Organo-lead halide perovskite solar cells have emerged as one of the most promising candidates for the next generation of solar cells. To date, these perovskite thin film solar cells have exclusively ...employed organic hole conducting polymers which are often expensive and have low hole mobility. In a quest to explore new inorganic hole conducting materials for these perovskite-based thin film photovoltaics, we have identified copper iodide as a possible alternative. Using copper iodide, we have succeeded in achieving a promising power conversion efficiency of 6.0% with excellent photocurrent stability. The open-circuit voltage, compared to the best spiro-OMeTAD devices, remains low and is attributed to higher recombination in CuI devices as determined by impedance spectroscopy. However, impedance spectroscopy revealed that CuI exhibits 2 orders of magnitude higher electrical conductivity than spiro-OMeTAD which allows for significantly higher fill factors. Reducing the recombination in these devices could render CuI as a cost-effective competitor to spiro-OMeTAD in perovskite solar cells.
The surface elemental composition of dwarf planet Ceres constrains its regolith ice content, aqueous alteration processes, and interior evolution. Using nuclear spectroscopy data acquired by NASA’s ...Dawn mission, we determined the concentrations of elemental hydrogen, iron, and potassium on Ceres. The data show that surface materials were processed by the action of water within the interior. The non-icy portion of Ceres’ carbon-bearing regolith contains similar amounts of hydrogen to those present in aqueously altered carbonaceous chondrites; however, the concentration of iron on Ceres is lower than in the aforementioned chondrites. This allows for the possibility that Ceres experienced modest ice-rock fractionation, resulting in differences between surface and bulk composition. At mid-to-high latitudes, the regolith contains high concentrations of hydrogen, consistent with broad expanses of water ice, confirming theoretical predictions that ice can survive for billions of years just beneath the surface.
During the past few years, crystallography of G protein-coupled receptors (GPCRs) has experienced exponential growth, resulting in the determination of the structures of 16 distinct receptors-9 of ...them in 2012 alone. Including closely related subtype homology models, this coverage amounts to approximately 12% of the human GPCR superfamily. The adrenergic, rhodopsin, and adenosine receptor systems are also described by agonist-bound active-state structures, including a structure of the receptor-G protein complex for the β(2)-adrenergic receptor. Biochemical and biophysical techniques, such as nuclear magnetic resonance and hydrogen-deuterium exchange coupled with mass spectrometry, are providing complementary insights into ligand-dependent dynamic equilibrium between different functional states. Additional details revealed by high-resolution structures illustrate the receptors as allosteric machines that are controlled not only by ligands but also by ions, lipids, cholesterol, and water. This wealth of data is helping redefine our knowledge of how GPCRs recognize such a diverse array of ligands and how they transmit signals 30 angstroms across the cell membrane; it also is shedding light on a structural basis of GPCR allosteric modulation and biased signaling.
Remote observations of the asteroid (1) Ceres from ground- and space-based telescopes have provided its approximate density and shape, leading to a range of models for the interior of Ceres, from ...homogeneous to fully differentiated. A previously missing parameter that can place a strong constraint on the interior of Ceres is its moment of inertia, which requires the measurement of its gravitational variation together with either precession rate or a validated assumption of hydrostatic equilibrium. However, Earth-based remote observations cannot measure gravity variations and the magnitude of the precession rate is too small to be detected. Here we report gravity and shape measurements of Ceres obtained from the Dawn spacecraft, showing that it is in hydrostatic equilibrium with its inferred normalized mean moment of inertia of 0.37. These data show that Ceres is a partially differentiated body, with a rocky core overlaid by a volatile-rich shell, as predicted in some studies. Furthermore, we show that the gravity signal is strongly suppressed compared to that predicted by the topographic variation. This indicates that Ceres is isostatically compensated, such that topographic highs are supported by displacement of a denser interior. In contrast to the asteroid (4) Vesta, this strong compensation points to the presence of a lower-viscosity layer at depth, probably reflecting a thermal rather than compositional gradient. To further investigate the interior structure, we assume a two-layer model for the interior of Ceres with a core density of 2,460-2,900 kilograms per cubic metre (that is, composed of CI and CM chondrites), which yields an outer-shell thickness of 70-190 kilometres. The density of this outer shell is 1,680-1,950 kilograms per cubic metre, indicating a mixture of volatiles and denser materials such as silicates and salts. Although the gravity and shape data confirm that the interior of Ceres evolved thermally, its partially differentiated interior indicates an evolution more complex than has been envisioned for mid-sized (less than 1,000 kilometres across) ice-rich rocky bodies.
Activation of the EGF receptor (EGFR) or the Hippo signaling pathway can control cell proliferation, apoptosis, and differentiation, and the dysregulation of these pathways can contribute to ...tumorigenesis. Previous studies showed that activation of EGFR signaling in renal epithelial cells can exacerbate diabetic kidney injury. Moreover, EGFR has been implicated in regulating the Hippo signaling pathway in Drosophila; thus, we examined this potential interaction in mammalian diabetic kidney disease. Yes-associated protein (YAP) is a transcriptional regulator regulated by the Hippo signaling pathway. We found YAP protein expression and phosphorylation were upregulated in diabetic mouse renal proximal tubule epithelial cells, which were inhibited in diabetic proximal tubule EGFR-knockout mice (EGFR(ptKO)) or administration of an EGFR tyrosine kinase inhibitor erlotinib. Furthermore, activation of an EGFR-PI3K-Akt-CREB signaling pathway mediated YAP gene expression and YAP nuclear translocation and interaction with the TEA domain (TEAD) transcription factor complex, which led to upregulated expression of two TEAD-dependent genes, the connective tissue growth factor and amphiregulin genes. In a renal proximal tubule cell line, either pharmacologic or genetic inhibition of EGFR, Akt, or CREB blunted YAP expression in response to high-glucose treatment. Additionally, knocking down YAP expression by specific siRNA inhibited cell proliferation in response to high glucose or exogenous EGF. Therefore, these results link the Hippo pathway to EGFR-mediated renal epithelial injury in diabetes.
Carbon-oxygen (CH···O) hydrogen bonding represents an unusual category of molecular interactions first documented in biological structures over 4 decades ago. Although CH···O hydrogen bonding has ...remained generally underappreciated in the biochemical literature, studies over the last 15 years have begun to yield direct evidence of these interactions in biological systems. In this minireview, we provide a historical context of biological CH···O hydrogen bonding and summarize some major advancements from experimental studies over the past several years that have elucidated the importance, prevalence, and functions of these interactions. In particular, we examine the impact of CH···O bonds on protein and nucleic acid structure, molecular recognition, and enzyme catalysis and conclude by exploring overarching themes and unresolved questions regarding unconventional interactions in biomolecular structure.
G protein-coupled receptors (GPCRs) comprise the most ‘prolific’ family of cell membrane proteins, which share a general mechanism of signal transduction, but greatly vary in ligand recognition and ...function. Crystal structures are now available for rhodopsin, adrenergic, and adenosine receptors in both inactive and activated forms, as well as for chemokine, dopamine, and histamine receptors in inactive conformations. Here we review common structural features, outline the scope of structural diversity of GPCRs at different levels of homology, and briefly discuss the impact of the structures on drug discovery. Given the current set of GPCR crystal structures, a distinct modularity is now being observed between the extracellular (ligand-binding) and intracellular (signaling) regions. The rapidly expanding repertoire of GPCR structures provides a solid framework for experimental and molecular modeling studies, and helps to chart a roadmap for comprehensive structural coverage of the whole superfamily and an understanding of GPCR biological and therapeutic mechanisms.
The gap between the demand and delivery of mental health services in mainland China can be reduced by validating freely available and psychometrically sound psychological instruments. The present ...research examined the Chinese version of the 21-item Depression Anxiety Stress Scales (DASS-21). Study 1 administered the DASS-21 to 1,815 Chinese college students and found internal consistency indices (Cronbach's alpha) of .83, .80, and .82 for the Depression, Anxiety, and Stress subscales, respectively, and .92 for the total DASS total. Test-retest reliability over a 6-month interval was .39 to .46 for each of the 3 subscales and .46 for the total DASS. Moderate convergent validity of the Depression and Anxiety subscales was demonstrated via significant correlations with the Chinese Beck Depression Inventory (r = .51 at Time 1 and r = .64 at Time 2) and the Chinese State-Trait Anxiety Inventory (r = .41), respectively. Confirmatory factor analyses supported the original 3-factor model with 1 minor change (nonnormed fit index NNFI = .964, comparative fit index CFI = .968, and root mean square error of approximation RMSEA = .079). Study 2 examined the clinical utility of the Chinese DASS-21 in 166 patients with schizophrenia and 90 matched healthy controls. Patients had higher Depression and Anxiety but not Stress subscale scores than healthy controls. A discriminant function composed of the linear combination of 3 subscale scores correctly discriminated 69.92% of participants, which again supported the potential clinical utility of the DASS in mainland China. Taken together, findings in these studies support the cross-cultural validity of the DASS-21 in China.
Pervasive structural violence causes higher organ failure rates among Black Americans and an excess of Black potential deceased organ donors. Underuse of Black donors would exacerbate organ shortages ...that disproportionately harm Black transplant candidates. This study investigates racial differences in transit between distinct donation steps among 132 968 potential donors across 557 hospitals and 6 organ procurement organizations (OPOs) from 2015 through 2021. Multilevel multistate modeling with patient covariates and OPO random effects shows adjusted likelihoods (95% confidence interval) of non-Black versus Black patients transitioning from OPO referral to approach of 1.39 (1.35, 1.44), approach to authorization: 1.64 (1.56, 1.72), authorization to procurement: 1.10 (1.04, 1.16), and procurement to transplant: 1.00 (0.95, 1.06). Overall organ utilization rates for Black, Latino, White, and other OPO referrals were 5.89%, 8.18%, 6.79%, and 5.24%, respectively. Adjusting for patient covariates and hospital and OPO random effects, multilevel logistic models estimated that compared with Black patients, Latino, White, and other patients had odds ratios of organ utilization of 1.81 (1.61, 2.03), 3.19 (2.91, 3.50), and 1.24 (1.05, 1.47), respectively. Nationwide in 2022, donor conversion disparities likely lost more than 1700 donors-two-thirds of whom would have been Black. Achieving racial equity for transplant candidates will require reducing racial disparities in organ donation.
•Submaxillary gland and kidney are predominant source of EGF production.•EGF/EGFR signaling promotes embryonic development and stem cell regeneration and regulates ion transport.•EGF plays pivotal ...role in ulcer/wound healing.•Dysregulation of EGF expression may contribute to the cancer development.
In 1962, epidermal growth factor (EGF) was discovered by Dr. Stanley Cohen while studying nerve growth factor (NGF). It was soon recognized that EGF is the prototypical member of a family of peptide growth factors that activate the EGF receptors, and that the EGF/EGF receptor signaling pathway plays important roles in proliferation, differentiation and migration of a variety of cell types, especially in epithelial cells. After the basic characterization of EGF function in the first decade or so after its discovery, the studies related to EGF and its signaling pathway have extended to a broad range of investigations concerning its biological and pathophysiological roles in development and in human diseases. In this review, we briefly describe the gene organization and tissue distribution of EGF, with emphasis on its biological and pathological roles in human diseases.
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