Direct Membrane Penetration and Cytosolic Delivery of Nanoparticles via Electrostatically Bound Amphiphiles.

Nanoparticles usually enter cells through energy-dependent endocytosis that involves their cytosolic entry via biomembrane-coated endosomes. In contrast, direct translocation of nanoparticles with straight access to cytosol/subcellular components without any membrane coating is limited to very selective conditions/approaches. Here we show that nanoparticles can switch from energy-dependent endocytosis to energy-independent direct membrane penetration once an amphiphile is electrostatically bound to their surface. Compared to endocytotic uptake, this direct cell translocation is faster and nanoparticles are distributed inside the cytosol without any lysosomal trafficking. We found that this direct cell translocation option is sensitive to the charges of both the nanoparticles and the amphiphile. We propose that an electrostatically bound amphiphile induces temporary opening of the cell membrane, which allows direct cell translocation of nanoparticles. This approach can be adapted for efficient subcellular targeting of nanoparticles and nanoparticle-based drug delivery application, bypassing the endosomal trapping and lysosomal degradation.

Exciton dynamics in two-dimensional metal halide perovskite: The impact of film processing.

We investigate the hot carrier and exciton dynamics in two-dimensional (2D) metal halide perovskites using time-resolved spectroscopy. 2D perovskite films were prepared with and without dimethyl sulfoxide treatment to elucidate the effect of film processing techniques on optoelectronic properties. Femtosecond transient absorption measurements reveal that the charge carrier dynamics are different in the two samples, and excitons survive for a longer time in the treated sample than the untreated one. While the early-time carrier dynamics in the untreated sample are dominated by charges trapped by defect states, the hot free carriers govern the dynamics in the treated sample due to fewer defects in it. Morphological and other spectroscopic studies, including time-resolved photoluminescence, further suggest the formation of more defects in the untreated sample. These results can guide the future development of efficient 2D perovskite-based optoelectronic devices.

Mutations of evolutionarily conserved aromatic residues suggest that misfolding of the mouse prion protein may commence in multiple ways.

The misfolding of the mammalian prion protein from its α-helix rich cellular isoform to its ß-sheet rich infectious isoform is associated with several neurodegenerative diseases. The determination of the structural mechanism by which misfolding commences, still remains an unsolved problem. In the current study, native-state hydrogen exchange coupled with mass spectrometry has revealed that the N state of the mouse prion protein (moPrP) at pH 4 is in dynamic equilibrium with multiple partially unfolded forms (PUFs) capable of initiating misfolding. Mutation of three evolutionarily conserved aromatic residues, Tyr168, Phe174, and Tyr217 present at the interface of the ß2-α2 loop and the C-terminal end of α3 in the structured C-terminal domain of moPrP significantly destabilize the native state (N) of the protein. They also reduce the free energy differences between the N state and two PUFs identified as PUF1 and PUF2**. It is shown that PUF2** in which the ß2-α2 loop and the C-terminal end of α3 are disordered, has the same stability as the previously identified PUF2*, but to have a very different structure. Misfolding can commence from both PUF1 and PUF2**, as it can from PUF2*. Hence, misfolding can commence and proceed in multiple ways from structurally distinct precursor conformations. The increased extents to which PUF1 and PUF2** are populated at equilibrium in the case of the mutant variants, greatly accelerate their misfolding. The results suggest that the three aromatic residues may have been evolutionarily selected to impede the misfolding of moPrP.

Ultrafast carrier dynamics in vanadium-doped MoS2 alloys.

Substitutional doping is a most promising approach to manipulate the electronic and optical properties of two-dimensional (2D) transition metal dichalcogenides (TMDCs). In addition to inducing magnetism, vanadium (V) doping can lead to semiconductor-metal transition in TMDCs. However, the dynamics of charge carriers that governs the optoelectronic properties of doped TMDCs has been rarely revealed. In this work, we have investigated the dynamics of photocarriers in pristine and V-doped monolayer (ML) MoS2. Comparison of the transient absorption (TA) spectra of ML MoS2 with lightly (≤1%) and heavily (3.62%) V-doped MoS2 infers the induction of additional energy states in the doped materials giving rise to new low energy bleach features in the TA spectra. The quasiparticle band structure of MoS2 is found to disappear at sufficiently high V doping due to the presence of impurity bands. An attempt has also been made to study the manipulation of the carrier lifetime with V doping in MoS2. Our TA kinetic measurements suggest that the decay kinetics of the carriers becomes slower with increasing doping percentage and at a higher doping level the carriers survive for a much longer time compared to pristine MoS2. Furthermore, we have identified a new electronic transition (NET) in heavily V-doped MoS2 at high pump fluences.

Defect-mediated saturable absorption and carrier dynamics in tin (II) monosulfide quantum dots.

Tin (II) monosulfide (SnS) has attracted considerable attention in emerging photonics and optoelectronics because of high carrier mobility, large absorption coefficient, anisotropic linear and nonlinear optical properties, and long-time stability. In this Letter, we report third-order nonlinear absorption and refraction of SnS quantum dots (QDs). Under excitation with 800-nm femtosecond pulses, QDs exhibit saturable absorption (saturation intensity ∼ 47.69 GW/cm2) and positive refractive nonlinearity (nonlinear refraction coefficient ∼ 1.24 × 10-15 cm2/W). Nonetheless, we investigate charge carrier dynamics using femtosecond transient absorption spectroscopy and propose the presence of midgap defect states which not only dictate carrier dynamics but also give rise to nonlinear optical properties in SnS QDs.

Interactively learning behavior trees from imperfect human demonstrations.

Introduction: In Interactive Task Learning (ITL), an agent learns a new task through natural interaction with a human instructor. Behavior Trees (BTs) offer a reactive, modular, and interpretable way of encoding task descriptions but have not yet been applied a lot in robotic ITL settings. Most existing approaches that learn a BT from human demonstrations require the user to specify each action step-by-step or do not allow for adapting a learned BT without the need to repeat the entire teaching process from scratch. Method: We propose a new framework to directly learn a BT from only a few human task demonstrations recorded as RGB-D video streams. We automatically extract continuous pre- and post-conditions for BT action nodes from visual features and use a Backchaining approach to build a reactive BT. In a user study on how non-experts provide and vary demonstrations, we identify three common failure cases of an BT learned from potentially imperfect initial human demonstrations. We offer a way to interactively resolve these failure cases by refining the existing BT through interaction with a user over a web-interface. Specifically, failure cases or unknown states are detected automatically during the execution of a learned BT and the initial BT is adjusted or extended according to the provided user input. Evaluation and results: We evaluate our approach on a robotic trash disposal task with 20 human participants and demonstrate that our method is capable of learning reactive BTs from only a few human demonstrations and interactively resolving possible failure cases at runtime.

Attitudes and beliefs towards COVID-19 and COVID-19 vaccination among rheumatology patients in a Los Angeles County safety net clinic.

BACKGROUND: The novel Coronavirus disease (COVID-19) pandemic has represented an evolving global threat with high morbidity and mortality. Patients with autoimmune rheumatic diseases and on immune-suppressing medications may be at increased risk to more severe disease, hospitalization, and death. Vaccines are essential to combat the COVID-19 pandemic and curb the spread of infection. Rheumatology patients may be more fearful to receive the vaccine compared to the general population. The Los Angeles County rheumatology patients are primarily Hispanic and represent a unique and possibly particularly vulnerable cohort warranting further exploration into barriers to receive the COVID-19 vaccine. We aimed to explore the willingness of COVID-19 vaccine acceptance among patients with rheumatic disease. METHODS: We conducted a cross-sectional survey to assess the perceptions and barriers to COVID-19 vaccine acceptance in our Los Angeles County rheumatology clinics between July 2021 to September 2021 and received responses from 116 patients. RESULTS: The majority of respondents were female (83.9%), 41-60 years of age (59.8%), Hispanic (89.2%), with high school or lower level of education (68.7%), and had Rheumatoid Arthritis (56.9%). We found most (88.4%) patients received at least one dose of the COVID-19 vaccine. We identified no differences in vaccine acceptance related to age, education, race, and ethnicity. Most respondents agreed that their health condition puts them at high risk of COVID-19 complications. In addition, individuals reported that they valued being engaged by their rheumatologists in discussions of the risk and benefits of the vaccine prior to receiving it. CONCLUSION: We found that the majority of patients were already vaccinated or willing to be vaccinated, at higher levels than general United States population and that a conversation initiated by a rheumatologist can have positive effect on patients' health behaviors related to COVID-19.

Cellular Uptake Mechanism of Nucleic Acid Nanocapsules and Their DNA-Surfactant Building Blocks.

Nucleic acid nanocapsules (NANs) are enzyme-responsive DNA-functionalized micelles built for the controlled release of DNA-surfactant conjugates (DSCs) that present sequences with demonstrated therapeutic potential. Here, we investigate the mechanisms by which DSCs gain access to intracellular space in vitro and determine the effects of serum on the overall uptake and internalization mechanism of NANs. Using pharmacological inhibitors to selectively block certain pathways, we show, through confocal visualization of cellular distribution and flow cytometry quantification of total cellular association, that scavenger receptor-mediated, caveolae-dependent endocytosis is the major cellular uptake pathway of NANs in the presence and absence of serum. Furthermore, as NANs can be triggered to release DSCs by external stimuli such as enzymes, we sought to examine the uptake profile of particles degraded by enzymes prior to cell-based assays. We found that while scavenger receptor-mediated, caveolae-dependent endocytosis is still at play, energy-independent pathways as well as clathrin-mediated endocytosis are also involved. Overall, this study has helped to elucidate early steps in the cytosolic delivery and therapeutic activity of DSCs packaged into a micellular NAN platform while shedding light on the way in which DNA functionalized nanomaterials in general can be trafficked into cells both as nanostructures and as molecular entities. Importantly, our study also shows that the NAN design in particular is able to stabilize nucleic acids when delivered in the presence of serum, a critical step for effective therapeutic nucleic acid delivery.

Surface Passivation by Sulfur-Based 2D (TEA)2PbI4 for Stable and Efficient Perovskite Solar Cells.

Perovskite solar cells (PSCs) with superior performance have been recognized as a potential candidate in photovoltaic technologies. However, defects in the active perovskite layer induce nonradiative recombination which restricts the performance and stability of PSCs. The construction of a thiophene-based 2D structure is one of the significant approaches for surface passivation of hybrid PSCs that may combine the benefits of the stability of 2D perovskite with the high performance of three-dimensional (3D) perovskite. Here, a sulfur-rich spacer cation 2-thiopheneethylamine iodide (TEAI) is synthesized as a passivation agent for the construction of a three-dimensional/two-dimensional (3D/2D) perovskite bilayer structure. TEAI-treated PSCs possess a much higher efficiency (20.06%) compared to the 3D perovskite (MA0.9FA0.1PbI3) devices (17.42%). Time-resolved photoluminescence and femtosecond transient absorption spectroscopy are employed to investigate the effect of surface passivation on the charge carrier dynamics of the 3D perovskite. Additionally, the stability test of TEAI-treated perovskite devices reveals significant improvement in humid (RH ∼ 46%) and thermal stability as the sulfur-based 2D (TEA)2PbI4 material self-assembles on the 3D surface, making the perovskite surface hydrophobic. Our findings provide a reliable approach to improve device stability and performance successively, paving the way for industrialization of PSCs.

Efficient Multiple Exciton Generation in Monolayer MoS2.

Utilization of the excess energy of photoexcitation that is otherwise lost as thermal effects can improve the efficiency of next-generation light-harvesting devices. Multiple exciton generation (MEG) in semiconducting materials yields two or more excitons by absorbing a single high-energy photon, which can break the Shockley-Queisser limit for the conversion efficiency of photovoltaic devices. Recently, monolayer transition metal dichalcogenides (TMDs) have emerged as promising light-harvesting materials because of their high absorption coefficient. Here, we report efficient MEGs with low threshold energy and high (86%) efficiency in a van der Waals (vdW) layered material, MoS2. Through different experimental approaches, we demonstrate the signature of exciton multiplication and discuss the possible origin of decisive MEG in monolayer MoS2. Our results reveal that vdW-layered materials could be a potential candidate for developing mechanically flexible and highly efficient next-generation solar cells and photodetectors.

Gender Parity in High Impact Cardiology Journals.

Despite increased female representation in medical training, women physicians continue to be under-represented in academic cardiology, particularly in senior roles of authorship and leadership. We analyzed the top 20 most-cited cardiology journals (31,540 total articles) between January 1, 2018 and October 31, 2021 for gender distribution of editorial staff and authorship. Our data demonstrated that only 27% of articles had women as first authors and 20% as senior authors. Women constituted 23% of editorial staff. There is a statistically significant negative correlation (R = 0.67, P = 0.0011) between the percentage of women as first authors and the percentage of men on editorial boards. Overall, female authorship increased from 26% first and 19% senior authors in 2018, to 29% first and 22% senior authors in 2021. Women authors are significantly under-represented in academic cardiology publications, and additional work is needed to identify and address barriers to publishing and academic advancement for women in cardiology.

Gender and Race-Based Health Disparities in COVID-19 Outcomes among Hospitalized Patients in the United States: A Retrospective Analysis of a National Sample.

COVID-19 has brought the disparities in health outcomes for patients to the forefront. Racial and gender identity are associated with prevalent healthcare disparities. In this study, we examine the health disparities in COVID-19 hospitalization outcome from the intersectional lens of racial and gender identity. The Agency for Healthcare Research and Quality (AHRQ) 2020 NIS dataset for hospitalizations from 1 January 2020 to 31 December 2020 was analyzed for primary outcome of in-patient mortality and secondary outcomes of intubation, acute kidney injury (AKI), AKI requiring hemodialysis (HD), cardiac arrest, stroke, and vasopressor use. A multivariate regression model was used to identify associations. A p value of <0.05 was considered significant. Men had higher rates of adverse outcomes. Native American men had the highest risk of in-hospital mortality (aOR 2.0, CI 1.7−2.4) and intubation (aOR 1.8, CI 1.5−2.1), Black men had highest risk of AKI (aOR 2.0, CI 1.9−2.0). Stroke risk was highest in Asian/Pacific Islander women (aOR 1.5, p = 0.001). We note that the intersection of gender and racial identities has a significant impact on outcomes of patients hospitalized for COVID-19 in the United States with Black, Indigenous, and people of color (BIPOC) men have higher risks of adverse outcomes.

COVID-19 and Influenza Coinfection Outcomes among Hospitalized Patients in the United States: A Propensity Matched Analysis of National Inpatient Sample.

This study aims to provide comparative data on clinical features and in-hospital outcomes among U.S. adults admitted to the hospital with COVID-19 and influenza infection using a nationwide inpatient sample (N.I.S.) data 2020. Data were collected on patient characteristics and in-hospital outcomes, including patient's age, race, sex, insurance status, median income, length of stay, mortality, hospitalization cost, comorbidities, mechanical ventilation, and vasopressor support. Additional analysis was performed using propensity matching. In propensity-matched cohort analysis, influenza-positive (and COVID-positive) patients had higher mean hospitalization cost (USD 129,742 vs. USD 68,878, p = 0.04) and total length of stay (9.9 days vs. 8.2 days, p = 0.01), higher odds of needing mechanical ventilation (OR 2.01, 95% CI 1.19-3.39), and higher in-hospital mortality (OR 2.09, 95% CI 1.03-4.24) relative to the COVID-positive and influenza-negative cohort. In conclusion, COVID-positive and influenza-negative patients had lower hospital charges, shorter hospital stays, and overall lower mortality, thereby supporting the use of the influenza vaccine in COVID-positive patients.

Evolutionarily Conserved Proline Residues Impede the Misfolding of the Mouse Prion Protein by Destabilizing an Aggregation-competent Partially Unfolded Form.

The misfolding of the prion protein has been linked to several neurodegenerative diseases. Despite extensive studies, the mechanism of the misfolding process remains poorly understood. The present study structurally delineates the role of the conserved proline residues present in the structured C-terminal domain of the mouse prion protein (moPrP) in the misfolding process. It is shown that mutation of these Pro residues to Ala leads to destabilization of the native (N) state, and also to rapid misfolding. Using hydrogen-deuterium exchange (HDX) studies coupled with mass spectrometry (MS), it has been shown that the N state of moPrP is in rapid equilibrium with a partially unfolded form (PUF2*) at pH 4. It has been shown that the Pro to Ala mutations make PUF2* energetically more accessible from the N state by stabilizing it relative to the unfolded (U) state. The apparent rate constant of misfolding is found to be linearly proportional to the extent to which PUF2* is populated in equilibrium with the N state, strongly indicating that misfolding commences from PUF2*. It has also been shown that the Pro residues restrict the boundary of the structural core of the misfolded oligomers. Overall, this study highlights how the conserved proline residues control misfolding of the prion protein by modulating the stability of the partially unfolded form from which misfolding commences.

Direct Synthesis of Benzo[c]carbazoles by Pd-Catalyzed C-H [4 + 2] Annulation of 3-Arylindoles with External 1,3-Dienes.

Herein, we present a regioselective Pd-catalyzed C-H [4 + 2] benzannulation of N-unprotected 3-arylindoles with external readily available 1,3-dienes via an original sequence involving a Pd-catalyzed domino carbopalladation of 1,3-dienes/direct C2-H allylation of an indole ring followed by an oxidation or reduction step. Depending on the nature of the solvent, DCE or CH3CN, two consecutive approaches, oxidative or reductive, have been validated and applied to the design of a novel library of C6-alkyl or (E)-C6-styryl-benzo[c]carbazoles in moderate to good yields.

COVID-19 vaccination and myocarditis: A review of current literature.

Vaccination for coronavirus disease 2019 (COVID-19) is a critical strategy in controlling the current pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). After widespread COVID-19 vaccine imple-mentation, isolated case reports about myocarditis as a potential adverse reaction started coming. As of November 12, 2021, Centers for Disease Control and Prevention (CDC) has reported 1793 cases of myocarditis or pericarditis among young people with age 12-29 years, most cases have been reported in the male adolescent age group after the second dose of mRNA COVID-19 vaccines. It is very important to monitor the safety standards and adverse reactions of vaccines to effectively implement the vaccination policies. The CDC and the United States Food and Drug Administration actively monitor vaccine-associated adverse reactions a well-known platform such as Vaccine Adverse Event Reporting System. CDC continues to recommend COVID-19 vaccines and booster doses for eligible individuals (age limit according to the type of vaccine) after careful consideration from risk-benefit assessment and favorable outcomes from vaccination. Mechanisms behind COVID-19 vaccine-induced myocarditis are not clear yet but several possibilities such as molecular mimicry between the spike protein of SARS-CoV-2 and self-antigens, immune response to mRNA, and activation of host immunological system, trigger of the pre-existing dysregulated immunological system have been documented in the literature. Overall, data suggests a good prognosis, especially in young patients. In this review article, we cover currently available data on COVID-19 vaccine-related myocarditis incidence, concerns, possible mechanisms of myocarditis, current treatment, and outcome trends, risk vs benefit assessment of COVID-19 vaccination in this current pandemic.

Mix-and-Match COVID-19 Vaccinations (Heterologous Boost): A Review.

Various safe and effective COVID-19 vaccines utilizing different platforms (mRNA, adenovirus vector, inactivated virus-based) are available against SARS-CoV-2 infection. A prime-boost regimen (administration of two doses) is recommended to induce an adequate and sustained immune response. Most of these vaccines follow a homologous regimen (the same type of vaccine as priming and booster doses). However, there is a growing interest in a heterologous prime-boost vaccination regimen to potentially help address concerns posed by fluctuating vaccine supplies, serious adverse effects (anaphylaxis and thromboembolic episodes following adenovirus-based vaccines), new emerging virulent strains, inadequate immune response in immunocompromised individuals, and waning immunity. Various studies have demonstrated that heterologous prime-boost vaccination may induce comparable or higher antibody (spike protein) titers and a similar reactogenicity profile to the homologous prime-boost regimen. Based on these considerations, the Center for Disease Control and Prevention has issued guidance supporting the "mix-and-match" heterologous boost COVID-19 vaccine strategy.

Impact of COVID-19 on the Changing Patterns of Respiratory Syncytial Virus Infections.

Seasonal epidemics of respiratory syncytial virus (RSV) is one of the leading causes of hospitalization and mortality among children. Preventive measures implemented to reduce the spread of SARS-CoV-2, including facemasks, stay-at-home orders, closure of schools and local-national borders, and hand hygiene, may have also prevented the transmission of RSV and influenza. However, with the easing of COVID-19 imposed restrictions, many regions are noticing a delayed RSV outbreak. Some of these regions have also noted an increase in severity of these delayed RSV outbreaks partly due to a lack of protective immunity in the community following a lack of exposure from the previous season. Lessons learned from the COVID-19 pandemic can be implemented for controlling RSV outbreaks, including: (1) measures to reduce the spread, (2) effective vaccine development, and (3) genomic surveillance tools and computational modeling to predict the timing and severity of RSV outbreaks. These measures can help reduce the severity and prepare the health care system to deal with future RSV outbreaks by appropriate and timely allocation of health care resources.

COVID-19 and the Endocrine System: A Review of the Current Information and Misinformation.

Coronavirus disease 2019 (COVID-19) infection primarily involves the respiratory system but has many noteworthy extra pulmonary manifestations as well. We write this review to highlight the basis of some pathophysiological mechanisms of COVID-19 infection-induced endocrine dysfunction. Different scientific databases and institutional websites were searched to collect and consolidate the most up-to-date data relating to COVID-19 infection and endocrine systems. Hypopituitarism, central diabetes insipidus, SIADH, thyroid abnormalities, hyperglycemia, adrenal insufficiency, orchitis and alteration in sperm morphology have been reported in case reports of patients with COVID-19 infection. Data focusing on COVID-19 vaccination was also searched to summarize the effect, if any, on the endocrine system. Endocrinopathies noted post COVID-19 vaccination, including cases of adrenal hemorrhage, new onset Type II Diabetes Mellitus and subacute thyroiditis, are also discussed in this review. This review calls attention to the misinformation relating to COVID-19 vaccination with supposed endocrine effects such as infertility and problems with pregnancy. Rebutting these misconceptions can help increase compliance and maximize COVID-19 vaccination to the public.