors, when injected intravenously in naïve mice, did not exhibit metastasis in various tissues which was observed in mice injected with cells from saline-treated tumors. Our results show that blocking of P2 receptors is a therapeutic alternative to inhibit COX-2 expression, and thereby, arrest tumor progression and metastasis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Persistent Organic Pollutants (POPs) have been in focus of research due to their massive contamination of environment and bio-accumulation. Bioremediation and high-throughput research have gained momentum to curb the harmful effects of POPs. The present research has explored the microbial diversity of Chumathang Hot Spring, Ladakh, India, through Illumina metagenomic HiSeq 4000 sequencing platform and their potential to degrade persistent pollutants, especially xenobiotics. Taxonomic characterization based on raw metagenomic data illuminated the abundance of members of Pseudomonadota and Actinomyceota. The re-construction of the microbial genomes from assembled contigs and scaffolds using de novo assembler metaSPAdes and their further annotation through contig alignment with available reference genomes elucidated the landscape of the hot spring's microbes. The predominantly occupied key genera reported were Pannonibacter and Novosphingobium. Comparative genomic analysis established evolutionary relationships and functional diversities among hot spring microbial communities. The function annotation through MG-RAST has revealed their metabolic versatility of degrading a wide array of xenobiotic compounds, including caprolactam, dioxin, chlorobenzene, benzoate, and. Further, the hydroxylating dioxygenase (Saro&#95;3901) was identified as a pivotal component in the aromatic degradation pathways, showcasing extensive metabolic interconnectivity. Interestingly, protein interaction network analysis identified hub genes like Saro&#95;1233 (protocatechuate 4,5-dioxygenase alpha subunit), while Saro&#95;3057 (amidase) was noted for its critical role in network communication and control. The resilience of thermal ecosystems, evidenced by robust enzymatic activity and degradation capability among organisms with < 95% genetic similarity, underscores their potential for industrial and bioremediation exploration, emphasizing the importance of preserving and studying biodiverse habitats., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study was conducted on indigenous Tharparkar cow ( Bos indicus ) to evaluate FSH stimulation on follicular attributes, oocyte recovery and morpho-molecular developmental competence parameters concerning oocyte quality. A total of 20 OPU sessions were performed, which included 10 sessions in each FSH stimulated at the dose of 130 µg divided into four sub-doses and non-stimulated. Findings on the size of follicles having ≥6 mm showed a significantly higher, however an opposite trend was observed in the case of smaller sized follicle (<6 mm) between stimulated and non-stimulated respectively. The stimulated cows had a significantly higher number as well as the percentage of oocytes of Grade A, having a diameter ≥120 µm and BCB +VE as compared to the non-stimulated cows. The relative mRNA expression profile of GDF9, BMP15, PCNA and BCL-2 genes was higher and BAX was lower in the FSH-stimulated cow. These results indicated that FSH stimulation before OPU in Bos indicus cows has a significant impact on follicle size, oocyte yield, recovery, and their quality with respect to COC's, diameter and BCB +VE oocytes. Further, a significant increase in the relative mRNA expression levels of GDF9, BMP15 and PCNA genes in the FSH-stimulated group suggests that FSH plays a key role in modulating the expression of these important candidate genes and thus influencing oocyte quality. The higher mRNA expression of BCL-2 genes and concomitantly lower expression of BAX gene in FSH Stimulated cows indicates the protective role of these genes and preventing programmed cell death and thus promoting cell survival, quality and embryo development.

Lung adenocarcinoma is considered to be one of the primary causes of cancer-related deaths globally. Conventional treatments, such as chemotherapy and radiation therapy taken together, have not significantly lowered mortality rates. Repositioning of authorized anticancer medications supported by nanotechnology has therefore emerged as an effective strategy to close such gaps. In this context, mesoporous silica nanoparticles (MSNs) were biosynthesized from cucumber peels and were loaded with doxorubicin, a common anticancer drug to form doxorubicin-bound mesoporous silica nanoparticles (DMSNs). The study addresses a sustainable method for turning waste materials into MSNs, which can be used to create multifunctional nanosystems. The therapeutic module (DMSNs) was designed specifically to target 2D monolayer cells and 3D tumor spheroids of lung adenocarcinoma cancer. The DMSNs demonstrated notable antiproliferative activity and effective intracellular localization in addition to being biocompatible and innately fluorescent. Subsequent investigations revealed significant antibacterial activity against Staphylococcal infection, which is primarily prevalent in lung cancer patients. Thus, the developed MSNs held promising potential for anticancer drug delivery systems and have antibacterial potential to treat bacterial infections in patients with lung cancer. Furthermore, the cucumber peel-mediated synthesis of MSNs could also aid in the management of food waste and promote the adoption of the waste-to-health paradigm for sustainable solutions.

Increased incidences of antibiotic resistance have necessitated the development of novel wound disinfection strategies with minimal risk of resistance development. This study aimed at developing a biocompatible wound dressing biomaterial with the potential to treat acute and chronic wounds infected with multidrug-resistant Pseudomonas aeruginosa . A multifunctional antibacterial nanoconjugate was synthesized by covalently coupling a synthetically designed peptide (DP1, i.e. , RFGRFLRKILRFLKK) with reduced graphene oxide (rGO). The conjugate displayed antibacterial and antibiofilm activities against multidrug-resistant Pseudomonas aeruginosa . In vitro studies demonstrated 94% hemocompatibility of the nanoconjugate even at concentrations as high as 512 μg mL -1 . Cytotoxicity studies on 3T3-L1 cells showed 95% cell viability, signifying biocompatibility. Owing to these properties, the biomedical applicability of the nanoconjugate was assessed as an antibacterial wound dressing agent. rGO-DP1-loaded wound dressing exhibited enhanced reduction in bacterial bioburden (6 log 10 CFU) with potential for wound re-epithelization (77.3%) compared to the uncoated bandage. Moreover, an improvement in the material properties of the bandage was observed in terms of enhanced tensile strength and decreased elongation at break (%). Collectively, these findings suggest that rGO-DP1 is an effective biomaterial that, when loaded on wound dressings, has the potential to be used as a facile, sustainable and progressive agent for bacterial wound disinfection as well as healing.

In this paper, the phototransistor behavior is investigated in the germanium-on-insulator (GeOI)-based junctionless nanowire (JL-NW) transistor under various light conditions. High responsivity and photosensitivity are attributed in the fully depleted regime within the visible and near-infrared bands. The impact of light is also investigated in detail on the electronic and transfer characteristics such as energy bandgap, carrier distribution, electrostatic potential, electric field, and generation and recombination rates. Further, the channel doping and thickness are tuned to optimize the optical responsivity. The significant tunability of responsivity is observed with increasing channel thickness. The device exhibits fast optical switching performance, which is further enhanced at higher input light power. Overall, at the nanoscale dimension, our proposed phototransistor demonstrates better detectivity with a significantly smaller illumination area. Thus, the GeOI-based JL-NW phototransistors can be used for imaging (visible wavelength range) and bioimaging (near-infrared wavelength range) applications in advanced technology nodes., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Three new low-dimensional quaternary sulfides, namely, Tl 2 Cu 2 GeS 4 ( 1 ), Tl 2 Ag 2 GeS 4 ( 2 ), and Tl 2 Ag 2 SnS 4 ( 3 ) were synthesized by solid-state reactions and characterized by single-crystal X-ray diffraction, spectroscopic, thermal, and photocatalytic studies. The compounds 1 , 2 , and 3 , respectively, have centrosymmetric layered, noncentrosymmetric layered, and noncentrosymmetric one-dimensional structures, in which Cu + , Ge 4+ , and Sn 4+ ions have tetrahedral coordination and Ag + ion has linear, trigonal planar and tetrahedral coordinations. The monovalent thallium cations have TlS 8 dodecahedral coordination and TlS 7 and TlS 6 coordination polyhedra of irregular shape. The compounds 1 , 2 , and 3 are semiconductors with the respective energy band gap values of 1.68, 2.02, and 1.90 eV. Compared to compounds 1 and 2 , compound 3 has a higher efficiency value of 22.9% for the photodegradation of aqueous solution of methylene blue. Band structures and projected density of states of all three compounds were computed using density functional theory, and these results are in good agreement with experiments.

Ethnopharmacological Relevance: This review explores the link between Type 2 Diabetes Mellitus (T2DM) and diabetes-induced Alzheimer's disease (AD). It emphasizes the shared pathophysiological links and mechanisms between the two conditions, focusing on reduced insulin levels and receptors, impaired glucose metabolism, insulin resistance, mitochondrial dysfunction, and oxidative damage in AD-affected brains-paralleling aspects of T2DM. The review suggests AD as a "diabetes of the brain," supported by cognitive enhancement through antidiabetic interventions. It focuses on the traditionally used Indian herbs as a means to manage both conditions while addressing developmental challenges., Aim of the Study: This study explores the DM-AD connection, reviewing medicinal herbs with protective potential for both ailments, considering traditional uses and developmental challenges., Materials and Methods: Studied research, reviews, and ethnobotanical and scientific data from electronic databases and traditional books., Results: The study analyzes the pathophysiological links between DM and AD, emphasizing their interconnected factors. Eight Ayurvedic plants with dual protective effects against T2DM and AD are thoroughly reviewed with preclinical/clinical evidence. Historical context, phytoconstituents, and traditional applications are explored. Innovative formulations using these plants are examined. Challenges stemming from phytoconstituents' physicochemical properties are highlighted, prompting novel formulation development, including nanotechnology-based delivery systems. The study uncovers obstacles in formulating treatments for these diseases., Conclusion: The review showcases the dual potential of chosen medicinal herbs against both diseases, along with their traditional applications, endorsing their use. It addresses formulation obstacles, proposing innovative delivery technologies for herbal therapies, while acknowledging their constraints. The review suggests the need for heightened investment and research in this area., 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 B.V.)

During of COVID-19 pandemic, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has continuously evolved, resulting in the emergence of several new variants of concerns (VOCs) with numerous mutations. These VOCs dominate in various regions due to increased transmissibility and antibody evasion, potentially reducing vaccine effectiveness. Nonetheless, it remains uncertain whether the recent SARS-CoV-2 VOCs have the ability to circumvent the T cell immunity elicited by either COVID-19 vaccination or natural infection. To address this, we conducted in-silico analysis to examine the impact of VOC-specific mutations at the epitope level and T cell cross-reactivity with the ancestral SARS-CoV-2. According to the in-silico investigation, T cell responses triggered by immunization or prior infections still recognize the variants in spite of mutations. These variants are expected to either maintain their dominant epitope HLA patterns or bind with new HLAs, unlike the epitopes of the ancestral strain. Our findings indicate that a significant proportion of immuno-dominant CD8 + and CD4 + epitopes are conserved across all the variants, implying that existing vaccines might maintain efficacy against new variations. However, further in-vitro and in-vivo studies are needed to validate the in-silico results and fully elucidate immune sensitivities to VOCs., (© 2024. The Author(s).)

Background: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is becoming increasingly important in head and neck oncology. At this year's conference of the American Society of Clinical Oncology (ASCO), a large number of papers were presented on the topic of HPV-associated HNSCC, particularly with regard to neoadjuvant treatment approaches, radiation de-escalation strategies, therapeutic vaccines, and treatment monitoring. In this context, study results on the treatment of HPV-related recurrent respiratory papillomatosis (RRP) were also presented., Objective: Based on contributions to the 2024 ASCO Annual Meeting, an insight into the latest developments in HPV-associated diseases of the head and neck is provided., Methods: The papers were reviewed for clinical relevance and contextualized based on current therapeutic concepts., Results and Conclusion: A large number of studies on liquid biopsies (LB) were presented. It was shown that although the methods for analyzing LBs for HPV-positive patients are well developed and can be used for diagnostics, risk classification, treatment management, or tumor follow-up, the methods vary considerably, and their clinical application has not yet been sufficiently validated. With regard to therapeutic HPV vaccination, three large studies were presented for the treatment of recurrent/metastatic HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). The only randomized study was on the vaccine ISA101b (peltopepimut-S) and did not reach its primary endpoint; however, the vaccine seemed to be highly effective in patients with a combined positive score (CPS) ≥ 20. Furthermore, data from a phase I study on PRGN2012, an adenovirus-based immunotherapy used therapeutically for the treatment of recurrent respiratory papillomatosis (RRP), were presented. PRGN2012 led to a reduction in surgical interventions for RRP, and the US Food and Drug Administration (FDA) designated PRGN2012 as a breakthrough therapy and orphan drug. However, the vaccine is not yet approved for the treatment of RRP., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The dataset contains leaf venation architecture and functional traits for a phylogenetically diverse set of 122 plant species (including ferns, basal angiosperms, monocots, basal eudicots, asterids, and rosids) collected from the living collections of the University of California Botanical Garden at Berkeley (37.87° N, 122.23° W; CA, USA) from February to September 2021. The sampled species originated from all continents, except Antarctica, and are distributed in different growth forms (aquatic, herb, climbing, tree, shrub). The functional dataset comprises 31 traits (mechanical, hydraulic, anatomical, physiological, economical, and chemical) and describes six main leaf functional axes (hydraulic conductance, resistance and resilience to damages caused by drought and herbivory, mechanical support, and construction cost). It also describes how architecture features vary across venation networks. Our trait dataset is suitable for (1) functional and architectural characterization of plant species; (2) identification of venation architecture-function trade-offs; (3) investigation of evolutionary trends in leaf venation networks; and (4) mechanistic modeling of leaf function. Data are made available under the Open Data Commons Attribution License., (© 2024 The Ecological Society of America.)

Synovial sarcoma (SS) is a rare genitourinary malignancy with a specific SS18::SSX 1/2 gene fusion in majority of the instances. The paratesticular location of this neoplasm is extremely rare and only 4 cases are reported in the literature. Herein, we describe the clinicopathologic features and molecular profile of paratesticular SS in the largest case series to date and to the best of our knowledge, and the only series to use novel SS18-SSX antibody for immunohistochemistry. Clinicopathologic, immunohistochemical (IHC), molecular, treatment, and follow-up data of the patients were analyzed. There were 14 patients, ranging from 15 to 47 years (mean: 30 y). The tumor size ranged from 4​​​​​​ to 15 cm. The tumors were unilateral, solid, and homogeneous tan-white with monomorphic spindle cell histology. All 14 tumors expressed SS18-SSX and TLE1 IHC and harbored SS18 rearrangement. In addition, the tumor with multifocal SS18-SSX expression had lower break-apart signals in the FISH assay (38% of the tumor cells; range: 29% to 85%). Radical orchiectomy was performed in all 14 patients and adjuvant chemotherapy was administered in 9 patients. Follow-up was available in 9 patients. The follow-up duration ranged from 5 to 24 months (median=10 mo). Four patients died of metastatic disease (range: 5 to 16 mo) and 2 patients who are alive had metastatic disease at the last follow-up. Based on our experience with the largest series to date and aggregate of the published data, paratesticular SS has a poor prognosis despite aggressive therapy. Owing to its rarity, the differential diagnosis is wide and requires a systematic approach for ruling out key morphologic mimics aided with SS18-SSX IHC and molecular confirmation because this distinction carries important therapeutic and prognostic implications. Due to the excellent concordance of SS18-SSX IHC results with FISH results as observed in our study, we would like to suggest inclusion of SS18-SSX in the diagnostic immunohistochemistry panel of all spindle cell sarcomas where synovial sarcoma is considered as a morphologic differential. SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Non-specific chronic low back pain (NSCLBP) is a prevalent condition causing significant disability and functional impairment. Whole-body vibration exercise (WBVE) has emerged as a new treatment method, but additional research is necessary to determine the optimal parameters of WBVE that would be beneficial for patients experiencing chronic low back pain (CLBP). This study aims to investigate the effects of two type of WBVE (constant vs progressive) on pain, disability, functional performance, and muscle activity in patients with NSCLBP., Methods: Thirty-two individuals diagnosed with chronic low back pain (CLBP) without any specific causes were enrolled and randomly assigned to one of two intervention groups: a constant/fixed protocol WBVE group or a progressive protocol WBVE group. Participants underwent WBVE sessions for around 30 min, thrice weekly over a period of 8 weeks. Primary outcomes assessed included pain intensity, functional disability, functional performance, and electromyographic activity of core musculature, measured at baseline and upon completion of the intervention period. Temporal changes of each outcome variable across different periods and between groups were measured with repeated measures 2×2 mixed ANOVA. Further, the paired t -test was performed to compare pre- and post-treatment values within each group., Results: Significant improvements were observed in both the constant and progressive WBVE protocol groups. Pain intensity decreased by 64.2% ( p  < 0.001) in the constant group and by 61.1% ( p  < 0.001) in the progressive group. Functional disability decreased by 48.1% ( p  < 0.001) in the constant group and by 53.3% ( p  < 0.001) in the progressive group. Functional performance improved by 16.5% ( p  < 0.001) in the constant group and by 16.9% ( p  < 0.001) in the progressive group. Electromyography (EMG) demonstrated significant improvements across all measured variables except % maximum voluntary isometric contraction (%MVIC) of external obliques (EO) in both intervention groups with time ( p  < 0.001). There was no statistically significant difference in the magnitude of improvement between the constant and progressive WBVE protocols ( p  > 0.05), indicating both modalities' effectiveness in ameliorating CLBP symptoms and associated functional impairments., Conclusion: The study demonstrates that both progressive and constant WBVE protocols are equally effective in reducing pain and disability in NSCLBP patients. These findings support the inclusion of progressive WBVE in clinical practice, offering a flexible treatment option that can be tailored to individual patient needs, ensuring both tolerability and effectiveness. This contributes valuable evidence towards optimizing WBVE protocols for managing NSCLBP., Competing Interests: The authors declare there are no competing interests., (©Zafar 2024 et al.)

Research on adolescent mental health in low and middle-income countries cites the paucity of human resources and emphasises non-specialist worker (NSW)-led counselling intervention within school and health-system platforms. This pilot study aimed to evaluate the feasibility and acceptability of a transdiagnostic stepped care model, for delivering preventive psychological treatment to adolescents through NSWs in urban vulnerable community settings. Conducted in three such settlements in Mumbai and Thane districts of Maharashtra in India, this mixed-methods study engaged 500 young people, their parents and 52 NSWs. Quantitative data, obtained through monitoring indicators, fidelity checklists and the Strengths and Difficulties Questionnaire (SDQ), revealed key stressors for adolescents, including poverty, structural inequity, cultural conformity pressures, academic anxieties and communication gap within families. Post-intervention, adolescents exhibited an enhanced capacity for positive emotions and agency. The qualitative component, incorporating observations, focus group discussions (FGDs) and in-depth interviews (IDIs) with various stakeholders, highlighted reduced stigma around mental health, yet identified barriers like time commitment, lack of incentivisation for NSWs, lack of privacy in densely populated communities and societal stigma. This implementation research underscores that adolescent mental health stressors often originate from social determinants, exacerbated by insufficient awareness and stigma. Such stepped care models offer a pathway for communities to establish enduring support networks., Competing Interests: The authors declare that no competing interests exist., (© The Author(s) 2024.)

Objective: This study describes the development, validation, and integration of a detector response model that accounts for the combined effects of x-ray crosstalk, charge sharing, and pulse pileup in photon-counting detectors., Approach: The x-ray photon transport was simulated using Geant4, followed by analytical charge sharing simulation in MATLAB. The analytical simulation models charge clouds with Gaussian-distributed charge densities, which are projected on a 3x3 pixel neighborhood of interaction location to compute detected counts. For pulse pileup, a prior analytical method for redistribution of energy-binned counts was implemented for delta pulses. The x-ray photon transport and charge sharing components were validated using experimental data acquired on the CdTe-based Pixirad-1/Pixie-III detector using monoenergetic beams at 26, 33, 37, and 50 keV. The pulse pileup implementation was verified with a comparable Monte Carlo simulation. The model output without pulse pileup was used to generate spatio-energetic response matrices for efficient simulation of scanner-specific photon-counting CT (PCCT) images with DukeSim, with pulse pileup modeled as a post-processing step on simulated projections. For analysis, images for the Gammex multi-energy phantom and the XCAT chest phantom were simulated at 120 kV, both with and without pulse pileup for a range of doses (27-1344 mAs). The XCAT images were evaluated qualitatively at 120 mAs, while images for the Gammex phantom were evaluated quantitatively for all doses using measurements of attenuation coefficients and Calcium concentrations., Main Results: Reasonable agreement was observed between simulated and experimental spectra with Mean Absolute Percentage Error Values (MAPE) between 10%-31% across all incident energies and detector modes. The increased pulse pileup from increased dose affected attenuation coefficients and calcium concentrations, with an effect on calcium quantification as high as MAPE of 28%., Significance: The presented approach demonstrates the viability of the model for enabling VITs to assess and optimize the clinical performance of PCCT., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

This work is based on probing photosensitization in carbon nanotubes (CNTs) by organotin(IV) compounds to fabricate a hybrid material with excellent photocatalytic activity and generation of reactive oxygen species. Two organotin(IV) compounds (compounds 1 and 2) were synthesized and characterized by spectroscopic and spectrometric studies, elemental analysis and single crystal X-ray diffraction followed by their impregnation inside the CNTs. The so obtained hybrid materials (1@CNT and 2@CNT) were characterized by FTIR, TGA, FE-SEM, HR-TEM, PXRD and XPS analysis, and assessed for photosensitization and generation of reactive oxygen species. The enhanced photocatalytic activity of the fabricated materials in comparison to bare CNTs is attributed to the reduction of band gap and suppression of rapid recombination rates due to the encapsulation of photogenerated electrons. The generation of reactive species in photocatalyst 1@CNT was validated by the degradation of Amoxicillin (AMX) under optimized conditions for catalytic dosage, H 2 O 2 concentration, response time and pH. The material 1@CNT could degrade ca. 83% of AMX by generating free radicals (˙OH and ˙O 2 - ) under visible light irradiation at pH 6 as investigated by UV-visible spectroscopy and supported by EPR and DFT studies. Furthermore, the structural stability and sustained photocatalytic properties of 1@CNT over four cycles highlight its potential as an eco-friendly solution for degrading environmental toxins.

Thermally activated delayed fluorescence (TADF)-based electroluminescence (EL) devices adopting a host/guest strategy in their emitting layer (EML) are capable of realizing high efficiency. However, TADF emitters composed of donor and acceptor moieties as guests dispersed in organic host materials containing a donor and/or an acceptor are subject to donor-acceptor (D-A) interactions. In addition, electron delocalization between neighboring emitter molecules could form different species of aggregates. Here, we investigate the effects of intermolecular interacting emission species on the optoelectronic properties of sky-blue/green/red (sB/G/R) TADF emitters as guests using poly(biphenyl-Si/Ge) grafted with various donor moieties as hosts. We found the presence of guest/guest exciplex (D g /A g )*, host/guest exciplexes (D h /A g )*, and aggregates through the exploration of interactions between neighboring TADF guest molecules and between host and TADF-guest molecules. The nonradiative 3 (D h /A g )* (Δ E ST ≈ 0.5 eV) could increase the internal conversion rate (k IC ) and reduce delayed luminescence, and both of them could cause a decrease in PLQY. The luminescence of 3 (D h /A g )* may have a positive or negative effect on PLQY depending on its triplet energy. As the singlet and triplet energies of (aggregate)* are lower than those of (ICT)*, energy transfer from (ICT)* to (aggregate)* could occur. The low PLQY nature of (aggregate)* means that it is more likely to cause quenching in device emission. The emissions from (D h /A g )* and (aggregate)* are found to have increased full width at half-maximum and lead to lower emission color purity. Such intermolecular interactions should also occur in host/guest (TADF) systems and nondoped TADF emitter systems and thus are important factors for the molecular design of the TADF emitter and/or its accompanying host for high device efficiency and emission color purity.

Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed to the absence of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER-2). The heterogenous tumor microenvironment (TME) of TNBC is composed of diverse constituents that intricately interact to evade immune response and facilitate cancer progression and metastasis. Based on molecular gene expression, TNBC is classified into four molecular subtypes: basal-like (BL1 and BL2), luminal androgen receptor (LAR), immunomodulatory (IM), and mesenchymal. TNBC is an aggressive histological variant with adverse prognosis and poor therapeutic response. The lack of response in most of the TNBC patients could be attributed to the heterogeneity of the disease, highlighting the need for more effective treatments and reliable prognostic biomarkers. Targeting certain signaling pathways and their components has emerged as a promising therapeutic strategy for improving patient outcomes. In this review, we have summarized the interactions among various components of the dynamic TME in TNBC and discussed the classification of its molecular subtypes. Moreover, the purpose of this review is to compile and provide an overview of the most recent data about recently discovered novel TNBC biomarkers and targeted therapeutics that have proven successful in treating metastatic TNBC. The emergence of novel therapeutic strategies such as chemoimmunotherapy, chimeric antigen receptor (CAR)-T cells-based immunotherapy, phytometabolites-mediated natural therapy, photodynamic and photothermal approaches have made a significant positive impact and have paved the way for more effective interventions., (© 2024 Wiley Periodicals LLC.)

Introduction: Myocarditis is an inflammatory disease of the myocardial layer of the heart that can be prone to dilation of chambers with presentation as heart failure secondary to dilated cardiomyopathy. Myocarditis can lead to remodeling and fibrosis that can affect the heart's relaxation-lusitropy and chronotropic function. The current techniques for identifying myocarditis, such as endomyocardial biopsy and imaging, are costly, and intrusive. The current literature aims to identify reliable, accurate, and prognostically educative biomarkers of myocarditis., Areas Covered: This review covers the definition, clinical features, diagnostic markers, cardiac imaging, prognosis, and complications of myocarditis. PubMed, Embase, and the Cochrane data bank were searched from inception to 1 January 2024 for relevant articles., Expert Opinion: By adopting these diagnostic and prognostic biomarkers, clinicians can have a better comprehension of the progression of the disease and provide early diagnosis and treatment for myocarditis.

Background: Metopic suture is a dense fibrous joint extending from nasion to bregma. Normally, closure of this suture takes place between 1-8 years of age. Failure of this closure beyond 8 years leads to persistent metopic suture. Persistent metopic suture may mimic skull fracture., Aim and Objective: To differentiate metopism from frontal bone fracture., Material and Method: 54 dry skull of adult humans in were studied. These skulls were observed for the presence (complete or incomplete suture) or absence of metopic suture., Result: Metopic suture was found in 3.7% skulls. Both complete and incomplete metopic suture were found in 1.85% of the dry skulls., Conclusion: Neurosurgeons, radiologists, otorhinolaryngologists, physicians, anatomists, forensic specialists, anthropologists and evolutionary biologists should have knowledge of this anatomical variation. This case series focusses on the importance of metopism. Metopism is a topic, which has not been much studied., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Malaria still causes over 600,000 deaths annually, with rising resistance to frontline drugs by Plasmodium falciparum increasing this number each year. New medicines with novel mechanisms of action are, therefore, urgently needed. In this work, we solved the cocrystal structure of the essential malarial kinase Pf CLK3 with the reversible inhibitor TCMDC-135051 ( 1 ), enabling the design of covalent inhibitors targeting a unique cysteine residue (Cys368) poorly conserved in the human kinome. Chloroacetamide 4 shows nanomolar potency and covalent inhibition in both recombinant protein and P. falciparum assays. Efficacy in parasites persisted after a 6 h washout, indicating an extended duration of action. Additionally, 4 showed improved kinase selectivity and a high selectivity index against HepG2 cells, with a low propensity for resistance (log MIR > 8.1). To our knowledge, compound 4 is the first covalent inhibitor of a malarial kinase, offering promising potential as a lead for a single-dose malaria cure.

In nature, numerous biomolecules are implicated in charge transfer (CT) and energy transfer (ET) mechanisms crucial for fundamental processes such as photosynthesis. Unveiling these mechanisms is pertinent to multiple disciplines including chemistry, engineering and biochemistry. This article presents a detailed study involving two molecules forming a model system with efficient ET properties. Specifically, their complex exhibits dark quenching phenomena arising from fluorescence resonance energy transfer (FRET) from the donor (imiquimod) to the acceptor (rifampicin). In addition, the energy transfer properties were also elucidated by considering the two forms of rifampicin (RIF), non-ionic and zwitter-ionic in the solution. Supplemented by spectroscopic findings, molecular dynamics simulations and time dependent density functional theory (TD-DFT) calculations conclusively validate the ET properties from imiquimod (IMQ) to RIF forms. Interestingly, these ET processes were found to be associated with pi-pi and hydrogen bond interactions. Their contribution was observed to depend upon the non-ionic and zwitter-ionic form of RIF.

Objectives: To profile a cohort of gyrate atrophy patients classified by widefield retinal imaging and correlate the structural, biochemical, and functional characteristics., Design: Retrospective observational cohort study., Participants: Sixty-five patients (129 eyes) with gyrate atrophy., Methods: Data of participants with a diagnosis of gyrate atrophy were retrieved from their electronic medical records (January 2015 to December 2023). Retinal involvement was classified into three zones using widefield retinal images. Zone 3 had atrophic patches in the area anterior to the equator; Zone 2 had involvement limited to the arcades but posterior to the equator; Zone 1 had involvement within the vascular arcades and/or peripapillary region, with or without any other zone involvement. Macular assessment was performed using swept-source OCT (n=104). Flash ERG was performed in 40 eyes. serum ornithine levels (n=35) were measured, and genetic analysis was conducted (n=18)., Main Outcome Measures: Demography, patient profile, zone of retina involved, macular features, and serum ornithine levels., Results: The average age at presentation was 26.4 (range: 5-67) years, majority were male. Nyctalopia (n=35, 53.8%) and blurred vision (n=29, 44.6%) were the most common symptoms. Positive family history was reported in 32.3% of patients. Most eyes were myopic (69.8%<-3 D). Posterior subcapsular cataracts were documented in 36.4% of eyes. The highest frequency of retinal area affected was Zone 1 (57.14%), followed by Zone 2 (33.33%) and Zone 3 (9.52%), correlating with age at presentation. Foveoschisis was observed in 57.7% of eyes, with a higher prevalence in eyes with Zone 1 disease. Elevated serum ornithine levels (>163 μmol/L) were found in 77.14% of patients. ERG showed non-recordable (n=32) or severely reduced (n=8) responses in scotopic and photopic phases. Genetic analysis of 18 patients identified mutations in the OAT gene, including a novel missense variant (c.290T>C)., Conclusions: This large cohort of patients with gyrate atrophy revealed symmetrical involvement, predominantly in Zone 1. Most patients presented between the first and third decades, experienced nyctalopia, vision reduction, early posterior subcapsular cataracts, and varying degrees of myopia. Zone 1 involvement was strongly associated with foveoschisis and visual compromise., (Copyright © 2024. Published by Elsevier Inc.)

Data on percutaneous coronary intervention (PCI) for left main coronary artery (LMCA) disease in patients of diverse race/ethnicity is scant. The aim of the study was to assess the impact of race/ethnicity on clinical outcomes at 12-month follow-up of patients with LMCA disease undergoing PCI with drug-eluting stent implantation. All patients undergoing PCI for LMCA disease between 2010 and 2019 at a tertiary care center were prospectively enrolled. Clinical outcomes were assessed per each race/ethnic group. The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stroke at 12 months. A total of 774 consecutive patients with known race/ethnicity were prospectively enrolled, 62.1% (n=481) Caucasians, 17.2% (n=133) Hispanics, 12.7% (n=98) Asians and 8.0% (n=62) African Americans. Compared with Caucasians, the hazard rate of the primary endpoint tended to be lower in Asian patients (6.1% vs 14.2%; hazard ratio [HR]: 0.41; 95% confidence interval [CI]: 0.16-1.03), and similar in African American (13.7% vs 14.2%; HR: 0.93; 95% CI: 0.40-2.16) and Hispanic patients (14.2% vs 14.2%; HR: 1.02; 95% CI: 0.58-1.78). Hazard rates of target vessel or lesion revascularization were comparable in the four groups. Cox multivariable regression adjustment confirmed consistent findings and revealed higher hazard rate of post-discharge bleeding in African Americans vs. Caucasians (HR: 5.89; 95% CI: 1.00-34.5). In conclusion, within a racially/ethnically diverse cohort of patients undergoing PCI for LMCA disease, when compared with Caucasians, Asians are at lower risk of all-cause death, MI or stroke, while African Americans are at increased risk of post-discharge bleeding., 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.)

Background: Cancer is regarded as one of the main causes of death globally. Future predictions indicate that the death rate from cancer will keep rising, which may reach 11.4 million in 2030. Carcinogenesis refers to the phenomenon of transforming a normal cell into a cancer cell. Cancer is characterized by unregulated and uncontrolled cell division due to alterations at the molecular and genetic levels. Gene mutations can speed up the rate of cell division, which leads to cancer. Metastasis entails the dissemination of cancer cells from the primary site to distant regions of the body via the circulatory or lymphatic systems., Objective: This review is mainly focusing on the anticancer properties of terpenoids. In the case of human beings, several types of cancers can be treated clinically based on the form and phase of the cancer. So, there are different types of treatment regimens available for the management of cancer, such as immunotherapy, hormonal therapy, radiation therapy, and chemotherapy., Methods: Several problems are associated with cancer therapy, including chemoresistance, severe toxicity, relapse, and metastasis. To minimize these complications, natural products like terpenoids seem to be beneficial for the effective management of cancer., Results: Experimental results revealed that the anticancer potential of terpenoids is due to activation of apoptosis and stimulation of cell cycle arrest. Some of the terpenoids exhibit anticancer effects by inhibiting angiogenesis and metastasis via the regulation of several signaling pathways intracellularly. Certain terpenoids have been shown to work in concert with anticancer medications (doxorubicin, cisplatin, paclitaxel, and 5-fluorouracil) to provide synergistic effects. These terpenoids have also been shown to be effective against cancer cells that are resistant to several drug therapies., Conclusion: The current study will focus on signaling pathways and mode of action of several types of terpenoids as anticancer agents. Further, it will provide insights into the ongoing clinical trials and prospective pathways for the advancement of terpenoids as possible anti-cancer agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Nanoflowers, an innovative class of nanoparticles with a distinctive flower-like structure, have garnered significant interest for their straightforward synthesis, remarkable stability, and heightened efficiency. Nanoflowers demonstrate versatile applications, serving as highly sensitive biosensors for rapidly and accurately detecting conditions such as diabetes, Parkinson's, Alzheimer's, and foodborne infections. Nanoflowers, with their intricate structure, show significant potential for targeted drug delivery and site-specific action, while also exhibiting versatility in applications such as enzyme purification, water purification from dyes and heavy metals, and gas sensing through materials like nickel oxide. This review also addresses the structural characteristics, surface modification, and operational mechanisms of nanoflowers. The nanoflowers play a crucial role in preventing premature drug leakage from nanocarriers. Additionally, the nanoflowers contribute to averting systemic toxicity and suboptimal therapy efficiency caused by hypoxia in the tumor microenvironment during chemotherapy and photodynamic therapy. This review entails the role of nanoflowers in cancer diagnosis and treatment. In the imminent future, the nanoflowers system is poised to revolutionize as a smart material, leveraging its exceptional surface-to-volume ratio to significantly augment adsorption efficiency across its intricate petals. This review delves into the merits and drawbacks of nanoflowers, exploring synthesis techniques, types, and their evolving applications in cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We investigated the relationship between personal relative deprivation (PRD)-resentment from the belief that one is worse off than people who are similar to oneself-and locus of control., Background: Research has yet to comprehensively investigate whether PRD is associated with a tendency to favor external (vs. internal) explanations for self- and other-relevant outcomes., Method: Eight studies (N total  = 6729) employed cross-sectional, experimental, and (micro)longitudinal designs and used established trait and state measures of PRD and loci of control., Results: Participants higher in PRD adopted more external (vs. internal) explanations for others' outcomes while controlling for socio-demographics (e.g., socioeconomic status; Studies 1-4). This relationship was mediated by a lowered sense of personal control (Study 1) and evident in a cross-national sample of participants in Asia (Study 2). PRD is more robustly associated with external than internal explanations for self and other-relevant outcomes (Studies 5-8), and within-person changes in PRD are positively associated with within-person changes in external explanations (month-to-month and day-to-day; Studies 7-8)., Conclusions: PRD is positively associated with external locus of control independent of socioeconomic status, within and between people, and across cultures. This research highlights the implications of PRD for people's construal of the causal forces that govern their lives., (© 2024 The Author(s). Journal of Personality published by Wiley Periodicals LLC.)

Endothelial dysfunction and microvascular remodeling underly the development and progression of a host of cardiovascular disease (CVD) . However, current methods to assess coronary epicardial microvascular function are invasive, time-intensive, and costly. Optical coherence tomography angiography (OCTA) is an established technology within ophthalmology that provides a quick, noninvasive assessment of vascular structures within the retina. As a growing body of evidence reveals strong associations between the retinal changes on OCTA and the development and progression of CVD, OCTA may indeed be a surrogate test for end-organ dysfunction. OCTA has potential to enhance diagnostic performance, refine cardiovascular risk assessment, strengthen prognostication, and ultimately, improve patient care. We explore the current literature on OCTA in cardiovascular diseases to summarize the clinical utility of retinal OCTA imaging and discuss next-generation cardiovascular applications., Competing Interests: Declaration of competing interest Dr. Srivastava received contracted research funding to institution from Regeneron, Eyevensys, Eyepoint, Gilead, and consulting fees from Adverum, Novartis, Zeiss, Bausch and Lomb. Dr. Sharma received contracted research funding to institution from Gilead, Abbvie, Genentech/Roche, Santen, IONIS, and received consulting fees from Alimera, Abbvie, Apellis, Clearside, Eyepoint, Iveric Bio, Genentech/Roche, Bausch and Lomb, Regenxbio, Regeneron, Ripple. Dr. Tang received consulting fees from Sequana Medical, Cardiol Therapeutics, Genomics plc, Zehna Therapeutics, WhiteSwell, Boston Scientific, CardiaTec Biosciences, Intellia Therapeutics, Bristol Myers Squibb, Alleviant Medical, Alexion Pharmaceuticals, Salubris Biotherapeutics, BioCardia Inc., and received honoraria from Springer, Belvoir Media Group, and American Board of Internal Medicine. All other authors have no relationships to disclosure., (Copyright © 2024. Published by Elsevier Inc.)

The accumulation of tau-containing neurofibrillary tangles and beta-amyloid deposits has been identified as the hallmark of Alzheimer's disease. Alzheimer's disease (AD) is a hereditary and neurological condition that can result in non-amnestic cognitive decline in less common forms and amnestic memory loss in its classic form. While Alzheimer's disease is the most prevalent cause of memory loss in middle-aged and older adults, other neurodegenerative and cerebrovascular disorders can have an impact on the disease's clinical course. Designing multi-target-directed ligands (MTDLs) is a very promising modern approach. This methodology was designed specifically for treating disorders with complex pathological mechanisms. Among these disorders is Alzheimer's disease (AD), which is currently the most prevalent multifactorial neurodegenerative illness. Increased amounts of the amyloid βpeptide (Aβ) and hyperphosphorylated tau protein, together with the loss of neurons and synapses, are linked to Alzheimer's disease (AD). Additionally, there is evidence that the pathophysiology of this condition is influenced by oxidative stress, metal ion dysregulation, inflammation, and failure of the cell cycle regulatory system. Since Alzheimer's disease (AD) is a multi-factor illness, there are many attractive targets for the development of anti-AD medications. These molecules can be useful in treating AD since they are multi-target-directed. This review focuses on the discovery of dual and multi-acting anti-AD drug candidates, especially hybrids made by combining chemically active moieties that function against distinct targets. The first group of substances consists of cholinesterase inhibitors with extra properties or those that function as multiple binding site inhibitors. Natural products also provide numerous options for slowing the progression and symptoms of many diseases, including Alzheimer's Meanwhile, Natural chemical structures with the following characteristics: alkaloids, sterols, triterpenes, tannins, flavonoids, polyphenols, and antioxidants as well as anti-inflammatory and anti-amyloidogenic properties. We provide an overview of Alzheimer's disease pathophysiology and therapy targets in this study. We also show several isolated chemicals and medicinal plants that are used to treat and prevent the symptoms of Alzheimer's disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ongoing competition between disease-causing bacteria and human hosts has resulted in the discovery of a wide array of antibacterials. The advent of antibacterials ushered in a promising period in the realm of microbiology, but its brilliance was short-lived and soon diminished. The excessive and incorrect use of antibacterials results in limited selection pressure on the targeted microorganisms, which in turn promotes the evolution of microbes instead of killing them. Consequently, antibacterial resistance has developed and given rise to strains that are resistant to many drugs, leading to a significant increase in mortality rates. The current review delves into the potential of novel natural phytocompounds as innovative solutions to combat these potential bacterial threats. The review begins by showcasing the modus operandi of conventional antibacterial drugs followed by addressing the mechanisms of resistance to antibacterial agents, which have significantly lowered the efficacy of conventional treatments. In contrast, the review explores the mechanism of antibacterial activity of plant-derived phytochemicals, unraveling the various ways in which natural compounds interact with bacterial targets. Furthermore, the review examines the synergism between plant phytochemicals and conventional antibiotics, showcasing the efficacy of this combinatorial approach in overcoming resistance. The review concludes by summarizing the current research and offering valuable insights into challenges in the use of plant phytochemicals as antibacterial therapeutics. This comprehensive overview reinforces the promise of incorporating modern scientific tools with traditional phytotherapy to develop effective strategies against resistant bacterial pathogens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Bacterial consortia exhibiting plant growth promoting properties have emerged as a sustainable approach for crop improvement. As the main challenge associated with them is viability loss and performance under natural conditions, a robust approach for designing bioformulation is needed. In this study, an efficient bioformulation was developed using spontaneous mutants of three bacterial strains for growth promotion of Cajanus cajan., Methods and Results: Optimization of additives for solid [carboxymethylcellulose (CMC), and glycerol) and liquid [polysorbate, CMC, and polyvinyl pyrrolidone (PVP)] bioformulations was done by Response Surface Methodology using Central Composite Design. The stability of each bioinoculant in the formulation was assessed at 30°C and 4°C. The efficiency of the liquid bioformulation was checked in planta in sterile, and subsequently in non-sterile, soil. The maximum cell count was observed in solid bioformulation with 0.1 g L-1 CMC and 50% glycerol (8.10 × 108, 3.69 × 108, and 7.39 × 108 for Priestia megaterium, Azotobacter chroococcum, and Pseudomonas sp. SK3, respectively) and in liquid bioformulation comprising 1% PVP, 0.1 g L-1 CMC, and 0.025% polysorbate (8 × 109, 3.8 × 109, and 6.82 × 109 for Priestia megaterium, Azotobacter chroococcum, and Pseudomonas sp. SK3, respectively). The bioinoculants showed a higher viability (6 months) at 4°C compared to 30°C. Triple culture consortia enhanced plant growth in comparison to the control. The strains could be detected in soil till 45 days after sowing., Conclusions: The study established a systematic process for developing a potent bioformulation to promote agricultural sustainability. Using mutant strains, the bioinoculants could be tracked. In planta assays revealed that the triple culture consortium out-performed mono and dual cultures in terms of impact on plant growth., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Radiation-mediated GI injury (RIGI) in humans either due to accidental or intentional exposures, can only be managed with supporting care with no approved countermeasures available till now. Early detection and monitoring of RIGI is important for effective medical management and improve survival chances in exposed individual. The present study aims to identify new signatures of RIGI using data mining approach followed by validation of selected hub genes in mouse model. Using microarray datasets from Gene Expression Omnibus database, differentially expressed genes were identified. Pathway analysis suggested lipid metabolism as one of the predominant pathways altered in irradiated GI tissue. A protein-protein interaction network revealed top 08 hub genes related to lipid metabolism, namely Fabp1, Fabp2, Fabp6, Npc1l1, Ppar-α, Abcg8, Hnf-4α, and Insig1. qRT-PCR analysis revealed significant up-regulation of Fabp6 and Hnf-4α and down-regulation of Fabp1, Fabp2 and Insig1 transcripts in irradiated intestine. Radiation dose and time kinetics study revealed that the selected 05 genes were altered differentially in the irradiated intestine. Extensive alteration in lipid profiles and modification was observed in irradiated intestine. Finding suggests that lipid metabolism is one of the key targets of radiation and its mediators may act as biomarkers in detection and progression of RIGI.

Background: As the prevalence of chemotherapy-related cognitive impairment rises, investigation into treatment options is critical. The objectives of this study were to test the effects of an aerobic exercise intervention initiated during chemotherapy compared to usual care (wait list control condition) on (1) objectively measured cognitive function and self-reported cognitive function, as well as on (2) the impact of cognitive impairment on quality of life (QOL) postintervention (commensurate with chemotherapy completion)., Methods: The Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial was a two-arm, two-center randomized controlled trial conducted in Ottawa and Vancouver (Canada). Fifty-seven women (M age , 48.8 ± 10 years) diagnosed with stage I-III breast cancer and awaiting chemotherapy were randomized to aerobic exercise initiated with chemotherapy (n EX  = 28) or usual care during chemotherapy with aerobic exercise after chemotherapy completion (n UC  = 29). The intervention lasted 12-24 weeks and consisted of supervised aerobic training and at-home exercise. The primary outcome was objective cognitive function measured via 13 neuropsychological tests (standardized to M ± SD, 0 ± 1); secondary outcomes of self-reported cognitive function and its impact on QOL were assessed via questionnaires. Data collected pre- and postintervention (the primary end point) were analyzed., Results: Although no significant differences between groups were found for objective cognitive function outcomes postintervention after accounting for multiple testing, four of six self-reported cognitive function outcomes showed significant differences favoring the aerobic exercise group., Conclusions: Among women initiating chemotherapy for breast cancer, aerobic exercise did not result in significant differences in objective cognitive function postintervention after chemotherapy completion; however, the results do support the use of this intervention for improving self-reported cognitive function and its impact on QOL., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

In recent years, driven by increasing consumer demand for natural and healthy convenient foods, the food industry has been shifting from synthetic to natural products. This shift is also reflected in the growing popularity of non-conventional extraction methods for pigments, which are favored for sustainability and environment-friendliness compared to conventional processes. This review aims to investigate the extraction of carotenoids from a variety of natural sources, including marine sources like fungus, microalgae, and crustaceans, as well as widely studied plants like tomatoes and carrots. Additionally, it delves into the recovery of valuable carotenoids from waste products like pomace and peels, highlighting the nutritional and environmental benefits. The review also emphasizes the role of green solvents such limonene, vegetable oils, ionic liquids, supercritical fluids, and natural deep eutectic solvents in effective and ecologically friendly carotenoid extraction. These technologies support the ideas of a circular and sustainable economy in addition to having a smaller negative impact on the environment. Overall, the present study highlights the crucial importance of green extraction technologies in achieving the dual goals of sustainability and public safety.

Holistic study of glacial lakes and glacial lake outburst floods (GLOFs) in the strategically important China-Nepal transportation corridors is imperative for regional connectivity and disaster risk reduction. This study focuses on four China-Nepal transportation corridors, namely Chentang-Kimathanka, Zhangmu-Kodari, Keyrung-Kathmandu and Taklakot-Hilsa from east to west in the Himalayan region. Within a remote integrated framework, we present the latest high-resolution inventory of glacial lakes, assess their decadal spatio-temporal changes (1992-2022), identify potentially dangerous glacial lakes, and apply hydrodynamic model to assess downstream impacts of possible GLOFs along the study area. The results show 2688 glacial lakes (≥0.001 km 2 ) with a total area of 116.10 ± 8.53 km 2 over the study area in 2022. Glacial lakes exhibited spatiotemporal heterogeneity in expansion, with overall expansion of 32 % during 30 years. Keyrung-Kathmandu corridor, among others, was assessed with high GLOF susceptibility. Furthermore, hydrodynamic modeling of four highly dangerous lakes in each transportation area reveals that GLOFs have cross-border effects, impacting ∼103 km of China-Nepal highway, 103 bridges, two major dry ports and 3301 buildings in both countries. Based on these findings, we emphasize the joint efforts of both countries for integrated disaster management for smooth connectivity between two countries and saving downstream population through joint cooperation from central to local government levels by initiating artificial lake lowering, developing cross-border early warning systems and cooperation. This study is valuable for presenting a synergistic study of glacial lakes and GLOF for informing decision- and policy-makers of both China and Nepal for a joint approach to disaster mitigation., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Extracellular vesicles are secretory vesicles involved in cell-to-cell communication via their encapsulated cargo of proteins, lipids, and nucleic acids. Bovine milk provides a rich source of extracellular vesicles (mEVs) that have been studied as therapeutics and drug delivery systems. Therefore, insight into the mEV cargo, such as its proteome, may help in understanding the molecular mechanism underlying the potential health benefits attributed to the mEVs. Hence, mEVs were isolated from healthy buffalo milk after screening the milk somatic cell count. The total proteins of mEVs were analyzed using LC-MS, and 331 proteins were found commonly present among three buffalo milk samples. These proteins were primarily derived from extracellular regions and lysosomes. The major biological roles associated with the proteins were immune response, metabolism, and cell cycle regulation. The molecular functions of the proteins were transporter activity, catalytic activity, and GTPase activity. Further, comparative analysis with the previously available bovine mEVs proteome data showed 114 proteins to be newly identified in the buffalo mEVs. The biological pathways associated with these proteins may play a major role in muscle development. These findings shed a light on the potential health benefits of buffalo mEVs as therapeutics as well as drug delivery vehicles., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Elimination of HCV infection as a public health concern by the end of this decade will require a concerted effort in all target populations, including drug-users in the inner-city. Several strategies have been proposed to identify, engage and provide HCV-infected residents with antiviral therapy and maximise treatment and cure achievement. This study aims to assess the effectiveness of a multidisciplinary approach in delivering HCV treatment to people who inject drugs (PWID) within Vancouver's inner city. We have evaluated a novel approach, the Community Pop-Up Clinic, for its ability to promote access to care and uptake of HCV therapy, with additional analyses of HCV reinfection and opioid-related mortality. From January 2021 to August 2023, we evaluated 1968 individuals. 620 (31.5%) were found to carry HCV antibodies and of these, 474 (76.5%) were found to be viremic. Treatment engagement has been secured in 387 (81.6%). 326 (84.2%) have started treatment, 60 in the pre-treatment phase and 1 died of an overdose in pre-treatment. Of 326, 302 completed treatments, 18 are currently on treatment and 1 died of an overdose. Of 302 who completed treatment, 286 confirmed as cured (SVR 12), 16 are awaiting SVR 4, 2 had documented virologic relapse and 1 was reinfected. Three patients withdrew from treatment. By mITT, the cure rate is 286/288 (99.3%). We documented 2 overdose deaths over 326 PY. The data presented validates multidisciplinary programs such as ours aimed at treating HCV in inner-cities and highlights societal benefits that could be achieved including lower overdose death rates., (© 2024 The Author(s). Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Poor air quality in urban areas increases the exposure of individuals to air pollutants. Hence, it becomes mandatory to grow such plant species that have more potential to tolerate air pollution and can aid in its mitigation. Air pollution tolerance index (APTI) and anticipated performance index (API) are two indices that help in scientific evaluation of plant species before recommending them for plantation. In this study, six plant species from three educational institutions of Amritsar city were screened for their tolerance and performance against air pollution as well as for their capability to act as accumulators of nine metals viz., aluminium (Al), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb) and zinc (Zn). On the basis of APTI, Cassia fistula (C. fistula) was categorized as a tolerant species while Alstonia scholaris (A. scholaris), Cascabela thevetia (C. thevetia), Monoon longifolium (M. longifolium), Pongamia pinnata (P. pinnata) and Syzygium cumini (S. cumini) were categorized as intermediately tolerant plant species. API results suggested that A. scholaris, C. fistula, M. longifolium, P. pinnata and S. cumini should be planted for air pollution mitigation. Geo-accumulation Index (Igeo) results showed that soil samples were moderately contaminated with three (Pb, Cu and Zn) metals. Bioaccumulation factor (BAF), for all metals among six plant species, was found to be less than one implying that these plants were absorbers of metals. Metal Accumulation Index (MAI) indicated that C. thevetia, C. fistula and P. pinnata exhibited relatively higher potential for metal accumulation., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to host intestinal microflora. A hyperactive inflammatory and immunological response in the gut has been shown to be one of the disease's long-term causes despite the complexity of the clinical pathology of IBD. The innate immune system activator known as human gut inflammasome is thought to be a significant underlying cause of pathology and is closely linked to the development of IBD. It is essential to comprehend the function of inflammasome activation in IBD to treat it effectively. Systemic inflammasome regulation may be a proper therapeutic and clinical strategy to manage IBD symptoms since inflammasomes may have a significant function in IBD. Non-coding RNAs (ncRNAs) are a type of RNA transcript that is incapable of encoding proteins or peptides. In IBD, inflammation develops and worsens as a result of its imbalance. Culminating evidence has been shown that ncRNAs, and particularly long non-coding RNAs (lncRNAs), may play a role in the regulation of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in IBD. The relationship between IBD and the gut inflammasome, as well as current developments in IBD research and treatment approaches, have been the main topics of this review. We have covered inflammasomes and their constituents, results from in vivo research, inflammasome inhibitors, and advancements in inflammasome-targeted therapeutics for IBD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Linezolid, an important component of rifampicin- and multidrug-resistant tuberculosis (RR/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level and linezolid pharmacokinetic risk factors for anemia have not been well described in children treated for RR/MDR-TB., Methods: We evaluated the pharmacokinetics of linezolid and longitudinal hemoglobin data to validate an existing population linezolid pharmacokinetic model. We assessed the impact of linezolid pharmacokinetics and the risk of developing anemia in a prospectively enrolled cohort of children. The validation of a previously published population pharmacokinetic linezolid model used nonlinear mixed effects modeling. A multivariable ordinal logistic regression model was built to predict the incidence of anemia., Results: A total of 112 children, median age 7.2 (IQR: 2.2-16.3) years, were included from South Africa (n=87) and India (n=25). Of these, 24 children contributed new linezolid pharmacokinetic data. The population pharmacokinetic model which informs the currently recommended linezolid dosing in children (10-15 mg/kg) was validated with these additional new data. For every 1 g/dL lower baseline hemoglobin, the odds of developing grade 3 or 4 anemia increased by 2.64 (95% CI 1.98-3.62). For every 1 mg/L*h higher linezolid area under the concentration-time curve (AUC), the odds of developing a grade 3 or 4 anemia increased by 1.012 (95% CI 1.007-1.017)., Conclusions: These data taken together, confirm currently recommended linezolid doses in children. The risk of anemia in children should be carefully considered and monitored throughout. Initiating linezolid in children with low baseline hemoglobin increases the probability of experiencing grade 3 or 4 anemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Messenger RNA (mRNA)-based therapeutics have emerged as a promising modality for various clinical applications, necessitating robust methods for mRNA quantification. This biodistribution study compares the performance of branched DNA and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays for measuring lipid nanoparticle-encapsulated mRNA. Following intravenous administration of nascent peptide imaging luciferase mRNA (1 mg/kg) to rats, mRNA levels in various tissues and serum were quantified using both assays. Statistical analyses, including Bland-Altman, Deming regression and Passing-Bablok regression, were employed to assess method comparability and reproducibility. The results indicated that mRNA pharmacokinetics measured by branched DNA and RT-qPCR were largely consistent across tissues, with RT-qPCR showing greater reproducibility across multiple laboratories. RT-qPCR also demonstrated a wider dynamic range and higher sensitivity, making it a more versatile option for large-scale studies. Despite some differences in data due to tissue types and timepoints, both methods provided comparable pharmacokinetic profiles for mRNA quantification. This study underscores the importance of selecting an appropriate quantification method based on study requirements and highlights RT-qPCR's adaptability for multisite research, especially for the clinical development of mRNA-based therapeutics.

This quantitative study examines the influence of innovative pedagogical approaches (IPA) on enhancing student critical thinking (SCT) and student learning outcomes (SLO) in higher education, with an emphasis on the mediating role of inclusive leadership(IL). Using a sample of 321 students from public and private universities in Pakistan, the research reveals that methods such as problem-based learning, flipped classrooms, and interactive teaching significantly boost academic performance and cultivate critical thinking skills. The findings indicate that innovative pedagogical approaches positively and significantly impact student critical thinking (β = 0.536, t = 6.539, p < 0.001) and learning outcomes (β = 0.551, t = 12.725, p < 0.001). Additionally, inclusive leadership mediates the relationship between innovative teaching methods and both student critical thinking (β = 0.331, t = 3.833, p < 0.001) and learning outcomes (β = 0.405, t = 8.662, p < 0.001). Data were collected using survey questionnaires adapted from established studies on inclusive leadership, innovative pedagogical approaches, student critical thinking, and learning outcomes. These results highlight the essential role of inclusive leadership in enhancing the efficacy of innovative pedagogies by creating a supportive and diverse learning environment. The study suggests that implementing active learning strategies and integrating technology in the classroom, along with inclusive leadership practices, can significantly improve student engagement, critical thinking, and overall academic performance. This research offers valuable insights for educators and policymakers seeking to enhance teaching and learning experiences in higher education., (© 2024. The Author(s).)

The need for efficient, economical, and clean energy systems is increasing, and as a result, interest in water-splitting techniques to produce green hydrogen is also increasing. However, the sluggish kinetics of the oxygen evolution reaction (OER) hinders the practical application and widespread use of water-splitting technologies; therefore, to address this challenge, it is essential to develop cost-effective and efficient OER catalysts. In this work, we have synthesized an inexpensive and tunable FeCoMn Prussian blue analogue (PBAs) as an efficient OER catalyst via a straightforward process. The ratio of the Co and Mn to optimize the electrochemical performance, and as a result, the FeCo 0.41 Mn 0.42 PBA catalyst demonstrated the best electrochemical performance (260/304 mV overpotential at 10/50 mA cm -2 , a low Tafel slope of 48 mV dec -1 and a good stability of 72 h at 10 mA cm -2 ). Additionally, X-ray absorption spectroscopy (XAS) measurements and density functional theory (DFT) calculations suggest that the FeCo 0.41 Mn 0.42 PBA possesses the optimized electronic density distribution at the active site (Co), and the doping of Mn and Fe can not only increase the electricity conductivity but also activate the critical H 2 O deprotonation step.

The utilization of nanoformulations derived from natural products for the treatment of many human diseases, including cancer, is a rapidly developing field. Conventional therapies used for cancer treatment have limited efficacy and a greater number of adverse effects. Hence, it is imperative to develop innovative anticancer drugs with superior effectiveness. Among the diverse array of natural anticancer compounds, resveratrol, curcumin, and epigallocatechin gallate (EGCG) have gained considerable attention in recent years. Despite their strong anticancer properties, medicinally significant phytochemicals such as resveratrol, curcumin, and EGCG have certain disadvantages, such as limited solubility in water, stability, and bioavailability problems. Encapsulating these phytochemicals in poly(lactic-co-glycolic acid) (PLGA), a polymer that is nontoxic, biodegradable, and biocompatible, is an effective method for delivering medication to the tumor location. In addition, PLGA nanoparticles can be modified with targeting molecules to specifically target cancer cells, thereby improving the effectiveness of phytochemicals in fighting tumors. Combining plant-based medicine (phytotherapy) with nanotechnology in a clinical environment has the potential to enhance the effectiveness of drugs and improve the overall health outcomes of patients. Therefore, it is crucial to have a comprehensive understanding of the different aspects and recent advancements in using PLGA-based nanocarriers for delivering anticancer phytochemicals. This review addresses the most recent advancements in PLGA-based delivery systems for resveratrol, EGCG, and curcumin, emphasizing the possibility of resolving issues related to the therapeutic efficacy and bioavailability of these compounds., (© 2024 Wiley Periodicals LLC.)

Amidst the existing literature on the effect of isotretinoin on serum interleukin-17 levels in acne patients, the effects of oral antibiotics azithromycin and doxycycline on serum interleukin-17 is scarce. We conducted an investigator blinded randomized interventional study to compare the effect of doxycycline, azithromycin and isotretinoin on inflammatory markers and Interleukin-17A (IL-17A) levels in acne. Patients were randomized and received the treatment according to treatment arm till 12 weeks. At baseline and 12 weeks/treatment completion, clinical improvement and Red-cell-distribution width (RDW),Neutrophil-lymphocyte ratio(NLR),Platelet-lymphocyte ratio(PLR), Mean-Platelet volume(MPV), Platelet-distribution width(PDW) and Interleukin-17A levels were analysed. P-value < 0.05 was considered statistically significant. Out of 120 patients, 110 patients completed the study. Baseline Global acne grading scale (GAGS) in doxycycline, azithromycin or isotretinoin group was 24.32  ± 3.119, 24.12 ± 2.804 and 25.10 ± 3.985 respectively and post-treatment was 5.216  ± 1.88, 7.265 ± 2.17 and 2.769 ± 1.08. All the drugs caused a statistically significant decrease in RDW and IL-17 A levels. Baseline levels of IL-17 A were significantly higher in patients with higher GAGS and post-acne scarring. One of the limitations of our study was that we excluded severe nodulocystic acne patients thereby these results have to be carefully extrapolated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)