Colloidal Synthesis of Monodisperse High-Entropy Spinel Oxide Nanocrystals.

Synthesis of high-entropy oxide (HEO) nanocrystals has focused on increasing the temperature in the entropy term (T(ΔS)) to overcome the enthalpy term. However, these high temperatures lead to large, polydisperse nanocrystals. In this work, we leverage the low solubility product (Ksp) of metal oxides and optimize the Lewis-acid-catalyzed esterification reaction for equal rate production of the cation monomers to synthesize HEO nanocrystals at low temperatures, producing the smallest (<4 nm) and most monodisperse (<15% size dispersity) HEOs to date. We apply these HEO nanocrystals as electrocatalysts, exhibiting promising activity toward the oxygen evolution reaction in alkaline media, with an overpotential of 345 mV at 10 mA/cm2.

Nitrophenol Reduction with Silver Oxide Nanostructures as a Sustainable Approach to Environmental Remediation.

We propose silver oxide as a cost-effective and sustainable alternative to noble metals for the catalytic reduction of nitroaromatics. In the present investigation, we adopt a facile and green synthetic route for the synthesis of silver oxide nanostructures. The prepared nanostructures were found to crystallize in the cuprite phase and exhibit absorbance across the entire visible range of the electromagnetic spectrum. The catalytic potential of the silver oxide was evaluated by following the kinetics of nitrophenol reduction under ambient conditions and is observed to follow pseudo-first order kinetics with the apparent rate constant k a p p = 4 . 24 × 10 - 3 ${{k}_{app}=4.24\ \times {10}^{-3}}$ s-1 at minimum concentration of the catalyst. We attribute the observed catalytic activity to the freshly generated catalytic surface featuring a partially reduced form of silver oxide during reaction. The findings highlight the efficacy of silver oxide in mitigating the environmental pollution originating from the recalcitrant nitroarenes.

Chiroptical Strain Sensors from Electrospun Cadmium Sulfide Quantum-Dot Fibers.

Controllable synthesis of homochiral nano/micromaterials has been a constant challenge for fabricating various stimuli-responsive chiral sensors. To provide an avenue to this goal, we report electrospinning as a simple and economical strategy to form continuous homochiral microfibers with strain-sensitive chiroptical properties. First, electrospun homochiral microfibers from self-assembled cadmium sulfide (CdS) quantum dot magic-sized clusters (MSCs) are produced. Highly sensitive and reversible strain sensors are then fabricated by embedding these chiroptically active fibers into elastomeric films. The chiroptical response on stretching is indicated quantitatively as reversible changes in magnitude, spectral position (wavelength), and sign in circular dichroism (CD) and linear dichroism (LD) signals and qualitatively as a prominent change in the birefringence features under cross-polarizers. The observed periodic twisted helical fibrils at the surface of fibers provide insights into the origin of the fibers' chirality. The measurable shifts in CD and LD are caused by elastic deformations of these helical fibrillar structures of the fiber. To elucidate the origin of these chiroptical properties, we used field emission-electron microscopy (FE-SEM), atomic force microscopy (AFM), synchrotron X-ray analysis, polarized optical microscopy, as well as measurements to isolate the true CD, and contributions from photoelastic modulators (PEM) and LD. Our findings thus offer a promising strategy to fabricate chiroptical strain-sensing devices with multiple measurables/observables using electric-field-assisted spinning of homochiral nano/microfibers.

Analysis of plasma metabolomes from 11 309 subjects in five population-based cohorts.

Plasma metabolomics holds potential for precision medicine, but limited information is available to compare the performance of such methods across multiple cohorts. We compared plasma metabolite profiles after an overnight fast in 11,309 participants of five population-based Swedish cohorts (50-80 years, 52% women). Metabolite profiles were uniformly generated at a core laboratory (Metabolon Inc.) with untargeted liquid chromatography mass spectrometry and a comprehensive reference library. Analysis of a second sample obtained one year later was conducted in a subset. Of 1629 detected metabolites, 1074 (66%) were detected in all cohorts while only 10% were unique to one cohort, most of which were xenobiotics or uncharacterized. The major classes were lipids (28%), xenobiotics (22%), amino acids (14%), and uncharacterized (19%). The most abundant plasma metabolome components were the major dietary fatty acids and amino acids, glucose, lactate and creatinine. Most metabolites displayed a log-normal distribution. Temporal variability was generally similar to clinical chemistry analytes but more pronounced for xenobiotics. Extensive metabolite-metabolite correlations were observed but mainly restricted to within each class. Metabolites were broadly associated with clinical factors, particularly body mass index, sex and renal function. Collectively, our findings inform the conduct and interpretation of metabolite association and precision medicine studies.

IFN-λ uniquely promotes CD8 T cell immunity against SARS-CoV-2 relative to type I IFN.

Optimization of protective immune responses against SARS-CoV-2 remains an urgent worldwide priority. In this regard, type III IFN (IFN-λ) restricts SARS-CoV-2 infection in vitro, and treatment with IFN-λ limits infection, inflammation, and pathogenesis in murine models. Furthermore, IFN-λ has been developed for clinical use to limit COVID-19 severity. However, whether endogenous IFN-λ signaling has an effect on SARS-CoV-2 antiviral immunity and long-term immune protection in vivo is unknown. In this study, we identified a requirement for IFN-λ signaling in promoting viral clearance and protective immune programming in SARS-CoV-2 infection of mice. Expression of both IFN and IFN-stimulated gene (ISG) in the lungs were minimally affected by the absence of IFN-λ signaling and correlated with transient increases in viral titers. We found that IFN-λ supported the generation of protective CD8 T cell responses against SARS-CoV-2 by facilitating accumulation of CD103+ DC in lung draining lymph nodes (dLN). IFN-λ signaling specifically in DCs promoted the upregulation of costimulatory molecules and the proliferation of CD8 T cells. Intriguingly, antigen-specific CD8 T cell immunity to SARS-CoV-2 was independent of type I IFN signaling, revealing a nonredundant function of IFN-λ. Overall, these studies demonstrate a critical role for IFN-λ in protective innate and adaptive immunity upon infection with SARS-CoV-2 and suggest that IFN-λ serves as an immune adjuvant to support CD8 T cell immunity.

MicroCycle: An Integrated and Automated Platform to Accelerate Drug Discovery.

We herein describe the development and application of a modular technology platform which incorporates recent advances in plate-based microscale chemistry, automated purification, in situ quantification, and robotic liquid handling to enable rapid access to high-quality chemical matter already formatted for assays. In using microscale chemistry and thus consuming minimal chemical matter, the platform is not only efficient but also follows green chemistry principles. By reorienting existing high-throughput assay technology, the platform can generate a full package of relevant data on each set of compounds in every learning cycle. The multiparameter exploration of chemical and property space is hereby driven by active learning models. The enhanced compound optimization process is generating knowledge for drug discovery projects in a time frame never before possible.

Imaging 3D chemistry at 1 nm resolution with fused multi-modal electron tomography.

Measuring the three-dimensional (3D) distribution of chemistry in nanoscale matter is a longstanding challenge for metrological science. The inelastic scattering events required for 3D chemical imaging are too rare, requiring high beam exposure that destroys the specimen before an experiment is completed. Even larger doses are required to achieve high resolution. Thus, chemical mapping in 3D has been unachievable except at lower resolution with the most radiation-hard materials. Here, high-resolution 3D chemical imaging is achieved near or below one-nanometer resolution in an Au-Fe3O4 metamaterial within an organic ligand matrix, Co3O4-Mn3O4 core-shell nanocrystals, and ZnS-Cu0.64S0.36 nanomaterial using fused multi-modal electron tomography. Multi-modal data fusion enables high-resolution chemical tomography often with 99% less dose by linking information encoded within both elastic (HAADF) and inelastic (EDX/EELS) signals. We thus demonstrate that sub-nanometer 3D resolution of chemistry is measurable for a broad class of geometrically and compositionally complex materials.

Gasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation.

Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of the inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation of GSDMD in knockout (KO) mice (Gsdmd-/-) significantly attenuates influenza virus-induced weight loss, lung dysfunction, lung histopathology, and mortality compared with wild type (WT) mice, despite similar viral loads. Infected Gsdmd-/- mice exhibit decreased inflammatory gene signatures shown by lung transcriptomics. Among these, diminished neutrophil gene activation signatures are corroborated by decreased detection of neutrophil elastase and myeloperoxidase in KO mouse lungs. Indeed, directly infected neutrophils are observed in vivo and infection of neutrophils in vitro induces release of DNA and tissue-damaging enzymes that is largely dependent on GSDMD. Neutrophil depletion in infected WT mice recapitulates the reductions in mortality, lung inflammation, and lung dysfunction observed in Gsdmd-/- animals, while depletion does not have additive protective effects in Gsdmd-/- mice. These findings implicate a function for GSDMD in promoting lung neutrophil responses that amplify influenza virus-induced inflammation and pathogenesis. Targeting the GSDMD/neutrophil axis may provide a therapeutic avenue for treating severe influenza.

A Multicenter Study of 2-year Outcomes Following Hyperthermia Therapy with Mitomycin C in Treating Non-Muscle Invasive Bladder Cancer: HIVEC-E.

INTRODUCTION: High grade, non-muscle invasive bladder cancer (NMIBC) is usually treated with intravesical Bacillus Calmette-Guérin. Chemohyperthermia therapy (CHT) may be a novel alternative therapy for the treatment of NMIBC. OBJECTIVE: To evaluate the recurrence-free survival (RFS) of patients treated with CHT using the Combat bladder recirculation system (BRS) for NMIBC. METHODS: This was a prospective multi-institutional study of 1,028 consecutive patients with NMIBC undergoing CHT between 2012 and 2020. A total of 835 patients were treated with CHT with Mitomycin C (MMC). Disease was confirmed on transurethral resection of bladder tumor (TURBT) prior to starting CHT. Follow-up included cystoscopy and subsequent TURBT if recurrence/progression was suspected. The primary endpoint was RFS. Secondary endpoints were progression-free survival (PFS) and adverse events from CHT. RESULTS AND LIMITATIONS: Median follow up was 22.4 months (Interquartile range (IQR): 12.8 -35.8). Median age was 70.4 years (IQR: 62.1 -78.6). A total of 557 (66.7%), 172 (20.6) and 74 (8.9%) of patients were classified to BCG naïve, BCG unresponsive and BCG failure, respectively. The RFS at 12 months and 24 months for BCG naïve was 87.6% (95% CI 85.0% - 90.4%) and 75.0% (95% CI 71.3% - 78.8%), respectively. The RFS at 12 months and 24 months for BCG unresponsive cohort was 78.1% (95% CI 72.0% - 84.7%) and 57.4% (95% CI 49.7% - 66.3%), respectively. The RFS at 24 months for the BCG unresponsive cohort for CIS with/without papillary disease and papillary only disease were 43.6% (95% CI 31.4% -60.4%) and 64.5% (95% CI 55.4% - 75.1%), respectively. Minor adverse events occurred in 216 (25.6%) patients and severe events occurred in 17 (2.0%) patients. CONCLUSIONS: CHT with MMC using the Combat BRS is effective in the medium term and has a favorable adverse event profile.

Diagnóstico y tratamiento de la retinopatía diabética y edema macular diabético: guía de práctica clínica del Seguro Social de Salud del Perú (EsSalud) / Diagnosis and treatment of diabetic retinopathy and diabetic macular edema: clinical practice guidelines of the Peruvian Health Social Security (EsSalud)

RESUMEN Introducción. El presente artículo resume la guía de práctica clínica (GPC) para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en el Seguro Social de Salud del Perú (EsSalud). Objetivo. Proveer recomendaciones clínicas basadas en evidencia para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud. Métodos. Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos. El GEG formuló 4 preguntas clínicas a ser respondidas por la presente GPC. Para cada una de estas preguntas se realizó búsquedas de revisiones sistemáticas y de estudios primarios (cuando se consideró pertinente) en PubMed durante el 2018. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y el flujograma de manejo. Resultados. La presente GPC abordó 4 preguntas clínicas sobre el tamizaje, diagnóstico, tratamiento de elección y tratamiento adyuvante. En base a estas preguntas se formularon 6 recomendaciones (4 fuertes y 2 condicionales), 19 puntos de buena práctica clínica y 1 flujograma de manejo. Conclusión. El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para el diagnóstico y tratamiento de la retinopatía diabética y el edema macular diabético en EsSalud.

ABSTRACT Introduction. This article summarizes the clinical practice guidelines (CPG) for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema of the Health Social Security of Peru (EsSalud). Objective. To provide clinical recommendations based on evidence for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud. Methods. A guidelines elaborating group (GEG) was conformed by medical specialists and methodologists. The GEG formulated 4 clinical questions intended to be answered by this CPG. For each of these questions systematic searches of systematic reviews and primary studies (when considered pertinent) were carried out in PubMed during 2018. Evidence was selected in order to reply each of the proposed clinical questions. The certainty of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. During periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, points of good clinical practice and the management flowchart. Results. The present CPG addressed 4 clinical questions of four topics: screening, diagnosis, treatment of choice and adjuvant treatment. Based on these questions, 6 recommendations (4 strong and 2 conditional), 19 points of good clinical practice, and 1 management flowchart were formulated. Conclusion. This article summarizes the methodology and conclusions based on evidence from the CPG for the diagnosis and treatment of diabetic retinopathy and diabetic macular edema in EsSalud.