Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents—ethynylbenziodoxolones (EBXs)—onto peptides. These ...peptide‐EBXs can be readily accessed, by both solution‐ and solid‐phase peptide synthesis (SPPS). They can be used to couple the peptide to other peptides or a protein through reaction with Cys, leading to thioalkynes in organic solvents and hypervalent iodine adducts in water buffer. Furthermore, a photocatalytic decarboxylative coupling to the C‐terminus of peptides was developed using an organic dye and was also successful in an intramolecular fashion, leading to macrocyclic peptides with unprecedented crosslinking. A rigid linear aryl alkyne linker was essential to achieve high affinity for Keap1 at the Nrf2 binding site with potential protein‐protein interaction inhibition.
The introduction of highly reactive hypervalent iodine reagents—ethynylbenziodoxolones (EBXs)—onto peptides is described. These peptide‐EBX chimeras can be used as versatile handles for peptide/protein modifications and peptide macrocyclization under mild photocatalytic conditions. The method was used to access new inhibitors of the Keap1‐Nrf2 interaction.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Photodynamic therapy (PDT) typically involves oxygen (O2) consumption and therefore suffers from greatly limited anticancer therapeutic efficacy in tumor hypoxia. Here, it is reported for the first ...time that amine‐terminated, PAMAM dendrimer‐encapsulated gold nanoclusters (AuNCs‐NH2) can produce O2 for PDT via their intrinsic catalase‐like activity. The AuNCs‐NH2 not only show optimum H2O2 consumption via the catalase‐like activity over the physiological pH range (i.e., pH 4.8–7.4), but also extend such activity to acidic conditions. The possible mechanism is deduced from that the enriched tertiary amines of dendrimers are easily protonated in acidic solutions to facilitate the preadsorption of OH on the metal surface, thereby favorably triggering the catalase‐like reaction. By taking advantage of the exciting feature on AuNCs‐NH2, the possibility to supply O2 via the catalase‐like activity of AuNCs‐NH2 for PDT against hypoxia of cancer cells was further studied. This proof‐of‐concept study provides a simple way to combine current O2‐dependent cancer therapy of PDT to overcome cancer cell hypoxia, thus achieving more effective anticancer treatments.
PAMAM dendrimer‐encapsulated gold nanoclusters (AuNCs‐NH2) exhibit their catalase‐like activity over a pH range relevant to biological microenvironments (i.e., pH 4.8–7.4), such that AuNCs‐NH2 can catalyze physiological hydrogen peroxide (H2O2) to produce O2 that self‐supplies for photodynamic therapy against hypoxic cancer cells.
Artificial synapses can boost neuromorphic computing to overcome the inherent limitations of von Neumann architecture. As a promising memristor candidate, ferroelectric tunnel junctions (FTJ) enable ...the authors to successfully emulate spike‐timing‐dependent synapses. However, the nonlinear and asymmetric synaptic weight update under repeated presynaptic stimulation hampers neuromorphic computing by favoring the runaway of synaptic weights during learning. Here, the authors demonstrate an FTJ whose conductivity varies linearly and symmetrically by judiciously combining ferroelectric domain switching and oxygen vacancy migration. The artificial neural network based on this FTJ‐synapse achieves classification accuracy of 96.7% during supervised learning, which is the closest to the maximum theoretical value of 98% achieved to date. This artificial synapse also demonstrates stable unsupervised learning in a noisy environment for its well‐balanced spike‐timing‐dependent plasticity response. The novel concept of controlling ionic migration in ferroelectric materials paves the way toward highly reliable and reproducible supervised and unsupervised learning strategies.
By combining ferroelectric domain switching and oxygen vacancy migration, a ferroelectric tunnel junction artificial synapse with intrinsic nonlinearity as low as 0.13–0.17 and symmetric weight updating is developed, which greatly improved the classification accuracy of neural network hardware in supervised learning to 96.7% and enhanced robustness to noise during unsupervised learning.
Perovskite photovoltaics are strong potential candidates to drive low‐power off‐grid electronics for indoor applications. Compared with rigid devices, flexible perovskite devices can provide a more ...suitable surface for indoor small electronic devices, enabling them have a broader indoor application prospect. However, the mechanical stability of flexible perovskite photovoltaics is an urgent issue solved. Herein, a kind of 3D crosslinking agent named borax is selected to carry out grain boundary penetration treatment on perovskite film to realize full‐dimensional stress release. This strategy improves the mechanical and phase stabilities of perovskite films subjected to external forces or large temperature changes. The fabricated perovskite photovoltaics deliver a champion power conversion efficiency (PCE) of 21.63% under AM 1.5G illumination, which is the highest one to date. The merit of low trap states under weak light makes the devices present a superior indoor PCE of 31.85% under 1062 lux (LED, 2956 K), which is currently the best flexible perovskite indoor photovoltaic device. This work provides a full‐dimensional grain boundary stress release strategy for highly stable flexible perovskite indoor photovoltaics.
A grain boundary stress release strategy is proposed for high‐stability flexible perovskite indoor photovoltaics by the grain boundary penetration with borax 3D stretchable molecules. The full‐dimensional grain boundary stress release enables the flexible perovskite photovoltaics deliver a champion power conversion efficiency (PCE) of 21.63% under AM 1.5G illumination and an indoor PCE of 31.85% under 1062 lux.
Ethynylbenziodoxol(on)es (EB(X)xs) reagents have emerged as useful reagents for peptide/protein modification due to their versatile reactivity and high selectivity. Herein, we report the successful ...introduction of ethynylbenziodoxoles (EBxs) on different amino acid building blocks (Lys/Orn/Dap), and show their compatibility with both solid phase peptide synthesis (SPPS) and solution phase peptide synthesis (SPS). The selective incorporation of the EBx core into peptide sequences enable efficient macrocyclizations under mild conditions for the synthesis of topologically unique cyclic and bicyclic peptides.
The development of non‐proteogenic amino acids (NPAAs) containing hypervalent iodine reagents ‐ethynylbenziodoxoles (EBxs)‐ is described. These NPAAs were compatible with both solid phase peptide synthesis (SPPS) and solution peptide synthesis (SPS), allowing the introduction of reactive handles on specific sites in the presence of multiple identical residues. The obtained peptide‐EBXs can be applied to the synthesis of cyclic peptides with unique topological properties.
Because of the high capacity of lithium (Li) metal and the intrinsic safety of solid-state electrolyte, solid-state Li-metal batteries are regarded as a promising candidate for next-generation energy ...storage. However, uncontrollable dendrite growth and large interfacial resistance severely hamper the practical applications. This review summarizes the issues generated by the marriage of Li-metal anodes and solid-state electrolytes. First, the current challenges are underscored. Specific attention is paid to the large interfacial resistance, uncontrolled dendrite growth, and low operation current or capacity. The second section is dedicated primarily to understanding the ionic channels in the composite electrolyte and the space charge layers in the interfacial region. Based on these dilemmas and working principles, emerging strategies to render solid-state Li-metal batteries are summarized. Finally, the general conclusion and perspective on the current limitations and recommended research of solid-state Li-metal batteries are presented.
Display omitted
Li metal is extensively focused because of its ultra-high theoretical capacity (3,860 mAh g−1, 10 times higher than that of graphite) and the most negative electrochemical potential (−3.040 V versus standard hydrogen electrode). Relative to non-aqueous electrolyte, solid-state electrolyte exhibits enhanced safety. Therefore, the marriage of Li metal and solid-state electrolyte is expected to inherit the merits of both. However, the competitive solid-state Li-metal batteries encounter formidable challenges, including dendrite issues and poor solid-solid contact. Investigating the interdisciplinary issues of solid-state electrolyte and Li metal in integrated cells is necessary to realize efficient and safe solid-state Li-metal batteries. This review focuses on the energy chemistry issues generated from the marriage of Li metal and solid-state electrolyte instead of their respective problems. The current strategies, limitations, and emerging research directions are presented.
The marriage of Li-metal anodes and solid-state electrolytes is highly expected to achieve a battery with high energy density and enhanced safety. This review focuses on the energy chemistry generated from the marriage of Li-metal anodes and solid-state electrolytes, as well as the strategies and prospects to render efficient and safe solid-state Li-metal batteries.
Mesoscale Auroral Curls in Antarctica Li, Xing‐Yu; Zong, Qiu‐Gang; Hu, Ze‐Jun ...
Geophysical research letters,
16 May 2024, Volume:
51, Issue:
9
Journal Article
Peer reviewed
Open access
The morphology and motion of auroras have been widely studied due to their indications on magnetospheric processes. Here, we report a new kind of “auroral curls,” which have wavelengths in the ...mesoscale (∼100 km) and propagate azimuthally. Utilizing data from the Chinese Antarctic Zhongshan Station (the all‐sky imager and the high‐frequency radar), the Active Magnetosphere and Planetary Electrodynamics Response Experiment and the Defense Meteorological Satellite Program, we analyze an event occurred on 23 April 2019. We find these curls are fine structures in the poleward boundary of multiple arcs. Corresponding field‐aligned currents manifest as a series of longitudinally arranged pairs, while ionospheric flow velocities nearby oscillate with periods in the Pc 5 band. Observational evidence suggests these curls are connected with ultra‐low frequency (ULF) waves, which opens the possibility of using auroras to globally image ULF waves.
Plain Language Summary
Auroras caused by precipitation of magnetospheric particles contain information about physical processes happened in the magnetosphere. In this letter, we report a new kind of auroral dynamic forms observed in Antarctica. These structures present both spatial and temporal periodic characteristics, which have similar scales with those of magnetospheric ultra‐low frequency (ULF) waves. We propose these auroral forms are connected with ULF waves, which provides a potential method to globally image ULF waves by analyzing properties of these auroras.
Key Points
Azimuthally propagating “auroral curls” with mesoscale wavelengths were observed in Antarctica
These curls are fine structures in the poleward boundary of multiple arcs formed by longitudinal‐arranged field‐aligned current pairs
Ionospheric flow velocities nearby oscillate with periods in the Pc 5 band, indicating connections with ultra‐low frequency waves
Abstract
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, and its etiology remains poorly understood. Altered activities of long ...noncoding RNAs (lncRNAs) have been associated with human diseases and development. However, the roles of lncRNAs are unknown in reproductive medicine. We investigated the potential role of lncRNAs in the pathogenesis of PCOS, using human granulosa cells (GCs) and the KGN cell line. We used microarrays to compare lncRNA expression profiles in GCs from seven patients with PCOS and seven matched women. GC samples were collected during 2014 to 2016 from infertile women in Guangzhou, China. Quantitative real-time polymerase chain reaction was used to measure levels of the lncRNA HCG26 in GCs from 53 patients with PCOS and 50 controls. HCG26 was knocked down with locked nucleic acid GapmeRs in KGN cells to examine its role in cell proliferation, aromatase and follicle-stimulating hormone receptor gene expression, and estradiol production. A total of 862 lncRNA transcripts and 998 messenger RNA transcripts were differentially expressed (greater than or equal to twofold change; P < 0.05) in PCOS GCs compared with those of controls. HCG26 levels were upregulated in patients with PCOS and were associated with antral follicle count. HCG26 knockdown in KGN cells inhibited cell proliferation and cell-cycle progression and increased aromatase gene expression and estradiol production. Our study reports the lncRNA profiles in GCs from patients who have PCOS and those from healthy women and suggests that dysregulated lncRNAs may play vital roles in GC proliferation and steroidogenesis, providing insights into the pathogenesis of PCOS.
A large number of lncRNAs were dysregulated in PCOS granulosa cells. lincRNA-HCG26 may affect cell proliferation and steroidogenesis in granulosa cells, contributing to the pathogenesis of PCOS.
Summary
Natural killer (NK) cells exert anti‐viral effects after haematopoietic stem cell transplantation (HSCT). The balance between inhibition and activation of NK cells determined by the inherited ...repertoire of killer cell immunoglobulin‐like receptors (KIR) genes may influence Epstein–Barr virus (EBV) reactivation after transplantation. To evaluate the relative contributions of KIR genotypes to EBV reactivation, we prospectively enrolled 300 patients with malignant haematological disease who were suitable for haploidentical HSCT. Univariate analysis showed that donors with KIR2DS1, KIR2DS3 or KIR3DS1 genes were associated with an increased risk of EBV reactivation hazard ratio (HR) 1·86, 95% confidence interval (CI) 1·19–2·9, P = 0·0067; HR 1·78, 95% CI 1·07‐2·97, P = 0·027; HR 1·86, 95% CI 1·19‐2·91, P = 0·0065 respectively. Multivariate analysis revealed that the presence of KIR2DS1, KIR2DS3 or KIR3DS1 genes was associated with increased EBV reactivation after HSCT. This effect was more evident in the absence of the cognate ligands for the corresponding activating receptors. Our present data firstly showed that donors with activating KIR genes, specifically activating KIR2DS1, KIR2DS3 and KIR3DS1, had an increased risk of EBV reactivation. Precaution for patients whose donors carry activating genes will help prevent EBV reactivation and improve patient prognosis after HSCT.