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Background: Mono-resistance to rifampicin/isoniazid increases poor treatment outcomes and the risk of multi-drug resistance (MDR) in tuberculosis (TB) patients. Limited information exists about mono-resistance status of TB patients in Uttar Pradesh, North India. This study aimed to estimate the burden of rifampicin and isoniazid mono-resistance in Western Uttar Pradesh., Methods and Results: 153 sputum samples of suspected pulmonary tuberculosis patients were processed to isolate Mycobacterium tuberculosis using the Lowenstein-Jensen (L-J) culture medium. The isolates were identified using an immuno-chromatographic test and IS6110 PCR. The confirmed Mycobacterium tuberculosis isolates were tested for drug susceptibility testing against rifampicin and isoniazid anti-tuberculosis drugs. The results of the drug susceptibility testing were compared with demographic information and analyzed statistically. Out of 153 sputum samples, 83 (54.24%) samples were positive for growth on L-J medium, including 82 (98.79%) Mycobacterium tuberculosis isolates. Of the 82 Mycobacterium tuberculosis isolates, 16 (19.51%), 7 (8.54%), and 5 (6.10%) isolates were MDR, mono-resistant to rifampicin and isoniazid, respectively. The occurrence of RIF/INH mono-resistant-TB was higher in patients of male gender, age above 45 years, living in rural conditions, history of weight loss, and previous anti-TB treatment, but the effect was not statistically significant., Conclusions: The study reported the status of rifampicin and isoniazid mono-resistance among TB patients and highlighted the need for continuous monitoring and improved intervention for the initial detection of mono-drug-resistant cases. This will improve clinical treatment outcomes and decrease the rate of drug-resistant TB in Uttar Pradesh, North India., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Abiotic and biotic stresses during seed germination are typically managed with conventional agrochemicals, known to harm the environment and reduce crop yields. Seeking sustainable alternatives, nanotechnology-based agrochemicals leverage unique physical and chemical properties to boost seed health and alleviate stress during germination. Nanoprimers in seed priming treatment are advanced nanoscale materials designed to enhance seed germination, growth, and stress tolerance by delivering bioactive compounds and nutrients directly to seeds. Present review aims to explores the revolutionary potential of nanoprimers in sustainable seed treatment, focusing on their ability to enhance crop productivity by improving tolerance to abiotic and biotic stresses. Key objectives include understanding the mechanisms by which nanoprimers confer resistance to stresses such as drought, salinity, pests, and diseases, and assessing their impact on plant physiological and biochemical pathways. Key findings reveal that nanoprimers significantly enhance seedling vigor and stress resilience, leading to improved crop yields. These advancements are attributed to the precise delivery of nanomaterials that optimize plant growth conditions and activate stress tolerance mechanisms. However, the study also highlights the importance of comprehensive toxicity and risk assessments. Current review presents a novel contribution, highlighting both the advantages and potential risks of nanoprimers by offering a comprehensive overview of advancements in seed priming with metal and metal oxide nanomaterials, addressing a significant gap in the existing literature. By delivering advanced molecular insights, the study underscores the transformative potential of nanoprimers in fostering sustainable agricultural practices and responsibly meeting global food demands., Competing Interests: Declaration of competing interest This article was not written, authored or published with any potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Non-coding RNAs (ncRNAs), specifically MicroRNAs or miRNAs, are now under-stood to be essential regulators in the complex field of gene expression. By selectively bind-ing to certain mRNA targets, these tiny RNA molecules control the expression of genes., leading to mRNA degradation or translational repression. The discovery of miRNAs has sig-nificantly advanced biomedical research, particularly in elucidating the molecular mecha-nisms underlying various diseases and exploring innovative therapeutic approaches. Recent progress in miRNA research has provided insights into their biogenesis, functional roles, and potential clinical applications. Despite the absence of established methodologies for clinical implementation, miRNAs show great promise as diagnostic and therapeutic agents for a wide array of diseases. Their distinctive attributes, such as high specificity, sensitivity, and accessibility, position them as ideal candidates for biomarker development and targeted therapy. Achieving a comprehensive understanding of miRNA biology and functionality is crucial to fully harnessing their potential in medicine. Ongoing research efforts aim to un-ravel the intricate mechanisms of miRNA-mediated gene regulation and to develop novel approaches for utilizing miRNAs in disease diagnosis, prognosis, and treatment. This review provides a comprehensive analysis of current knowledge on miRNAs, focusing on their bio-genesis, regulatory mechanisms, and potential clinical applications. By synthesizing existing evidence and highlighting key research findings, this review aims to inspire further explora-tion into the diverse roles of miRNAs in health and disease. Ultimately, this endeavour could result in the development of innovative miRNA-based diagnostic and therapeutic strategies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The pursuit of sustainable bioinspired materials for regenerative medicine demands a nuanced balance between scientific advancement, ethical considerations, and environmental consciousness. This abstract encapsulates a comprehensive perspective paper exploring the intricate dynamics of toxicology, environmental impact, and ethical concerns within the realm of bioinspired materials. As the landscape of regenerative medicine evolves, ensuring the biocompatibility and safety of these materials emerges as a pivotal challenge. Our paper delves into the multidimensional aspects of toxicity assessment, encompassing cytotoxicity, genotoxicity, and immunotoxicity analyses. Additionally, we shed light on the complexities of evaluating the environmental impact of bioinspired materials, discussing methodologies such as life cycle assessment, biodegradability testing, and sustainable design approaches. Amid these scientific endeavors, we emphasize the paramount importance of ethical considerations in bioinspired material development, navigating the intricate web of international regulations and ethical frameworks guiding medical materials. Furthermore, our abstract underscores the envisioned future directions and challenges in toxicology techniques, computational modeling, and holistic evaluation, aiming for a comprehensive understanding of the synergistic interplay between sustainable bioinspired materials, toxicity assessment, environmental stewardship, and ethical deliberation., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Context: The public health workforce encountered challenges during the COVID-19 pandemic that exposed areas for improvement in preparation for future public health threats. Key among these is well-trained public health leaders equipped with an array of crisis leadership skills., Objectives: To examine the training background, assess the perceived preparedness, and garner recommendations for training of the future public health workforce from public health leaders who navigated the COVID-19 pandemic., Design: This exploratory research gleaned information by utilizing an online questionnaire and interviews to provide lessons learned regarding improvements needed for public health leader preparedness., Setting: Three California public health departments representing urban, suburban, and rural populations., Participants: Thirty public health leaders who were directly involved in public health work for ≥3 years in a leadership/management role and involved in COVID-19-related work for at least 6 months participated., Results: Questionnaire findings revealed gaps in crisis leadership, communication, and collaboration training. Interview results supported and expanded upon the quantitative findings, including the value of various competencies and recommendations to improve the preparedness of future public health leaders., Conclusions: The findings suggested that although many of the skills needed are competencies for accredited public health training programs, effective leadership during public health emergencies may require additional training beyond what is generally provided. Recommendations include integrating study findings into public health training programs to address competency gaps, leveraging results to enhance leadership skills, and promoting collaboration between public health departments and academic institutions to develop evidence-informed crisis leadership training. These findings inform strategies to ensure the preparedness of the public health workforce for future crises., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently unavailable. Loss of integrity in the blood-brain barrier (BBB) is one of the distinct MS hallmarks. Brain homeostasis is ensured by an endothelial cell-based monolayer at the interface between the central nervous system (CNS) and systemic bloodstream, acting as a selective barrier. MS results in enhanced barrier permeability, mainly due to the breakdown of tight (TJs) and adherens junctions (AJs) between endothelial cells. Specifically, proinflammatory mediator release causes failure in cytoplasmic exposure of junctions, resulting in compromised BBB integrity that enables blood cells to cross the barrier, establishing iron deposition and neuronal impairment. Cells with a compromised cytoskeletal protein network, fiber reorganization, and discontinuous junction structure can occur, resulting in BBB dysfunction. Recent investigations on spatial transcriptomics have proven circularRNAs (circRNAs) to be powerful multi-functional molecules able to epigenetically regulate transcription and structurally support proteins. In the present review, we provide an overview of the recent role ascribed to circRNAs in maintaining BBB integrity/permeability via cytoskeletal stability. Increased knowledge of the mechanisms responsible for impairment and circRNA's role in driving BBB damage and dysfunction might be helpful for the recognition of novel therapeutic targets to overcome BBB damage and unrestrained neurodegeneration.

Background/aim: Helicobacter pylori (H. pylori) colonization affects the gastric microbiome, causing gastrointestinal (GI) diseases. Modern sequencing technology provides insights into GI microbe interaction with H. pylori and their metabolic pathways in causing GI diseases. We aim to compare the gastric microbiota alteration due to H. pylori infection in patients suffering from GI diseases., Materials and Methods: Genomic DNA were isolated from gastric antrum tissue from 37 H.pylori-infected patients diagnosed with GERD, duodenal ulcers, and gastritis. We conducted the genomic library preparation and sequencing of the amplified product using 16S rRNA NGS analysis. Using microbiome analyst tool diversity analysis, random forest analysis and ANOVA were conducted to find out the comparison of microbial abundance. We have also conducted functional pathway prediction analysis using PICRUSt., Results: Metagenomic analysis shows high bacterial diversity in H. pylori-positive gastritis patients. Streptococcus infantis and Neisseria subflava were significantly higher in duodenal ulcer (DU) and gastritis groups. Acinetobacter lwoffii and Helicobacter pullorum were significantly high in the gastritis group only. The functional metabolic pathway analyses revealed that gastroesophageal reflux disease (GERD) samples were significantly enriched with the energy metabolism and xenobiotic biodegradation and metabolism pathways, whereas fructose-1,6-bisphosphatase III was found less in gastritis and DU groups., Conclusion: There is a difference in microbiota composition in different disease outcomes. We found positive association between microbial diversity and H. pylori in gastritis group only, whereas negative association was found in DU and GERD groups. The functional metabolic pathway analysis revealed significant differences in various disease outcomes., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Agriculture stands as a thriving enterprise in India, serving as both the bedrock of economy and vital source of nutrition. In response to the escalating demands for high-quality food for swiftly expanding population, agricultural endeavors are extending their reach into the elevated terrains of the Himalayas, tapping into abundant resources for bolstering food production. Nonetheless, these Himalayan agro-ecosystems encounter persistent challenges, leading to crop losses. These challenges stem from a combination of factors including prevailing frigid temperatures, suboptimal farming practices, unpredictable climatic shifts, subdivided land ownership, and limited resources. While the utilization of chemical fertilizers has been embraced to enhance the quality of food output, genuine concerns have arisen due to the potential hazards they pose. Consequently, the present investigation was initiated with the objective of formulating environmentally friendly and cold-tolerant broad ranged bioinoculants tailored to enhance the production of Kidney bean while concurrently enriching its nutrient content across entire hilly regions. The outcomes of this study unveiled noteworthy advancements in kidney bean yield, registering a substantial increase ranging from 12.51 ± 2.39 % to 14.15 ± 0.83 % in regions of lower elevation (Jeolikote) and an even more remarkable surge ranging from 20.60 ± 3.03 % to 29.97 ± 5.02 % in higher elevated areas (Chakrata) compared to the control group. Furthermore, these cold-tolerant bioinoculants exhibited a dual advantage by fostering the enhancement of essential nutrients within the grains and fostering a positive influence on the diversity and abundance of microbial life in the rhizosphere. As a result, to effectively tackle the issues associated with chemical fertilizers and to achieve sustainable improvements in both the yield and nutrient composition of kidney bean across varying elevations, the adoption of cold-tolerant Enterobacter hormaechei CHM16, and Pantoea agglomerans HRM 23, including the consortium, presents a promising avenue. Additionally, this study has contributed significant insights-into the role of organic acids like oxalic acid in the solubilization of nutrients, thereby expanding the existing knowledge in this specialized field., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The current study aimed to characterize the contribution of bacterium CP17 in zinc (Zn) biofortification in wheat under saline and non-saline conditions. This bacterial strain effectively solubilized Zn and tolerated up to 20% NaCl concentration. The Zn-solubilization potential was also quantified using AAS in a liquid broth supplemented with zinc oxide and zinc carbonate at various NaCl concentrations. Lowering the pH of liquid broth and analyzing a wide range of organic acids (thioacetic acid, glutamic acid, carboxylic acid, propionic acid, and so on) using UPLC-MS provided mechanistic insight for zinc solubilization. This strain was also shown to possess plant probiotic characteristics like phosphate solubilization, production of siderophore, indole acetic acid (IAA), exopolysaccharide (EPS), ACC deaminase, and ammonia. CP17 was identified as a Pseudomonas protegens based on the 16S rRNA gene analysis. In addition, the amplified product of the ACC deaminase producing gene (acdS) provided a molecular indication of the strain's endurance towards stress. The towel paper assay confirmed that the inoculation of Pseudomonas protegens CP17 significantly increased wheat seedlings' germination, growth, and biomass under different NaCl concentrations (0 mM, 100 mM, and 150 mM). Afterward, In situ pot experiment study was designed with the inoculation of Pseudomonas protegens in wheat under saline and non-saline conditions. The harvested wheat plants showed an elevated pattern of zinc content in the grain (i.e. 24.33 and 29.33mg/kg), straw (i.e. 45.73 and 50.23mg/kg) and soil (i.e. 0.978 and 1.32mg/kg) under saline and non-saline conditions, respectively and shown significant improvement over control. The results of the pot study revealed the amelioration in plant health, yield and uptake of available zinc from rhizospheric soil to straw and grain, along with enhanced dehydrogenase and phosphatase activities of rhizospheric soil under saline and non-saline conditions. This study supports the integrative role of Pseudomonas protegens CP17 as a bioinoculant for the efficacious strategy of zinc biofortification and growth promotion in wheat and ensures sustainable nutrient quality production under salinity stress., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

This comprehensive review explores the emerging landscape of Nano-QSAR (quantitative structure-activity relationship) for assessing the risk and potency of nanomaterials in agricultural settings. The paper begins with an introduction to Nano-QSAR, providing background and rationale, and explicitly states the hypotheses guiding the review. The study navigates through various dimensions of nanomaterial applications in agriculture, encompassing their diverse properties, types, and associated challenges. Delving into the principles of QSAR in nanotoxicology, this article elucidates its application in evaluating the safety of nanomaterials, while addressing the unique limitations posed by these materials. The narrative then transitions to the progression of Nano-QSAR in the context of agricultural nanomaterials, exemplified by insightful case studies that highlight both the strengths and the limitations inherent in this methodology. Emerging prospects and hurdles tied to Nano-QSAR in agriculture are rigorously examined, casting light on important pathways forward, existing constraints, and avenues for research enhancement. Culminating in a synthesis of key insights, the review underscores the significance of Nano-QSAR in shaping the future of nanoenabled agriculture. It provides strategic guidance to steer forthcoming research endeavors in this dynamic field.

Spontaneous abortion is a pregnancy complication characterized by complex and multifactorial etiology. About 5% of childbearing women are globally affected by early pregnancy loss (EPL) and most of them experience recurrence (RPL). Epigenetic mechanisms and controlled inflammation are crucial for pregnancy maintenance and genetic predispositions may increase the risk affecting the maternal-fetal crosstalk. Combined analyses of global methylation, inflammation and inherited predispositions may contribute to define pregnancy loss etiopathogenesis. LINE-1 epigenetic regulation plays crucial roles during embryo implantation, and its hypomethylation has been associated with senescence and several complex diseases. By analysing a group of 230 women who have gone through pregnancy interruption and comparing those experiencing spontaneous EPL (n = 123; RPL, 54.5%) with a group of normal pregnant who underwent to voluntary interruption (VPI, n = 107), the single statistical analysis revealed significant lower (P < 0.00001) LINE-1 methylation and higher (P < 0.0001) mean cytokine levels (CKs: IL6, IL10, IL17A, IL23) in EPL. Genotyping of the following SNPs accounted for different EPL/RPL risk odds ratio: F13A1 rs5985 (OR = 0.24; 0.06-0.90); F13B rs6003 (OR = 0.23; 0.047-1.1); FGA rs6050 (OR = 0.58; 0.33-1.0); CRP rs2808635/rs876538 (OR = 0.15; 0.014-0.81); ABO rs657152 (OR = 0.48; 0.22-1.08); TP53 rs1042522 (OR = 0.54; 0.32-0.92); MTHFR rs1801133/rs1801131 (OR = 2.03; 1.2-3.47) and FGB rs1800790 (OR = 1.97; 1.01-3.87), although Bonferroni correction did not reach significant outputs. Principal Component Analysis (PCA) and logistic regression disclosed further SNPs positive/negative associations (e.g. APOE rs7412/rs429358; FGB rs1800790; CFH rs1061170) differently arranged and sorted in four significant PCs: PC1 (F13A, methylation, CKs); PC3 (CRP, MTHFR, age, methylation); PC4 (F13B, FGA, FGB, APOE, TP53, age, methylation); PC6 (F13A, CFH, ABO, MTHFR, TP53, age), yielding further statistical power to the association models. In detail, positive EPL risk association was with PC1 (OR = 1.81; 1.33-2.45; P < 0.0001) and negative associations with PC3 (OR = 0.489; 0.37-0.66; P < 0.0001); PC4 (OR = 0.72; 0.55-0.94; P = 0.018) and PC6 (OR = 0.61; 0.46-0.81; P = 0.001). Moreover, significant inverse associations were detected between methylation and CKs levels in the whole group (r IL10  = - 0.22; r IL17A  = - 0.25; r IL23  = - 0.19; r IL6  = - 0.22), and methylation with age in the whole group, EPL and RPL subgroups (r 2 TOT  = 0.147; r 2 EPL  = 0.136; r 2 RPL  = 0.248), while VPI controls lost significance (r 2 VPI  = 0.011). This study provides a valuable multilayer approach for investigating epigenetic abnormalities in pregnancy loss suggesting genetic-driven dysregulations and anomalous epigenetic mechanisms potentially mediated by LINE-1 hypomethylation. Women with unexplained EPL might benefit of such investigations, providing new insights for predicting the pregnancy outcome and for treating at risk women with novel targeted epidrugs., (© 2024. The Author(s).)

Abstract: From an initial thought of being used as a cellular garbage bin to a promising target for liquid biopsies, the role of exosomes has drastically evolved in just a few years of their discovery in 1983. Exosomes are naturally secreted nano-sized vesicles, abundant in all types of body fluids and can be isolated intact even from the stored biological samples. Being stable carriers of genetic material (cellular DNA, mRNA and miRNA) and having specific cargo (signature content of originating cells), exosomes play a crucial role in pathogenesis and have been identified as a novel source of biomarkers in a variety of disease conditions. Recently exosomes have emerged as a promising 'liquid biopsy tool'and have shown great potential in the field of non-invasive disease diagnostics, prognostics and treatment response monitoring in both communicable as well as non-communicable diseases. However, there are certain limitations to overcome which restrict the use of exosome-based liquid biopsy as a gold standard testing procedure in routine clinical practices. The present review summarizes the current knowledge on the role of exosomes as the liquid biopsy tool in diagnosis, prognosis and treatment response monitoring in communicable and non-communicable diseases and highlights the major limitations, technical advancements and future prospects of the utilization of exosome-based liquid biopsy in clinical interventions., (Copyright © 2024 Copyright: © 2024 Indian Journal of Medical Research.)

Background: Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity., Results: We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 - 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54-7.29 and OR = 1.47; 1.02-2.12, respectively). Moreover, LINE-1 methylation was inversely related (r 2  = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 - 8CG and HAMP - 582AG genotype stratification (Δ SLC40A1  = + 8.99 dB HL and Δ HAMP  = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFE C282Y , SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42-0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35-0.76; P = 0.001)., Conclusion: Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL., (© 2023. The Author(s).)

Addressing the pressing issues of increased food demand, declining crop productivity under varying agroclimatic conditions, and the deteriorating soil health resulting from the overuse of agricultural chemicals, requires innovative and effective strategies for the present era. Microbial bioformulation technology is a revolutionary, and eco-friendly alternative to agrochemicals that paves the way for sustainable agriculture. This technology harnesses the power of potential microbial strains and their cell-free filtrate possessing specific properties, such as phosphorus, potassium, and zinc solubilization, nitrogen fixation, siderophore production, and pathogen protection. The application of microbial bioformulations offers several remarkable advantages, including its sustainable nature, plant probiotic properties, and long-term viability, positioning it as a promising technology for the future of agriculture. To maintain the survival and viability of microbial strains, diverse carrier materials are employed to provide essential nourishment and support. Various carrier materials with their unique pros and cons are available, and choosing the most appropriate one is a key consideration, as it substantially extends the shelf life of microbial cells and maintains the overall quality of the bioinoculants. An exemplary modern bioformulation technology involves immobilizing microbial cells and utilizing cell-free filters to preserve the efficacy of bioinoculants, showcasing cutting-edge progress in this field. Moreover, the effective delivery of bioformulations in agricultural fields is another critical aspect to improve their overall efficiency. Proper and suitable application of microbial formulations is essential to boost soil fertility, preserve the soil's microbial ecology, enhance soil nutrition, and support crop physiological and biochemical processes, leading to increased yields in a sustainable manner while reducing reliance on expensive and toxic agrochemicals. This manuscript centers on exploring microbial bioformulations and their carrier materials, providing insights into the selection criteria, the development process of bioformulations, precautions, and best practices for various agricultural lands. The potential of bioformulations in promoting plant growth and defense against pathogens and diseases, while addressing biosafety concerns, is also a focal point of this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khan, Singh, Gautam, Agarwal, Punetha, Upadhayay, Kukreti, Bundela, Jugran and Goel.)

Background: Tumor necrosis factor (TNF) is known to promote T cell migration and increase the expression of vascular endothelial growth factor (VEGF) and chemokines. The administration of Xpro-1595, a dominant-negative TNF (DN-TNF) engineered to selectively inactivate soluble TNF (solTNF), has been extensively studied and proven effective in reducing TNF production without suppressing innate immunity during infection. The literature also supports the involvement of glutamic acid-leucine-arginine (ELR+) chemokines and VEGF in angiogenesis and the spread of infections., Materials and Methods: In this study, we administered Xpro-1595 to guinea pigs to selectively inhibit solTNF, aiming to assess its impact on Mycobacterium tuberculosis (M.tb) dissemination, bacterial growth attenuation, and immunological responses. We conducted immunohistochemical analyses, immunological assays, and colony enumeration to comprehensively study the effects of Xpro-1595 by comparing with anti-TB drugs treated M.tb infected guinea pigs. Throughout the infection and treatment period, we measured the levels of Interleukin-12 subunit alpha (IL-12), Interferon-gamma (IFN-γ), TNF, Tumor growth factor (TGF), and T lymphocytes using ELISA., Results: Our findings revealed a reduction in M.tb dissemination and inflammation without compromising the immune response during Xpro-1595 treatment. Notably, Xpro-1595 therapy effectively regulated the expression of VEGFA and ELR + chemokines, which emerged as key factors contributing to infection dissemination. Furthermore, this treatment influenced the migration of CD4 T cells in the early stages of infection, subsequently leading to a reduced T cell response and controlled proinflammatory signalling, thus mitigating inflammation., Conclusion: Our study underscores the pivotal role of solTNF in the dissemination of M.tb to other organs. This preliminary investigation sheds light on the involvement of solTNF in the mechanisms underlying M.tb dissemination, although further in-depth research is warranted to fully elucidate its role in this process., (© 2023. The Author(s).)

To preserve male fertility after diagnosis of any kind of cancer, a prompt assessment of the semen quality and an appropriate semen cryopreservation must be performed before radio-chemotherapy starts. The present work aims to evaluate the semen parameters at diagnosis of different cancer patients before cryopreservation and after thawing. Testicular tumors and lymphomas are among the most common cancers in younger patients, and while chemotherapy significantly increases patients' survival, it can epigenetically alter the semen fluid, resulting in temporary or permanent infertility. We analyzed data from the database of the Gamete Cryopreservation Center (Annunziata Hospital, CS; Italy) in the period of 2011-2020 from a cohort of 254 cancer patients aged 18-56 years. The evaluation was performed in a blind manner and anonymously recovered; the main parameters referring to semen quality were assessed in accordance with the WHO guidelines and decision limits (6th edition; 2021). The cancer types were as follows: testis cancers (TC; n = 135; 53.1%), hematological cancers (HC; n = 76; 29.9%), and other types of cancer (OC; n = 43; 17%). Comparing TC vs. HC (P 1 ) and vs. OC (P 2 ), TC had the worst semen quality: sperm number/mL (P 1 = 0.0014; P 2 = 0.004), total motility (P 1 = 0.02; P 2 = 0.07), progressive motility (P 1 = 0.04; P 2 = 0.05), viability (P 1 = 0.01; P 2 = 0.02), and percentage of atypical morphology (P 1 = 0.05; P 2 = 0.03). After semen thawing, viability and progressive motility recovery lowered, accounting for 46.82% and 16.75%, respectively, in the whole cohort; similarly, in the subgroups ascribed to TC, they showed the lowest recovery. Strong correlation existed between pre- and post-cryopreservation viability and progressive motility in the whole cohort ( p < 0.001) and in the TC subgroup ( p < 0.05). All cancer subgroups, to significantly different extents, had semen findings below the WHO reference values, suggesting diverse sperm susceptibilities to different cancers and cryodamage. Cancer and associated treatments epigenetically affect patients' semen quality, meaning cryopreservation should be considered a useful personalized prerogative for any kind of cancer in a timely manner., Competing Interests: The authors declare no conflict of interest.

Drought is the prime abiotic stress that rigorously influences plant growth, yield and quality of crops. The current investigation illustrated the bio-protective characters of Serratia marcescens and Pseudomonas sp. to ameliorate drought stress tolerance, plant growth and nutrient status of wheat. The present study aimed for search of potential drought tolerant plant growth-promoting rhizobacteria (PGPR). All screened bacterial isolates exhibited potential plant growth promoting (PGP) attributes such as production of ACC deaminase, exo-polysaccharide, siderophore, ammonia, IAA, and efficiently solubilized zinc and phosphate under in vitro conditions. To assess the in situ plant growth promotion potential of PGPR, a greenhouse experiment was conducted by priming wheat seeds with screened plant PGPR. Improved water status, reactive oxygen species, osmolyte accumulation, chlorophyll and carotenoids content in plant leaves confirmed the excellent drought tolerance conferring ability of RRN II 2 and RRC I 5. Among all PGPR, RRN II 2 and RRC I 5 inoculated plants not only demonstrated greater harvest index but also exhibited more micronutrient (zinc and iron) content in wheat grains. Further, RRN II 2 and RRC I 5 were identified through 16S rDNA sequencing as S. marcescens and Pseudomonas sp., respectively. Furthermore, amplification of acdS gene (Amplified band size of acdS gene was ~ 1.8 Kb) also confirmed ACC deaminase enzyme producing ability of Pseudomonas sp. Moreover, correlation coefficient, principal component analysis and cluster analysis also demonstrated that nutrient status and values of agronomical parameters of wheat primed with S. marcescens and Pseudomonas sp. were at par with the positive control. Thus, the outcome of this comparative investigation indicates that Pseudomonas sp. and S. marcescens could be utilized as bioinoculant in wheat since they can improve the physiological status, productivity and nutrient status in wheat crop under drought., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Myocardial infarction (MI) is one of the leading causes of death in Western countries. An early diagnosis decreases subsequent severe complications such as wall remodeling or heart failure and improves treatments and interventions. Novel therapeutic targets have been recognized and, together with the development of direct and indirect epidrugs, the role of non-coding RNAs (ncRNAs) yields great expectancy. ncRNAs are a group of RNAs not translated into a product and, among them, microRNAs (miRNAs) are the most investigated subgroup since they are involved in several pathological processes related to MI and post-MI phases such as inflammation, apoptosis, angiogenesis, and fibrosis. These processes and pathways are finely tuned by miRNAs via complex mechanisms. We are at the beginning of the investigation and the main paths are still underexplored. In this review, we provide a comprehensive discussion of the recent findings on epigenetic changes involved in the first phases after MI as well as on the role of the several miRNAs. We focused on miRNAs function and on their relationship with key molecules and cells involved in healing processes after an ischemic accident, while also giving insight into the discrepancy between males and females in the prognosis of cardiovascular diseases.

Herbal medications have an extensive history of use in treating various diseases, attributed to their perceived efficacy and safety. Traditional medicine practitioners and contemporary healthcare providers have shown particular interest in herbal syrups, especially for respiratory illnesses associated with the SARS-CoV-2 virus. However, the current understanding of the pharmacokinetic and toxicological properties of phytochemicals in these herbal mixtures is limited. This study presents a comprehensive computational analysis utilizing novel approach methodologies (NAMs) to investigate the pharmacokinetic and toxicological profiles of phytochemicals in herbal syrup, leveraging in-silico techniques and prediction tools such as PubChem, SwissADME, and Molsoft's database. Although molecular dynamics, docking, and broader system-wide analyses were not considered, future studies hold potential for further investigation in these areas. By combining drug-likeness with molecular simulation, researchers identify diverse phytochemicals suitable for complex medication development examining their pharmacokinetic-toxicological profiles in phytopharmaceutical syrup. The study focuses on herbal solutions for respiratory infections, with the goal of adding to the pool of all-natural treatments for such ailments. This research has the potential to revolutionize environmental and alternative medicine by leveraging in-silico models and innovative analytical techniques to identify novel phytochemicals with enhanced therapeutic benefits and explore network-based and systems biology approaches for a deeper understanding of their interactions with biological systems. Overall, our study offers valuable insights into the computational analysis of the pharmacokinetic and toxicological profiles of herbal concoction. This paves the way for advancements in environmental and alternative medicine. However, we acknowledge the need for future studies to address the aforementioned topics that were not adequately covered in this research., Competing Interests: 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., (© 2023 The Author(s).)

More information about a person's genetic makeup, drug response, multi-omics response, and genomic response is now available leading to a gradual shift towards personalized treatment. Additionally, the promotion of non-animal testing has fueled the computational toxicogenomics as a pivotal part of the next-gen risk assessment paradigm. Artificial Intelligence (AI) has the potential to provid new ways analyzing the patient data and making predictions about treatment outcomes or toxicity. As personalized medicine and toxicogenomics involve huge data processing, AI can expedite this process by providing powerful data processing, analysis, and interpretation algorithms. AI can process and integrate a multitude of data including genome data, patient records, clinical data and identify patterns to derive predictive models anticipating clinical outcomes and assessing the risk of any personalized medicine approaches. In this article, we have studied the current trends and future perspectives in personalized medicine & toxicology, the role of toxicogenomics in connecting the two fields, and the impact of AI on personalized medicine & toxicology. In this work, we also study the key challenges and limitations in personalized medicine, toxicogenomics, and AI in order to fully realize their potential., Competing Interests: Conflict of interest The authors declare no competing interest of interest at this point., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Toxicology is undergoing a digital revolution, with mobile apps, sensors, artificial intelligence (AI), and machine learning enabling better record-keeping, data analysis, and risk assessment. Additionally, computational toxicology and digital risk assessment have led to more accurate predictions of chemical hazards, reducing the burden of laboratory studies. Blockchain technology is emerging as a promising approach to increase transparency, particularly in the management and processing of genomic data related with food safety. Robotics, smart agriculture, and smart food and feedstock offer new opportunities for collecting, analyzing, and evaluating data, while wearable devices can predict toxicity and monitor health-related issues. The review article focuses on the potential of digital technologies to improve risk assessment and public health in the field of toxicology. By examining key topics such as blockchain technology, smoking toxicology, wearable sensors, and food security, this article provides an overview of how digitalization is influencing toxicology. As well as highlighting future directions for research, this article demonstrates how emerging technologies can enhance risk assessment communication and efficiency. The integration of digital technologies has revolutionized toxicology and has great potential for improving risk assessment and promoting public health., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Evidence of type 2 diabetes mellitus (T2DM) associated with hippocampal atrophy is reported by researchers all around the globe. The majority of such studies were conducted among the geriatric and elderly populations with other substantial co-morbid diseases. Hence, the present study aims to evaluate the hippocampal volume of T2DM subjects below 60 years without any concomitant disorders and assess the declarative memory., Materials and Methods: The cross-sectional observational study was conducted among the ethnic population of Manipur. A total of 17 T2DM subjects and 17 healthy controls, who are apparently healthy, matched by age, sex, and comparable education, were enrolled in the study. Magnetic Resonance Imaging (MRI) of high-resolution sagittal structural T1-weighted anatomical sequence was acquired using a three-dimension magnetization-prepared rapid-acquisition gradient echo (MPRAGE). The hippocampus volume was measured using the volBrain Automated MRI Brain Volumetry System. Declarative memory was estimated by the Rey Auditory Verbal Learning Test (RAVLT)., Results: No statistically significant differences were found in hippocampal volume, and RAVLT scores between T2DM subjects, and healthy controls group (P > 0.05)., Conclusions: The study data indicates that there is no particular hippocampal volume vulnerability in T2DM participants within the ethnic population of Manipur., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Recent advances in the orthopedic prostheses design have significantly improved the quality of life for individuals with orthopedic disabilities. However, there are still critical challenges that need to be addressed to further enhance the functionality of orthopedic prostheses improving biocompatibility to promote better integration with natural tissues, enhancing durability to withstand the demands of daily use, and improving sensory feedback for better control of movement are the most pressing issues. To address these challenges, promising emerging solutions such as smart prosthetics, 3D printing, regenerative medicine, and artificial intelligence have been developed. These innovative technologies hold the potential to significantly enhance the functionality of orthopedic prostheses. Realizing the full potential of these next-generation orthopedic prostheses requires addressing several critical factors. These include interdisciplinary collaboration between experts in orthopedics, materials science, biology, and engineering, increased investment in research and development, standardization of components to ensure quality and reliability, and improved access to prosthetics. A comprehensive review of these challenges and considerations for future orthopedic prosthesis design is s provided in this paper addressing the further advances to the field. By addressing these issues, we can continue to improve the lives of individuals with orthopedic disabilities and further enhance the field of orthopedic prosthetics., Competing Interests: Conflict of interestAuthors state no conflict of interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Postpartum intrauterine contraceptive device (PPIUCD) is safe method of contraception, but with low acceptability rate. Factors that govern acceptability needs to be addressed for increasing its rate. This study was done to assess the acceptance, efficiency, and complications of PPIUCD in tertiary centre of Jharkhand, India., Methods: This prospective study included antenatal women >34 weeks of gestational age who attended antenatal women in the department of Obstetrics and Gynaecology between 1st January 2020 to 1 st September 2020. Details related to age, parity, education, awareness of PPIUCD, reasons for acceptance/refusal of PPIUCD were recorded. The types of insertion were postplacental, postcaesarean, and postabortal. Postinsertion counselling was done for PPIUCD, and women were followed-up at 6 weeks and 10 weeks for assessing complications., Results: The overall acceptance rate was 36.23% ( n = 100). The main reasons for rejecting the use of PPIUCD included fear of pain, bleeding, and other complications (59.09%) and COVID-19 (10.23%). In majority (80%), type of insertion was postplacental with postcaesarean in 18% and postabortal in 2%. Complications were present in 14% women that included abdominal pain (8%), heavy menstrual bleeding (6%), infection (4%), thread not visible (1%), and IUCD not located by USG or X-ray (1%). At 6 months, expulsion occurred in 2 women. There was no significant association of age ( P = 0.312), religion ( P = 1), tribal/non-tribal ( P = 1), education level ( P = 0.628), and type of insertion ( P = 0.356) with complications. At 1 year of follow up, none of the women conceived again showing the efficacy to be 100% as a contraceptive., Conclusion: In spite of limited awareness, PPIUCD proved to be an effective and safe method of long-acting reversible contraception. However, it had low rate of acceptability. PPIUCD was related to lesser complications as expulsion occurred in only 2 women at 6 months. Factors such as age, religion, tribal/non-tribal, education level, and type of insertion were not associated with acceptability rate. PPIUCD was 100% effective as a contraceptive., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

The use of nanomaterials in medicine depends largely on nanotoxicological evaluation in order to ensure safe application on living organisms. Artificial intelligence (AI) and machine learning (MI) can be used to analyze and interpret large amounts of data in the field of toxicology, such as data from toxicological databases and high-content image-based screening data. Physiologically based pharmacokinetic (PBPK) models and nano-quantitative structure-activity relationship (QSAR) models can be used to predict the behavior and toxic effects of nanomaterials, respectively. PBPK and Nano-QSAR are prominent ML tool for harmful event analysis that is used to understand the mechanisms by which chemical compounds can cause toxic effects, while toxicogenomics is the study of the genetic basis of toxic responses in living organisms. Despite the potential of these methods, there are still many challenges and uncertainties that need to be addressed in the field. In this review, we provide an overview of artificial intelligence (AI) and machine learning (ML) techniques in nanomedicine and nanotoxicology to better understand the potential toxic effects of these materials at the nanoscale., (© 2023. The Author(s).)

Various biological processes involve the translocation of macromolecules across nanopores; these pores are basically protein channels embedded in membranes. Understanding the mechanism of translocation is crucial to a range of technological applications, including DNA sequencing, single molecule detection, and controlled drug delivery. In this spirit, numerous efforts have been made to develop polymer translocation-based sequencing devices, these efforts include findings and insights from theoretical modeling, simulations, and experimental studies. As much as the past and ongoing studies have added to the knowledge, the practical realization of low-cost, high-throughput sequencing devices, however, has still not been realized. There are challenges, the foremost of which is controlling the speed of translocation at the single monomer level, which remain to be addressed in order to use polymer translocation-based methods for sensing applications. In this article, we review the recent studies aimed at developing control over the dynamics of polymer translocation through nanopores.

Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 μm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability., 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 © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Agro seeds are vulnerable to environmental stressors, adversely affecting seed vigor, crop growth, and crop productivity. Different agrochemical-based seed treatments enhance seed germination, but they can also cause damage to the environment; therefore, sustainable technologies such as nano-based agrochemicals are urgently needed. Nanoagrochemicals can reduce the dose-dependent toxicity of seed treatment, thereby improving seed viability and ensuring the controlled release of nanoagrochemical active ingredients However, the applications of nanoagrochemicals to plants in the field raise concerns about nanomaterial safety, exposure levels, and toxicological implications to the environment and human health. In the present comprehensive review, the development, scope, challenges, and risk assessments of nanoagrochemicals on seed treatment are discussed. Moreover, the implementation obstacles for nanoagrochemicals use in seed treatments, their commercialization potential, and the need for policy regulations to assess possible risks are also discussed. Based on our knowledge, this is the first time that we have presented legendary literature to readers in order to help them gain a deeper understanding of upcoming nanotechnologies that may enable the development of future generation seed treatment agrochemical formulations, their scope, and potential risks associated with seed treatment., (© 2023. The Author(s).)

The majority of preclinical research has shown that Mycobacterium tuberculosis can modify host lipids in various ways. To boost its intramacrophage survival, M. tuberculosis causes host lipids to build up, resulting in the development of lipid-laden foam cells. M. tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration. Here, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on the bacterial burden by increasing the drug concentration at the infection site. We looked into how atorvastatin could be used in conjunction with first-line drugs to promote drug permeation. In this study, we detected an accumulation of drugs at the peripheral sites of the lungs and impaired drug distribution to the diseased sites. The efficacy of antituberculosis drugs, with atorvastatin as an adjunct, on the viability of M. tuberculosis cells was demonstrated. A nontoxic statin dosage established phenotypic and normal granuloma vasculature and showed an additive effect with rifampicin and isoniazid. Our data show that statins help to reduce the tuberculosis bacterial burden. Our findings reveal that the bacterial load is connected with impaired drug permeability resulting from lipid accumulation in the bacterial cell wall. Statin therapy combined with antituberculosis medications have the potential to improve treatment in tuberculosis patients. IMPORTANCE Mycobacterium tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. M. tuberculosis limits phagosomal maturation and activation without engaging in phagocytosis. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in the vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration, which can be increased through a reduction in cholesterol and vascularity. Herein, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on bacterial burden through increasing the drug concentration at the infection site. Our main research goal is to diminish mycobacterial dissemination and attenuate bacterial growth by increasing drug permeability.

Kidney bean ( Phaseolus vulgaris ) productivity and nutritional quality are declining due to less nutrient accessibility, poor soil health, and indigent agronomic practices in hilly regions, which collectively led to a fall in farmer's income, and to malnutrition in consumers. Addressing such issues, the present investigation was designed to assess the impact of Pseudomonas jesenii MP1 and Pseudomonas palleroniana N26 treatment on soil health, microbial shift, yield, and nutrient status of the kidney bean in the Harsil and Chakrata locations of Indian Central Himalaya. P. jesenii MP1 and P. palleroniana N26 were characterized as cold adaptive PGPR as they possessed remarkable in vitro plant growth promoting traits. Further, field trial study with PGPR treatments demonstrated remarkable and prolific influence of both strains on yield, kidney bean nutrient status, and soil health at both geographical locations, which was indicated with improved grain yield (11.61%-23.78%), protein (6.13%-24.46%), and zinc content (21.86%-61.17%) over control. The metagenomic study revealed that use of bioinoculants also concentrated the nutrient mobilizing and plant beneficial microorganisms in the rhizosphere of the kidney bean. Moreover, correlation analysis also confirmed that the plant growth-promoting traits of P. jesenii MP1 and P. palleroniana N26 are the basis for improved yield and nutrient status of the kidney bean. Further, cluster and principal component analysis revealed that both P . jesenii MP1 and P. palleroniana N26 exhibited pronounced influence on yield attributes of the kidney bean at both the locations. At the Harsil location, the P. jesenii MP1-treated seed demonstrated highest grain yield over other treatments, whereas at Chakarata, P. jesenii MP1, and P. palleroniana N26 treatment showed almost equal enhancement (~23%) in grain yield over control. The above results revealed that these bioinoculants are efficient plant growth promoters and nutrient mobilizers; they could be used as green technology to improve human health and farmer's income by enhancing soil health, yield, and nutrient status of the kidney bean at hilly regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khan, Singh, Pareek, Arya, Upadhayay, Kumar Jugran, Kumar Mishra and Goel.)

Background The orthodontist is often confronted with the need to predict soft tissue profile changes that may result from the orthodontic treatment. The problem arises because the contribution of many of the factors influencing the soft tissue profile still needs to be fully understood. The complexity of the problem is increased in growing patients in whom the post-treatment soft tissue profile is the result of both growth and orthodontic treatment. A primary motivation for seeking orthodontic treatment is a desire to improve dental and facial aesthetics. To achieve balance in the facial profile treated orthodontically, it is essential to identify the underlying skeletal hard tissue and soft tissue parameters. The present study evaluated the changes in facial profile and aesthetics in relation to incisor position. Materials and methods Samples for this study consisted of pre-treatment lateral cephalograms of the Indian population (n = 450) having different incisor relationships. Subjects aged between 18 and 30 years were included. Angular and linear measurements were taken to analyse the incisor relationship with soft tissue parameters. Results The majority (61.2%) of subjects belonged to the age group of 18-30 years. The overall female-to-male ratio in the study was 7:3. The parameter U1 to L1 was abnormal in 86.8% of subjects. Similarly, the parameters S-line upper lip (UL), S-line lower lip (LL), E-line UL, and E-line LL were found abnormal in 93.9%, 86.8%, 82.6%, and 70.1% of subjects, respectively. A significant agreement was found between U1 to L1 and E-line UL and U1 to L1 and E-line LL. Conclusions The present study concludes that facial aesthetics combines soft and hard tissue corrections, not just based on occlusal relationships but also considering facial harmony. Thus, the incisor relationship is an important asset and strongly correlates with other soft tissue and hard tissue parameters that improve facial aesthetics for the individual undergoing orthodontic treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Singh et al.)

Acute myocardial infarction (AMI) is a severe disease with elevated morbidity and mortality rate worldwide. This is attributed to great losses of cardiomyocytes, which can trigger the alteration of gene expression patterns. Although several attempts have been made to assess the AMI biomarkers, to date their role in rescuing myocardial injury remains unclear. Therefore, the current study investigated three independent microarray-based gene expression datasets from AMI patients (n = 85) and their age-sex-matched healthy controls (n = 70), to identify novel gene signatures that might be involved in cardioprotection. The differentially expressed genes (DEGs) were analyzed using 'GEO2R', and weighted gene correlation network analysis (WGCNA) was performed to identify biomarkers/modules. We found 91 DEGs, of which the number of upregulated and downregulated genes were 22 and 5, respectively. Specifically, we found that the deregulated genes such as ADOR-A3, BMP6, VPS8, and GPx3, may be associated with AMI. WGCNA revealed four highly preserved modules among all datasets. The 'Enrichr' unveiled the presence of miR-660 and STAT1, which is known to affect AMI severity. Conclusively, these genes and miRNA might play a crucial role the rescue of cardiomyocytes from severe damage, which could be helpful in developing appropriate therapeutic strategies for the management of AMI.

Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types. Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer-BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations. Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up ( r 2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination ( r 2 = 0.789; p = 0.0001) and 91-190 days (T2) after vaccination ( r 2 = 0.764; p = 0.0001) for both vaccine types ( r 2 = 0.842; p = 0.0001 and r 2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age ( p < 0.01), sex ( p = 0.03), and type of vaccine ( p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated ( TP53 , rs1042522; APOE , rs7412/rs429358; ABO , rs657152; ACE2 , rs2285666; HLA-A rs2571381/rs2499; CRP , rs2808635/rs876538; LZTFL1 , rs35044562; OAS3 , rs10735079; SLC6A20 , rs11385942; CFH , rs1061170; and ACE1 , ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P 1 and P 2 , respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53 , rs1042522 (P 1 = 0.03; P 2 = 0.04); ABO , rs657152 (P 1 = 0.01; P 2 = 0.03); APOE , rs7412/rs429358 (P 1 = 0.0018; P 2 = 0.0002); ACE2 , rs2285666 (P 1 = 0.014; P 2 = 0.009); HLA-A , rs2571381/rs2499 (P 1 = 0.02; P 2 = 0.03); and CRP , rs2808635/rs876538 (P 1 = 0.01 and P 2 = 0.09). Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gemmati, Longo, Gallo, Silva, Secchiero, Zauli, Hanau, Passaro, Pellegatti, Pizzicotti, Serino, Singh and Tisato.)

This review article aimed to determine the obstetric and maternal outcomes after B-Lynch compression sutures to control atonic postpartum hemorrhage (PPH). This meta-analysis was performed after registering the protocol in the PROSPERO database with the registration number CRD42022355358. Two independent reviewers systematically searched electronic databases and search engines (PubMed, Cochrane Library, and Google Scholar) to retrieve published articles from inception to July 2022. The obstetric and maternal outcomes after the B-Lynch compression suture were computed using the random-effects model in pooled proportion with a 95% confidence interval (CI). Meta-regression analysis and subgroup analysis were performed to explain any source of possible heterogeneity. Quality assessment of the included studies was done using Joanna Briggs Institute (JBI) tools which are critical appraisal tools for systematic reviews and meta-analyses. This meta-analysis included a total of 30 studies involving 1,270 subjects. The pooled proportion of B-Lynch suture alone was 91% (95% CI = 82-97%). The combined proportion of B-Lynch suture plus another compression suture was 1% (95% CI = 0-3%), and the pooled proportion of B-Lynch suture plus vessel ligation was 3% (95% CI = 1-6%). The pooled proportions of PPH controlled and hysterectomies were 94% (95% CI = 91-97%, I 2 = 65.3%) and 7% (95% CI = 4-10%, I 2 = 72.13%), respectively. Therefore, B-Lynch suture (either alone or in combination with other techniques) is a simple and effective measure to control atonic PPH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Nalini et al.)

Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration number CRD42022324947., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Nalini et al.)

A hybrid blood-brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet-outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte-endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus.

Segmentation of abdominal Computed Tomography (CT) scan is essential for analyzing, diagnosing, and treating visceral organ diseases (e.g., hepatocellular carcinoma). This paper proposes a novel neural network (Res-PAC-UNet) that employs a fixed-width residual UNet backbone and Pyramid Atrous Convolutions, providing a low disk utilization method for precise liver CT segmentation. The proposed network is trained on medical segmentation decathlon dataset using a modified surface loss function. Additionally, we evaluate its quantitative and qualitative performance; the Res16-PAC-UNet achieves a Dice coefficient of 0.950 ± 0.019 with less than half a million parameters. Alternatively, the Res32-PAC-UNet obtains a Dice coefficient of 0.958 ± 0.015 with an acceptable parameter count of approximately 1.2 million., (© 2022. The Author(s).)

DNA-mediated self-assembly of colloids has emerged as a powerful tool to assemble the materials of prescribed structure and properties. The uniqueness of the approach lies in the sequence-specific, thermo-reversible hybridization of the DNA-strands based on Watson-Crick base pairing. Grafting particles with DNA strands, thus, results into building blocks that are fully programmable, and can, in principle, be assembled into any desired structure. There are, however, impediments that hinder the DNA-grafted particles from realizing their full potential, as building blocks, for programmable self-assembly. In this short review, we focus on these challenges and highlight the research around tackling these challenges.

The severity of global pandemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has engaged the researchers and clinicians to find the key features triggering the viral infection to lung cells. By utilizing such crucial information, researchers and scientists try to combat the spread of the virus. Here, in this work, we performed in silico analysis of the protein-protein interactions between the receptor-binding domain (RBD) of the viral spike protein and the human angiotensin-converting enzyme 2 (hACE2) receptor to highlight the key alteration that happened from SARS-CoV to SARS-CoV-2. We analyzed and compared the molecular differences between spike proteins of the two viruses using various computational approaches such as binding affinity calculations, computational alanine, and molecular dynamics simulations. The binding affinity calculations showed that SARS-CoV-2 binds a little more firmly to the hACE2 receptor than SARS-CoV. The major finding obtained from molecular dynamics simulations was that the RBD-ACE2 interface is populated with water molecules and interacts strongly with both RBD and ACE2 interfacial residues during the simulation periods. The water-mediated hydrogen bond by the bridge water molecules is crucial for stabilizing the RBD and ACE2 domains. Near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) confirmed the presence of vapor and molecular water phases in the protein-protein interfacial domain, further validating the computationally predicted interfacial water molecules. In addition, we examined the role of interfacial water molecules in virus uptake by lung cell A549 by binding and maintaining the RBD/hACE2 complex at varying temperatures using nanourchins coated with spike proteins as pseudoviruses and fluorescence-activated cell sorting (FACS) as a quantitative approach. The structural and dynamical features presented here may serve as a guide for developing new drug molecules, vaccines, or antibodies to combat the COVID-19 pandemic.