Inflammation is a complex physiological process that poses a serious threat to people's health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is ...lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.
Adaptive evolution following colonization can affect the impact of invasive species. The fall webworm (FWW) invaded China 40 years ago through a single introduction event involving a severe ...bottleneck and subsequently diverged into two genetic groups. The well‐recorded invasion history of FWW, coupled with a clear pattern of genetic divergence, provides an opportunity to investigate whether there is any sign of adaptive evolution following the invasion. Based on genome‐wide SNPs, we identified genetically separated western and eastern groups of FWW and correlated spatial variation in SNPs with geographical and climatic factors. Geographical factors explained a similar proportion of the genetic variation across all populations compared with climatic factors. However, when the two population groups were analysed separately, environmental factors explained more variation than geographical factors. SNP outliers in populations of the western group had relatively stronger response to precipitation than temperature‐related variables. Functional annotation of SNP outliers identified genes associated with insect cuticle protein potentially related to desiccation adaptation in the western group and genes associated with lipase biosynthesis potentially related to temperature adaptation in the eastern group. Our study suggests that invasive species may maintain the evolutionary potential to adapt to heterogeneous environments despite a single invasion event. The molecular data suggest that quantitative trait comparisons across environments would be worthwhile.
Conspectus Supramolecular self-assembly, which creates the ordered structures as a result of spontaneous organization of building blocks driven by noncovalent interactions (NCIs), is ubiquitous in ...nature. Recently, it has become increasingly clear that nature often builds up complex structures by employing a hierarchical self-assembly (HSA) strategy, in which the components are brought together in a stepwise process via multiple NCIs. Inspired by the dedicated biological structures in nature, HSA has been widely explored to construct well-defined assemblies with increasing complexity. The employment of direct metal–ligand bonds to drive the formation of discrete metallosupramolecular architectures has proven to be a highly efficient strategy to prepare structurally diverse architectures like two-dimensional (2-D) polygons and three-dimensional (3-D) polyhedra with well-defined shapes, sizes, and geometries. Such well-defined organometallic assemblies provide an ideal platform for designing novel artificial supramolecular systems with the increasing complexity though HSA. The presence of a well-defined organometallic scaffold brings an additional dimension to the final nanoscale structures. Moreover, the multilevel dynamic nature of hierarchical self-assemblies brings more structural and functional possibilities of resultant supramolecular systems. This Account will focus on our recent advance on construction of stimuli-responsive functional materials through HSA involving coordination interactions. In our study, a series of functionalized metallacycles were first constructed through coordination-driven self-assembly (CDSA). Then, the secondary noncovalent interaction sites were integrated within the functionalized metallacycle system via either preassembly or postassembly approach. Different segments, such as alkyl chains, dendrimers, cholesteryl moiety, covalent macrocycles, and even polymeric fragments, which could provide hydrophobic and hydrophilic interactions, van der Waals forces, hydrogen bonding, CH−π and π–π interactions, and host–guest interactions, have been utilized to provide the secondary NCIs. Further self-assembly of functionalized metallacycles gives rise to the formation of complex higher-order structures driven by other NCIs by taking advantages of orthogonal property of coordination bonds with other NCIs. By changing the type of additional NCIs embodied in building blocks, different supramolecular architectures, such as the ordered nanostructures, supramolecular polymers and gels, fluorescent materials and sensors, have been successfully prepared with the tailored chemical and physical properties. In particular, the dynamic nature of coordination bonds as well as other NCIs endows final assemblies with stimuli-responsive functions. Collectively, our studies suggest that combining coordination and other NCIs in a well-defined and precise manner is a highly efficient strategy to achieve the complex architectures and functional materials. Therefore, it is very promising to develop the desired functional materials with high precision and fidelity by employing HSA involving coordination interactions.
Single-atom catalysts not only maximize metal atom efficiency, they also display properties that are considerably different to their more conventional nanoparticle equivalents, making them a ...promising family of materials to investigate. Herein we developed a general host-guest strategy to fabricate various metal single-atom catalysts on nitrogen-doped carbon (M
/CN, M = Pt, Ir, Pd, Ru, Mo, Ga, Cu, Ni, Mn). The iridium variant Ir
/CN electrocatalyses the formic acid oxidation reaction with a mass activity of 12.9 Formula: see text whereas an Ir/C nanoparticle catalyst is almost inert (~4.8 × 10
Formula: see text). The activity of Ir
/CN is also 16 and 19 times greater than those of Pd/C and Pt/C, respectively. Furthermore, Ir
/CN displays high tolerance to CO poisoning. First-principle density functional theory reveals that the properties of Ir
/CN stem from the spatial isolation of iridium sites and from the modified electronic structure of iridium with respect to a conventional nanoparticle catalyst.
Inherent poor stability of perovskite nanocrystals (NCs) is the main impediment preventing broad applications of the materials. Here, TiO2 shell coated CsPbBr3 core/shell NCs are synthesized through ...the encapsulation of colloidal CsPbBr3 NCs with titanium precursor, followed by calcination at 300 °C. The nearly monodispersed CsPbBr3/TiO2 core/shell NCs show excellent water stability for at least three months with the size, structure, morphology, and optical properties remaining identical, which represent the most water‐stable inorganic shell passivated perovskite NCs reported to date. In addition, TiO2 shell coating can effectively suppress anion exchange and photodegradation, therefore dramatically improving the chemical stability and photostability of the core CsPbBr3 NCs. More importantly, photoluminescence and (photo)electrochemical characterizations exhibit increased charge separation efficiency due to the electrical conductivity of the TiO2 shell, hence leading to an improved photoelectric activity in water. This study opens new possibilities for optoelectronic and photocatalytic applications of perovskites‐based NCs in aqueous phase.
TiO2 shell coated CsPbBr3 core/shell nanocrystals are successfully constructed, resulting in excellent water, photo and thermal stability. TiO2 shell coating effectively increases charge separation efficiency, hence leading to an improved photoelectric activity in water.
In response to the call for safer high‐energy‐density storage systems, high‐voltage solid‐state Li metal batteries have attracted extensive attention. Therefore, solid electrolytes are required to be ...stable against both Li anode and high‐voltage cathodes; nevertheless, the requirements still cannot be completely satisfied. Herein, a heterogeneous multilayered solid electrolyte (HMSE) is proposed to broaden electrochemical window of solid electrolytes to 0–5 V, through different electrode/electrolyte interfaces to overcome the interfacial instability problems. Oxidation‐resistance poly(acrylonitrile) (PAN) is in contact with the cathode, while reduction tolerant polyethylene glycol diacrylate contacts with Li metal anode. A Janus and flexible PAN@Li1.4Al0.4Ge1.6(PO4)3 (80 wt%) composite electrolyte is designed as intermediate layer to inhibit dendrite penetration and ensure compact interface. Paired with LiNi0.6Co0.2Mn0.2O2 and LiNi0.8Co0.1Mn0.1O2 cathodes, which are rarely used in solid‐state batteries, the solid‐state Li metal batteries with HMSE exhibit excellent electrochemical performance including high capacity and long cycle life. Besides, the Li||Li symmetric batteries maintain a stable polarization less than 40 mV for more than 1000 h under 2 mA cm−2 and effective inhibition of dendrite formation. This study offers a promising approach to extend the applications of solid electrolytes for high‐voltage solid‐state Li metal batteries.
A heterogeneous multilayered structure that expands the electrochemical window of solid electrolytes is designed. The oxidation‐resistant poly(acrylonitrile) (PAN) and reduction‐tolerant polyethylene glycol diacrylate integrated with the Janus and flexible PAN@Li1.4Al0.4Ge1.6(PO4)3 (80 wt%) composite electrolyte broaden the electrochemical window to 0–5 V, resulting in excellent performance for high‐voltage solid‐state Li‐metal batteries. Additionally, the thickness of electrolyte is below 25 μm.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) ...represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A
dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A
DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
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