Abstract
Background and Objectives
The coronavirus disease 2019 (COVID-19) pandemic resulted in social isolation globally, creating heightened levels of stress and anxiety. This study investigates ...the link between social isolation and mental well-being in later life, and how it varies across countries.
Research Design and Methods
We draw on a subset of older adults from Global Behaviors and Perceptions in the COVID-19 Pandemic, a unique global online survey of 13,660 participants from 62 countries. We use mixed-effects models to analyze the data.
Results
Social isolation (distancing) significantly predicts poor mental health operationalized as coronavirus-induced distress (p < .01). At the aggregate level, average distress varies positively across countries with higher numbers of coronavirus-related deaths (p < .10) and more fragile state capacity (p < .05), while varying negatively across those with more stringent anticoronavirus policies (p < .05). Finally, we report several cross-level interactions between social isolation and the total number of deaths (p = .025), policy stringency (p = .065), state fragility (p = .061), and globalization index (p = .071).
Discussion and Implications
Our study shows that a proper understanding of the impact of COVID-19 on the mental well-being of older adults should consider the moderating role of national context.
Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract mainly occurring in the uterine cervix. To date, only a few cases of MNAC arising from of the uterine body (UB-MNAC) have ...been reported. The clinicopathologic and molecular characteristics of UB-MNAC remain unknown. In this study, we investigated the clinical, histopathologic, immunohistochemical, and genetic features of UB-MNAC. In total, 11 cases were included. Six patients developed metastatic disease, most commonly in lungs (5/6). Histopathologically, UB-MNAC was characterized by an admixture of tubular, glandular, papillary, retiform, glomeruloid, sex cord-like, and comedonecrosis-like architectural patterns. Three adverse pathologic characteristics, including advanced International Federation of Gynecology and Obstetrics stage, high mitotic activity, and presence of lymphovascular the invasion, were independent factors predicting the development of metastasis. All cases were positive for GATA-binding protein 3 and paired box 2 expression and showed wild-type p53, patchy p16, and preserved PTEN expression, as indicated by immunohistochemistry. Next-generation sequencing using 12 samples (11 primary tumors and 1 metastatic tumor) revealed 42 single nucleotide variations in 16 genes, mostly in KRAS (10/12) and ARID1A (9/12). Copy number variation was found in 16 genomic regions, and consisted of 57 gains and 10 losses, with 1q gain (11/12) being the most prevalent. In conclusion, UB-MNAC displays an aggressive biological behavior, with a tendency to metastasize to the lungs. Adverse pathologic characteristics reflect the aggressive nature of UB-MNAC. Distinct molecular features of UB-MNAC include frequent somatic mutations of KRAS and ARID1A and gain of 1q.
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•Pluripotent stem cell (PSC)-derived expandable human hepatocyte-like liver organoids were generated.•PSC-derived human hepatic organoids are capable of long-term expansion with ...competent liver functionality.•PSC-derived human hepatic organoids provide a robust hepatic model for toxicity prediction and drug screening.
The development of hepatic models capable of long-term expansion with competent liver functionality is technically challenging in a personalized setting. Stem cell-based organoid technologies can provide an alternative source of patient-derived primary hepatocytes. However, self-renewing and functionally competent human pluripotent stem cell (PSC)-derived hepatic organoids have not been developed.
We developed a novel method to efficiently and reproducibly generate functionally mature human hepatic organoids derived from PSCs, including human embryonic stem cells and induced PSCs. The maturity of the organoids was validated by a detailed transcriptome analysis and functional performance assays. The organoids were applied to screening platforms for the prediction of toxicity and the evaluation of drugs that target hepatic steatosis through real-time monitoring of cellular bioenergetics and high-content analyses.
Our organoids were morphologically indistinguishable from adult liver tissue-derived epithelial organoids and exhibited self-renewal. With further maturation, their molecular features approximated those of liver tissue, although these features were lacking in 2D differentiated hepatocytes. Our organoids preserved mature liver properties, including serum protein production, drug metabolism and detoxifying functions, active mitochondrial bioenergetics, and regenerative and inflammatory responses. The organoids exhibited significant toxic responses to clinically relevant concentrations of drugs that had been withdrawn from the market due to hepatotoxicity and recapitulated human disease phenotypes such as hepatic steatosis.
Our organoids exhibit self-renewal (expandable and further able to differentiate) while maintaining their mature hepatic characteristics over long-term culture. These organoids may provide a versatile and valuable platform for physiologically and pathologically relevant hepatic models in the context of personalized medicine.
A functionally mature, human cell-based liver model exhibiting human responses in toxicity prediction and drug evaluation is urgently needed for pre-clinical drug development. Here, we develop a novel human pluripotent stem cell-derived hepatocyte-like liver organoid that is critically advanced in terms of its generation method, functional performance, and application technologies. Our organoids can contribute to the better understanding of liver development and regeneration, and provide insights for metabolic studies and disease modeling, as well as toxicity assessments and drug screening for personalized medicine.
Ni-rich layered LiNi
Co
Mn
O
cathode material was modified by doping with vanadium to enhance the electrochemical performances. The XRD, FESEM and XPS analyses were indicated that the vanadium is ...successfully doped in the crystal lattice of LiNi
Co
Mn
O
with high crystallinity. 0.05 mol% vanadium doped LiNi
Co
Mn
O
exhibits superior initial discharge capacity of 204.4 mAh g
, cycling retention of 88.1% after 80 cycles and rate capability of 86.2% at 2 C compared to those of pristine sample. It can be inferred that the vanadium doping can stabilize the crystal structure and improve the lithium-ion kinetics of the layered cathode materials.
Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and ...proteoglycans. ECM provides the bulk, shape and strength of many tissues in vivo, such as basement membrane, bone and cartilage. In vitro, most animal cells can only grow when they are attached to surfaces through ECM. ECM is also the substrate for cell migration. However, ECM provides much more than just mechanical and structural support, with implications in developmental patterning, stem cell niches and cancer. ECM imparts spatial context for signalling events by various cell surface growth factor receptors and adhesion molecules such as integrins. The external physical properties of ECM may also have a role in the signalling process. ECM molecules can be flexible and extendable, and mechanical tension can expose cryptic sites, which could further interact with growth factors or their receptors. ECM proteins and structures can determine the cell behaviour, polarity, migration, differentiation, proliferation and survival by communicating with the intracellular cytoskeleton and transmission of growth factor signals. Integrins and proteoglycans are the major ECM adhesion receptors which cooperate in signalling events, determining the signalling outcomes, and thus the cell fate. This review focuses on the emerging concept of spatial cell biology of ECM, especially the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Precise control over the polarity of transistors is a key necessity for the construction of complementary metal–oxide–semiconductor circuits. However, the polarity control of 2D transistors remains a ...challenge because of the lack of a high‐work‐function electrode that completely eliminates Fermi‐level pinning at metal–semiconductor interfaces. Here, a creation of clean van der Waals contacts is demonstrated, wherein a metallic 2D material, chlorine‐doped SnSe2 (Cl–SnSe2), is used as the high‐work‐function contact, providing an interface that is free of defects and Fermi‐level pinning. Such clean contacts made from Cl–SnSe2 can pose nearly ideal Schottky barrier heights, following the Schottky–Mott limit and thus permitting polarity‐controllable transistors. With the integration of Cl–SnSe2 as contacts, WSe2 transistors exhibit pronounced p‐type characteristics, which are distinctly different from those of the devices with evaporated metal contacts, where n‐type transport is observed. Finally, this ability to control the polarity enables the fabrication of functional logic gates and circuits, including inverter, NAND, and NOR.
A creation of clean van der Waals contacts is reported. Clean contacts made from 2D metal Cl–SnSe2 can completely eliminate the Femi‐level pinning, permitting ideal Schottky barrier heights and polarity‐controllable transistors. With the ability to control the carrier polarity, various functional logic gates and circuits (inverter, NAND, and NOR) are demonstrated by integrating WSe2 transistors with Cl–SnSe2 contacts.
Structural and electrical properties of Al‐doped ZnO (AZO) films deposited by atomic layer deposition (ALD) are investigated to study the extrinsic doping mechanism of a transparent conducting oxide. ...ALD‐AZO films exhibit a unique layer‐by‐layer structure consisting of a ZnO matrix and Al2O3 dopant layers, as determined by transmission electron microscopy analysis. In these layered AZO films, a single Al2O3 dopant layer deposited during one ALD cycle could provide ≈4.5 × 1013 cm−2 free electrons to the ZnO. The effective field model for doping is suggested to explain the decrease in the carrier concentration of ALD‐AZO films when the interval between the Al2O3 layers is reduced to less than ≈2.6 nm (>3.4 at% Al). By correlating the electrical and structural properties, an extrinsic doping mechanism of ALD‐AZO films is proposed in which the incorporated Al atoms take oxygen from the ZnO matrix and form doubly charged donors, such as oxygen vacancies or zinc interstitials.
Layer‐by‐layer Al‐doped ZnO films are deposited by atomic layer deposition to study the extrinsic doping mechanism of a transparent conducting oxide. A combined understanding of structural and electrical properties of these films based on an effective field model suggests that doubly charged donors, such as oxygen vacancies and zinc interstitials, would be formed by extrinsic doping of Al atoms.
Abstract
Ni-rich cathode is one of the promising candidate for high-energy lithium-ion batteries. In this work, we prepare the different super-P carbon black amounts 0.1 (SPB 0.1 wt%), 0.3 (SPB ...0.3 wt%), 0.5 (SPB 0.5 wt%) and 0.7 wt% (SPB 0.7 wt%) of carbon coated LiNi
0.8
Co
0.1
Mn
0.1
O
2
(NCM811) cathodes and their electrochemical performances are investigated. Carbon coating does not change the crystal structure and morphology of NCM811. Among the coated NCM811, the SPB 0.5 wt% NCM811 delivers the excellent cyclability (87.8% after 80 cycles) and rate capability (86.5% at 2 C) compared to those of pristine NCM811. It is ascribed to that the carbon coating not only increase the Li ion and electron transfer as well as protect the NCM811 cathode materials from side reaction at the electrolyte/NCM811 interface. Therefore, we can conclude that the appropriate amount of carbon coating can be regarded as an effective approach for Ni-rich NCM cathode.
Background
Although several studies have documented the histological features of uterine mesonephric‐like adenocarcinoma (MLA), its cytological features have been rarely reported.
Methods
We searched ...for histologically confirmed uterine MLA cases in the pathology archives of three institutions between 2010 and 2021. All available cytology slides were examined to identify the cytological features of uterine MLA.
Results
We included 16 patients with uterine MLA and reviewed the slides obtained from 21 cytology samples. Samples were obtained from the cervicovagina (9/21, 42.9%), peritoneal washing (8/21, 38.1%), pleural effusion (2/21, 9.5%), and transbronchial needle aspiration of mediastinal lymph node (2/21, 9.5%). Preparation methods included ThinPrep (11/21, 52.4%), SurePath (8/21, 38.1%), and conventional smear (2/21, 9.5%). Regardless of the sampling site and preparation method, cytology samples displayed tight three‐dimensional cellular clusters showing monotonous, small‐to‐medium‐sized, round, hyperchromatic nuclei, indistinct nucleoli, scant cytoplasm, and high nuclear‐to‐cytoplasmic ratio. Approximately half of the samples (10/21, 47.6%) showed hyaline‐like globules. Mitotic figures (7/21, 33.3%) and apoptotic bodies (13/21, 61.9%) were also observed. No tumor diathesis or nuclear feathering was identified.
Conclusions
Irrespective of sampling site and preparation method, the majority of uterine MLA cases showed the following cytological features: tight three‐dimensional cellular clusters showing small‐to‐medium‐sized, round, hyperchromatic nuclei with indistinct nucleoli and high nuclear‐to‐cytoplasm ratio. In case a cytology sample suspicious of a glandular lesion displays these cytological features, which are distinct from those of endocervical adenocarcinoma, uterine MLA should be included in the differential diagnosis.
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