Convergence of Nanotechnology and Machine Learning: The State of the Art, Challenges, and Perspectives.

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.

Drug Discovery in the Age of Artificial Intelligence: Transformative Target-Based Approaches.

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.

Modulation of Paracellular Permeability in SARS-CoV-2 Blood-to-Brain Transcytosis.

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.

Blood within the bone: orbital intraosseous venous malformation.

Purpose: Description of clinical features, radiological characteristics, and management strategies in primary orbital intraosseous venous malformation (OIVM) with pertinent literature review.

Methods: A retrospective analysis including clinical, radiologic, operative, and histopathological data of six cases of histopathologically proven OIVM was done. A comprehensive literature review was conducted using online databases and augmented with manual search to identify reported cases of OIVM.

Acetate-encapsulated Linolenic Acid Liposomes Reduce SARS-CoV-2 and RSV Infection.

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.

Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer.

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.

Multispectral optoacoustic tomography (MSOT): Monitoring neurovascular changes in a mouse repetitive traumatic brain injury model.

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.

Targeting an evolutionarily conserved "E-L-L" motif in spike protein to identify a small molecule fusion inhibitor against SARS-CoV-2.

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 "ExLxL" ("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.

The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans.

Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities.

Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2.

EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools.

Epidermal Growth Factor Receptor (EGFR) signaling and EGFR mutations play key roles in cancer pathogenesis, particularly in the development of drug resistance. For the ∼20% of all non-small cell lung cancer (NSCLC) patients that harbor an activating mutation, EGFR tyrosine kinase inhibitors (TKIs) provide initial clinical responses. However, long-term efficacy is not possible due to acquired drug resistance.

Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges.

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.

SARS-CoV-2 infection increases the gene expression profile for Alzheimer's disease risk.

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).

Ultrafast-UV laser integrating cavity device for inactivation of SARS-CoV-2 and other viruses.

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.

Identification of SARS-CoV-2 Spike Palmitoylation Inhibitors That Results in Release of Attenuated Virus with Reduced Infectivity.

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.

Targeting an evolutionarily conserved "E-L-L" motif in the spike protein to develop a small molecule fusion inhibitor against SARS-CoV-2.

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 towards sustenance. Here, we identify an evolutionary conserved E-L-L motif present within the HR2 domain of all human and non-human coronavirus spike (S) proteins that play a crucial role in stabilizing the post-fusion 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.

Changing pattern of childhood blindness in eight North-Eastern states and review of the epidemiological data of childhood blindness of India.

Purpose: To assess the causes of visual impairment and blindness in children in all the schools for the blind in eight northeastern states and to determine its temporal trend, and to analyze the result with reference to various regional epidemiological data on childhood blindness in India.

Methods: Children aged ≤16 years, with a visual acuity of ≤6/18 in the better eye, attending 17 schools for the blind were examined between November 2018 and March 2020. WHO protocol and reporting format was used for the evaluation, diagnosis, and classification of the causes.

Activation of Intracellular Complement in Lungs of Patients With Severe COVID-19 Disease Decreases T-Cell Activity in the Lungs.

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.

Surface-enhanced infrared absorption spectroscopy for microorganisms discrimination on silver nanoparticle substrates.

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.

Combination Therapy of Mithramycin A and Immune Checkpoint Inhibitor for the Treatment of Colorectal Cancer in an Orthotopic Murine Model.

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.

Extracellular vesicles derived from inflammatory-educated stem cells reverse brain inflammation-implication of miRNAs.

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.

Macula Densa NOS1β Modulates Renal Hemodynamics and Blood Pressure during Pregnancy: Role in Gestational Hypertension.

Background: Regulation of renal hemodynamics and BP via tubuloglomerular feedback (TGF) may be an important adaptive mechanism during pregnancy. Because the β-splice variant of nitric oxide synthase 1 (NOS1β) in the macula densa is a primary modulator of TGF, we evaluated its role in normal pregnancy and gestational hypertension in a mouse model. We hypothesized that pregnancy upregulates NOS1β in the macula densa, thus blunting TGF, allowing the GFR to increase and BP to decrease.