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This study explored the metagenome of the Pir Panjal Hot Spring (PPHS) to identify thermostable hydrolases. The carboxypeptidase (CarP) gene was successfully amplified and cloned into Escherichia coli DH5-α cells, followed by expression in E. coli BL21-DE3 cells. The CarP enzyme was comprehensively characterized in vitro. Sequencing analysis revealed an open reading frame encoding a functional protein of 504 amino acids, with a molecular weight of 58.65 kDa and an isoelectric point of 4.81. The CarP protein was purified using Ni-His affinity chromatography, and the experimental molecular weight matched in silico predictions. The enzyme exhibited significant thermostability and alkaliphilic properties, with optimal activity at 70 °C and pH 10.0. Additionally, the presence of Zn +2 ions at concentrations of 5 and 10 mmol/L enhanced protease activity by 1.4 and 1.5-fold, respectively. This study reports the discovery of a novel, multifunctional, and thermostable CarP from hot-spring metagenomes. The enzyme's stability against high temperatures, metal ions, surfactants, and inhibitors, along with its specific substrate interactions, highlights its potential for various biotechnological applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To compare the clinical outcomes and surgical safety between femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification cataract surgery (CPCS) in vitrectomized eyes., Methods: A prospective interventional comparative study was conducted at a tertiary eye care center. Sixty consecutive cases requiring cataract surgery following pars plana vitrectomy were allocated into Group 1 ( n = 30), who underwent FLACS with intraocular lens implantation, and Group 2 ( n = 30), who underwent CPCS with intraocular lens implantation, and followed up for 3 months. Primary outcome measures were intraoperative ultrasonic cumulative dissipated energy (CDE) and intraoperative and postoperative complications. The secondary outcome measures were postoperative changes in endothelial cell count (ECC) and central corneal thickness (CCT)., Results: Baseline corrected distance visual acuity (CDVA), ECC, and CCT were comparable. Intraoperative CDE was significantly less in the FLACS group (8.11 vs. 15.83 percentage seconds; P = 0.012) with no intraoperative complication in either group. The postoperative CDVA was comparable between the groups with a trend toward earlier visual recovery in the FLACS group. The postoperative day (POD) 1 endothelial cell loss was higher in the CPCS group (7.54% vs. 2.05%), with the mean endothelial cell density being significantly higher in the FLACS group throughout the follow-up period ( P < 0.05). POD-1 corneal edema was higher in the CPCS group compared to FLACS with no significant difference on follow-up. Intraoperative migration of silicone oil to the anterior chamber was observed in 40% versus 0% in the CPCS versus FLACS groups, respectively., Conclusion: FLACS can be safely performed in post-vitrectomy eyes with lesser intraoperative ultrasonic energy used, postoperative endothelial cell loss, and change in CCT compared to CPCS., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

Introduction: Breast cancer is the second most prevalent disease among women in India and one of the most dangerous and lethal. Chemotherapy-treated breast cancer patients may have perceived stress, which is defined as emotions of mental or physical exhaustion that make them feel angry or anxious. Mindfulness-based intervention (MBI) gives some ideas in line with the conventional mindfulness technique., Purposes: (i) To assess the effect of MBI on perceived stress among breast cancer patients undergoing chemotherapy. (ii) To determine the association between perceived stress with selected demographic variables among breast cancer patients undergoing chemotherapy., Methods: The current quantitative pre- and postexperimental study was carried out in two oncology departments of selected cancer hospitals, Bhubaneswar. A total number of 40 breast cancer patients of perceived stress receiving chemotherapy and data were gathered by using a self-structured socio-demographic proforma and a structured Perceived Stress Scale 10. The experimental group received MBI, and a posttest was conducted on the 17 th day on both the groups after 10 days of the termination of intervention. This MBI was provided to breast cancer patients for five sessions over five days continuously, each session for 45 min with mindfulness breathing exercises, progressive muscle relaxation techniques, practising meditation, and guided imagery technique., Results: The study findings illustrated that reduction of perceived stress among female breast cancer patients undergoing chemotherapy with ( t = 2.2463) ( P = 0.0306) at the P < 0.05; furthermore, there is one socio-demographic variable which had association with perceived stress that is history of psychiatric illness ( χ 2 = 14.1176) ( P = 0.0009) and others had no association with perceived stress., Conclusion: MBI was an effective therapy for reducing the perceived stress of breast cancer patients undergoing chemotherapy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

A 7-week-old boy presented to pediatric ophthalmology with a mass inferior to the medial canthus of the OS that was first noticed on day 3 of life. Crigler massages, warm compresses, and moxifloxacin HCl drops were administered without resolution of symptoms. Probing and irrigation for a presumed dacryocystocele were performed, but the nasolacrimal system was patent, and the mass persisted after the procedure. Oculoplastics was consulted for further evaluation and management. On exam, the tear lake was normal, there was no discharge to palpation of either lacrimal sac, and there was no erythema. An MRI was obtained that showed a mass with nonspecific features abutting the lacrimal sac. A gross total resection of the mass was performed, and it was sent for histopathologic evaluation. Pathology results yielded a diagnosis of sclerosing perineurioma, a rare soft tissue tumor previously unreported in the orbit., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Ethnopharmacological Relevance: Rheum webbianum Royle (RW) holds significant ethnopharmacological importance owing to its 5000-year history of cultivation for medicinal and culinary purposes. Demonstrating therapeutic advantages in traditional and contemporary medical practices, RW exhibits key pharmacological effects including anticancer activity, gastrointestinal control, anti-inflammatory properties, and suppression of fibrosis. Despite its recognized vast bioactivities in ethnopharmacology, its efficacy against the colorectal cancer (CRC) remains incompletely understood., Aim of the Study: This study for the first time aims to investigate the chemo-preventive capabilities of various extracts derived from RW rhizomes against CRC development., Materials and Methods: Four types of RW extracts were prepared by using different solvents viz: Hexane, Ethy-acetate, Ethanol and Methanol. All the four extracts were evaluated for cytotoxicity on HCT-116 human CRC cells. Promising extracts were further investigated in-vivo at varying doses using 1,2-dimethylhydrazine (DMH) induced rat CRC model to assess the anti-oxidant and anticancer properties as well as their effects on the associated hepatic deterioration and hematological alterations., Results: Cell viability: In-vitro assessments demonstrated a dose and time-dependent reduction in HCT-116 cell viability following treatment with methanolic and ethanolic extracts of RW, reducing viability by up to 85% and 90%, respectively, at 200 μg/ml., Histopathology: Histopathological analyses revealed significant improvements in colon tissue morphology in RW extract-treated groups compared to DMH-only treated animals. RW-treated groups showed reduced structural abnormalities, congestion, inflammatory cell infiltration, crypt abscess formation, and dysplasia. In contrast, the DMH-only group exhibited irregular glandular structure, mucosal destruction, extensive inflammatory cell infiltration, crypt abscess formation, and dysplasia. These results highlight the potential of RW methanolic and ethanolic extracts in mitigating colon cancer-related histopathological alterations. Haematological, and hepatic parameters: In the DMH-induced colorectal cancer rat model, significant hematological imbalances were evident, including a 49.13% decrease in erythrocytes, 32.18% in hemoglobin, and 26.79% in hematocrit, along with a 79.62% increase in white blood cells and 68.96% rise in platelets. Administration of RW rhizome extracts effectively restored these hematological parameters to levels comparable to those in the control group. Furthermore, RW treatment significantly reduced serum ALT and AST levels, which had increased by 36.78% and 33.12%, respectively, due to DMH exposure. RW intervention also mitigated the onset of atherosclerosis, evidenced by notable reductions in serum total cholesterol and triglyceride levels. Comparative analysis indicated that RW-treated DMH groups effectively restored lipid profiles, contrasting with the DMH-only group which exhibited markers indicative of colon cancer. Oxidative stress: The DMH-treated group showed a significant increase in MDA levels by 195.59%, indicative of heightened free radical production, coupled with decreased levels of SOD (33%), CAT (48%), GSH (58%), and GR activity (49%), signifying oxidative stress. Treatment with RW extracts in DMH-treated rats markedly reduced MDA levels and enhanced SOD, CAT, GSH, and GR activities. These results underscore the antioxidant efficacy of RW extracts., Conclusion: This study underscores the significant potential of RW rhizome extracts in inhibiting colorectal cancer development. Further investigations are warranted to identify the active constituents responsible for these promising outcomes, positioning RW as a natural and potential agent in combating colon cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The seafood industry generates waste, including shells, bones, intestines, and wastewater. The discards are nutrient-rich, containing varying concentrations of carotenoids, proteins, chitin, and other minerals. Thus, it is imperative to subject seafood waste, including shrimp waste (SW), to secondary processing and valorization for demineralization and deproteination to retrieve industrially essential compounds. Although several chemical processes are available for SW processing, most of them are inherently ecotoxic. Bioconversion of SW is cost-effective, ecofriendly, and safe. Microbial fermentation and the action of exogenous enzymes are among the significant SW bioconversion processes that transform seafood waste into valuable products. SW is a potential raw material for agrochemicals, microbial culture media, adsorbents, therapeutics, nutraceuticals, and bio-nanomaterials. This review comprehensively elucidates the valorization approaches of SW, addressing the drawbacks of chemically mediated methods for SW treatments. It is a broad overview of the applications associated with nutrient-rich SW, besides highlighting the role of major shrimp-producing countries in exploring SW to achieve safe, ecofriendly, and efficient bio-products., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The reactivity of six Mn IV -oxo complexes in C-H bond oxidation has been examined using a combination of kinetic experiments and computational methods. Variable-temperature studies of the oxidation of 9,10-dihydroanthracene (DHA) and ethylbenzene by these Mn IV -oxo complexes yielded activation parameters suitable for evaluating electronic structure computations. Complementary kinetic experiments of the oxidation of deuterated DHA provided evidence for hydrogen-atom tunneling in C-H bond oxidation for all Mn IV -oxo complexes. These results are in accordance with the Bell model, where tunneling occurs near the top of the transition-state barrier. Density functional theory (DFT) and DLPNO-CCSD(T 1 ) computations were performed for three of the six Mn IV -oxo complexes to probe a previously predicted multistate reactivity model. The DFT computations predicted a thermal crossing from the 4 B 1 ground state to a 4 E state along the C-H bond oxidation reaction coordinate. DLPNO-CCSD(T 1 ) calculations further confirm that the 4 E transition state offers a lower energy barrier, reinforcing the multistate reactivity model for these complexes. We discuss how this multistate model can be reconciled with recent computations that revealed that the kinetics of C-H bond oxidation by this set of Mn IV -oxo complexes can be well-predicted on the basis of the thermodynamic driving force for these reactions.

Global imperatives have recently shown a paradigm shift in the prevailing resource utilization model from a linear approach to a circular bioeconomy. The primary goal of the circular bioeconomy model is to minimize waste by effective re-usage of organic waste and efficient nutrient recycling. In essence, circular bioeconomy integrates the fundamental concept of circular economy, which strives to offer sustainable goods and services by leveraging biological resources and processes. Notably, the circular bioeconomy differs from conventional waste recycling by prioritizing the safeguarding and restoration of production ecosystems, focusing on harnessing renewable biological resources and their associated waste streams to produce value-added products like food, animal feed, and bioenergy. Amidst these sustainability efforts, fruit seeds are getting considerable attention, which were previously overlooked and commonly discarded but were known to comprise diverse chemicals with significant industrial applications, not limited to cosmetics and pharmaceutical industries. While, polyphenols in these seeds offer extensive health benefits, the inadequate conversion of fruit waste into valuable products poses substantial environmental challenges and resource wastage. This review aims to comprehend the known information about the application of non-edible fruit seeds for synthesising metallic nanoparticles, carbon dots, biochar, biosorbent, and biodiesel. Further, this review sheds light on the potential use of these seeds as functional foods and feed ingredients; it also comprehends the safety aspects associated with their utilization. Overall, this review aims to provide a roadmap for harnessing the potential of non-edible fruit seeds by adhering to the principles of a sustainable circular bioeconomy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Varicose vein is a chronic condition that affects the lower extremities of the human body. Several factors have been implicated in the development of this disease, viz age, gender, weight, height and prolonged standing. Recently, genome-wide studies have identified genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where the prevalence of varicose veins is high, and it is important to replicate these variants in the stated population. The study aimed to replicate the association of genetic variants associated with varicose veins in this target population, which were found to be associated with the other ethnic groups., Methodology: The studied cohort is of the Indian population comprising unrelated 104 varicose veins cases and 448 non-varicose vein controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. The allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p-value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians., Result: Variant rs3791679 of EFEMP1 was found to be associated with varicose veins in Indians. After observing the association of the EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1 to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEMP1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect ranges from 0.37-1.58., Conclusion: This study identifies EFEMP1 as a potential gene related to the risk of varicose veins in Indians. It also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins., (© 2024. The Author(s).)

Rare cancers (RCs), which account for over 20% of cancer cases, face significant research and treatment challenges due to their limited prevalence. This results in suboptimal outcomes compared to more common malignancies. Rare bone tumors (RBTs) constitute 5-10% of rare cancer cases and pose unique diagnostic complexities. The therapeutic potential of anti-cancer drugs for RBTs remains largely unexplored. Identifying molecular alterations in cancer-related genes and their associated pathways is essential for precision medicine in RBTs. Small molecule inhibitors and monoclonal antibodies targeting specific RBT-associated proteins show promise. Ongoing clinical trials aim to define RBT biomarkers, subtypes, and optimal treatment contexts, including combination therapies and immunotherapeutic agents. This review addresses the challenges in diagnosing, treating, and studying RBTs, shedding light on the current state of RBT biomarkers, potential therapeutic targets, and promising inhibitors. Rare cancers demand attention and innovative solutions to improve clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antibiotic pollution poses a potential risk of genotoxicity, as antibiotics released into the environment can induce DNA damage and mutagenesis in various organisms. This pollution, stemming from pharmaceutical manufacturing, agriculture, and improper disposal, can disrupt aquatic ecosystems and potentially impact human health through the consumption of contaminated water and food. The removal of genotoxic antibiotics using algae-mediated approaches has gained considerable attention due to its potential for mitigating the environmental and health risks associated with these compounds. The paper provides an in-depth examination of the molecular aspects concerning algae and bioreactor-driven methodologies utilized for the elimination of deleterious antibiotics. The molecular analysis encompasses diverse facets, encompassing the discernment and profiling of algae species proficient in antibiotic degradation, the explication of enzymatic degradation pathways, and the refinement of bioreactor configurations to augment removal efficacy. Emphasizing the significance of investigating algal approaches for mitigating antibiotic pollution, this paper underscores their potential as a sustainable solution, safeguarding both the environment and human health., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

» Negative margin resection of musculoskeletal sarcomas is associated with reduced risk of local recurrence.» There is limited evidence to support an absolute margin width of soft tissue or bone that correlates with reduced risk of local recurrence.» Factors intrinsic to the tumor, including histologic subtype, grade, growth pattern and neurovascular involvement impact margin status and local recurrence, and should be considered when evaluating a patient's individual risk after positive margins.» Appropriate use of adjuvant therapy, critical analysis of preoperative advanced cross-sectional imaging, and the involvement of a multidisciplinary team are essential to obtain negative margins when resecting sarcomas., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B67)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Surgical resection is the primary treatment for bone and soft tissue tumors. Negative margin status is a key factor in prognosis. Given the three-dimensional (3D) anatomic complexity of musculoskeletal tumor specimens, communication of margin results between surgeons and pathologists is challenging. We sought to perform ex vivo 3D scanning of musculoskeletal oncology specimens to enhance communication between surgeons and pathologists., Methods: Immediately after surgical resection, 3D scanning of the fresh specimen is performed prior to frozen section analysis. During pathologic grossing, whether frozen or permanent, margin sampling sites are annotated on the virtual 3D model using computer-aided design (CAD) software., Results: 3D scanning was performed in seven cases (six soft tissue, one bone), with specimen mapping on six cases. Intraoperative 3D scanning and mapping was performed in one case in which the location of margin sampling was shown virtually in real-time to the operating surgeon to help achieve a negative margin. In six cases, the 3D model was used to communicate final permanent section analysis. Soft tissue, cartilage, and bone (including lytic lesions within bone) showed acceptable resolution., Conclusions: Virtual 3D scanning and specimen mapping is feasible and may allow for enhanced documentation and communication. This protocol provides useful information for anatomically complex musculoskeletal tumor specimens. Future studies will evaluate the effect of the protocol on positive margin rates, likelihood that a re-resection contains additional malignancy, and exploration of targeted adjuvant radiation protocols using a patient-specific 3D specimen map., (© 2023. Society of Surgical Oncology.)

The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sarcoma is a heterogeneous group of malignancies often resistant to conventional chemotherapy and radiation therapy. The phosphatidylinositol-3-kinase/ protein kinase B /mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway has emerged as a critical cancer target due to its central role in regulating key cellular processes such as cell growth, proliferation, survival, and metabolism. Dysregulation of this pathway has been implicated in the development and progression of bone sarcomas (BS) and soft tissue sarcomas (STS). PI3K/Akt/mTOR inhibitors have shown promising preclinical and clinical activity in various cancers. These agents can inhibit the activation of PI3K, Akt, and mTOR, thereby reducing the downstream signaling events that promote tumor growth and survival. In addition, PI3K/Akt/mTOR inhibitors have been shown to enhance the efficacy of other anticancer therapies, such as chemotherapy and radiation therapy. The different types of PI3K/Akt/mTOR inhibitors vary in their specificity, potency, and side effect profiles and may be effective depending on the specific sarcoma type and stage. The molecular targeting of PI3K/Akt/mToR pathway using drugs, phytochemicals, nanomaterials (NMs), and microbe-derived molecules as Pan-PI3K inhibitors, selective PI3K inhibitors, and dual PI3K/mTOR inhibitors have been delineated. While there are still challenges to be addressed, the preclinical and clinical evidence suggests that these inhibitors may significantly improve patient outcomes. Further research is needed to understand the potential of these inhibitors as sarcoma therapeutics and to continue developing more selective and effective agents to meet the clinical needs of sarcoma patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Zoonotic viral infections continue to pose significant threats to global public health, as highlighted by the COVID-19 pandemic caused by the SARS-CoV-2 virus. The emergence of SARS-CoV-2 served as a stark reminder of the potential for zoonotic transmission of viruses from animals to humans. Understanding the origins and dynamics of zoonotic viruses is critical for early detection, prevention, and effective management of future outbreaks. Metagenomics has emerged as a powerful tool for investigating the virome of diverse ecosystems, shedding light on the diversity of viral populations, their hosts, and potential zoonotic spillover events. We provide an in-depth examination of metagenomic approaches, including, NGS metagenomics, shotgun metagenomics, viral metagenomics, and single-virus metagenomics, highlighting their strengths and limitations in identifying and characterizing zoonotic viral pathogens. This review underscores the pivotal role of metagenomics in enhancing our ability to detect, monitor, and mitigate zoonotic viral infections, using SARS-CoV-2 analogues as a case study. We emphasize the need for continued interdisciplinary collaboration among virologists, ecologists, and bioinformaticians to harness the full potential of metagenomic approaches in safeguarding public health against emerging zoonotic threats., Competing Interests: Declaration of Competing Interest None of the authors report a conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: Rinaie Marwah hot spring Kishtwar (RMHSK) is one of the geothermal springs located at 33°51'51″N 75°32'07″E with an elevation of 2134 meters above sea level in Jammu and Kashmir, India. We aimed to study the microbial diversity of this geothermal spring using metagenomics., Materials and Methods: In the present study, physiochemical parameters including temperature (65-75°C), pH (6. 9-8. 8), hardness (250 ppm), and mineral content was measured along with the microbial diversity using Illumina MiSeq metagenome-based 16s amplicon sequencing (V3-V4). The sequence reads were classified taxonomically into 31 phyla, 71 classes, 152 orders, 256 families, 410 genus, and 665 species. QIIME 2 (Quantitative Insights into Microbial Ecology), an extensible, powerful, and decentralized analytical tool, was used for taxonomic analysis., Results: Bacteroidota (32. 57%) was the dominant phylum, Bacteroidia (32. 51%) the dominant class, Bacteroidales (16. 6%) the dominant order, and Lentimicrobiaceae (14. 23%) was the dominant family per the abundance analysis. Shannon (2. 28) and Chao 1 (87. 0) diversity indices support the existence of higher microbial diversity in RMHSK (50717 OTUs)., Conclusion: The microbial diversity of RMHSK is reported for the first time through a metagenomic study. Identification of microorganisms with characteristics that are relevant to industries., (Copyright © 2023 The Authors. Published by Tehran University of Medical Sciences.)

Four new pentadentate N5-donor ligands, [ N -(1-methyl-2-imidazolyl)methyl- N -(2-pyridyl)-methyl- N -(bis-2-pyridylmethyl)-amine] ( L 1 ), [ N -bis(1-methyl-2-imidazolyl)methyl- N -(bis-2-pyridylmethyl)amine] ( L 2 ), ( N -(isoquinolin-3-ylmethyl)-1,1-di(pyridin-2-yl)- N -(pyridin-2-ylmethyl)methanamine ( L 3 ), and N , N -bis(isoquinolin-3-ylmethyl)-1,1-di(pyridin-2-yl)methanamine ( L 4 ), have been synthesized based on the N4Py ligand framework, where one or two pyridyl arms of the N4Py parent are replaced by ( N -methyl)imidazolyl or N -(isoquinolin-3-ylmethyl) moieties. Using these four pentadentate ligands, the mononuclear complexes [Fe II (CH 3 CN)( L 1 )] 2+ ( 1a ), [Fe II (CH 3 CN)( L 2 )] 2+ ( 2a ), [Fe II (CH 3 CN)( L 3 )] 2+ ( 3a ), and [Fe II (CH 3 CN)( L 4 )] 2+ ( 4a ) have been synthesized and characterized. The half-wave potentials ( E 1/2 ) of the complexes become more positive in the order: 2a < 1a < 4a ≤ 3a ≤ [Fe(N4Py)(CH 3 CN)] 2+ . The order of redox potentials correlates well with the Fe-N amine distances observed by crystallography, which are 2a > 1a ≥ 4a > 3a ≥ [Fe(N4Py)(CH 3 CN)] 2+ . The corresponding ferryl complexes [Fe IV (O)( L 1 )] 2+ ( 1b ), [Fe IV (O)( L 2 )] 2+ ( 2b ), [Fe IV (O)( L 3 )] 2+ ( 3b ), and [Fe IV (O)( L 4 )] 2+ ( 4b ) were prepared by the reaction of the ferrous complexes with isopropyl 2-iodoxybenzoate (IBX ester) in acetonitrile. The greenish complexes 3b and 4b were also isolated in the solid state by the reaction of the ferrous complexes in CH 3 CN with ceric ammonium nitrate in water. Mössbauer spectroscopy and magnetic measurements (using superconducting quantum interference device) show that the four complexes 1b, 2b, 3b , and 4b are low-spin ( S = 1) Fe IV ═O complexes. UV/vis spectra of the four Fe IV ═O complexes in acetonitrile show typical long-wavelength absorptions of around 700 nm, which are expected for Fe IV ═O complexes with N4Py-type ligands. The wavelengths of these absorptions decrease in the following order: 721 nm ( 2b ) > 706 nm ( 1b ) > 696 nm ( 4b ) > 695 nm ( 3b ) = 695 nm ([Fe IV (O) (N4Py)] 2+ ), indicating that the replacement of the pyridyl arms with ( N -methyl) imidazolyl moieties makes L 1 and L 2 exert weaker ligand fields than the parent N4Py ligand, while the ligand field strengths of L 3 and L 4 are similar to the N4Py parent despite the replacement of the pyridyl arms with N -(isoquinolin-3-ylmethyl) moieties. Consequently, complexes 1b and 2b tend to be less stable than the parent [Fe IV (O)(N4Py)] 2+ complex: the half-life sequence at room temperature is 1.67 h ( 2b ) < 16 h ( 1b ) < 45 h ( 4b ) < 63 h ( 3b ) ≈ 60 h ([Fe IV (O)(N4Py)] 2+ ). Compared to the parent complex, 1b and 2b exhibit enhanced reactivity in both the oxidation of thioanisole in the oxygen atom transfer (OAT) reaction and the oxygenation of C-H bonds of aromatic and aliphatic substrates, presumed to occur via an oxygen rebound process. Furthermore, the second-order rate constants for hydrogen atom transfer (HAT) reactions affected by the ferryl complexes can be directly related to the C-H bond dissociation energies of a range of substrates that have been studied. Using either IBX ester or H 2 O 2 as an oxidant, all four new Fe II complexes display good performance in catalytic reactions involving both HAT and OAT reactions.

A series of manganese(II) and oxomanganese(IV) complexes supported by neutral, pentadentate ligands with varied equatorial ligand-field strength (N3pyQ, N2py2I, and N4py Me2 ) were synthesized and then characterized using structural and spectroscopic methods. On the basis of electronic absorption spectroscopy, the [Mn IV (O)(N4py Me2 )] 2+ complex has the weakest equatorial ligand field among a set of similar Mn IV -oxo species. In contrast, [Mn IV (O)(N2py2I)] 2+ shows the strongest equatorial ligand-field strength for this same series. We examined the influence of these changes in electronic structure on the reactivity of the oxomanganese(IV) complexes using hydrocarbons and thioanisole as substrates. The [Mn IV (O)(N3pyQ)] 2+ complex, which contains one quinoline and three pyridine donors in the equatorial plane, ranks among the fastest Mn IV -oxo complexes in C-H bond and thioanisole oxidation. While a weak equatorial ligand field has been associated with high reactivity, the [Mn IV (O)(N4py Me2 )] 2+ complex is only a modest oxidant. Buried volume plots suggest that steric factors dampen the reactivity of this complex. Trends in reactivity were examined using density functional theory (DFT)-computed bond dissociation free energies (BDFEs) of the Mn III O-H and Mn IV ═ O bonds. We observe an excellent correlation between Mn IV ═O BDFEs and rates of thioanisole oxidation, but more scatter is observed between hydrocarbon oxidation rates and the Mn III O-H BDFEs.

Rectovaginal endometriosis is a severe variant of deeply infiltrating endometriosis. Laparoscopic assessment with tissue sampling remains the gold standard for diagnosis of endometriosis. However, transvaginal (TVUS) and transrectal ultrasound (TRUS) have been shown to be especially helpful in the diagnosis of deep endometriosis. We present the case of a 49-year-old female with menorrhagia, dysmenorrhea, and constipation. Upon pelvic examination, an incidental mass was palpated. A computed tomography (CT) scan revealed an anterior rectal wall mass and colonoscopy was non-diagnostic. Further work-up with MRI showed a 3.9 cm mass centered within the upper rectovaginal septum. TRUS guided fine-needle aspiration (TRUS-FNA) revealed cohesive epithelial cell groups without significant cytologic atypia and a second population of bland spindle cells. Cell block slides showed glandular epithelium with associated stroma that exhibited endometrial morphology and immunophenotype. Nodular fragments of spindle cells with smooth muscle immunophenotype and fibrosis were also present. The overall morphologic findings were consistent with rectovaginal endometriosis with nodular smooth muscle metaplasia. Medical management with nonsteroidal aromatase inhibitor with radiologic follow-up was selected. Rectovaginal endometriosis represents a type of deep endometriosis usually associated with severe pelvic symptoms. Metaplastic smooth muscle cells are a frequent component of endometriosis in the rectovaginal pouch with nodular growth and may present diagnostic challenges. TRUS-FNA is a minimally invasive procedure that can provide an accurate diagnosis of endometriosis, even in this variant of deep infiltrating disease., (© 2023 Wiley Periodicals LLC.)

Cells produce reactive oxygen species (ROS) as a metabolic by-product. ROS molecules trigger oxidative stress as a feedback response that significantly initiates biological processes such as autophagy, apoptosis, and necrosis. Furthermore, extensive research has revealed that hydrogen peroxide (H 2 O 2 ) is an important ROS entity and plays a crucial role in several physiological processes, including cell differentiation, cell signalling, and apoptosis. However, excessive production of H 2 O 2 has been shown to disrupt biomolecules and cell organelles, leading to an inflammatory response and contributing to the development of health complications such as collagen deposition, aging, liver fibrosis, sepsis, ulcerative colitis, etc. Extracts of different plant species, phytochemicals, and Lactobacillus sp (probiotic) have been reported for their anti-oxidant potential. In this view, the researchers have gained significant interest in exploring the potential plants spp., their phytochemicals, and the potential of Lactobacillus sp. strains that exhibit anti-oxidant properties and health benefits. Thus, the current review focuses on comprehending the information related to the formation of H 2 O 2, the factors influencing it, and their pathophysiology imposed on human health. Moreover, this review also discussed the anti-oxidant potential and role of different extract of plants, Lactobacillus sp. and their fermented products in curbing H 2 O 2 ‑induced oxidative stress in both in-vitro and in-vivo models via boosting the anti-oxidative activity, inhibiting of important enzyme release and downregulation of cytochrome c, cleaved caspases-3, - 8, and - 9 expression. In particular, this knowledge will assist R&D sections in biopharmaceutical and food industries in developing herbal medicine and probiotics-based or derived food products that can effectively alleviate oxidative stress issues induced by H 2 O 2 generation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Microplastics (MPs) are ubiquitous pollutants persisting almost everywhere in the environment. With the increase in anthropogenic activities, MP accumulation is increasing enormously in aquatic, marine, and terrestrial ecosystems. Owing to the slow degradation of plastics, MPs show an increased biomagnification probability of persistent, bioaccumulative, and toxic substances thereby creating a threat to environmental biota. Thus, remediation of MP-pollutants requires efficient strategies to circumvent the mobilization of contaminants leaching into the water, soil, and ultimately to human beings. Over the years, several microorganisms have been characterized by the potential to degrade different plastic polymers through enzymatic actions. Metagenomics (MGs) is an effective way to discover novel microbial communities and access their functional genetics for the exploration and characterization of plastic-degrading microbial consortia and enzymes. MGs in combination with metatranscriptomics and metabolomics approaches are a powerful tool to identify and select remediation-efficient microbes in situ. Advancement in bioinformatics and sequencing tools allows rapid screening, mining, and prediction of genes that are capable of polymer degradation. This review comprehensively summarizes the growing threat of microplastics around the world and highlights the role of MGs and computational biology in building effective response strategies for MP remediation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Direct-acting antiviral medications have the potential to eliminate the hepatitis C virus (HCV) epidemic among people who inject drugs; yet, suboptimal adherence remains a barrier. Directly observed treatment (DOT), an effective strategy for optimizing adherence, has been frequently implemented in opioid treatment programs but less commonly in community health settings due to the heavy burden of daily visits. An alternative is video-observed therapy (VOT), which uses mobile health technology to monitor adherence. VOT has not been widely studied among people who inject drugs with HCV., Objective: This qualitative study, part of a larger implementation evaluation, investigates stakeholder perceptions and experiences with VOT in Project HERO (Hepatitis C Real Outcomes), a multisite pragmatic trial testing treatment delivery models for people who inject drugs with HCV. Our goal was to understand the potential barriers and facilitators to the implementation of the VOT technology., Methods: Qualitative interviews were conducted with 27 Project HERO study staff and 7 patients. Interviews focused on perceptions and experiences with the VOT app and barriers and facilitators to implementation. Team meeting minutes over the first 2 years of the project were transcribed. A coding system was developed and applied to the data. We summarized thematic data and compared participant perceptions to generate a close understanding of the data., Results: Frequent barriers to VOT included mechanical failure, stolen or lost phones, and a steep learning curve for participants and study staff. In sites with older and less technically skilled participants, staff found it difficult to implement the VOT app. Research staff found that the routine monitoring of app use led to closer engagement with participants. This was both a benefit and a potential threat to the validity of this pragmatic trial. Patient participants reported mixed experiences., Conclusions: VOT may be a useful alternative to DOT for some patients, but it may not be feasible for all. Significant staff involvement may be required., (©Alison Karasz, Krupa Merchant, Julia Arnsten, Judith Feinberg, Arthur Y Kim, Paula J Lum, Melissa Diane McKee, Shruti H Mehta, Paul Meissner, Brianna L Norton, Kimberly Page, Irene Pericot-Valverde, Reena Singh, Ellen Stein, Lynn E Taylor, Judith I Tsui, Katherine Wagner, Alain Litwin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 02.06.2023.)

Introduction: Highly effective direct-acting antiviral (DAA) agents have changed the landscape of hepatitis C virus infection (HCV) treatment and have become more available to people who inject drugs (PWID) over the past several years. Although many achieve a sustained virologic response (SVR), a small proportion will become re-infected. This study examined experiences of re-infection among participants in Project HERO, a large multi-site treatment trial designed to test alternative treatment delivery models for DAAs., Methods: Study staff conducted qualitative interviews with twenty-three HERO participants who experienced reinfection following successful treatment for HCV. Interviews focused on life circumstances and experiences with treatment/re-infection. We conducted a thematic analysis, followed by a narrative analysis., Results: Participants described challenging life circumstances. The initial experience of cure was joyful, leading participants to feel that they had escaped a defiled, stigmatized identity. Re-infection was very painful. Feelings of shame were common. Participants with fully developed narratives of re-infection described both a strong emotional response as well as a plan for avoiding re-infection during retreatment. Participants who lack such stories showed signs of hopelessness and apathy., Conclusion: Though the promise of personal transformation through SVR may be motivating for patients, clinicians should be cautious about how they describe the "cure" when educating patients about HCV treatment. Patients should be encouraged to avoid stigmatizing, dichotomizing language of the self, including terms such as "dirty" and "clean." In acknowledging the benefits of HCV cure, clinicians should emphasize that re-infection does not mean failed treatment; and that current treatment guidelines support retreatment of re-infected PWID., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study is focused on the modelling of the composite effect of corrosion factors using Design Expert 13 software on the corrosion rate in the water distribution network of Patna (Bihar), India. A total of nine variables, including pH, temperature, total dissolved solid (TDS), alkalinity, calcium hardness, chloride, sulphate, dissolved oxygen (DO) and time, were considered for modelling. The physicochemical parameters were determined through regular monitoring of water samples. The corrosion rate was determined by the direct monitoring of water distribution pipes using adjustments of seven GI coupons for 45, 90, 135, 180, 225, 270 and 315 days. Modelling was performed for various corrosion factors using the low-level and high-level experimental ranges. Nine of the corrosion factors, i.e. pH, temperature, TDS, alkalinity, calcium hardness, chloride, sulphate, DO and time, were considered in this study. The data used for low-level and high-level range were 7.28, 23, 430, 115, 24, 18, 10.94, 3.5 and 0 and 7.86, 28, 704, 284, 180, 98, 38.7, 6.8 and 315, respectively. Using the Box-Behnken design (BBD), 160 runs were conducted, including ten replicates at the central point of each block. The results of ANOVA indicate that the values of R 2 , adjusted R 2 and predicted R 2 are 0.9714, 0.9507 and 0.8941, respectively. The value of R 2 (0.9714) was close to 1, which indicates a good fit. The adequate precision was found to be 30.8442, indicating a good signal. The coefficient of variance discusses reproducibility, and in this case, it was 9.90%. On the basis of the ANOVA result, the quadratic model is well-fitted and can be accepted as a suitable model. A total of seven parameters, such as chloride, sulphate, hardness, alkalinity, pH, calcium and hardness, were used for the design of the experimental corrosion rate (CR). Corrosion rate as observed by direct monitoring of the water distribution system was 1.37, 3.08, 1.90, 1.38, 1.09, 2.05 and 1.45 MPY for 45, 90, 135, 180, 225, 270 and 315 days, respectively. These individual CR versus synthetic aqueous solutions were used to validate the interaction of the response surface. It was observed that the trend of individual corrosion rates in synthetic aqueous solutions and the interaction of composite variables with corrosion rates in a quadratic model of response surfaces were clearly correlated., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Livestock is an essential life commodity in modern agriculture involving breeding and maintenance. The farming practices have evolved mainly over the last century for commercial outputs, animal welfare, environment friendliness, and public health. Modifying genetic makeup of livestock has been proposed as an effective tool to create farmed animals with characteristics meeting modern farming system goals. The first technique used to produce transgenic farmed animals resulted in random transgene insertion and a low gene transfection rate. Therefore, genome manipulation technologies have been developed to enable efficient gene targeting with a higher accuracy and gene stability. Genome editing (GE) with engineered nucleases-Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) regulates the targeted genetic alterations to facilitate multiple genomic modifications through protein-DNA binding. The application of genome editors indicates usefulness in reproduction, animal models, transgenic animals, and cell lines. Recently, CRISPR/Cas system, an RNA-dependent genome editing tool (GET), is considered one of the most advanced and precise GE techniques for on-target modifications in the mammalian genome by mediating knock-in (KI) and knock-out (KO) of several genes. Lately, CRISPR/Cas9 tool has become the method of choice for genome alterations in livestock species due to its efficiency and specificity. The aim of this review is to discuss the evolution of engineered nucleases and GETs as a powerful tool for genome manipulation with special emphasis on its applications in improving economic traits and conferring resistance to infectious diseases of animals used for food production, by highlighting the recent trends for maintaining sustainable livestock production., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Taxonomic and functional characterization of a total of 90 bacterial isolates representing bulk and rhizosphere soils of diverse niches of Andaman and Nicobar Islands, India were carried out. Twelve bacterial isolates were found promising for the biological suppression of agriculturally important fungal and bacterial plant pathogens such as Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, and Colletotrichum gloeosporioides. The 16S rRNA gene sequence analysis revealed their identity as belonging to Bacillus subtilis, Bacillus amyloliquefaciens, and Lysinibacillus sphaericus. The isolates were positive for plant growth promotion (PGP) traits including siderophore production, and nutrient solubilization especially phosphorous, zinc, and potassium. Interestingly, the PCR test confirmed the presence of 62 antimicrobial peptides (AMP) biosynthesis genes specific to the genus Bacillus. Whilst all tested species of Bacillus harboured the bacD biosynthesis gene, the B. subtilis (Ba&#95;Abi), and B. amyloliquefaciens (Ba&#95;Abi) harboured the maximum AMP biosynthesis genes analysed in the study. Upon in planta evaluation, the biocontrol potential of the bacterial isolates against leaf spot disease of chilli was observed. The study culminated in the isolation and identification of diverse Bacillus species for exploitation as bioinoculants for plant health management programmes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microorganisms dwell in diverse plant niches as non-axenic biotic components that are beneficial as well pathogenic for the host. They improve nutrients-uptake, stress tolerance, phytohormone synthesis, and strengthening the defense system through phyllosphere, rhizosphere, and endosphere. The negative consequences of the microbial communities are largely in the form of diseases characterized by certain symptoms such as gall, cankers, rots etc. Uncultivable and unspecified nature of different phytomicrobiomes communities is a challenge in the management of plant disease, a leading cause for the loss of the plant products. Metagenomics has opened a new gateway for the exploration of microorganisms that are hitherto unknown, enables investigation of the functional aspect of microbial gene products through metatranscriptomics and metabolomics. Metagenomics offers advantages of characterizing previously unknown microorganisms from extreme environments like hot springs, glaciers, deep seas, animal gut etc. besides bioprospecting gene products such as Taq polymerase, bor encoded indolotryptoline, hydrolases, and polyketides. This review provides a detailed account of the phytomicrobiome networks and highlights the importance and limitations of metagenomics and other meta-omics approaches for the understanding of plant microbial diversity with special focus on the disease control and its management., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Type 1 diabetes results from the loss of pancreatic β cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost β cells with stem cell-derived β cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostasis. However, to achieve this goal of restoration of glucose balance requires work to optimise β cell function within implants. We know that native β cell function is enhanced by cell-cell and cell-extracellular matrix interactions within the islets of Langerhans. Reproducing these interactions in 2D, such as culture on matrix proteins, does enhance insulin secretion. However, the impact of matrix proteins on the 3D organoids that would be in implants has not been widely studied. Here, we use native β cells that are dispersed from islets and reaggregated into small spheroids. We show these β cell spheroids have enhanced glucose-dependent insulin secretion when embedded into softer alginate hydrogels conjugated with RGD peptide (a common motif in extracellular matrix proteins). Embedding into alginate-RGD causes activation of integrin responses and repositioning of liprin, a protein that controls insulin secretion. We conclude that insulin secretion from β cell spheroids can be enhanced through manipulation of the surrounding environment.

This study demonstrates the therapeutic potential of indole-3-butanoyl-polyethylenimine (IBP) nanostructures formed via self-assembly in aqueous system. Dynamic light scattering (DLS) analysis confirmed the formation of the nanostructures in the size range of ~ 194-331 nm. These nanostructures showed commendable antimicrobial activity against wide range of microbes including multi-drug resistant bacteria. Besides, appreciable antioxidant and anti-inflammatory activities were also observed. Results of cytotoxicity studies, performed on normal transformed human embryonic kidney (HEK 293) cells and human red blood cells (hRBCs), revealed almost non-toxic behavior of these nanostructures, however, remarkable toxicity on human breast cancer cells (MCF-7), human osteosarcoma cells (Mg63) and human liver cancer cells (HepG2) was observed. The pre-apoptotic and anti-proliferative activity of IBP nanostructures were confirmed by acridine orange/propidium iodide dual staining assay followed by confocal microscopy and scratch assay on Mg63 cells. Taken together, these results advocate the promising potential of the synthesized IBP nanostructures in the therapeutic applications., Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-022-01015-y., Competing Interests: Conflict of interestAuthors do not have any conflict of interest., (© Association of Microbiologists of India 2022.)

Introduction: Increasingly, people who inject drugs (PWID) infected with hepatitis C virus (HCV) are gaining access to highly effective direct-acting antiviral agents (DAAs). Although past studies examined patient experiences with interferon-based treatments, few have explored patient experiences with these new generation therapeutics. Research and real world experience indicate that many PWID can be successfully treated with the new DAAs. Yet a substantial minority fail to complete treatment or achieve only suboptimal adherence. This qualitative study examines experiences with treatment among participants in Project HERO, a large multisite trial designed to compare treatment delivery methods for DAAs. We explored treatment experiences among HERO participants, with the goal of understanding potential barriers to treatment engagement and completion., Methods: We conducted qualitative interviews with a sample of 21 participants, including 14 who completed HCV treatment and 7 participants who discontinued treatment before the end of the 12-week medication course. The first phase of the analysis was descriptive, examining participants' life experiences, histories of disease and treatment seeking, experiences with the program, and barriers to treatment completion. The second phase of the analysis examined differences between completers and noncompleters., Results: Participants offered a variety of reasons for seeking treatment. Both groups of participants reported highly positive experiences of the HERO trial. Participants described research staff as caring, respectful, and nonjudgmental. Substance use was reported by both groups, yet completers described "manageable" substance use, while noncompleters described substance use that sapped their energy and motivation. Shame over drug use was a barrier to treatment completion. Homelessness and a reported lack of social support were much more common in the noncompleter group., Conclusions: Reasons for noncompletion were not related to features of the clinical trial or treatment program. Our results indicate the importance of: 1) recognizing and addressing severe social and economic challenges such as homelessness; and 2) building a program culture of respect and compassion in treatment programs for PWID infected with HCV., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Ovarian cancer most commonly presents at an advanced stage where survival is approximately 30% compared with >80% if diagnosed and treated before disease spreads. Diagnostic capabilities have progressed from surgical staging via laparotomy to image-guided biopsies and immunohistochemistry staining, along with advances in technology and medicine. Despite improvements in diagnostic capabilities, population-level screening for ovarian cancer is not recommended. Extracellular vesicles (EVs) are 40-150 nm structures formed when the cellular lipid bilayer invaginates. These structures function in cell signaling, immune responses, cancer progression, and establishing the tumor microenvironment. EVs are found in nearly every bodily fluid, including serum, plasma, ascites, urine, and effusion fluid, and contain molecular cargo from their cell of origin. This cargo can be analyzed to yield information about a possible malignancy. In this review we describe how the cargo of EVs has been studied as biomarkers in ovarian cancer. We bring together studies analyzing evidence for various cargos as ovarian cancer biomarkers. Then, we describe the role of EVs in modulation of the tumor microenvironment. This review also summarizes the therapeutic and translational potential of EVs for their optimal utilization as non-invasive biomarkers for novel treatments against cancer., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Aging is a progressive, unalterable physiological degradation process of living organisms, which leads to deterioration of biological function and eventually to senescence. The most prevalent factor responsible for aging is the accumulation of damages resulting from oxidative stress and dysbiosis. D-galactose-induced aging has become a hot topic, and extensive research is being conducted in this area. Published literature has reported that the continuous administration of D-galactose leads to the deterioration of motor and cognitive skills, resembling symptoms of aging. Hence, this procedure is employed as a model for accelerated aging. This review aims to emphasize the effect of D-galactose on various bodily organs and underline the role of the Lactobacillus sp. in the aging process, along with its anti-oxidative potential. A critical consideration to the literature describing animal models that have used the Lactobacillus sp. in amending D-galactose-induced aging is also given. KEY POINTS: • D-Galactose induces the aging process via decreasing the respiratory chain enzyme activity as well as ATP synthesis, mitochondrial dysfunction, and increased ROS production. • D-Galactose induced aging primarily affects the brain, heart, lung, liver, kidney, and skin. • The anti-oxidative potential of Lactobacillus sp. in improving D-galactose-induced aging in animal models via direct feeding and feeding of Lactobacillus-fermented food., (© 2022. The Author(s).)

We report a case of a 48-year-old female who presented to the emergency department with pelvic/abdominal pain and a recent history of irregular periods. Pelvic ultrasound and computed tomography (CT) scan of the abdomen/pelvis revealed a 7.3 cm adnexal mass with suspicious features. During the intraoperative evaluation, a frozen section slide and a cytological smear were prepared. The cytological preparation was moderately cellular, showing cohesive groups of atypical cells with anisonucleosis, high nuclear to cytoplasmic ratio, and oval nuclei with prominent nucleoli. The tumor cells surrounded extracellular, magenta hyaline globules, forming raspberry bodies. Raspberry bodies are comprised of basement membrane deposits and are a unique finding in ovarian clear cell carcinoma. Raspberry bodies were also found in the frozen section slide, but, in comparison to the cytological preparation, were rare, difficult to identify, and resembled necrotic debris. The intraoperative diagnosis of a clear cell carcinoma is important because the surgical management will be more aggressive, as optimal tumor debulking is shown to have better overall survival. In this manuscript, we detail the intraoperative evaluation of an ovarian mass, the utility of cytological preparation and importance of identifying raspberry bodies in the evaluation of ovarian masses, and surgical management of clear cell carcinoma., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The isolation, characterization, and dioxygen reactivity of monomeric [(TPA)M II (mandelate)] + (M = Fe, 1 ; Co, 3 ) and dimeric [(BPMEN) 2 M II 2 (μ-mandelate) 2 ] 2+ (M = Fe, 2 ; Co, 4 ) (TPA = tris(2-pyridylmethyl)amine and BPMEN = N 1 , N 2 -dimethyl- N 1 , N 2 -bis(pyridin-2-yl-methyl)ethane-1,2-diamine) complexes are reported. The iron(II)- and cobalt(II)-mandelate complexes react with dioxygen to afford benzaldehyde and benzoic acid in a 1:1 ratio. In the reactions, one oxygen atom from dioxygen is incorporated into benzoic acid, but benzaldehyde does not derive any oxygen atom from dioxygen. While no O 2 -derived intermediate is observed with the iron(II)-mandelate complexes, the analogous cobalt(II) complexes react with dioxygen at a low temperature (-80 °C) to generate the corresponding cobalt(III)-superoxo species ( S ), a key intermediate implicated in the initiation of mandelate decarboxylation. At -20 °C, the cobalt(II)-mandelate complexes bind dioxygen reversibly leading to the formation of μ-1,2-peroxo-dicobalt(III)-mandelate species ( P ). The geometric and electronic structures of the O 2 -derived intermediates ( S and P ) have been established by computational studies. The intermediates S and P upon treatment with a protic acid undergo decarboxylation to afford benzaldehyde (50%) with a concomitant formation of the corresponding μ-1,2-peroxo - μ-mandelate-dicobalt(III) ( P1 ) species. The crystal structure of a peroxide species isolated from the cobalt(II)-carboxylate complex [(TPA)Co II (MPA)] + ( 5 ) (MPA = 2-methoxyphenylacetate) supports the composition of P1 . The observations of the dioxygen-derived intermediates from cobalt complexes and their electronic structure analyses not only provide information about the nature of active species involved in the decarboxylation of mandelate but also shed light on the mechanistic pathway of two-electron versus four-electron reduction of dioxygen.

In today's time, nanotechnology is being utilized to develop efficient products in the cosmetic and pharmaceutical industries. The application of nanotechnology in transforming bioactive material into nanoscale products substantially improves their biocompatibility and enhances their effectiveness, even when used in lower quantities. There is a significant global market potential for these nanoparticles because of which research teams around the world are interested in the advancements in nanotechnology. These recent advances have shown that fungi can synthesize metallic nanoparticles via extra- and intracellular mechanisms. Moreover, the chemical and physical properties of novel metallic nanoparticles synthesised by fungi are improved by regulating the surface chemistry, size, and surface morphology of the nanoparticles. Compared to chemical synthesis, the green synthesis of nanoparticles offers a safe and sustainable approach for developing nanoparticles. Biosynthesised nanoparticles can potentially enhance the bioactivities of different cellular fractions, such as plant extracts, fungal extracts, and metabolites. The nanoparticles synthesised by fungi offer a wide range of applications. Recently, the biosynthesis of nanoparticles using fungi has become popular, and various ways are being explored to maximize nanoparticles synthesis. This manuscript reviews the characteristics and applications of the nanoparticles synthesised using the different taxa of fungi. The key focus is given to the applications of these nanoparticles in medicine and cosmetology., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Dhanjal et al.)

Cholesterol is essential for normal human health, but elevations in its serum levels have led to the development of various complications, including hypercholesterolemia (HC). Cholesterol accumulation in blood circulation formsplaques on artery walls and worsens the individuals' health. To overcome this complication, different pharmacological and non-pharmacological approaches are employed to reduce elevated blood cholesterol levels. Atorvastatin and rosuvastatin are the most commonly used drugs, but their prolonged use leads to several acute side effects. In recent decades, the potential benefit of ingesting yogurt on lipid profile has attracted the interest of researchers and medical professionals worldwide. This review aims to give an overview of the current knowledge about HC and the different therapeutic approaches. It also discusses the health benefits of yogurt consumption and highlights the overlooked phyto-enrichment option to enhance the yogurt's quality. Finally, clinical studies using different phyto-enriched yogurts for HC management are also reviewed. Yogurt has a rich nutritional value, but its processing degrades the content of minerals, vitamins, and other vital constituents with beneficial health effects. The option of enriching yogurt with phytoconstituents has drawn a lot of attention. Different pre-clinical and clinical studies have provided new insights on their benefits on gut microbiota and human health. Thus, the yogurtphyto-enrichment with stanol and β-glucan have opened new paths in functional food industries and found healthy andeffective alternatives for HC all along with conventional treatment approaches.

Mycobacterium kansasii is a nontuberculous mycobacterium that is a rare cause of prosthetic joint infections (PJIs). This case report presents a 58-year-old man who developed rapidly progressive arthritis after exposing his right knee to an unknown fluid at a microbial pharmaceutical company. Within a year, he underwent a right total knee arthroplasty (TKA). At 5 months postoperatively, he presented with pain and swelling of that knee. Imaging revealed extensive periprosthetic osteolysis with diffuse intracapsular and posterior extracapsular fluid collections. Multiple knee aspirates had negative cultures, and infectious laboratory test results were equivocal. Two years after his primary arthroplasty, the patient underwent posterior débridement and one-stage revision TKA with antibiotic cement. Synovial fluid mycobacterial cultures aspirated 2 weeks before the revision surgery became positive on postoperative day 1. PCR identified M kansasii. At 3 weeks postoperatively, intraoperative periprosthetic cultures grew mycobacterium. M kansasii was confirmed using mass spectrometry. Once susceptibilities returned, the patient was treated with targeted antimycobacterial therapy. This case report demonstrates the importance of considering atypical PJI in painful TKA with negative cultures and equivocal laboratory results. In the future, when there is concern for an atypical PJI, molecular diagnostic tools and mycobacterial cultures should be used before surgical intervention., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Purpose: Management of adult soft tissue sarcomas entails a multidisciplinary approach with surgery and radiation therapy with or without chemotherapy. The use of preoperative irradiation has been well established, and although conventional fractionation involves daily treatments over the course of 5 weeks, higher doses per fraction may be beneficial due to the radiobiologic profile of sarcoma. In this study we report long-term oncologic outcomes from a single-institution, phase II study evaluating a 5-fraction hypofractionated course of preoperative radiation., Methods and Materials: Preoperative hypofractionated radiation therapy was administered to 35 Gy in 5 fractions every other day followed by resection 4 to 6 weeks later. If given, chemotherapy consisted of a doxorubicin-ifosfamide-based regimen delivered neoadjuvantly. The primary endpoint was local control. Additional survival and pathologic outcomes, including overall and distant metastasis-free survival, tumor, and treatment-related pathology, as well as acute and late toxicity were examined., Results: Thirty-two patients were enrolled in this prospective, single-arm phase II trial. At a median follow-up of 36.4 months (range, 3-56), no patient developed a local recurrence, and the 3-year overall and distant metastasis-free survival was 82.2% and 69%, respectively. Major acute postoperative wound complications occurred in 25% of patients. Grade 2 and 3 fibrosis occurred in 21.7% and 13% of patients, respectively. The 2-year median and mean Musculoskeletal Tumor Society score for all patients was 28 and 27.4, respectively., Conclusions: A condensed course of preoperative hypofractionated radiation therapy leads to excellent rates of local control and survival with acceptable toxicity profiles. Potential studies ideally with phase II or III randomized trials would help corroborate these findings and other preoperative hypofractionated results in soft tissue sarcomas., (© 2021 The Author(s).)

A series of iron(II) complexes with the general formula [Fe II ( L2-Qn )(L)] n + ( n = 1, L = F - , Cl - ; n = 2, L = NCMe, H 2 O) have been isolated and characterized. The X-ray crystallographic data reveals that metal-ligand bond distances vary with varying ligand field strengths of the sixth ligand. While the complexes with fluoride, chloride and water as axial ligand are high spin, the acetonitrile-coordinated complex is in a mixed spin state. The steric bulk of the quinoline moieties forces the axial ligands to deviate from the Fe-N axial axis. A higher deviation/tilt is noted for the high spin complexes, while the acetonitrile coordinated complex displays least deviation. This deviation from linearity is slightly less in the analogous low-spin iron(II) complex [Fe II ( L1-Qn )(NCMe)] 2+ of the related asymmetric ligand L1-Qn due to the presence of only one sterically demanding quinoline moiety. The two iron(II)-acetonitrile complexes [Fe II ( L2-Qn )(NCMe)] 2+ and [Fe II ( L1-Qn )(NCMe)] 2+ generate the corresponding iron(IV)-oxo species with higher thermal stability of the species supported by the L1-Qn ligand. The crystallographic and spectroscopic data for [Fe IV (O)( L1-Qn )](ClO 4 ) 2 bear resemblance to other crystallographically characterized S = 1 iron(IV)-oxo complexes. The hydrogen atom transfer (HAT) and oxygen atom transfer (OAT) reactivities of both the iron(IV)-oxo complexes were investigated, and a Box-Behnken multivariate optimization of the parameters for catalytic oxidation of cyclohexane by [Fe II ( L2-Qn )(NCMe)] 2+ using hydrogen peroxide as the terminal oxidant is presented. An increase in the average Fe-N bond length in [Fe II ( L1-Qn )(NCMe)] 2+ is also manifested in higher HAT and OAT rates relative to the other reported complexes of ligands based on the N4Py framework. The results reported here confirm that the steric influence of the ligand environment is of critical importance for the reactivity of iron(IV)-oxo complexes, but additional electronic factors must influence the reactivity of iron-oxo complexes of N4Py derivatives.

One of the major global health care crises in the 21st century is antibiotic resistance. Almost all clinically used antibiotics have resistance emerging to them. Antibiotic Resistance can be regarded as the 'Faceless Pandemic' that has enthralled the entire world. It has become peremptory to develop treatment options as an alternative to antibiotic therapy for combating antibiotic-resistant pathogens. A clearer understanding of antibiotic resistance is required to prevent the rapid spread of antibiotic-resistant genes and the re-emergence of infections. The present review provides an insight into the different classifications and modes of action of antibiotics to understand how the hosts develop resistance to them. In addition, the association of genetics in the development of antibiotic resistance and environmental factors has also been discussed, emphasizing developing action plans to counter this "quiescent pandemic". It is also pertinent to create models that can predict the early resistance so that treatment strategies may build up in advance with the evolving resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Autism is a neurodevelopmental disorder belonging to the autism spectrum disorder (ASD). In ASDs, the individuals show substantial impairments in social communication, repetitive behaviours, and sensory behaviours deficits in the early stages of their life. Globally, the prevalence of autism is estimated to be less than 1%, especially in high- -income countries. In recent decades, there has been a drastic increase in the incidence of ASD, which has put ASD into the category of epidemics. Presently, two US Food and Drug Administration-approved drugs, aripiprazole and risperidone, are used to treat symptoms of agitation and irritability in autistic children. However, to date, no medication has been found to treat the core symptoms of ASD. The adverse side effects of conventional medicine and limited treatment options have led families of autistic children to turn to complementary and alternative medicine (CAM) treatments, which are perceived as relatively safe compared to conventional medicine. Recently N, N-dimethylglycine (DMG), a dietary supplement, has emerged as a useful supplement to improve the mental and physical state of children with ASD. The current review discusses ASD, the prevalence of ASD, the CAM approach, and the efficacy of CAM treatment in children with ASD. Moreover, it highlights the chemistry, pharmacological effect, and clinical studies of DMG, highlighting its potential for improving the lifestyle of children with ASD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Polyethylenimines (PEIs) have been shown as efficient gene delivery vectors due to their unique properties, however, toxicity as well as non-specific interactions with the tissues/cells because of high charge density have hampered their use in clinical applications. To counter these concerns, here, we have prepared disachharide-PEI organic nanoparticles by mixing PEIs with non-reducing disaccharides, i.e. trehalose (TPONs) and sucrose (SPONs), under mild conditions. The fabricated nanoparticles were complexed with pDNA and size of these complexes was found in the range of ~130-162 nm with zeta potential ~ +8-25 mV. Further evaluation of these nanoparticles revealed that substitution of disaccharides on PEIs successfully augmented cell viability. Transfection efficiency exhibited by these complexes was significantly higher than the unmodified polymer and the standard, Lipofectamine, complexes. Fabrication of organic nanoparticles did not alter the buffering capacity considerably which was found to be instrumental during endosomal escape of the complexes. Among both the series of nanoparticles, trehalose-PEI organic nanoparticles (TPONs) exhibited greater pDNA transportation potential than sucrose-PEI organic nanoparticles (SPONs) which was also established by flow cytometric data, wherein percent cells expressing GFP was higher in case of TP/pDNA complexes as compared to SP/pDNA complexes. Interestingly, TPONs also showed promising anticancer activity on cancer cell lines i.e. Mg63, MCF-7 and HepG2. Overall, the results advocate promising potential of disaccharide-PEI organic nanoparticles as efficient gene delivery agents which can be used effectively in future gene therapy applications along with anti-cancer competence of TPONs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The purpose of this prospective observational study is to analyse posture-induced cyclotorsion in eyes undergoing conventional phacoemulsification with toric intraocular lens (IOL) implantation and femtolaser-assisted cataract surgery (FLACS) using the Verion image-guided system., Methods: Cyclotorsion was assessed in patients who underwent conventional phacoemulsification with toric IOL implantation and FLACS between June 2017 and November 2017 with registration of iris architecture, limbal and bulbar conjunctival blood vessels acquired preoperatively using the Verion Reference Unit (the patient in sitting position) and intraoperatively under the microscope using the digital marker of the Verion image-guided system with the patient in supine position., Results: Forty-four eyes of 30 patients (21 men and 9 women) were included with the mean age of 56.5 ± 17.1 (range, 19-89; median, 62) years. The mean cyclotorsion induced by change in posture from sitting to supine position was 5.84 ± 3.25° (range, 1-17; median, 5). Overall, clockwise (CW) rotation (59.1%) was noted to be more common than counter clockwise (CCW) rotation (40.9%). Furthermore, CW rotation was more common in men than in women, and CCW rotation was significantly more common in women. Patients who underwent bilateral sequential cataract surgery show similar cyclorotation (CW or CCW) in both eyes more often than mixed rotation (85.7% vs 14.3%)., Conclusion: Significant cyclotorsion can occur in supine position during cataract surgery. Accurate assessment of the amount and direction of cyclotorsion aids in appropriate alignment of the toric IOL for optimal visual outcomes., Competing Interests: All authors have none to declare., (© 2020 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

The ingestion of contaminated water and food is known to cause food illness. Moreover, on assessing the patients suffering from foodborne disease has revealed the role of microbes in such diseases. Concerning which different methods have been developed for protecting food from microbes, the treatment of food with chemicals has been reported to exhibit an unwanted organoleptic effect while also affecting the nutritional value of food. Owing to these challenges, the demand for natural food preservatives has substantially increased. Therefore, the interest of researchers and food industries has shifted towards fruit polyphenols as potent inhibitors of foodborne bacteria. Recently, numerous fruit polyphenols have been acclaimed for their ability to avert toxin production and biofilm formation. Furthermore, various studies have recommended using fruit polyphenols solely or in combination with chemical disinfectants and food preservatives. Currently, different nanoparticles have been synthesized using fruit polyphenols to curb the growth of pathogenic microbes. Hence, this review intends to summarize the current knowledge about fruit polyphenols as antibacterial agents against foodborne pathogens. Additionally, the application of different fruit extracts in synthesizing functionalized nanoparticles has also been discussed.

Currently, the food and agricultural sectors are concerned about environmental problems caused by raw material waste, and they are looking for strategies to reduce the growing amount of waste disposal. Now, approaches are being explored that could increment and provide value-added products from agricultural waste to contribute to the circular economy and environmental protection. Edible mushrooms have been globally appreciated for their medicinal properties and nutritional value, but during the mushroom production process nearly one-fifth of the mushroom gets wasted. Therefore, improper disposal of mushrooms and untreated residues can cause fungal disease. The residues of edible mushrooms, being rich in sterols, vitamin D2, amino acids, and polysaccharides, among others, makes it underutilized waste. Most of the published literature has primarily focused on the isolation of bioactive components of these edible mushrooms; however, utilization of waste or edible mushrooms themselves, for the production of value-added products, has remained an overlooked area. Waste of edible mushrooms also represents a disposal problem, but they are a rich source of important compounds, owing to their nutritional and functional properties. Researchers have started exploiting edible mushroom by-products/waste for value-added goods with applications in diverse fields. Bioactive compounds obtained from edible mushrooms are being used in media production and skincare formulations. Furthermore, diverse applications from edible mushrooms are also being explored, including the synthesis of biosorbent, biochar, edible films/coating, probiotics, nanoparticles and cosmetic products. The primary intent of this review is to summarize the information related to edible mushrooms and their valorization in developing value-added products with industrial applications.

Prebiotics are either natural or synthetic non-digestible (non-)carbohydrate substances that boost the proliferation of gut microbes. Undigested fructooligosaccharides in the large intestine are utilised by the beneficial microorganisms for the synthesis of short-chain fatty acids for their own growth. Although various food products are now recognized as having prebiotic properties, several others, such as almonds, artichoke, barley, chia seeds, chicory, dandelion greens, flaxseeds, garlic, and oats, are being explored and used as functional foods. Considering the benefits of these prebiotics in mineral absorption, metabolite production, gut microbiota modulation, and in various diseases such as diabetes, allergy, metabolic disorders, and necrotising enterocolitis, increasing attention has been focused on their applications in both food and pharmaceutical industries, although some of these food products are actually used as food supplements. This review aims to highlight the potential and need of these prebiotics in the diet and also discusses data related to the distinct types, sources, modes of action, and health benefits.

The differentiation of human stem cells into insulin secreting beta-like cells holds great promise to treat diabetes. Current protocols drive stem cells through stages of directed differentiation and maturation and produce cells that secrete insulin in response to glucose. Further refinements are now needed to faithfully phenocopy the responses of normal beta cells. A critical factor in normal beta cell behavior is the islet microenvironment which plays a central role in beta cell survival, proliferation, gene expression and secretion. One important influence on native cell responses is the capillary basement membrane. In adult islets, each beta cell makes a point of contact with basement membrane protein secreted by vascular endothelial cells resulting in structural and functional polarization. Interaction with basement membrane proteins triggers local activation of focal adhesions, cell orientation, and targeting of insulin secretion. This study aims to identifying the role of basement membrane proteins on the structure and function of human embryonic stem cell and induced pluripotent stem cell-derived beta cells. Here, we show that differentiated human stem cells-derived spheroids do contain basement membrane proteins as a diffuse web-like structure. However, the beta-like cells within the spheroid do not polarize in response to this basement membrane. We demonstrate that 2D culture of the differentiated beta cells on to basement membrane proteins enforces cell polarity and favorably alters glucose dependent insulin secretion., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)