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In the current research, enhancement in the film and transition boiling regime is tried to obtain using Al2O3 nanofluid as coolant. The coolant properties such as physical, thermal and interfacial and the droplet dynamics during evaporation are the prime controlling factors for defining the effectiveness of dropwise evaporative cooling. In the current study, aluminium oxide nanoparticle with water is considered as coolant. The quality of the aluminium oxide nanoparticle has been confirmed by performing various characterizations such as X-ray diffraction analysis, scanning electron microscope with energy dispersive spectroscopy and transmission electron microscope. Using aluminium oxide + water as the coolant, the augmentation was obtained by altering the thermo-physical properties of the coolant in the favourable direction of heat transfer. The thermal analysis and the comparative study ensures step up in heat transfer. With the increase in the concentration of nanoparticles from 0.1%–0.2% in the base fluid, the evaporation rate increases significantly due to the decrease in the residence time, increase in the maximum spreading diameter and minimisation or elimination in blasting characteristics. [ABSTRACT FROM AUTHOR]

Objective: This study analyzed a relationship between prenatal mood states and serologic evidence of immune response to Toxoplasma gondii. A secondary aim was to determine whether thyroid peroxidase autoantibody status was related to T gondii status.Study Design: Pregnant women (n = 414) were measured at 16-25 weeks' gestation with demographic and mood questionnaires and a blood draw. All plasma samples were analyzed for thyroid peroxidase and T gondii immunoglobulin G, tryptophan, kynurenine, and neopterin. T gondii serotypes were also measured in the women who were T gondii positive. Cytokines were available on a subset (n = 142).Results: Women with serologic evidence of exposure to T gondii (n = 44) showed positive correlations between immunoglobulin G levels and the Profile of Mood States depression and anxiety subscales. Plasma tumor necrosis factor-α was higher in women who were positive for T gondii. Serotypes were type I (27%), type II (31%), and unclassified (42%, which shows intermediate levels of reactivity). The depression and anxiety scores were highest in type I, but this was not significant. The Profile of Mood States vigor score was lowest in type II, compared with the type I or unclassified groups.Conclusion: Higher T gondii immunoglobulin G titers in infected women were related to anxiety and depression during pregnancy. Subclinical reactivation of T gondii or immune responses to T gondii may worsen mood in pregnant women. [ABSTRACT FROM AUTHOR]

Studies a novel barley gene that is abscisic acid (ABA) inducible and expressed specifically in embryo and aleurone. Genomic sequence of aba45; Absence of homology between aba45 and any known DNA or protein sequences.

Nanotechnology and machine learning (ML) are rapidly emerging fields with numerous real-world applications in medicine, materials science, computer engineering, and data processing. ML enhances nanotechnology by facilitating the processing of dataset in nanomaterial synthesis, characterization, and optimization of nanoscale properties. Conversely, nanotechnology improves the speed and efficiency of computing power, which is crucial for ML algorithms. Although the capabilities of nanotechnology and ML are still in their infancy, a review of the research literature provides insights into the exciting frontiers of these fields and suggests that their integration can be transformative. Future research directions include developing tools for manipulating nanomaterials and ensuring ethical and unbiased data collection for ML models. This review emphasizes the importance of the coevolution of these technologies and their mutual reinforcement to advance scientific and societal goals.

The complexities inherent in drug development are multi-faceted and often hamper accuracy, speed and efficiency, thereby limiting success. This review explores how recent developments in machine learning (ML) are significantly impacting target-based drug discovery, particularly in small-molecule approaches. The Simplified Molecular Input Line Entry System (SMILES), which translates a chemical compound's three-dimensional structure into a string of symbols, is now widely used in drug design, mining, and repurposing. Utilizing ML and natural language processing techniques, SMILES has revolutionized lead identification, high-throughput screening and virtual screening. ML models enhance the accuracy of predicting binding affinity and selectivity, reducing the need for extensive experimental screening. Additionally, deep learning, with its strengths in analyzing spatial and sequential data through convolutional neural networks (CNNs) and recurrent neural networks (RNNs), shows promise for virtual screening, target identification, and de novo drug design. Fragment-based approaches also benefit from ML algorithms and techniques like generative adversarial networks (GANs), which predict fragment properties and binding affinities, aiding in hit selection and design optimization. Structure-based drug design, which relies on high-resolution protein structures, leverages ML models for accurate predictions of binding interactions. While challenges such as interpretability and data quality remain, ML's transformative impact accelerates target-based drug discovery, increasing efficiency and innovation. Its potential to deliver new and improved treatments for various diseases is significant.

The onset of COVID-19 due to the SARS CoV-2 virus has spurred an urgent need for potent therapeutics and vaccines to combat this global pandemic. The main protease (Mpro) of the virus, crucial in its replication, has become a focal point in developing anti-COVID-19 drugs. The cysteine protease Mpro in SARS CoV-2 bears a significant resemblance to the same protease found in SARS CoV-1. Previous research highlighted phlorotannins derived from Ecklonia cava, an edible marine algae, as inhibitors of SARS CoV-1 Mpro activity. However, it remains unclear whether these marine-derived phlorotannins also exert a similar inhibitory effect on SARS CoV-2 Mpro. To unravel this, our study utilized diverse in-silico methodologies. We explored the pharmacological potential of various phlorotannins (phloroglucinol, triphloretol-A, eckol, 2-phloroeckol, 7-phloroeckol, fucodiphloroethol G, dieckol, and phlorofucofuroeckol-A) and assessed their binding efficacies alongside established Mpro inhibitors (N3 and lopinavir) through molecular docking studies. Among these compounds, five phlorotannins (eckol, 2-phloroeckol, 7-phloroeckol, dieckol, and phlorofucofuroeckol-A) exhibited potent binding affinities comparable to or surpassing N3 and lopinavir, interacting especially with the catalytic residues His41 and Cys145 of Mpro. Moreover, molecular dynamics simulations revealed that these five Mpro-phlorotannin complexes displayed enhanced stability and maintained comparable or slightly reduced compactness. They exhibited reduced conformational changes and increased expansion relative to the Mpro-N3 and/or Mpro-lopinavir complex. Our MM-GBSA analysis further supported these findings. Overall, our investigation highlights the potential of these five phlorotannins in inhibiting the proteolytic function of SARS CoV-2 Mpro, offering promise for anti-COVID-19 drug development., 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 rising incidence of antimicrobial resistance (AMR) and the diminishing antibiotics discovery pipeline have created an unprecedented scenario where minor infections could become untreatable. AMR phenomenon is genetically encoded, and various genetic determinants have been implicated in their emergence and spread. Nevertheless, several non-genetic phenomena are also involved in antibiotic treatment failure which requires a systematic investigation. It has been observed that in an isogenic population of bacteria, not all cells behave or respond the same way to an antibiotic, because of the inherent heterogeneity among them. This heterogeneity is not always heritable but rather phenotypic. Three distinct types of phenotypic heterogeneity, namely tolerance, persistence, and heteroresistance have been observed in bacteria having significant clinical implications influencing the treatment outcome. While tolerance is when a population can survive high doses of antibiotics without changing the minimum inhibitory concentration (MIC) of the drug, persistence occurs in a subpopulation of bacteria that can survive exposure to high antibiotic doses. In contrast, when a subpopulation shows a very high MIC in comparison to the rest of the population, the phenomenon is called heteroresistance. In this article, we have highlighted bacterial persistence with a focus on their emergence and the underlying molecular mechanisms. Moreover, we have tried to associate the genome-wide methylation status with that of the heterogeneity at a single-cell level that may explain the role of epigenetic mechanisms in the development of persistence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The rapid rise of nosocomial infections and the growing ineffectiveness of frontline antibiotics against Gram-negative bacteria (GNB) have put the healthcare sector under unprecedented stress. In this scenario, colistin, an antibiotic of the polymyxin class, has become the last resort treatment option. However, the unrestricted use of colistin in the preceding decades has led to the emergence of colistin-resistant (Col R ) bacterial strains. Unfortunately, comprehensive data on the prevalence of Col R nosocomial pathogens in India are scarce. This study was conducted to address this information gap. A systematic review and meta-analysis were conducted to determine the prevalence of Col R among the nosocomial GNB species in India and their geographical distribution. A systematic search of the online databases was performed and eligible studies meeting the inclusion criteria were used for qualitative synthesis. The combined event rate and 95% confidence interval were estimated using a forest plot with a random-effect model. Cochrane Q statistics and I 2 statistics were used to detect possible heterogeneity. From a total of 1865 retrieved records from 4 databases, 33 studies were included in the study. Among the most common nosocomial pathogens , Klebsiella pneumoniae showed a rate of Col R at 16.1% (95% CI: 10.1 to 24.6), followed by Pseudomonas aeruginosa (13.3%) (95% CI: 9.1 to 19.2), Acinetobacter baumannii (10%) (95% CI: 7.5 to 13.2), and Escherichia coli (7.8%) (95% CI: 5.3 to 11.2). Interestingly, our analysis revealed that Enterobacter cloacae have the highest rate of Col R at 27.9% (95% CI: 12.7 to 50.9). The results indicate that the prevalence of Col R nosocomial pathogens vary among regions and over time; however, continuous monitoring, and sustained efforts are crucial to ensure the effectiveness of colistin antibiotic.

Introduction: Polymyxins, the cationic lipopeptide antibiotics, are the last line of therapeutics against the MDR Gram-negative bacterial (GNB) pathogens. Unfortunately, the rising cases of polymyxin-resistant strains from across the globe have adversely impacted their utility. While the molecular mechanisms responsible for developing polymyxin resistance (PolR) are largely understood, the prevalence of PolR strains in India has not been investigated systematically. The current study was undertaken to primarily determine the prevalence of PolR strains in India. Moreover, the extent of the spread of mobile colistin resistance (mcr) genes among the GNB strains in India was also determined., Method: A systematic search for articles using the relevant inclusion and exclusion criteria was performed in the applicable databases for the period January 2015 to December 2023. The included 41 studies were subjected to a meta-analysis using the Comprehensive Meta-Analysis software (V4.0). Publication biases were assessed using funnel plots and Egger's regression analysis., Result: Considering a total of 41 studies including 24 589 bacterial isolates the present meta-analysis found the rate of PolR bacteria in India to be at 15.0% (95% CI: 11.2 to 19.8). Among the Indian States, Tamil Nadu topped with the highest prevalence of PolR at 28.3%. Investigating the contribution of the mcr genes, it was observed that among the PolR strains, 8.4% (95% CI: 4.8 to 14.3) were mcr positive., Conclusion: The study determined the prevalence of PolR strains in India at 15.0%, which is higher than that of the global average at 10%. The study also determined that 8.4% of the PolR strains carried the mcr genes. The mcr-positive strains reported from India could be an underestimation of the actual numbers due to the non-inclusion of mcr screening in many previous studies. This study provides insight into the state of the PolR situation in India, which may be useful to develop a monitoring strategy to contain the spread of such strains and preserve the efficacy of the polymyxins., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

With the rising incidences of antimicrobial resistance (AMR) and the diminishing options of novel antimicrobial agents, it is paramount to decipher the molecular mechanisms of action and the emergence of resistance to the existing drugs. Polymyxin, a cationic antimicrobial lipopeptide, is used to treat infections by Gram-negative bacterial pathogens as a last option. Though polymyxins were identified almost seventy years back, their use has been restricted owing to toxicity issues in humans. However, their clinical use has been increasing in recent times resulting in the rise of polymyxin resistance. Moreover, the detection of "mobile colistin resistance (mcr)" genes in the environment and their spread across the globe have complicated the scenario. The mechanism of polymyxin action and the development of resistance is not thoroughly understood. Specifically, the polymyxin-bacterial lipopolysaccharide (LPS) interaction is a challenging area of investigation. The use of advanced biophysical techniques and improvement in molecular dynamics simulation approaches have furthered our understanding of this interaction, which will help develop polymyxin analogs with better bactericidal effects and lesser toxicity in the future. In this review, we have delved deeper into the mechanisms of polymyxin-LPS interactions, highlighting several models proposed, and the mechanisms of polymyxin resistance development in some of the most critical Gram-negative pathogens., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

SARS-CoV-2 primarily infects the lungs via the ACE2 receptor but also other organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to the brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it affects the molecular functions of the BBB are unclear. In this study, we investigated the roles of the receptors ACE2 and DPP4 in the SARS-CoV-2 infection of the discrete cellular components of a transwell BBB model comprising HUVECs, astrocytes, and pericytes. Our results demonstrate that direct infection on the BBB model does not modulate paracellular permeability. Also, our results show that SARS-CoV-2 utilizes clathrin and caveolin-mediated endocytosis to traverse the BBB, resulting in the direct infection of the brain side of the BBB model with a minimal endothelial infection. In conclusion, the BBB is susceptible to SARS-CoV-2 infection in multiple ways, including the direct infection of endothelium, astrocytes, and pericytes involving ACE2 and/or DPP4 and the blood-to-brain transcytosis, which is an event that does not require the presence of host receptors.

Background: There are many subjective and objective tools to detect, assess, and quantify fatigue. This study is a novice attempt to assess the occupational fatigue among the aviation personnel employing a computerized work-rest schedule tool integrated with actigraphy., Methods: Thirty-eight aviation personnel were assessed for their sleep by using an actigraphy device. A work-rest scheduling software program called Fatigue Avoidance Scheduling Tool (FAST) was used to obtain fatigue parameters like Fatigue Risk Time (FRT), Fatigue Free Time (FFT), and Fatigue Free Occupational Time (FFOT)., Results: The percentages of crew having a night sleep of the duration of more than 6 hours were 50% (Mon), 44.7% (Tue), 44.7% (Wed), and 47.3% (Thu) for weekdays and 65.8% (Fri), 57.9% (Sat), and 57.9% (Sun) for the weekend. There was a gradual increase in FRT, FFT, and FFOT from Day 1 to Day 5 of the week, and the differences were statistically significant., Conclusion: Increase in the FRT with a reciprocal drop of FFT and FFOT was observed with the progress of the week. Total Sleep Time (TST) of less than 8 hours could be the reason for a gradual increase in sleep debt, leading to fatigue depicted as increase in fatigue risk parameter FRT and gradual decrease in fatigue preventing parameters like FFT and FFOT. It was further confirmed by regression analysis in which TST was found to be a statistically significant predictor for all fatigue parameters. Regression equation for FFOT as 498.53 + (0.39 x TST) - (58.8 x Day of the week) can be used., (© 2022 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Background: Fatigue Avoidance Scheduling Tool (FAST) is a computerized fatigue prevention tool, which was developed based on a Bio-mathematical model called SAPTE (Sleep, Activity, Performance and Task Effectiveness). Similarly, actigraphy technology is used as a tool for sleep evaluation. This study was an attempt to assess the employability of FAST (both independently and integrated with actigraphy) for detecting operational fatigue by determining the 'Measures for diagnostic accuracy'., Methods: 103 pre-flight medical checks from 51 aircrew were evaluated to detect fatigue both clinically and by using objective measures (FAST and actigraphy integrated FAST). The 'measures of diagnostic accuracy' namely sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio positive (LR +ve), likelihood ratio negative (LR -ve) and Youden's Index were determined and compared., Results: The diagnostic measures for FAST were: sensitivity (68.4%), specificity (92.8%), PPV (68.4%), NPV (92.8%), LR+ve (9.5), LR-ve (0.34) and Youden's Index (0.61). For actigraphy integrated FAST these values were: sensitivity (84.2%), specificity (96.4%), PPV (94.2%), NPV (94.4%), LR+ve (23.5), LR-ve (0.16) and Youden's Index (0.80)., Conclusion: The increase in sensitivity (from 68.4% to 84.2%), specificity (from 92.8% to 96.4%), PPV (from 68.4% to 94.2%), NPV (92.8% to 94.4%), LR+ve (9.5 to 23.5) and Youden's Index (0.61 to 0.80) indicated that actigraphy integrated FAST is a better screening tool in comparison to the independently employed FAST., Competing Interests: The authors have none to declare., (© 2021 Director General, Armed Forces Medical Services. Published by Elsevier, a division of RELX India Pvt. Ltd.)

Introduction: In order to enhance the existing body of research regarding the prevalence of violations committed by pedestrians and bicyclists, this observational study utilized personal-specific, train-specific, operational, and behavioral data extracted from recorded videos at seven railroad grade crossings (RRGCs)., Method: A total of 7,332 pedestrians and 1,684 bicyclist crossing events were observed during 279 gate operation phases at seven study locations. First, two separate violation models (binary logit) for pedestrians and bicyclists were developed to determine the influence of personal-specific characteristics and other behavioral traits on probability of pedestrians' and bicyclists' violation. Later, the impact of various geometrical (railway track, distance between gates, distance between gate and nearest track, and road width) and operational (train vehicle unit) parameters on the factors that caused non-motorist violations was examined by developing distinctbinary logit models., Results: The probability of pedestrians'and bicyclists' violationwas found to be significantly influenced by train characteristics (train speed and train occupancy time), gate operational attributes (warning time and gate blockage duration), and personal-specificcharacteristics (gender, age, crossing speed, and looking both side). Furthermore, geometrical attributes along with train vehicle unit were observed to have impact over various factors that significantly influenced the behavior of pedestrians and bicyclists to violate., Practical Applications: The findings of this research provide essential information that could be applied in the initiatives of user awareness and enforcement program, emphasis on situational awareness and design of operational and geometricalelementsto significantlylimitthe effects of risky walking andbicycling behavior at RRGCs., 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 National Safety Council and Elsevier Ltd. All rights reserved.)

Purpose: Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. Mounting evidence suggests that even mild TBI injuries, which comprise >75% of all TBIs, can cause chronic post-concussive neurological symptoms, especially when experienced repetitively (rTBI). The most common post-concussive symptoms include auditory dysfunction in the form of hearing loss, tinnitus, or impaired auditory processing, which can occur even in the absence of direct damage to the auditory system at the time of injury. The mechanism by which indirect damage causes loss of auditory function is poorly understood, and treatment is currently limited to symptom management rather than preventative care. We reasoned that secondary injury mechanisms, such as inflammation, may lead to damage of the inner ear and parts of the brain used for hearing after rTBI. Herein, we established a model of indirect damage to the auditory system induced by rTBI and characterized the pathology of hearing loss., Methods: We established a mouse model of rTBI in order to determine a timeline of auditory pathology following multiple mild injuries. Mice were subject to controlled cortical impact at the skull midline once every 48 h, for a total of 5 hits. Auditory function was assessed via the auditory brainstem response (ABR) at various timepoints post injury. Brain and cochleae were collected to establish a timeline of cellular pathology., Results: We observed increased ABR thresholds and decreased (ABR) P1 amplitudes in rTBI vs sham animals at 14 days post-impact (dpi). This effect persisted for up to 60 days (dpi). Auditory temporal processing was impaired beginning at 30 dpi. Spiral ganglion degeneration was evident at 14 dpi. No loss of hair cells was detected at this time, suggesting that neuronal loss is one of the earliest notable events in hearing loss caused by this type of rTBI., Conclusions: We conclude that rTBI results in chronic auditory dysfunction via damage to the spiral ganglion which occurs in the absence of any reduction in hair cell number. This suggests early neuronal damage that may be caused by systemic mechanisms similar to those leading to the spread of neuronal death in the brain following TBI. This TBI-hearing loss model provides an important first step towards identifying therapeutic targets to attenuate damage to the auditory system following head injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the research described in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA-liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.

Treatment of late-stage lung cancers remains challenging with a five-year survival rate of 8%. Immune checkpoint blockers (ICBs) revolutionized the treatment of non-small cell lung cancer (NSCLC) by reactivating anti-tumor immunity. Despite achieving durable responses, ICBs are effective in only 20% of patients due to immune resistance. Therefore, synergistic combinatorial approaches that overcome immune resistance are currently under investigation. Herein, we studied the immunomodulatory role of Withaferin A (WFA)-a herbal compound-and its effectiveness in combination with an ICB for the treatment of NSCLC. Our in vitro results show that WFA induces immunogenic cell death (ICD) in NSCLC cell lines and increases expression of the programmed death ligand-1 (PD-L1). The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process. Further, we found that a combination of WFA and α-PD-L1 significantly reduced tumor growth in an immunocompetent tumor model. Our results showed that WFA increases CD-8 T-cells and reduces immunosuppressive cells infiltrating the tumor microenvironment. Administration of NAC partially inhibited the anti-tumor response of the combination regimen. In conclusion, our results demonstrate that WFA sensitizes NSCLC to α-PD-L1 in part via activation of ROS.

Background: Evidence suggests that mild TBI injuries, which comprise > 75% of all TBIs, can cause chronic post-concussive symptoms, especially when experienced repetitively (rTBI). rTBI is a major cause of cognitive deficit in athletes and military personnel and is associated with neurovascular changes. Current methods to monitor neurovascular changes in detail are prohibitively expensive and invasive for patients with mild injuries., New Method: We evaluated the potential of multispectral optoacoustic tomography (MSOT) to monitor neurovascular changes and assess therapeutic strategies in a mouse model of rTBI. Mice were subjected to rTBI or sham via controlled cortical impact and administered pioglitazone (PG) or vehicle. Oxygenated and deoxygenated hemoglobin were monitored using MSOT. Indocyanine green clearance was imaged via MSOT to evaluate blood-brain-barrier (BBB) integrity., Results: Mice subjected to rTBI show a transient increase in oxygenated/total hemoglobin ratio which can be mitigated by PG administration. rTBI mice also show BBB disruption shortly after injury and reduction of oxygenated/total hemoglobin in the chronic stage, neither of which were affected by PG intervention., Comparison With Existing Methods: MSOT imaging has the potential as a noninvasive in vivo imaging method to monitor neurovascular changes and assess therapeutics in mouse models of rTBI. In comparison to standard methods of tracking inflammation and BBB disruption, MSOT can be used multiple times throughout the course of injury without the need for surgery. Thus, MSOT is especially useful in research of rTBI models for screening therapeutics, and with further technological improvements may be extended for use in rTBI patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the research described in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Nanotechnology is an interdisciplinary domain of science, technology and engineering that deals with nano-sized materials/particles. Usually, the size of nanoparticles lies between 1 and 100 nm. Due to their small size and large surface area-to-volume ratio, nanoparticles exhibit high reactivity, greater stability and adsorption capacity. These important physicochemical properties attract scientific community to utilize them in biomedical field. Various types of nanoparticles (inorganic and organic) have broad applications in medical field ranging from imaging to gene therapy. These are also effective drug carriers. In recent times, nanoparticles are utilized to circumvent different treatment limitations. For example, the ability of nanoparticles to cross the blood-brain barrier and having a certain degree of specificity towards amyloid deposits makes themselves important candidates for the treatment of Alzheimer's disease. Furthermore, nanotechnology has been used extensively to overcome several pertinent issues like drug-resistance phenomenon, side effects of conventional drugs and targeted drug delivery issue in leprosy, tuberculosis and cancer. Thus, in this review, the application of different nanoparticles for the treatment of these four important diseases (Alzheimer's disease, tuberculosis, leprosy and cancer) as well as for the effective delivery of drugs used in these diseases has been presented systematically. Although nanoformulations have many advantages over traditional therapeutics for treating these diseases, nanotoxicity is a major concern that has been discussed subsequently. Lastly, we have presented the promising future prospective of nanoparticles as alternative therapeutics. In that section, we have discussed about the futuristic approach(es) that could provide promising candidate(s) for the treatment of these four diseases., (© 2023 The Author(s).)

The development of modern cutting-edge technology relies heavily on the huge success and advancement of nanotechnology, in which nanomaterials and nanostructures provide the indispensable material cornerstone. Owing to their nanoscale dimensions with possible quantum limit, nanomaterials and nanostructures possess a high surface-to-volume ratio, rich surface/interface effects, and distinct physical and chemical properties compared with their bulk counterparts, leading to the remarkably expanded horizons of their applications. Depending on their degree of spatial quantization, low-dimensional nanomaterials are generally categorized into nanoparticles (0D); nanorods, nanowires, and nanobelts (1D); and atomically thin layered materials (2D). This review article provides a comprehensive guide to low-dimensional nanomaterials and nanostructures. It begins with the classification of nanomaterials, followed by an inclusive account of nanofabrication and characterization. Both top-down and bottom-up fabrication approaches are discussed in detail. Next, various significant applications of low-dimensional nanomaterials are discussed, such as photonics, sensors, catalysis, energy storage, diverse coatings, and various bioapplications. This article would serve as a quick and facile guide for scientists and engineers working in the field of nanotechnology and nanomaterials.

The coronavirus disease 2019 (COVID-19) pandemic has caused over 600,000,000 infections globally thus far. Up to 30% of individuals with mild to severe disease develop long COVID, exhibiting diverse neurologic symptoms including dementias. However, there is a paucity of knowledge of molecular brain markers and whether these can precipitate the onset of Alzheimer's disease (AD). Herein, we report the brain gene expression profiles of severe COVID-19 patients showing increased expression of innate immune response genes and genes implicated in AD pathogenesis. The use of a mouse-adapted strain of SARS-CoV-2 (MA10) in an aged mouse model shows evidence of viral neurotropism, prolonged viral infection, increased expression of tau aggregator FKBP51, interferon-inducible gene Ifi204 , and complement genes C4 and C5AR1. Brain histopathology shows AD signatures including increased tau-phosphorylation, tau-oligomerization, and α-synuclein expression in aged MA10 infected mice. The results of gene expression profiling of SARS-CoV-2-infected and AD brains and studies in the MA10 aged mouse model taken together, for the first time provide evidence suggesting that SARS-CoV-2 infection alters expression of genes in the brain associated with the development of AD. Future studies of common molecular markers in SARS-CoV-2 infection and AD could be useful for developing novel therapies targeting AD., Competing Interests: The authors have no competing interests to declare.

There is currently a growing interest in the use of cannabidiol (CBD) to alleviate the symptoms caused by cancer, including pain, sleep disruption, and anxiety. CBD is often self-administered as an over-the-counter supplement, and patients have reported benefits from its use. However, despite the progress made, the mechanisms underlying CBD's anti-cancer activity remain divergent and unclear. Herein, we provide a comprehensive review of molecular mechanisms to determine convergent anti-cancer actions of CBD from pre-clinical and clinical studies. In vitro studies have begun to elucidate the molecular targets of CBD and provide evidence of CBD's anti-tumor properties in cell and mouse models of cancer. Furthermore, several clinical trials have been completed testing CBD's efficacy in treating cancer-related pain. However, most use a mixture of CBD and the psychoactive, tetrahydrocannabinol (THC), and/or use variable dosing that is not consistent between individual patients. Despite these limitations, significant reductions in pain and opioid use have been reported in cancer patients using CBD or CBD+THC. Additionally, significant improvements in quality-of-life measures and patients' overall satisfaction with their treatment have been reported. Thus, there is growing evidence suggesting that CBD might be useful to improve the overall quality of life of cancer patients by both alleviating cancer symptoms and by synergizing with cancer therapies to improve their efficacy. However, many questions remain unanswered regarding the use of CBD in cancer treatment, including the optimal dose, effective combinations with other drugs, and which biomarkers/clinical presentation of symptoms may guide its use.

As newer variants of SARS-CoV-2 continue to pose major threats to global human health and economy, identifying novel druggable antiviral targets is the key toward sustenance. Here, we identify an evolutionarily conserved "Ex 3 Lx 6 L" ("E-L-L") motif present within the HR2 domain of all human and nonhuman coronavirus spike (S) proteins that play a crucial role in stabilizing its postfusion six-helix bundle (6-HB) structure and thus, fusion-mediated viral entry. Mutations within this motif reduce the fusogenicity of the S protein without affecting its stability or membrane localization. We found that posaconazole, an FDA-approved drug, binds to this "E-L-L" motif and impedes the formation of 6-HB, thus effectively inhibiting SARS-CoV-2 infection in cells. While posaconazole exhibits high efficacy in blocking S protein-mediated viral entry, mutations within the "E-L-L" motif rendered the protein completely resistant to the drug, establishing its specificity toward this motif. Our data demonstrate that posaconazole restricts early stages of infection through specific inhibition of membrane fusion and viral genome release into the host cell and is equally effective toward all major variants of concerns of SARS-CoV-2, including Beta, Kappa, Delta, and Omicron. Together, we show that this conserved essential "E-L-L" motif is an ideal target for the development of prophylactic and therapeutic interventions against SARS-CoV-2., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

Ultraviolet (UV) irradiation-based methods used for viral inactivation have provided an important avenue targeting severe acute respiratory-syndrome coronavirus-2 (SARS-CoV-2) virus. A major problem with state-of-the-art UV inactivation technology is that it is based on UV lamps, which have limited efficiency, require high power, large doses, and long irradiation times. These drawbacks limit the use of UV lamps in air filtering systems and other applications. To address these limitations, herein we report on the fabrication of a device comprising a pulsed nanosecond 266 nm UV laser coupled to an integrating cavity (LIC) composed of a UV reflective material, polytetrafluoroethylene. Previous UV lamp inactivation cavities were based on polished walls with specular reflections, but the diffuse reflective UV ICs were not thoroughly explored for virus inactivation. Our results show that LIC device can inactivate several respiratory viruses including SARS-CoV-2, at ~ 1 ms effective irradiation time, with > 2 orders of magnitude higher efficiency compared to UV lamps. The demonstrated 3 orders of magnitude cavity enhancement relative to direct exposure is crucial for the development of efficient real-time UV air and water purification systems. To the best of our knowledge this is the first demonstration of LIC application for broad viral inactivation with high efficiency., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Extracting molecular level label-free information from complex biological processes for a range of purposes including disease diagnosis and microbial identification and discrimination is always a challenging task. This is mostly due to lack of a technique providing rich molecular information with a high spatial and temporal resolution properties. Two surface-enhanced vibrational spectroscopic (SEVS) techniques, surface-enhanced Raman scattering (SERS) and surface-enhanced infrared absorption spectroscopy (SEIRAS), are recently attracting considerable attention to study biosystems at an interface since they can satisfy these requirements to a certain level by providing rich intrinsic molecular information from molecules and molecular systems in a close proximity of nanostructured noble metal surfaces. In this study, these two surface-enhanced vibrational spectroscopic techniques are comparatively evaluated for the discrimination and identification of Candida albicans (C. albicans), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by paying attention to the source of the observed spectral pattern. The citrate-reduced colloidal silver nanoparticles (AgNPs) were used as substrates. The results show that the SEIRAS provides very rich molecular information about the biomolecular species adsorbed onto AgNPs similar to the case of SERS. The discrimination power of SEIRAS is much improved compared to FTIR demonstrated by PCA analysis. This study suggests that SEIRAS can be a potential technique for microbial analysis., 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 © 2021 Elsevier B.V. All rights reserved.)

The spike proteins of enveloped viruses are transmembrane glycoproteins that typically undergo post-translational attachment of palmitate on cysteine residues on the cytoplasmic facing tail of the protein. The role of spike protein palmitoylation in virus biogenesis and infectivity is being actively studied as a potential target of novel antivirals. Here, we report that palmitoylation of the first five cysteine residues of the C-terminal cysteine-rich domain of the SARS-CoV-2 S protein are indispensable for infection, and palmitoylation-deficient spike mutants are defective in membrane fusion. The DHHC9 palmitoyltransferase interacts with and palmitoylates the spike protein in the ER and Golgi and knockdown of DHHC9 results in reduced fusion and infection of SARS-CoV-2. Two bis-piperazine backbone-based DHHC9 inhibitors inhibit SARS-CoV-2 S protein palmitoylation and the resulting progeny virion particles released are defective in fusion and infection. This establishes these palmitoyltransferase inhibitors as potential new intervention strategies against SARS-CoV-2.

Adenosine triphosphate (ATP) is an important fuel of life for humans and Mycobacterium species. Its potential role in modulating cellular functions and implications in systemic, pulmonary, and ocular diseases is well studied. Plasma ATP has been used as a diagnostic and prognostic biomarker owing to its close association with disease's progression. Several stresses induce altered ATP generation, causing disorders and illnesses. Small heat shock proteins (sHSPs) are dynamic oligomers that are dominantly β-sheet in nature. Some important functions that they exhibit include preventing protein aggregation, enabling protein refolding, conferring thermotolerance to cells, and exhibiting anti-apoptotic functions. Expression and functions of sHSPs in humans are closely associated with several diseases like cataracts, cardiovascular diseases, renal diseases, cancer, etc. Additionally, there are some mycobacterial sHSPs like Mycobacterium leprae HSP18 and Mycobacterium tuberculosis HSP16.3, whose molecular chaperone functions are implicated in the growth and survival of pathogens in host species. As both ATP and sHSPs, remain closely associated with several human diseases and survival of bacterial pathogens in the host, therefore substantial research has been conducted to elucidate ATP-sHSP interaction. In this mini review, the impact of ATP on the structure and function of human and mycobacterial sHSPs is discussed. Additionally, how such interactions can influence the onset of several human diseases is also discussed., 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 Nandi, Panda, Chakraborty, Rathee, Roy, Barik, Mohapatra and Biswas.)

Inflammation plays a key role in the development of age-related diseases. In Alzheimer's disease, neuronal cell death is attributed to amyloidbeta oligomers that trigger microglial activation. Stem cells have shown promise as therapies for inflammatory diseases- because of their paracrine activity combined with their ability to respond to the inflammatory environment. However, the mechanisms underlying stem cell-promoted neurological recovery are poorly understood. To elucidate these mechanisms, we first primed stem cells with the secretome of lipopolysaccharide- or amyloidbeta-activated microglia. Then, we compared the immunomodulatory effects of extracellular vesicles (EVs) secreted from primed and non-primed stem cells. Our results demonstrate that EVs from primed cells are more effective in inhibiting microglia and astrocyte activation, amyloid deposition, demyelination, memory loss and motor and anxiety-like behavioral dysfunction, compared to EVs from non-primed cells. MicroRNA (miRNA) profiling revealed the upregulation of at least 19 miRNAs on primed-stem cell EVs. The miRNA targets were identified, and KEGG pathway analysis showed that the overexpressed miRNAs target key genes on the toll-like receptor-4 (TLR4) signaling pathway. Overall, our results demonstrate that priming mesenchymal stem cells (MSCs) with the secretome of activated microglia results in the release of miRNAs from EVs with enhanced immune regulatory potential able to fight neuroinflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Without hindering the taste, making a cigarette less harmful by reducing the percentage of toxic and carcinogenic compounds in the smoke of the cigarette is a challenging task for the current generation of researchers. In the current work, by implementing mechanical, chemical and combined modification techniques, the above stated is tried to mitigate. In addition to the above, the optimum suction pressure, burning time and the number of puffing are also determined. Mechanical modification technique considers filter to cigarette ratio and filter design as the controlling parameters. The mathematical calculation reveals that puffing should stop when the cigarette length reaches 0.15 times of its original length. Furthermore, it is also identified that the concentrations of suspended solids and droplets in the smoke decrease significantly (separation efficiency = 56.81%) if the cigarette to filter ratio is maintained at 2.32. In case of chemical modification, by using various types of adsorbents such as charcoal and Zeolite 13X, the harmful effects are further reduced. These processes depict significant reduction in harmful effect (separation efficiency up to 62.1%) by showing the decrement in the suspended solids and droplets in the smoke due to the adsorption on the active sites of adsorbents. In case of combined modification, the achieved separation efficiency is 66.51%. For the experimentation, an experimental setup fitted with artificial lungs was used., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Railroad grade crossings (RRGCs) have emerged as critical transportation infrastructures from the point of safety and operational aspects because two modes of transportation intermingle at the intersecting zone; the understanding of safety and traffic operation at RRGC is of prime concern while planning and designing this transportation facility., Method: In this context, this work tries to comprehend RRGC performance-related parameters from published literature and figure out critical gaps. An international synthesis on the identified potential parameters influencing the RRGC performance (i.e., safety, driver behavior, and operational impact) was carried out by critically reviewing the articles published worldwide. Furthermore, key findings, used variables, analysis methods, research gaps, and recommendations were studied., Results: The review revealed that many researchers had explored the driver behavior and safety aspect based on past crash data and violations prevailing at RRGC. However, little research has been done to evaluate the effect of highways' operational characteristics on the performance of RRGC. Moreover, limited investigation has been carried out to understand the dilemma of drivers and the proactive safety evaluation of pedestrians and non-motorized vehicles at RRGC. A total of seven critical research gaps concerning parameters are recognized, facilitating a clear agenda for further research pertaining to RRGC performance., (Copyright © 2021. Published by Elsevier Ltd.)

A novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear. To shed light on the potential mechanisms, we examined publicly available RNA-Sequencing data using CIBERSORTx and conducted a Ingenuity Pathway Analysis to address this knowledge gap. In complement to these findings, we used bioinformatics tools to analyze publicly available RNA sequencing data and found that upregulation of complement may be leading to a downregulation of T-cell activity in lungs of severe COVID-19 patients. Thus, targeting treatments aimed at the modulation of classical complement and T-cell activity may help alleviate the proinflammatory effects of COVID-19, reduce lung pathology, and increase the survival of COVID-19 patients., 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 © 2021 Howell, Green, McGill, Kahlil, Dutta, Mohapatra and Mohapatra.)

The axis of Programmed cell death-1 receptor (PD-1) with its ligand (PD-L1) plays a critical role in colorectal cancer (CRC) in escaping immune surveillance, and blocking this axis has been found to be effective in a subset of patients. Although blocking PD-L1 has been shown to be effective in 5-10% of patients, the majority of the cohorts show resistance to this checkpoint blockade (CB) therapy. Multiple factors assist in the growth of resistance to CB, among which T cell exhaustion and immunosuppressive effects of immune cells in the tumor microenvironment (TME) play a critical role along with other tumor intrinsic factors. We have previously shown the polyketide antibiotic, Mithramycin-A (Mit-A), an effective agent in killing cancer stem cells (CSCs) in vitro and in vivo in a subcutaneous murine model. Since TME plays a pivotal role in CB therapy, we tested the immunomodulatory efficacy of Mit-A with anti-PD-L1 mAb (αPD-L1) combination therapy in an immunocompetent MC38 syngeneic orthotopic CRC mouse model. Tumors and spleens were analyzed by flow cytometry for the distinct immune cell populations affected by the treatment, in addition to RT-PCR for tumor samples. We demonstrated the combination treatment decreases tumor growth, thus increasing the effectiveness of the CB. Mit-A in the presence of αPD-L1 significantly increased CD8 + T cell infiltration and decreased immunosuppressive granulocytic myeloid-derived suppressor cells and anti-inflammatory macrophages in the TME. Our results revealed Mit-A in combination with αPD-L1 has the potential for augmented CB therapy by turning an immunologically "cold" into "hot" TME in CRC., Competing Interests: SM (founder and scientific advisor) and SSM (founder and scientific advisor) have an equity interest in Transgenex Nanobiotech Inc. The terms of this arrangement have been reviewed and approved by the USF in accordance with its conflict of interest policies. The remaining 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 © 2021 Dutta, Khalil, Mayilsamy, Green, Howell, Bharadwaj, Mohapatra and Mohapatra.)

The RFamide-related peptides (RFRPs) are the group of neuropeptides synthesized predominantly from the hypothalamus that negatively affects the hypothalamo-hypophyseal-gonadal (hypothalamic-pituitary-gonadal [HPG]) axis. These peptides are first identified in quail brains and emerged as the mammalian orthologs of avian gonadotropin inhibitory hormones. The RFRP-3 neurons in the hypothalamus are present in several mammalian species. The action of RFRP-3 is mediated through a G-protein-coupled receptor called OT7T022. The predominant role of RFRP-3 is the inhibition of HPG axis with several other effects such as the regulation of metabolic activity, stress regulation, controlling of non-sexual motivated behavior, and sexual photoperiodicity in concert with other neuropeptides such as kisspeptin, neuropeptide-Y (NPY), pro-opiomelanocortin, orexin, and melanin. RFamide peptides synthesized in the granulosa cells, interstitial cells, and seminiferous tubule regulate steroidogenesis and gametogenesis in the gonads. The present review is intended to provide the recent findings that explore the role of RFRP-3 in regulating HPG axis and its potential applications in the synchronization of reproduction and its therapeutic interventions to prevent stress-induced amenorrhea., (Copyright: © Mohapatra, et al.)

The emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019 led to a worldwide pandemic with over 170 million confirmed infections and over 3.5 million deaths (as of May 2021). Early studies have shown higher mortality rates from SARS-CoV-2 infection in cancer patients than individuals without cancer. Herein, we review the evidence that the gut microbiota plays a crucial role in health and has been linked to the development of colorectal cancer (CRC). Investigations have shown that SARS-CoV-2 infection causes changes to the gut microbiota, including an overall decline in microbial diversity, enrichment of opportunistic pathogens such as Fusobacterium nucleatum bacteremia, and depletion of beneficial commensals, such as the butyrate-producing bacteria. Further, these changes lead to increased colonic inflammation, which leads to gut barrier disruption, expression of genes governing CRC tumorigenesis, and tumor immunosuppression, thus further exacerbating CRC progression. Additionally, a long-lasting impact of SARS-CoV-2 on gut dysbiosis might result in a greater possibility of new CRC diagnosis or aggravating the condition in those already afflicted. Herein, we review the evidence relating to the current understanding of how infection with SARS-CoV-2 impacts the gut microbiota and the effects this will have on CRC carcinogenesis and progression., Competing Interests: The authors declare no potential conflict of interest.

Background and Aims: Artificial intelligence (AI)-based computer-aided diagnostic (CADx) algorithms are a promising approach for real-time histology (RTH) of colonic polyps. Our aim is to present a novel in situ CADx approach that seeks to increase transparency and interpretability of results by generating an intuitive augmented visualization of the model's predicted histology over the polyp surface., Methods: We developed a deep learning model using semantic segmentation to delineate polyp boundaries and a deep learning model to classify subregions within the segmented polyp. These subregions were classified independently and were subsequently aggregated to generate a histology map of the polyp's surface. We used 740 high-magnification narrow-band images from 607 polyps in 286 patients and over 65,000 subregions to train and validate the model., Results: The model achieved a sensitivity of .96, specificity of .84, negative predictive value (NPV) of .91, and high-confidence rate (HCR) of .88, distinguishing 171 neoplastic polyps from 83 non-neoplastic polyps of all sizes. Among 93 neoplastic and 75 non-neoplastic polyps ≤5 mm, the model achieved a sensitivity of .95, specificity of .84, NPV of .91, and HCR of .86., Conclusions: The CADx model is capable of accurately distinguishing neoplastic from non-neoplastic polyps and provides a histology map of the spatial distribution of localized histologic predictions along the delineated polyp surface. This capability may improve interpretability and transparency of AI-based RTH and offer intuitive, accurate, and user-friendly guidance in real time for the clinical management and documentation of optical histology results., (Published by Elsevier Inc.)

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process's key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants.

Respiratory Syncytial Virus (RSV) has been a major health concern globally for decades, yet no effective prophylactic or treatment regimen is available. The key viral proteins responsible for RSV pathology include the fusion protein (F), the immunomodulatory non-structural-protein 1 (NS1) and the phosphoprotein (P) involved in viral replication. Herein, we developed a novel shell-core multifunctional nanosystem with dual payload: a plasmid construct encoding for shRNAs against NS1 and P, and an anti-fusion peptide (HR2D). Anti-ICAM1 antibody conjugated on the nanoparticle (NP) surface is used to target RSV infected cells. Our data show the potential of this nanosystem as a prophylactic and/or a therapeutic regimen against RSV infection. Furthermore, therapy of RSV infected mice with this nanosystem, in addition to reducing viral load, modulated expression of Th2 and allergy-associated cytokines such as IL4, IL-13 and IL-17 indicating a direct role of this nanosystem in the mechanisms involved in the immunoregulation of disease pathogenesis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ocular diseases can deteriorate vision to the point of blindness and thus can have a major impact on the daily life of an individual. Conventional therapies are unable to provide absolute therapy for all ocular diseases due to the several limitations during drug delivery across the blood-retinal barrier, making it a major clinical challenge. With recent developments, the vast number of publications undergird the need for nanotechnology-based drug delivery systems in treating ocular diseases. The tool of nanotechnology provides several essential advantages, including sustained drug release and specific tissue targeting. Additionally, comprehensive in vitro and in vivo studies have suggested a better uptake of nanoparticles across ocular barriers. Nanoparticles can overcome the blood-retinal barrier and consequently increase ocular penetration and improve the bioavailability of the drug. In this review, we aim to summarize the development of organic and inorganic nanoparticles for ophthalmic applications. We highlight the potential nanoformulations in clinical trials as well as the products that have become a commercial reality.

Infections caused by multi-drug resistant (MDR) bacterial pathogens are a leading cause of mortality and morbidity across the world. Indiscriminate use of broad-spectrum antibiotics has seriously affected this situation. With the diminishing discovery of novel antibiotics, new treatment methods are urgently required to combat MDR pathogens. Polymyxins, the cationic lipopeptide antibiotics, discovered more than half a century ago, are considered to be the last-line of antibiotics available at the moment. This antibiotic shows a great bactericidal effect against Gram-negative bacteria. Polymyxins primarily target the bacterial membrane and disrupt them, causing lethality. Because of their membrane interacting mode of action, polymyxins cause nephrotoxicity and neurotoxicity in humans, limiting their usability. However, recent modifications in their chemical structure have been able to reduce the toxic effects. The development of better dosing regimens has also helped in getting better clinical outcomes in the infections caused by MDR pathogens. Since the mid1990s the use of polymyxins has increased manifold in clinical settings, resulting in the emergence of polymyxin-resistant strains. The risk posed by the polymyxin-resistant nosocomial pathogens such as the Enterobacteriaceae group, Pseudomonas aeruginosa , and Acinetobacter baumannii , etc. is very serious considering these pathogens are resistant to almost all available antibacterial drugs. In this review article, the mode of action of the polymyxins and the genetic regulatory mechanism responsible for the emergence of resistance are discussed. Specifically, this review aims to update our current understanding in the field and suggest possible solutions that can be pursued for future antibiotic development. As polymyxins primarily target the bacterial membranes, resistance to polymyxins arises primarily by the modification of the lipopolysaccharides (LPS) in the outer membrane (OM). The LPS modification pathways are largely regulated by the bacterial two-component signal transduction (TCS) systems. Therefore, targeting or modulating the TCS signalling mechanisms can be pursued as an alternative to treat the infections caused by polymyxin-resistant MDR pathogens. In this review article, this aspect is also highlighted.

Aim: Intracranial solitary fibrous tumors (SFTs) and hemangiopericytomas (HPCs) are rare nonmeningothelial mesenchymal tumors sharing fusion of NGF1-A binding protein 2 (NAB2) and signal transducers and activators of transcription (STAT6.).The WHO classification of central nervous system (CNS) tumors (2016) highlights that molecular confirmation of NAB2/STAT6 fusion or immunohistochemical nuclear expression of STAT6 is mandatory for the diagnosis of SFT/HPC.Herein, we present a series of four cases of SFT/HPC of the brain, which mimicked other CNS tumors both clinically and radiologically., Material and Methods: This is a retrospective study over a period of two and a half years. Out of the 156 operated cases of brain tumors, four patients (2.56%) were diagnosed with SFT/HPC. The clinicoradiological details with the surgical procedure were retrieved from the archived hospital records., Results: All cases were males, of which three were in their 5th decade while one was a 14-month-old baby. Two cases were primary and the rest were recurrent.The location of tumors was extra-axial left cerebellotentorial,clivaldural-based,left cerebellar, and in the left frontoparietal region,respectively. The clinical impression was meningioma in three cases,while it was primitive neuroectodermal tumor (PNET) /atypical teratoid/rhabdoid tumor (ATRT) in one case.With the detailed histomorphology and immunohistochemistry, the final diagnosis was anaplastic hemangiopericytoma(WHO grade III) for all the cases. During our follow-up, one patient died with the disease, while the rest are doing well., Conclusion: SFT/HPC should be kept in the differential diagnosis of all dura-based hypervascular masses, especially in recurrent cases, due to its aggressiveness and high recurrence rate.

The tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and drug resistance. However, models recapitulating the complex 3D structure, heterogeneous cell environment, and cell-cell interactions found in vivo are lacking. Herein, we report on a gravitational microfluidic platform (GMP) retrofitted with MEMS sensors, which is integrated with 3D nanofiber scaffold-aided tumoroid culture. The results showed that this GMP for tumoroid growth mimics the tumor microenvironment more precisely than static culture models of colon cancer, including higher drug resistance, enhanced cancer stem cell properties, and increased secretion of pro-tumor cytokines. In addition, the GMP includes an integrated surface acoustic wave-based biosensing to monitor cell growth and pH changes to assess drug efficacy. Thus, this simple-to-use perfused GMP tumoroid culture system for in vitro and ex vivo studies may accelerate the drug development process and be a tool in personalized cancer treatment., (Copyright © 2020. Published by Elsevier Inc.)

Aim: The present investigation was intended to generate some basic data on electrocardiography (ECG) parameters in different breeds and their alterations in respect to sex and age., Materials and Methods: The present investigation was carried out on 239 owned dogs of 11 different breeds presented to the Institute Veterinary Clinic during 2018-2019. The animals, irrespective of breed and sex were grouped on the basis of their age groups. Recordings of rdiartR, BPL, India) at 25 mm/s paper speed and 10 mm=1 mV calibration keeping the animals on the right lateECG were performed by a single-channel ECG machine (Caral recumbence without any anesthesia. Heart rate, along with the amplitude and duration of different waves and complexes was measured., Results: Heart rate did not vary significantly among breeds, sex, and different age groups. The highest heart rate has been reported in Doberman and the lowest in Beagle. The heart rate was lowest at the age group of 6 months-2.5 years and highest around 10.5-12.5 years irrespective of breed and sex. The incidence of sinus arrhythmia was mostly seen in older dogs. All the waves and complexes did not vary significantly between breeds, age, and sex except P duration which was significantly (p<0.05) higher in Golden retriever and Doberman breeds., Conclusion: The present investigation generated some reference values of ECG in dogs which will help the clinicians to diagnose different cardiac abnormalities through ECG., (Copyright: © Mukherjee, et al.)

Traumatic brain injury (TBI) is a devastating neurological disorder, although the underlying pathophysiology is poorly understood. TBI causes blood-brain barrier (BBB) disruption, immune cell trafficking, neuroinflammation and neurodegeneration. CCL20 is an important chemokine mediating neuroinflammation. Human mesenchymal stem cell (hMSC) therapy is a promising regenerative approach but the inflammatory microenvironment in the brain tends to decrease the efficacy of the hMSC transplantation. Reducing the inflammation prior to hMSC therapy improves the outcome. We developed a combined nano-cell therapy by using dendrimers complexed with plasmids (dendriplexes) targeting CCL20 and its sole receptor CCR6 to reduce inflammation followed by hMSC transplantation. Treatment of TBI mice with shRNA conjugated dendriplexes followed by hMSC administration downregulated the inflammatory markers and significantly increased brain-derived neurotrophic factor (BDNF) expression in the cerebral cortex indicating future possible neurogenesis and improved behavioral deficits. Taken together, this nano-cell therapy ameliorates neuroinflammation and promotes brain tissue repair after TBI., (Published by Elsevier Inc.)

In Caulobacter crescentus the combined action of chromosome replication and the expression of DNA methyl-transferase CcrM at the end of S-phase maintains a cyclic alternation between a full- to hemi-methylated chromosome. This transition of the chromosomal methylation pattern affects the DNA-binding properties of the transcription factor GcrA that controls the several key cell cycle functions. However, the molecular mechanism by which GcrA and methylation are linked to transcription is not fully elucidated yet. Using a combination of cell biology, genetics, and in vitro analysis, we deciphered how GcrA integrates the methylation pattern of several S-phase expressed genes to their transcriptional output. We demonstrated in vitro that transcription of ctrA from the P1 promoter in its hemi-methylated state is activated by GcrA, while in its fully methylated state GcrA had no effect. Further, GcrA and methylation together influence a peculiar distribution of creS transcripts, encoding for crescentin, the protein responsible for the characteristic shape of Caulobacter cells. This gene is duplicated at the onset of chromosome replication and the two hemi-methylated copies are spatially segregated. Our results indicated that GcrA transcribed only the copy where coding strand is methylated. In vitro transcription assay further substantiated this finding. As several of the cell cycle-regulated genes are also under the influence of methylation and GcrA-dependent transcriptional regulation, this could be a mechanism responsible for maintaining the gene transcription dosage during the S-phase., (© 2020 John Wiley & Sons Ltd.)