Buried Interface Passivation Using Organic Ammonium Salts for Efficient Inverted CsMAFA Perovskite Solar Cell Performance.

This study uses different doping ratios of CsCl and MACl dual additives to improve the quality of the perovskite, where CsCl reduces the perovskite trap density and increases the resistance of charge recombination, and MACl was used to improve the phase stability. Finally, the composition of Cs0.1MA0.09FA0.81PbCl0.14I2.86 perovskite solar cell (PeSC) can achieve better open-circuit voltage (Voc), short-circuit current density (Jsc), and photoelectric conversion efficiency (PCE). To achieve a better PCE of PeSC, the use of organic ammonium salt butane-1,4-diammonium iodide (BDAI2) to passivate the perovskite bottom surface (buried interface) can effectively suppress the formation of defects at the perovskite buried interface, obtain higher crystallinity, and thereby reduce the probability of carrier recombination. The Jsc, fill factor (FF), and PCE of the PeSC based on BDAI2 passivation increased from 24.0 mA cm-2, 74.1%, and 18.6% to 24.5 mA cm-2, 79.9%, and 20.5%, respectively.

Effect of High Energy Low Protein Diet on Lipid Metabolism and Inflammation in the Liver and Abdominal Adipose Tissue of Laying Hens.

The aim of this study was to evaluate the effects of a high-energy low-protein (HELP) diet on lipid metabolism and inflammation in the liver and abdominal adipose tissue (AAT) of laying hens. A total of 200 Roman laying hens (120 days old) were randomly divided into two experimental groups: negative control group (NC group) and HELP group, with 100 hens per group. The chickens in the NC group were fed with a basic diet, whereas those in the HELP group were given a HELP diet. Blood, liver, and AAT samples were collected from 20 chickens per group at each experimental time point (30, 60, and 90 d). The morphological and histological changes in the liver and AAT were observed, and the level of serum biochemical indicators and the relative expression abundance of key related genes were determined. The results showed that on day 90, the chickens in the HELP group developed hepatic steatosis and inflammation. However, the diameter of the adipocytes of AAT in the HELP group was significantly larger than that of the NC group. Furthermore, the results showed that the extension of the feeding time significantly increased the lipid contents, lipid deposition, inflammatory parameters, and peroxide levels in the HELP group compared with the NC group, whereas the antioxidant parameters decreased significantly. The mRNA expression levels of genes related to lipid synthesis such as fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor gamma (PPARγ) increased significantly in the liver and AAT of the HELP group, whereas genes related to lipid catabolism decreased significantly in the liver. In addition, the expression of genes related to lipid transport and adipokine synthesis decreased significantly in the AAT, whereas in the HELP group, the expression levels of pro-inflammatory parameters such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß) increased significantly in the liver and AAT. Conversely, the expression level of the anti-inflammatory parameter interleukin-10 (IL-10) decreased significantly in the liver. The results indicated that the HELP diet induced lipid peroxidation and inflammation in the liver and AAT of the laying hens. Hence, these results suggest that chicken AAT may be involved in the development of fatty liver.

Diphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects.

Diphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient's mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient's mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.

RNA-Seq Analysis Reveals the Molecular Mechanisms Regulating the Development of Different Adipose Tissues in Broiler Chicks.

In an effort to enhance growth rates, chicken breeders have undertaken intensive genetic selection. In the selection process, the primary aim is to accelerate growth, inadvertently leading to new chicken breeds having an increased capacity for rapid adipose tissue accumulation. However, little is known about the relationship between changes in gene expression and adipose tissue accumulation and deposition in chickens. Therefore, in this study, RNA-seq analysis was utilized, and transcriptome data were obtained from the abdominal fat, thoracic subcutaneous fat, and clavicular fat on day 1 (d1), day 4, day 7, day 11, and day 15 to reveal the molecular mechanisms regulating the development and deposition of different adipose tissues in broiler chicks. The results showed that the key period for adipocyte differentiation and proliferation was between d4 and d7 (abdominal fat development) and between d1 and d4 (chest subcutaneous fat and clavicular fat). In addition, candidate genes such as MYOG, S100A9, CIDEC, THRSP, CXCL13, and NMU related to adipose tissue growth and development were identified. Further, genes (HOXC9, AGT, TMEM182, ANGPTL3, CRP, and DSG2) associated with the distribution of adipose tissue were identified, and genes (MN1, ANK2, and CAP2) related to adipose tissue growth were also identified. Taken together, the results from this study provide the basis for future studies on the mechanisms regulating adipose tissue development in chickens. Further, the candidate genes identified could be used in the selection process.

In situ topotactic formation of an inorganic intergrowth bulk NiS/FeS@MgFe-LDH heterojunction to simulate CODH for the photocatalytic reduction of CO2.

Enzyme-mimetic photocatalysis has been attracting much attention in bionic research, in which carbon monoxide dehydrogenase (CODH) is a suitable prototype for simulation to meet environmental and energy needs. In this study, we utilized the structural memory effect of layered double hydroxides (LDHs) to build inorganic intergrowth bulk heterojunctions (IIBHs) NiS/FeS@MgFe-LDHs via a pyrolytic topological vulcanization (PTV) method that imitated active C-clusters [Ni-4Fe-4S] in CODH. Enzyme mimicry was evaluated in terms of the microstructure and catalytic reaction site. The similarity between the microstructure of NiS/FeS@MgFe-LDHs and the CODH active group was demonstrated through XRD, XAFS and other characterisations. Subsequently, the obtained in situ irradiated X-ray photoelectron spectra and transient absorption spectra indicated the photogenerated electron transfer of the IIBH, wherein electrons finally accumulated in the conduction band of the NiS domain for the photocatalytic CO2 reduction reaction, which was similar to that of C-clusters [Ni-4Fe-4S] in which the Ni2+ ion was the reactive site. As a result, NiS/FeS@MgFe-LDHs achieved a high yield of CO at a rate of 2151.974 µmol g-1 h-1, which was 39.8 and 9.7 times more than that of NiMgFe-LDHs and NiMgFe-MMO, respectively. The study offers an innovative design route for developing IIBHs, providing novel opportunities for enzyme-mimetic photocatalysis.

Characterization of Agronomic and Seed Oil Features for Different Cultivars of Tree Peony.

Tree peony is a unique oil plant resource in China, and tree peony seed oil is one of the healthy edible oils with a very promising future. However, the main oil tree peony cultivars promoted in China are Paeonia ostii 'Fengdan' and Paeonia rockii. In order to explore new oil tree peony cultivars, 68 tree peony cultivars were investigated and cultivars with oil potential were selected by cluster analysis and grey relational analysis (GRA) in this study. The results demonstrated that the 68 cultivars varied significantly in terms of agronomic characteristics (p < 0.05), with the coefficient of variation in seed yield per plant reaching a high of 75.36%. The oil content of 46 cultivars was higher than 'Fengdan' (20.87 ± 0.26%) and 'Zibanbai' (21.24 ± 1.01%), while the alpha-linolenic acids and total unsaturated fatty acid contents of 26 cultivars were higher than 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%) and 'Zibanbai' (40.51 ± 0.09% and 93.59 ± 0.09%). Finally, three cultivars with better integrated traits were selected by cluster analysis and grey relational analysis (GRA), comprising of 'Changshoule', 'Xianchizhenghui', and 'Yupantuojin'. The contents of alpha-linolenic acids and total unsaturated fatty acids in 'Changshoule' (47.98 ± 0.17% and 93.60 ± 0.08%), 'Xianchizhenghui' (49.44 ± 0.63% and 93.80 ± 0.06%), and 'Yupantuojin' (40.46 ± 0.26% and 93.58 ± 0.06%) were higher than that of 'Fengdan' (39.79 ± 1.13% and 88.99 ± 0.47%). In general, these cultivars can be used as hybrid parental materials for breeding new excellent oil tree peony cultivars.

Selectfluor-mediated tandem cyclization of enaminones with diselenides toward the synthesis of 3-selenylated chromones.

A practical and metal-free approach for the regioselective selenation of chromones employing Selectfluor reagent under mild conditions is described. The developed method is suitable for a wide substrate scope and affords 3-selenylated chromones in good to excellent yield with high selectivity. An ionic mechanism is proposed for this transformation. Furthermore, the application of potassium thiocyanate with enaminones for the synthesis of thiocyano chromones in this transformation is also successful.

Whole-genome sequencing revealed genetic diversity, structure and patterns of selection in Guizhou indigenous chickens.

BACKGROUND: The eight phenotypically distinguishable indigenous chicken breeds in Guizhou province of China are great resources for high-quality development of the poultry industry in China. However, their full value and potential have yet to be understood in depth. To illustrate the genetic diversity, the relationship and population structure, and the genetic variation patterns shaped by selection in Guizhou indigenous chickens, we performed a genome-wide analysis of 240 chickens from 8 phenotypically and geographically representative Guizhou chicken breeds and 60 chickens from 2 commercial chicken breeds (one broiler and one layer), together with 10 red jungle fowls (RJF) genomes available from previous studies. RESULTS: The results obtained in this present study showed that Guizhou chicken breed populations harbored higher genetic diversity as compared to commercial chicken breeds, however unequal polymorphisms were present within Guizhou indigenous chicken breeds. The results from the population structure analysis markedly reflected the breeding history and the geographical distribution of Guizhou indigenous chickens, whereas, some breeds with complex genetic structure were ungrouped into one cluster. In addition, we confirmed mutual introgression within Guizhou indigenous chicken breeds and from commercial chicken breeds. Furthermore, selective sweep analysis revealed candidate genes which were associated with specific and common phenotypic characteristics evolved rapidly after domestication of Guizhou local chicken breeds and economic traits such as egg production performance, growth performance, and body size. CONCLUSION: Taken together, the results obtained from the comprehensive analysis of the genetic diversity, genetic relationships and population structures in this study showed that Guizhou indigenous chicken breeds harbor great potential for commercial utilization, however effective conservation measures are currently needed. Additionally, the present study drew a genome-wide selection signature draft for eight Guizhou indigenous chicken breeds and two commercial breeds, as well as established a resource that can be exploited in chicken breeding programs to manipulate the genes associated with desired phenotypes. Therefore, this study will provide an essential genetic basis for further research, conservation, and breeding of Guizhou indigenous chickens.

A Bioinspired Self-Healing Conductive Hydrogel Promoting Peripheral Nerve Regeneration.

The development of self-healing conductive hydrogels is critical in electroactive nerve tissue engineering. Typical conductive materials such as polypyrrole (PPy) are commonly used to fabricate artificial nerve conduits. Moreover, the field of tissue engineering has advanced toward the use of products such as hyaluronic acid (HA) hydrogels. Although HA-modified PPy films are prepared for various biological applications, the cell-matrix interaction mechanisms remain poorly understood; furthermore, there are no reports on HA-modified PPy-injectable self-healing hydrogels for peripheral nerve repair. Therefore, in this study, a self-healing electroconductive hydrogel (HASPy) from HA, cystamine (Cys), and pyrrole-1-propionic acid (Py-COOH), with injectability, biodegradability, biocompatibility, and nerve-regenerative capacity is constructed. The hydrogel directly targets interleukin 17 receptor A (IL-17RA) and promotes the expression of genes and proteins relevant to Schwann cell myelination mainly by activating the interleukin 17 (IL-17) signaling pathway. The hydrogel is injected directly into the rat sciatic nerve-crush injury sites to investigate its capacity for nerve regeneration in vivo and is found to promote functional recovery and remyelination. This study may help in understanding the mechanism of cell-matrix interactions and provide new insights into the potential use of HASPy hydrogel as an advanced scaffold for neural regeneration.

Aligned Electroactive Electrospun Fibrous Scaffolds for Peripheral Nerve Regeneration.

Effective repair and functional recovery of large peripheral nerve deficits are urgent clinical needs. A biofunctional electroactive scaffold typically acts as a "bridge" for the repair of large nerve defects. In this study, we constructed a biomimetic piezoelectric and conductive aligned polypyrrole (PPy)/polydopamine (PDA)/poly-l-lactic acid (PLLA) electrospun fibrous scaffold to improve the hydrophilicity and cellular compatibility of PLLA and restore the weakened piezoelectric effect of PDA, which is beneficial in promoting Schwann cell differentiation and dorsal root ganglion neuronal extension and alignment. The aligned PPy/PDA/PLLA fibrous scaffold bridged the sciatic nerve of Sprague-Dawley rats with a 10 mm deficit, prevented autotomy, and promoted nerve regeneration and functional recovery, thereby activating the calcium and AMP-activated protein kinase signaling pathways. Therefore, electroactive fibrous scaffolds exhibit great potential for neural tissue regeneration.

Modulation of taxane binding to tubulin curved and straight conformations by systematic 3'N modification provides for improved microtubule binding, persistent cytotoxicity and in vivo potency.

The taxane class of microtubule stabilizers are some of the most effective and widely used chemotherapeutics. The anticancer activity of taxanes arises from their ability to induce tubulin assembly by selectively recognizing the curved (c-) conformation in unassembled tubulin as compared to the straight (s-) conformation in assembled tubulin. We first designed and synthesized a series of 3'N-modified taxanes bearing covalent groups. Instead of discovering covalent taxanes, we found a series of non-covalent taxanes 2, in which the 3'N side chain was found to be essential for cytotoxicity due to its role in locking tubulin in the s-conformation. A representative compound bearing an acrylamide moiety (2h) exhibited increased binding affinity to the unassembled tubulin c-conformation and less cytotoxicity than paclitaxel. Further exploration of chemical space around 2h afforded a new series 3, in which derivatives such as 3l bind more tightly to both the s- and c-conformations of tubulin compared to paclitaxel, leading to more efficient promotion of tubulin polymerization and a greater persistence of in vitro efficacy against breast cancer cells after drug washout. Although 3l also had improved in vivo potency as compared to paclitaxel, it was also associated with increased systemic toxicity that required localized, intratumoral injection to observe potent and prolonged antitumor efficacy.

Structural insight into the stabilization of microtubules by taxanes.

Paclitaxel (Taxol) is a taxane and a chemotherapeutic drug that stabilizes microtubules. While the interaction of paclitaxel with microtubules is well described, the lack of high-resolution structural information on a tubulin-taxane complex precludes a comprehensive description of the binding determinants that affect its mechanism of action. Here, we solved the crystal structure of baccatin III the core moiety of paclitaxel-tubulin complex at 1.9 Å resolution. Based on this information, we engineered taxanes with modified C13 side chains, solved their crystal structures in complex with tubulin, and analyzed their effects on microtubules (X-ray fiber diffraction), along with those of paclitaxel, docetaxel, and baccatin III. Further comparison of high-resolution structures and microtubules' diffractions with the apo forms and molecular dynamics approaches allowed us to understand the consequences of taxane binding to tubulin in solution and under assembled conditions. The results sheds light on three main mechanistic questions: (1) taxanes bind better to microtubules than to tubulin because tubulin assembly is linked to a ßM-loopconformational reorganization (otherwise occludes the access to the taxane site) and, bulky C13 side chains preferentially recognize the assembled conformational state; (2) the occupancy of the taxane site has no influence on the straightness of tubulin protofilaments and; (3) longitudinal expansion of the microtubule lattices arises from the accommodation of the taxane core within the site, a process that is no related to the microtubule stabilization (baccatin III is biochemically inactive). In conclusion, our combined experimental and computational approach allowed us to describe the tubulin-taxane interaction in atomic detail and assess the structural determinants for binding.

Amyloid-Mediated Nanoarchitectonics with Biomimetic Mineralization of Polyetheretherketone for Enhanced Osseointegration.

Polyetheretherketone (PEEK), a widely used implant material, has attracted the attention of scientific researchers because of its bone-matched elastic modulus, radiolucency, and chemical resistance. However, the bioinert chemical properties of PEEK do not promote bone apposition once implanted. In this study, using a phase-transitioned lysozyme (PTL) nanofilm as a sandwiched layer, a robust hydroxyapatite (HAp) coating on PEEK (HAp@PTL@PEEK) is constructed. The PTL nanofilm shows strong adhesion to the PEEK surface and induces biomimetic mineralization to form a compact HAp coating on PEEK in simulated body fluids. This HAp coating not only shares a higher adhesion strength and better stability but can also be applied to implants with complex 3D structures. HAp@PTL@PEEK showed significantly enhanced osteogenic capacity when cultured with rat bone marrow mesenchymal stem cells by promoting initial cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo evaluations utilizing models of femoral condyle defects and skull defects confirm that the HAp coating substantially augments bone remodeling and osseointegration ability. Compared with the traditional method, our modified method is simpler, more environmentally friendly, and uses less hazardous components. Furthermore, the obtained HAp coating shares a higher adhesion strength to PEEK and a better osteogenic capacity. The study offers a novel method to improve the osseointegration of PEEK-based implants in biointerfaces and tissue engineering.

Montelukast Inhibits Lung Cancer Cell Migration by Suppressing Cysteinyl Leukotriene Receptor 1 Expression In vitro.

BACKGROUND: Lung cancer is a major threat to public health and remains difficult to treat. Repositioning of existing drugs has emerged as a therapeutic strategy in lung cancer. Clinically, low-dose montelukast has been used to treat asthma. OBJECTIVE: We evaluated the potential of using montelukast to treat lung cancer. METHODS: Migration was detected using wound-healing and Transwell assays, the expression of CysLT1 using western blotting, and subcellular localization of CysLT1 using immunofluorescence. CRISPR/Cas9 technology was used to further investigate the function of CysLT1. RESULTS: Subcellular localization staining showed that the CysLT1 distribution varied in murine and human lung cancer cell lines. Furthermore, montelukast suppressed CysLT1 expression in lung cancer cells. The treated cells also showed weaker migration ability compared with control cells. Knockout of CysLT1 using CRISPR/Cas9 editing in A549 cells further impaired the cell migration ability. CONCLUSION: Montelukast inhibits the migration of lung cancer cells by suppressing CysLT1 expression, demonstrating the potential of using CysLT1 as a therapeutic target in lung cancer.

Targeting the tubulin C-terminal tail by charged small molecules.

The disordered tubulin C-terminal tail (CTT), which possesses a higher degree of heterogeneity, is the target for the interaction of many proteins and cellular components. Compared to the seven well-described binding sites of microtubule-targeting agents (MTAs) that localize on the globular tubulin core, tubulin CTT is far less explored. Therefore, tubulin CTT can be regarded as a novel site for the development of MTAs with distinct biochemical and cell biological properties. Here, we designed and synthesized linear and cyclic peptides containing multiple arginines (RRR), which are complementary to multiple acidic residues in tubulin CTT. Some of them showed moderate induction and promotion of tubulin polymerization. The most potent macrocyclic compound 1f was found to bind to tubulin CTT and thus exert its bioactivity. Such RRR containing compounds represent a starting point for the discovery of tubulin CTT-targeting agents with therapeutic potential.

Clinical features of elderly patients with COVID-19 in Wuhan, China.

BACKGROUND: Elderly patients with coronavirus disease 2019 (COVID-19) who have comorbidities, frailty or profound disabilities experience poor outcomes. We analyzed the clinical characteristics of elderly patients from Wuhan who had COVID-19 during the early stages of the pandemic. AIM: To identify factors affecting the early mortality of elderly patients with COVID-19. METHODS: The records of 234 patients who were 65-years-old or more and were hospitalized in Wuhan Huoshenshan Hospital from February 4 to March 4, 2020 were reviewed. All patients had confirmed COVID-19 and the final date of follow-up was April 4, 2020. RESULTS: There were 163 cases of mild disease (69.66%), 39 cases of severe disease (16.67%) and 32 cases of critical disease (13.68%). Twenty-nine patients died within 1 mo (12.40%), all of whom had critical disease. Surviving patients and deceased patients had no significant differences in age or chronic diseases. Overall, the most common symptoms were fever (65.4%), dry cough (57.3%), fatigue (47.4%) and shortness of breath (41%). The deceased patients had higher levels of multiple disease markers (C-reactive protein, D-dimer, lactate dehydrogenase, alanine amino transferase, aspartate aminotransferase, creatinine kinase and creatinine kinase-MB) and higher incidences of lymphocytopenia and hypoproteinemia. CONCLUSION: This single-center study of elderly patients from Wuhan, China who were hospitalized with COVID-19 indicated that age and chronic diseases were not associated with mortality. Hypertension, diabetes and cardiovascular disease were the most common comorbidities and the most common symptoms were fever, dry cough, fatigue and shortness of breath. Lymphocytopenia, increased levels of D-dimer and other markers indicative of damage to the heart, kidneys or liver were associated with an increased risk of death.

Three-layer core-shell structure of polypyrrole/polydopamine/poly(l-lactide) nanofibers for wound healing application.

Poor wound healing is a very common clinical problem, so far there is no completely satisfactory treatment. Electropsun nanofibrous wound dressings may provide an ideal structure to improve wound healing. Therefore, development of nanofibrous wound dressings with rapid hemostasis, antibacterial and tissue regenerative multi-functions has been a hotspot in the field of skin tissue engineering. In this work, polydopamine (PDA) and polypyrrole (PPy) were uniformly coated onto the surface of poly(l-lactide) (PLLA) nanofibers by in-situ polymerization, forming a novel PPy/PDA/PLLA three-layer core-shell structure. The homogeneously coated PPy and PDA two layers could significantly increase the hydrophilicity, conductivity, near-infrared photothermal antibacterial property, the speed of wound hemostasis, antioxidant capacity and reactive oxygen species (ROS) scavenging capacity, respectively. In addition, PPy/PDA/PLLA nanofibers showed good biocompatibility. Rat wound healing model confirmed that PPy/PDA/PLLA nanofibers could significantly accelerate wound repair in vivo. Thus, this novel nanofibrous wound dressing is a promising candidate for clinical wound healing.