Deposition and Optical Characterization of Sputter Deposited p-Type Delafossite CuGaO2 Thin Films Using Cu2O and Ga2O3 Targets.

CuGaO2 thin films were deposited using the RF magnetron sputtering technique using Cu2O and Ga2O3 targets. The films were deposited at room temperature onto a quartz slide. The sputtering power of Cu2O remained constant at 50 W, while the sputtering power of Ga2O3 was systematically varied from 150 W to 200 W. The films were subsequently subjected to annealing at temperatures of 850 °C and 900 °C in a nitrogen atmosphere for a duration of 5 h. XRD analysis on films deposited with a Ga2O3 sputtering power of 175 W annealed at 900 °C revealed the development of nearly single-phase delafossite CuGaO2 thin films. SEM images of films annealed at 900 °C showed an increasing trend in grain size with a change in sputtering power level. Optical studies performed on the film revealed a transmission of 84.97% and indicated a band gap of approximately 3.27 eV. The film exhibited a refractive index of 2.5 within the wavelength range of 300 to 450 nm.

Crystal size, shape, and conformational changes drive both the disappearance and reappearance of ritonavir polymorphs in the mill.

Organic compounds can crystallize in different forms known as polymorphs. Discovery and control of polymorphism is crucial to the pharmaceutical industry since different polymorphs can have significantly different physical properties which impacts their utilization in drug delivery. Certain polymorphs have been reported to 'disappear' from the physical world, irreversibly converting to new ones. These unwanted polymorph conversions, initially prevented by slow nucleation kinetics, are eventually observed driven by significant gains in thermodynamic stabilities. The most infamous of these cases is that of the HIV drug ritonavir (RVR): Once its reluctant form was unwillingly nucleated for the first time, its desired form could no longer be produced with the same manufacturing process. Here we show that RVR's extraordinary disappearing polymorph as well as its reluctant form can be consistently produced by ball-milling under different environmental conditions. We demonstrate that the significant difference in stability between its polymorphs can be changed and reversed in the mill-a process we show is driven by crystal size as well as crystal shape and conformational effects. We also show that those effects can be controlled through careful design of milling conditions since they dictate the kinetics of crystal breakage, dissolution, and growth processes that eventually lead to steady-state crystal sizes and shapes in the mill. This work highlights the huge potential of mechanochemistry in polymorph discovery of forms initially difficult to nucleate, recovery of disappearing polymorphs, and polymorph control of complex flexible drug compounds such as RVR.

Role of renin-angiotensin system/angiotensin converting enzyme-2 mechanism and enhanced COVID-19 susceptibility in type 2 diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV.

The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-converting enzyme 2 (ACE2) fused to the IgM Fc. This ACE2 decamer viral trap is designed to inhibit SARS-CoV-2 entry function, regardless of viral RBD sequence variations as shown by its high neutralization potency against all known SARS-CoV-2 variants, including Omicron BQ.1, BQ.1.1, XBB.1 and XBB.1.5. In addition, it demonstrates potency against SARS-CoV-1, human NL63, as well as bat and pangolin CoVs. The multivalent trap is effective in both prophylactic and therapeutic settings since a single intranasal dosing confers protection in human ACE2 transgenic mice against viral challenges. Lastly, this molecule is stable at ambient temperature for more than twelve weeks and can sustain physical stress from aerosolization. These results demonstrate the potential of a decameric ACE2 viral trap as an inhalation solution for ACE2-dependent coronaviruses of current and future pandemic concerns.

Phase biasing of a Josephson junction using Rashba-Edelstein effect.

A charge-current-induced shift in the spin-locked Fermi surface leads to a non-equilibrium spin density at a Rashba interface, commonly known as the Rashba-Edelstein effect. Since this is an intrinsically interfacial property, direct detection of the spin moment is difficult. Here we demonstrate that a planar Josephson Junction, realized by placing two closely spaced superconducting electrodes over a Rashba interface, allows for a direct detection of the spin moment as an additional phase in the junction. Asymmetric Fraunhofer patterns obtained for Nb-(Pt/Cu)-Nb nano-junctions, due to the locking of Rashba-Edelstein spin moment to the flux quantum in the junction, provide clear signatures of this effect. This simple experiment offers a fresh perspective on direct detection of spin polarization induced by various spin-orbit effects. In addition, this platform also offers a magnetic-field-controlled phase biasing mechanism in conjunction with the Rashba-Edelstein spin-orbit effect for superconducting quantum circuits.

Host specificity of passerine Lankesterella (Apicomplexa: Coccidia).

Lankesterella parasites are blood coccidians that have recently gained attention as their records in common passerine species emerge. To date, their occurrence has been molecularly confirmed in several passerine genera, mainly among members of the families Paridae and Acrocephalidae. Despite their relatively high prevalence in some host populations, their life cycles remain unclear, mosquitoes or mites being the proposed vectors. The aim of this study was to reveal Lankesterella host specificity, focusing mainly on parasites of tit and warbler species (families Paridae and Acrocephalidae). We have determined the 18S rRNA gene sequences of Lankesterella from 35 individuals belonging to eight different host species. Phylogenetic analysis revealed that passerine Lankesterella are host-specific, with specificity at the host genus or species level. Besides Lankesterella, Isospora sequences were obtained from avian blood as well, pointing out the need for barcoding.

Cryptococcal infection causing longitudinal extensive transverse myelitis in an immunocompetent individual: Case report and literature review.

Cryptococcal CNS infections in immunocompetent individuals are occasionally reported in literature. The spinal manifestations of cryptococcal CNS infections are epidural abscess, chronic arachnoiditis, intramedullary granuloma, myelitis and vasculitis. We report a rare case of CNS cryptococcal infection presenting as a longitudinal extensive transverse myelitis (LETM) in an immunocompetent male. This report highlights cryptococcus as an important etiology among infectious causes in acute LETM patients in-spite of the immunocompetent status of the patient and the utility of CRAG (cryptococcal antigen) for diagnosis in such patients. We also present a literature review of all reported cases of cryptococcal myelitis.

Current aspects of organoid technology for biomaterial toxicity analysis.

Organoids provide us an opportunity to understand how diseases affect cellular physiology, human tissues or organs. They are indespensible tools for biomaterial toxicity analysis, drug discovery and regenerative medicine.

Development of chemically synthesized hydroxyapatite composite with reduced graphene oxide for enhanced mechanical properties.

A successful attempt has been made to improve the mechanical properties of Hydroxyapatite (HAp) and reduced graphene oxide (rGO) composite nanoparticles (NPs). Various proportions of HAp and rGO were synthesized to improve the mechanical properties. HAp NPs were prepared using the wet precipitation method and further calcined to form crystalline particles. The physicochemical characterization of the HAp NPs revealed that the crystalline size and percentage of crystallinity were calculated to be 42.49 ± 1.2 nm and 44% post calcination. Furthermore, the rGO-HA composites were prepared using ball milling and obtained in the shape of pellets with different ratios of rGO (10, 20, 30, 40, 50% wt.). The mechanical properties have been evaluated through a Universal testing machine. Compared to calcined HAp (cHAp), the strength of variants significantly enhanced with the increased concentration of rGO. The compressive strength of HA-rGO with the ratio of the concentration of 60:40% by weight is a maximum of about 10.39 ± 0.43 MPa. However, the porosity has also been bolstered by increasing the concentration of rGO, which has been evaluated through the liquid displacement method. The mean surface roughness of the composites has also been evaluated from the images through Image J (an image analysis program).

Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy.

OBJECTIVES: Type 2 diabetes (T2D) imposes an enormous burden all over the world in both developed and developing countries. Inter-individual differences are attributed to polymorphisms in candidate genes resulting in altered absorption, transportation, distribution, and metabolism of oral antidiabetic drugs (OADs). Hence, the present study was undertaken to evaluate the pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) on metformin monotherapy in newly diagnosed untreated T2D patients. METHODS: Newly diagnosed T2D patients ( n = 500) were enrolled according to inclusion/exclusion criteria. Initially, enrolled subjects were prescribed metformin monotherapy and followed up for at least 12 weeks. Response to metformin was evaluated in 478 patients who revisited for follow-up by measuring HbA1c. RESULT: Out of 478 patients, 373 were responders to metformin monotherapy while 105 were non-responders. The pharmacogenetic impact was evaluated by genotype, haplotype, and pharmacogenetic analyses. 'GG' genotype and 'G' allele of SLC22A1 rs628031 G/A were observed in 48.8% and 67.7% of Met responders, respectively, while 20.9% and 49.1 % were in non-responders. Therefore, there was a 2.18-fold increase in the success rate of Met therapeutics. CONCLUSION: Individuals carrying the 'GG' genotype or 'G' allele for SLC22A1 gene variant rs628031 G/A are better responders for Metformin monotherapy.

Online 3D Characterization of Micrometer-Sized Cuboidal Particles in Suspension.

Characterization of particle size and shape is central to the study of particulate matter in its broadest sense. Whilst 1D characterization defines the state of the art, the development of 2D and 3D characterization methods has attracted increasing attention, due to a common need to measure particle shape alongside size. Herein, ensembles of micrometer-sized cuboidal particles are studied, for which reliable sizing techniques are currently missing. Such particles must be characterized using three orthogonal dimensions to completely describe their size and shape. To this end, the utility of an online and in-flow multiprojection imaging tool coupled with machine learning is experimentally assessed. Central to this activity, a methodology is outlined to produce micrometer-sized, non-spherical analytical standards. Such analytical standards are fabricated using photolithography, and consist of monodisperse micro-cuboidal particles of user-defined size and shape. The aforementioned activities are addressed through an experimental framework that fabricates analytical standards and subsequently uses them to validate the performance of our multiprojection imaging tool. Significantly, it is shown that the same set of data collected for particle sizing can also be used to estimate particle orientation in flow, thus defining a rapid and robust protocol to investigate the behavior of dilute particle-laden flows.

Drug repurposing and sequence analysis in S-glycoprotein variants reveals critical signature patterns and destabilization of receptor-binding domain in omicron variant.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus since its emergence in 2019 has yielded several new viral variants with varied infectivity, disease severity, and antigenicity. Although most mutations are expected to be relatively neutral, mutations at the Spike region of the genome have shown to have a major impact on the viral transmission and infection in humans. Therefore, it is crucial to survey the structures of spike protein across the global virus population to contextualize the rate of therapeutic success against these variants. In this study, high-frequency mutational variants from different geographic regions were pooled in order to study the structural evolution of the spike protein through drug docking and MD simulations. We investigated the mutational burden in the spike subregions and have observed that the different variants harbour unique signature patterns in the spike subregions, with certain domains being highly prone to mutations. Further, the MD simulations and docking study revealed that different variants show differential stability when docked for the same set of drug targets. This work sheds light on the mutational burden and the stability landscape of the spike protein across the variants from different geographical regions.Communicated by Ramaswamy H. Sarma.

Recent Trends and Opportunities for the Targeted Immuno-Nanomaterials for Cancer Theranostics Applications.

The targeted delivery of cancer immunotherapies has increased noticeably in recent years. Recent advancements in immunotherapy, particularly in blocking the immune checkpoints (ICs) axis, have shown favorable treatment outcomes for multiple types of cancer including melanoma and non-small-cell lung cancer (NSLC). Engineered micromachines, including microparticles, and nanoplatforms (organic and inorganic), functionalized with immune agonists can effectively deliver immune-targeting molecules to solid tumors. This review focuses on the nanomaterial-based strategies that have shown promise in identifying and targeting various immunological markers in the tumor microenvironment (TME) for cancer diagnosis and therapy. Nanomaterials-based cancer immunotherapy has improved treatment outcomes by triggering an immune response in the TME. Evaluating the expression levels of ICs in the TME also could potentially aid in diagnosing patients who would respond to IC blockade therapy. Detecting immunological checkpoints in the TME using noninvasive imaging systems via tailored nanosensors improves the identification of patient outcomes in immuno-oncology (IO). To enhance patient-specific analysis, lab-on-chip (LOC) technology is a rapid, cost-effective, and accurate way of recapitulating the TME. Such novel nanomaterial-based technologies have been of great interest for testing immunotherapies and assessing biomarkers. Finally, we provide a perspective on the developments in artificial intelligence tools to facilitate ICs-based nano theranostics toward cancer immunotherapy.

Simultaneous Estimation of Gas Adsorption Equilibria and Kinetics of Individual Shaped Adsorbents.

Shaped adsorbents (e.g., pellets, extrudates) are typically employed in several gas separation and sensing applications. The performance of these adsorbents is dictated by two key factors, their adsorption equilibrium capacity and kinetics. Often, adsorption equilibrium and textural properties are reported for materials. Adsorption kinetics are seldom presented due to the challenges associated with measuring them. The overarching goal of this work is to develop an approach to characterize the adsorption properties of individual shaped adsorbents with less than 100 mg of material. To this aim, we have developed an experimental dynamic sorption setup and complemented it with mathematical models, to describe the mass transport in the system. We embed these models into a derivative-free optimizer to predict model parameters for adsorption equilibrium and kinetics. We evaluate and independently validate the performance of our approach on three adsorbents that exhibit differences in their chemistry, synthesis, formulation, and textural properties. Further, we test the robustness of our mathematical framework using a digital twin. We show that the framework can rapidly (i.e., in a few hours) and quantitatively characterize adsorption properties at a milligram scale, making it suitable for the screening of novel porous materials.

Solubility of Organic Salts in Solvent-Antisolvent Mixtures: A Combined Experimental and Molecular Dynamics Simulations Approach.

We combine molecular dynamics simulations with experiments to estimate solubilities of an organic salt in complex growth environments. We predict the solubility by simulations of the growth and dissolution of ions at the crystal surface kink sites at different solution concentrations. Thereby, the solubility is identified as the solution's salt concentration, where the energy of the ion pair dissolved in solution equals the energy of the ion pair crystallized at the kink sites. The simulation methodology is demonstrated for the case of anhydrous sodium acetate crystallized from various solvent-antisolvent mixtures. To validate the predicted solubilities, we have measured the solubilities of sodium acetate in-house, using an experimental setup and measurement protocol that guarantees moisture-free conditions, which is key for a hygroscopic compound like sodium acetate. We observe excellent agreement between the experimental and the computationally evaluated solubilities for sodium acetate in different solvent-antisolvent mixtures. Given the agreement and the rich data the simulations produce, we can use them to complement experimental tasks, which in turn will reduce time and capital in the design of complicated industrial crystallization processes of organic salts.

A microfluidic device for real-time on-demand intravenous oxygen delivery.

SignificanceThe treatment of hypoxemia that is refractory to the current standard of care is time-sensitive and requires skilled caregivers and use of specialized equipment (e.g., extracorporeal membrane oxygenation). Most patients experiencing refractory hypoxemia will suffer organ dysfunction, and death is common in this cohort. Here, we describe a new strategy to stabilize and support patients using a microfluidic device that administers oxygen gas directly to the bloodstream in real time and on demand using a process that we call sequential shear-induced bubble breakup. If successful, the described technology may help to avoid or decrease the incidence of ventilator-related lung injury from refractory hypoxemia.

Unveiling the masked native blood group following thalidomide therapy in a thalassemia patient: A 5 WHY analysis approach.

Blood grouping discrepancy in patients with hematological disorders can occur due to red cell sensitization following transfusion, transplantation, and pregnancy or pre-analytical errors. Prompt initiation of root cause analysis is vital to avoid complications of wrong blood transfusion. We present an unusual case of Rh mismatched grouping report of 24 year old female thalassemia patient being managed in our hospital since 2015. Her current type and screen were observed as O Rh D negative with negative antibody screen while the historical blood group was O Rh D positive. The pre-analytical errors were ruled out and blood grouping performed from fresh sample also demonstrated as O Rh D negative despite antigen enhancement techniques and had no recent transfusion history. We sought to reason out the possibilities for discordant Rh grouping report, historical and present group through "Funnel based problem solving 5 WHY analysis" approach. The review of the past clinical history revealed that the patient had undergone Rh mismatch bone marrow transplant (Rh D positive donor and Rh D negative recipient) at 5 years of age which soon resulted in graft failure. Yet, she continued to receive Rh D positive blood thereafter with no development of anti-D which explains the historical blood group. Recently the patient was started on thalidomide, the Hb F inducer drug, which helped in maintaining her hemoglobin level between 9 and 10 g/dl without transfusion support for two months. This allowed unmasking of native Rh D negative blood and the review of clinical history played a significant role in resolution of grouping discrepancy.

Advances and opportunities in nanoimaging agents for the diagnosis of inflammatory lung diseases.

The development of rapid, noninvasive diagnostics to detect lung diseases is a great need after the COVID-2019 outbreak. The nanotechnology-based approach has improved imaging and facilitates the early diagnosis of inflammatory lung diseases. The multifunctional properties of nanoprobes enable better spatial-temporal resolution and a high signal-to-noise ratio in imaging. Targeted nanoimaging agents have been used to bind specific tissues in inflammatory lungs for early-stage diagnosis. However, nanobased imaging approaches for inflammatory lung diseases are still in their infancy. This review provides a solution-focused approach to exploring medical imaging technologies and nanoprobes for the detection of inflammatory lung diseases. Prospects for the development of contrast agents for lung disease detection are also discussed.

On Demand Biosensors for Early Diagnosis of Cancer and Immune Checkpoints Blockade Therapy Monitoring from Liquid Biopsy.

Recently, considerable interest has emerged in the development of biosensors to detect biomarkers and immune checkpoints to identify and measure cancer through liquid biopsies. The detection of cancer biomarkers from a small volume of blood is relatively fast compared to the gold standard of tissue biopsies. Traditional immuno-histochemistry (IHC) requires tissue samples obtained using invasive procedures and specific expertise as well as sophisticated instruments. Furthermore, the turnaround for IHC assays is usually several days. To overcome these challenges, on-demand biosensor-based assays were developed to provide more immediate prognostic information for clinicians. Novel rapid, highly precise, and sensitive approaches have been under investigation using physical and biochemical methods to sense biomarkers. Additionally, interest in understanding immune checkpoints has facilitated the rapid detection of cancer prognosis from liquid biopsies. Typically, these devices combine various classes of detectors with digital outputs for the measurement of soluble cancer or immune checkpoint (IC) markers from liquid biopsy samples. These sensor devices have two key advantages: (a) a small volume of blood drawn from the patient is sufficient for analysis, and (b) it could aid physicians in quickly selecting and deciding the appropriate therapy regime for the patients (e.g., immune checkpoint blockade (ICB) therapy). In this review, we will provide updates on potential cancer markers, various biosensors in cancer diagnosis, and the corresponding limits of detection, while focusing on biosensor development for IC marker detection.

Material Screening for Gas Sensing Using an Electronic Nose: Gas Sorption Thermodynamic and Kinetic Considerations.

To detect multiple gases in a mixture, one must employ an electronic nose or sensor array, composed of several materials, as a single material cannot resolve all the gases in a mixture accurately. Given the many candidate materials, choosing the right combination of materials to be used in an array is a challenging task. In a sensor whose sensing mechanism depends on a change in mass upon gas adsorption, both the equilibrium and kinetic characteristics of the gas-material system dictate the performance of the array. The overarching goal of this work is twofold. First, we aim to highlight the impact of thermodynamic characteristics of gas-material combination on array performance and to develop a graphical approach to rapidly screen materials. Second, we aim to highlight the need to incorporate the gas sorption kinetic characteristics to provide an accurate picture of the performance of a sensor array. To address these goals, we have developed a computational test bench that incorporates a sensor model and a gas composition estimator. To provide a generic study, we have chosen, as candidate materials, hypothetical materials that exhibit equilibrium characteristics similar to those of metal-organic frameworks. Our computational studies led to key learnings, namely, (1) exploit the shape of the sensor response as a function of gas composition for material screening purposes for gravimetric arrays; (2) incorporate both equilibrium and kinetics for gas composition estimation in a dynamic system; and (3) engineer the array by accounting for the kinetics of the materials, the feed gas flow rate, and the size of the device.