Engineering a Carotenoid Cleavage Oxygenase for Coenzyme-Free Synthesis of Vanillin from Ferulic Acid.

One-pot biosynthesis of vanillin from ferulic acid without providing energy and cofactors adds significant value to lignin waste streams. However, naturally evolved carotenoid cleavage oxygenase (CCO) with extreme catalytic conditions greatly limited the above pathway for vanillin bioproduction. Herein, CCO from Thermothelomyces thermophilus (TtCCO) was rationally engineered for achieving high catalytic activity under neutral pH conditions and was further utilized for constructing a one-pot synthesis system of vanillin with Bacillus pumilus ferulic acid decarboxylase. TtCCO with the K192N-V310G-A311T-R404N-D407F-N556A mutation (TtCCOM3) was gradually obtained using substrate access channel engineering, catalytic pocket engineering, and pocket charge engineering. Molecular dynamics simulations revealed that reducing the site-blocking effect in the substrate access channel, enhancing affinity for substrates in the catalytic pocket, and eliminating the pocket's alkaline charge contributed to the high catalytic activity of TtCCOM3 under neutral pH conditions. Finally, the one-pot synthesis of vanillin in our study could achieve a maximum rate of up to 6.89 ± 0.3 mM h-1. Therefore, our study paves the way for a one-pot biosynthetic process of transforming renewable lignin-related aromatics into valuable chemicals.

Combustion Characteristics of Vat-Photopolymerized Fuels with a Spiral Star Port for Hybrid Propulsion.

Despite hybrid rocket motors offering distinct advantages over solid or liquid rocket motors, their low regression rate and insufficient combustion efficiency remain significantly unimproved. This study focuses on the effects of the helix lead on the regression rate distribution and combustion efficiency of vat-polymerized fuel grains with a spiral star port for a hybrid rocket. Both experimental and numerical investigations were conducted to study the combustion characteristics and regression rate distribution of three-dimensional (3D) print grains. Spiral star grains with varying helix leads of 60, 90, and 120 mm were fabricated using light-curing 3D printing technology. A 3D simulation model was developed to obtain the temperature distribution, species mass distribution, and combustion efficiency. Furthermore, firing tests were performed on a two-dimensional radial hybrid combustion test stand to measure the regression rate. Digital image processing of computed tomography images was used to determine the regression rate. Simulation results indicated that the spiral star grain port helps to improve the combustion efficiency compared with those seen with round tube and straight star port grains. With an increase in the axial distance, the flame zone gradually shrinks, and the smaller the helix lead, the faster the shrinkage. At a mass flow rate of 1.50 g/s for oxygen, the regression rate of the spiral star grains is significantly higher than that of the straight star grain and the conventional round tubular grains, and the regression rate gradually increases with a decrease in the helix lead. This finding is expected to solve the problem of the low regression rate of solid fuels with spiral star pore-shaped grains prepared by the light-curing 3D printing method.

The Interaction between Collagen 1 and High Mannose Type CD133 Up-Regulates Glutamine Transporter SLC1A5 to Promote the Tumorigenesis of Glioblastoma Stem Cells.

Targeting the niche components surrounding glioblastoma stem cells (GSCs) helps to develop more effective glioblastoma treatments. However, the mechanisms underlying the crosstalk between GSCs and microenvironment remain largely unknown. Clarifying the extracellular molecules binding to GSCs marker CD133 helps to elucidate the mechanism of the communication between GSCs and the microenvironment. Here, it is found that the extracellular domain of high mannose type CD133 physically interacts with Collagen 1 (COL1) in GSCs. COL1, mainly secreted by cancer-associated fibroblasts, is a niche component for GSCs. COL1 enhances the interaction between CD133 and p85 and activates Akt phosphorylation. Activation of Akt pathway increases transcription factor ATF4 protein level, subsequently enhances SLC1A5-dependent glutamine uptake and glutathione synthesis. The inhibition of CD133-COL1 interaction or down-regulation of SLC1A5 reduces COL1-accelerated GSCs self-renewal and tumorigenesis. Analysis of glioma samples reveals that the level of COL1 is correlated with histopathological grade of glioma and the expression of SLC1A5. Collectively, COL1, a niche component for GSCs, enhances the tumorigenesis of GSCs partially through CD133-Akt-SLC1A5 signaling axis, providing a new mechanism underlying the cross-talk between GSCs and extracellular matrix (ECM) microenvironment.

Loss of α-1,2-mannosidase MAN1C1 promotes tumorigenesis of intrahepatic cholangiocarcinoma through enhancing CD133-FIP200 interaction.

CD133 is widely used as a marker to isolate tumor-initiating cells in many types of cancers. The structure of N-glycan on CD133 is altered during the differentiation of tumor-initiating cells. However, the relationship between CD133 N-glycosylation and stem cell characteristics remains elusive. Here, we found that the level of α-1,2-mannosylated CD133 was associated with the level of stemness genes in intrahepatic cholangiocarcinoma (iCCA) tissues. α-1,2-mannosylated CD133+ cells possessed the characteristics of tumor-initiating cells. The loss of the Golgi α-mannosidase I coding gene MAN1C1 resulted in the formation of α-1,2-mannosylated CD133 in iCCA-initiating cells. Mechanistically, α-1,2-mannosylation promoted the cytoplasmic distribution of CD133 and enhanced the interaction between CD133 and the autophagy gene FIP200, subsequently promoting the tumorigenesis of α-1,2-mannosylated CD133+ cells. Analysis of iCCA samples showed that the level of cytoplasmic CD133 was associated with poor iCCA prognosis. Collectively, α-1,2-mannosylated CD133 is a functional marker of iCCA-initiating cells.

Climate change and women employment in agriculture in the Sahel region: An empirical insight

In recent times, the Sahel region has been particularly identified as the flash point of climate change crisis in Africa, due to the persistent reliance on both biophysical factors and natural resources, especially agriculture for economic livelihood. Agains t this scenario, this study provides an empirical evidence to establish the nexus between climate change and women employment in agriculture within the Sahel region. The study employed panel data from 1990 to 2020 of 9 countries within the Sahel region. Consequently, a panel Fully Modified Ordinary Least Squares (FMOLS) was used to estimate the relationship between the variables of interest. Thus, the results showed that about 60% of women in the Sahel region are actively employed in agriculture. However, change in rainfall pattern has a significant adverse effect on women employment in agriculture. In view of these findings, we conclude that a rise in women's employment in agriculture would be mitigated if adverse effects of changes in rainfall pattern are controlled. Additionally, policymakers should be proactive in policy formulation that increases the region's resilience and adaptation to the future adverse effects of agriculturally induced climate change.

Ces derniers temps, la région du Sahel a été particulièrement identifiée comme le foyer de la crise du changement climatique en Afrique, en raison de sa dépendance persistante à l'égard des facteurs biophysiques et des ressources naturelles, en particulier l'agriculture, pour ses moyens de subsistance. Face à ce scénario, cette étude fournit une preuve empirique permettant d'établir le lien entre le changement climatique et l'emploi des femmes dans l'agriculture dans la région du Sahel. L'étude a utilisé des données de panel de 1990 à 2020 provenant de 9 pays de la région du Sahel. Par conséquent, un panel de moindres carrés ordinaires entièrement modifiés (FMOLS) a été utilisé pour estimer la relation entre les variables d'intérêt. Ainsi, les résultats ont montré qu'environ 60 % des femmes de la région du Sahel sont activement employées dans l'agriculture. Cependant, le changement du régime des précipitations a un effet négatif important sur l'emploi des femmes dans l'agriculture. Au vu de ces résultats, nous concluons qu'une augmentation de l'emploi des femmes dans l'agriculture serait atténuée si les effets négatifs des changements dans le régime des précipitations étaient contrôlés. En outre, les décideurs politiques doivent être proactifs dans la formulation de politiques qui augmentent la résilience et l'adaptation de la région aux futurs effets néfastes du changement climatique induit par l'agriculture.

Controlled preparation of CoNi2S4 nanorods derived from MOF-74 nanoarrays involving an exchange reaction for high energy density supercapacitors.

Binary transition metal sulfides are considered to be a promising material for supercapacitors, possessing richer electrochemically active sites and superior electrochemical performance. Metal-organic frameworks (MOFs) are often used as self-sacrificing templates in the preparation of metal sulfides. Usually, direct sulfidation of MOFs tends to cause collapse of the morphological structure and blockage of the ion transport channels, so that the morphology of the original MOF template can be well preserved by using pyrolysis followed by S2- ion exchange. In this paper, we first prepared NiCo-MOF-74 on nickel foam by an in situ transformation method from layered double hydroxides (LDHs) through a ligand exchange reaction. Then, CoNi2S4 was synthesized in two steps involving the pyrolysis of NiCo-MOF-74 and a subsequent S2- ion exchange reaction. Compared with direct sulfidation, this synthetic strategy can well maintain the rod-like morphology of MOF-74 arrays and prevent structural collapse. The surface of CoNi2S4 has a fine nanosheet structure, which exposes more active sites and shows a high specific capacitance of 7.50 F cm-2 at 2 mA cm-2 and an excellent Coulomb efficiency (96.32%). In addition, the hybrid supercapacitor assembled with activated carbon shows a high energy density of 0.64 mW h cm-2 at a power density of 1.64 mW cm-2 and a high capacitance retention of 88.39% after 5000 cycles. These results indicate that rod-shaped CoNi2S4 can be controllably prepared from MOF-74 involving an exchange reaction and has promising application in high-performance supercapacitors.

Siglec15 promotes the migration of thyroid carcinoma cells by enhancing the EGFR protein stability.

PURPOSE: Sialic acid-bound immunoglobulin-like lectin 15 (Siglec15) has emerged as a novel therapeutic target in tumor immunotherapy. This study is designed to investigate the function and mechanism of Siglec15 in thyroid carcinoma (THCA). MATERIALS AND METHODS: The information on patients with THCA from TGCA and GEO database were used to analyze the expression of Siglec15 in THCA. THCA cells were treated with Siglec15-mFc, a recombinant fusion protein consisting of the extracellular domain of human Siglec15 and murine IgG Fc. THP-1 cells expressing human Siglec15 and its mutant were co-cultured with THCA cells to mimic the contact between Siglec15-expressing tumor-associated macrophages and THCA cells. Wound-healing assay and transwell migration assay were used to examine the migration abilities of BCPAP and C643 cells. Pull-down assay was performed to examine the interaction between Siglec15 and epidermal growth factor receptor (EGFR) on the cancer cells. Cycloheximide (CHX) assay was used to evaluate the stability of the protein. RESULTS: The expression of Siglec15 in thyroid carcinoma tissues is higher than in normal tissues. Siglec15 promotes the migration of THCA cells by binding to EGFR in a sialic acid-dependent manner and increases EGFR protein expression. Inhibition of the EGFR pathway blocks the effect of Siglec15 on the migration of THCA cells. CONCLUSIONS: Our findings reveals that Siglec15 promotes the migration of thyroid carcinoma cells by enhancing the EGFR protein stability.

The plastome reveals new insights into the evolutionary and domestication history of peonies in East Asia.

BACKGROUD: Paeonia holds considerable value in medicinal, ornamental horticultural, and edible oil industries, but the incomplete state of phylogenetic research in this genus poses a challenge to the effective conservation and development of wild germplasm, and also impedes the practical utilization of existing cultivars. Due to its uniparental inheritance and lack of recombination, the plastome (i.e., plastid genome), which is a valuable molecular marker for phylogenetic analyses, is characterized by an appropriate rate of nucleotide evolution. METHODS: In this study, 10 newly assembled data and available reported data were combined to perform a comparative genomics and phylogenetics analysis of 63 plastomes of 16 Paeonia species, primarily from East Asia, which is the origin and diversity center of Paeonia. RESULTS: Ranging between 152,153 and 154,405 bp, most plastomes displayed a conserved structure and relatively low nucleotide diversity, except for six plastomes, which showed obvious IR construction or expansion. A total of 111 genes were annotated in the Paeonia plastomes. Four genes (rpl22, rps3, rps19 and ycf1) showed different copy numbers among accessions while five genes (rpl36, petN, psbI, rpl33 and psbJ) showed strong codon usage biases (ENC < 35). Additional selection analysis revealed that no genes were under positive selection during the domestication of tree peony cultivars whereas four core photosynthesis-related genes (petA, psaA, psaB and rbcL) were under positive selection in herbaceous peony cultivars. This discovery might contribute to the wide adaption of these cultivars. Two types of molecular markers (SSR and SNP) were generated from the 63 plastomes. Even though SSR was more diverse than SNP, it had a weaker ability to delimit Paeonia species than SNP. The reconstruction of a phylogenetic backbone of Paeonia in East Asia revealed significant genetic divergence within the P. ostii groups. Evidence also indicated that the majority of P. suffruticosa cultivars had a maternal origin, from P. ostii. The results of this research also suggest that P. delavayi var. lutea, which likely resulted from hybridization with P. ludlowii, should be classified as a lineage within the broader P. delavayi group. CONCLUSIONS: Overall, this study's research findings suggest that the Paeonia plastome is highly informative for phylogenetic and comparative genomic analyses, and could be useful in future research related to taxonomy, evolution, and domestication.

The 2210408F21Rik/miR-1968-5p/Hras axis regulates synapse-related proteins in a mouse model of depressive-like behaviors through a ceRNA mechanism.

Abnormal expression of long non-coding RNAs (lncRNAs) has been correlated with depressive disorders, but limited data are available on the lncRNA-microRNA (miRNA/miR)-messenger RNA (mRNA) competitive endogenous RNA (ceRNA) mechanism in depression. Herein, we address this issue based on transcriptome sequencing and in vitro experiments. Mouse hippocampus tissues were obtained from chronic unpredictable mild stress (CUMS)-induced mice to screen out differentially expressed mRNAs and lncRNAs based on the transcriptome sequencing. Next, the depression-related differentially expressed genes (DEGs) were obtained, followed by Gene Ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) enrichment analysis. A total of 1018 differentially expressed mRNAs, 239 differentially expressed lncRNAs, and 58 DEGs related to depression were acquired. The miRNAs targeting Harvey rat sarcoma virus oncogene (Hras) and miRNAs sponged by Hras-related lncRNA were intersected to identify the ceRNA regulatory network. In addition, the synapse-related genes related to depression were acquired by bioinformatics analysis. Hras was identified as the core gene related to depression, mainly related to neuronal excitation. We also found that 2210408F21Rik competitively bound to miR-1968-5p that targeted Hras. The effects of 2210408F21Rik/miR-1968-5p/Hras axis on neuronal excitation were verified in primary hippocampal neurons. The experimental data indicated that the downregulation of 2210408F21Rik increased the level of miR-1968-5p to diminish Hras expression, thereby affecting neuronal excitation in CUMS mice. In conclusion, the 2210408F21Rik/miR-1968-5p/Hras ceRNA network can potentially affect the expression of synapsia-related proteins and is a promising target for preventing and treating depression.

Sialylation-dependent interaction between PD-L1 and CD169 promotes monocyte adhesion to endothelial cells.

The monocyte adhesion to endothelial cells is an early step in chronic inflammation. Interferon-γ (IFN-γ) is regarded as a master regulator of inflammation development. However, the significance and mechanisms of IFN-γ in the monocyte adhesion to endothelial cells remains largely unknown. IFN-γ up-regulates PD-L1 on various types of cells. Here, we performed flow cytometry to examine the contribution of IFN-γ-induced PD-L1 expression on monocyte adhesion to endothelial cells. Up-regulation of PD-L1 by IFN-γ enhanced the adhesion of monocytes to endothelial cells. By immunoprecipitation and lectin blot, PD-L1 in endothelial cells interacted with CD169/Siglec 1 in monocytes depending on the α2,3-sialylation of PD-L1. ST3Gal family (ST3ß-galactoside α-2,3-sialyltransferase) was the major glycosyltransferase responsible for the α2,3-sialylation of membrane proteins. Down-regulation of ST3Gal4 by RNAinterference partially reduced the α2,3-sialylation of PD-L1 and the PD-L1-CD169 interaction. Finally, purified PD-L1 protein with α2,3-sialylation, but not PD-L1 protein without α2,3-sialylation, partially reduced IFN-γ-induced monocyte adhesion to endothelial cells. These findings provide evidence that the interaction between PD-L1 and CD169 promoted monocyte adhesion to endothelial cells and might elucidate a new mechanism of monocyte adhesion to endothelial cells.

Rapid Amorphization in MOF/Metal Selenite Nanocomposites for Enhanced Capacity in Supercapacitors.

MOF/inorganic nanocomposites combine the advantages of each component. Herein, two MOF/metal selenite nanocomposites, Co-NH2-BDC/CoSeO3·H2O and Co-BDC/CoSeO3·H2O, are prepared on nickel foam through a facile two-step hydrothermal method, which inherit the 2D morphology and porosity properties of their MOF precursors. Furthermore, during the electrochemical activation process, the crystallized nanocomposites can easily transform into amorphous structures in a short time of 20 min in the presence of an electric field, similar to CoSeO3·H2O. Due to amorphization, the electrochemical performance of the two nanocomposites is much enhanced relative to that of their MOF precursors. Specifically, the areal capacitances of Co-NH2-BDC/CoSeO3·H2O and Co-BDC/CoSeO3·H2O are 5.35 and 10.65 F·cm-2 at 2 mA·cm-2, respectively. The assembled asymmetric supercapacitor (ASC) using Co-NH2-BDC/CoSeO3·H2O as positive electrodes delivers an energy density of 0.207 mWh·cm-2 at a power density of 0.799 mW·cm-2 with outstanding cycling stability (93% capacity retention after 5000 cycles). Using Co-BDC/CoSeO3·H2O as positive electrodes, the ASC can reach a high energy density of 0.483 mWh·cm-2 at a power density of 0.741 mW·cm-2 and 84% capacity retention after 5000 cycles. This work provides an efficient strategy for constructing MOF/metal selenite nanocomposites for energy storage and conversion.

Engineering a Feruloyl-Coenzyme A Synthase for Bioconversion of Phenylpropanoid Acids into High-Value Aromatic Aldehydes.

Aromatic aldehydes find extensive applications in food, perfume, pharmaceutical, and chemical industries. However, a limited natural enzyme selectivity has become the bottleneck of bioconversion of aromatic aldehydes from natural phenylpropanoid acids. Here, based on the original structure of feruloyl-coenzyme A (CoA) synthetase (FCS) from Streptomyces sp. V-1, we engineered five substrate-binding domains to match specific phenylpropanoid acids. FcsCIAE407A/K483L, FcsMAE407R/I481R/K483R, FcsHAE407K/I481K/K483I, FcsCAE407R/I481R/K483T, and FcsFAE407R/I481K/K483R showed 9.96-, 10.58-, 4.25-, 6.49-, and 8.71-fold enhanced catalytic efficiency for degrading CoA thioesters of cinnamic acid, 4-methoxycinnamic acid, 4-hydroxycinnamic acid, caffeic acid, and ferulic acid, respectively. Molecular dynamics simulation illustrated that novel substrate-binding domains formed strong interaction forces with substrates' methoxy/hydroxyl group and provided hydrophobic/alkaline catalytic surfaces. Five recombinant E. coli with FCS mutants were constructed with the maximum benzaldehyde, p-anisaldehyde, p-hydroxybenzaldehyde, protocatechualdehyde, and vanillin productivity of 6.2 ± 0.3, 5.1 ± 0.23, 4.1 ± 0.25, 7.1 ± 0.3, and 8.7 ± 0.2 mM/h, respectively. Hence, our study provided novel and efficient enzymes for the bioconversion of phenylpropanoid acids into aromatic aldehydes.

The Interaction between DNMT1 and High-Mannose CD133 Maintains the Slow-Cycling State and Tumorigenic Potential of Glioma Stem Cell.

The quiescent/slow-cycling state preserves the self-renewal capacity of cancer stem cells (CSCs) and leads to the therapy resistance of CSCs. The mechanisms maintaining CSCs quiescence remain largely unknown. Here, it is demonstrated that lower expression of MAN1A1 in glioma stem cell (GSC) resulted in the formation of high-mannose type N-glycan on CD133. Furthermore, the high-mannose type N-glycan of CD133 is necessary for its interaction with DNMT1. Activation of p21 and p27 by the CD133-DNMT1 interaction maintains the slow-cycling state of GSC, and promotes chemotherapy resistance and tumorigenesis of GSCs. Elimination of the CD133-DNMT1 interaction by a cell-penetrating peptide or MAN1A1 overexpression inhibits the tumorigenesis of GSCs and increases the sensitivity of GSCs to temozolomide. Analysis of glioma samples reveals that the levels of high-mannose type N-glycan are correlated with glioma recurrence. Collectively, the high mannose CD133-DNMT1 interaction maintains the slow-cycling state and tumorigenic potential of GSC, providing a potential strategy to eliminate quiescent GSCs.

The synthesis of high-energy CT images from low-energy CT images using an improved cycle generative adversarial network.

BACKGROUND: The dose of radiation a patient receives when undergoing dual-energy computed tomography (CT) is of significant concern to the medical community, and balancing the tradeoffs between the level of radiation used and the quality of CT images is challenging. This paper proposes a method of synthesizing high-energy CT (HECT) images from low-energy CT (LECT) images using a neural network that achieves an alternative to HECT scanning by employing an LECT scan, which greatly reduces the radiation dose a patient receives. METHODS: In the training phase, the proposed structure cyclically generates HECT and LECT images to improve the accuracy of extracting edge and texture features. Specifically, we combine multiple connection methods with channel attention (CA) and pixel attention (PA) mechanisms to improve the network's mapping ability of image features. In the prediction phase, we use a model consisting of only the network component that synthesizes HECT images from LECT images. RESULTS: Our proposed method was conducted on clinical hip CT image data sets from Guizhou Provincial People's Hospital. In a comparison with other available methods [a generative adversarial network (GAN), a residual encoder-to-decoder network with a visual geometry group (VGG) pretrained model (RED-VGG), a Wasserstein GAN (WGAN), and CycleGAN] in terms of metrics of peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), normalized mean square error (NMSE), and a visual effect evaluation, the proposed method was found to perform better on each of these evaluation criteria. Compared with the results produced by CycleGAN, the proposed method improved the PSNR by 2.44%, the SSIM by 1.71%, and the NMSE by 15.2%. Furthermore, the differences in the statistical indicators are statistically significant, proving the strength of the proposed method. CONCLUSIONS: The proposed method synthesizes high-energy CT images from low-energy CT images, which significantly reduces both the cost of treatment and the radiation dose received by patients. Based on both image quality score metrics and visual effects comparisons, the results of the proposed method are superior to those obtained by other methods.

Siglec-15 promotes the migration of liver cancer cells by repressing lysosomal degradation of CD44.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as a novel potential target for cancer immunotherapy. Here, we explored the role of Siglec-15 in human hepatoma cells. In this study, we found that the expression of Siglec-15 is substantially upregulated in liver cancer tissues in comparison with the nontumor tissues. Functionally, in vitro experiments show that Siglec-15 promotes the migration of hepatoma cells. Furthermore, the data demonstrated an interaction between Siglec-15 and CD44, a transmembrane glycoprotein that mediates tumor progression and metastasis. In addition, we show that CD44 is modified by α2,6-linked sialic acids on N-glycans in hepatoma cells and that CD44 sialylation affects its interaction with Siglec-15. Removal of the sialic acid residues from CD44 resulted in suppressed interaction between Siglec-15 and CD44. We further demonstrate that Siglec-15 interacts and promotes the stability of CD44 by preventing its lysosomal-mediated degradation. Taken together, our findings demonstrate that Siglec-15 promotes the migration of hepatoma cells by regulating the CD44 protein stability.

Conjugated Microporous Polymer with C≡C and C-F Bonds: Achieving Remarkable Stability and Super Anhydrous Proton Conductivity.

Introducing nonvolatile liquid acids into porous solids is a promising solution to construct anhydrous proton-conducting electrolytes, but due to weak coordination or covalent bonds building these solids, they often suffer from structural instability in acidic environments. Herein, we report a series of steady conjugated microporous polymers (CMPs) linked by robust alkynyl bonds and functionalized with perfluoroalkyl groups and incorporate them with phosphoric acid. The resulting composite electrolyte exhibits high anhydrous proton conductivity at 30-120 °C (up to 4.39 × 10-3 S cm-1), and the activation energy is less than 0.4 eV. The excellent proton conductivity is attributed to the hydrophobic pores that provide nanospace for continuous proton transport, and the hydrogen bonding between phosphoric acid and perfluoroalkyl chains of CMPs promotes short-distance proton hopping from one side to the other.

Idiopathic Pulmonary Fibrosis Registry China study (PORTRAY): protocol for a prospective, multicentre registry study.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterised by a fibrotic histological pattern found in usual interstitial pneumonia. Its causes, pathogenesis, clinical phenotype and molecular mechanisms are poorly defined. Large-scale, multicentre studies are warranted to better understand IPF as a disease in China, its associated risk factors, clinical characteristics, diagnosis, disease progression and treatment. METHODS AND ANALYSIS: The Idiopathic Pulmonary Fibrosis Registry China Study (PORTRAY) is a prospective, multicentre registry study of patients with IPF in China. Eight hundred patients will be enrolled over a 36-month period and followed for at least 3 years to generate a comprehensive database on baseline characteristics and various follow-up parameters including patient-reported outcomes. Biological specimens will also be collected from patients to develop a library of blood, bronchoalveolar lavage fluid and lung biopsy samples, to support future research. As of 15 December 2019, 204 patients from 19 large medical centres with relatively high IPF diagnosis and treatment rates had been enrolled. Patient characteristics will be presented using descriptive statistics. The Kaplan-Meier method will be used for survival analyses. Repeated measures will be used to compare longitudinal changes in lung function, imaging and laboratory tests. Results following analysis have been projected to be available by July 2025. ETHICS AND DISSEMINATION: The study protocol was reviewed and approved by the Institutional Review Board from all the study sites currently recruiting patients. Study results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03666234.

Germplasm resources and genetic breeding of Paeonia: a systematic review.

Members of the genus Paeonia, which consists of globally renowned ornamentals and traditional medicinal plants with a rich history spanning over 1500 years, are widely distributed throughout the Northern Hemisphere. Since 1900, over 2200 new horticultural Paeonia cultivars have been created by the discovery and breeding of wild species. However, information pertaining to Paeonia breeding is considerably fragmented, with fundamental gaps in knowledge, creating a bottleneck in effective breeding strategies. This review systematically introduces Paeonia germplasm resources, including wild species and cultivars, summarizes the breeding strategy and results of each Paeonia cultivar group, and focuses on recent progress in the isolation and functional characterization of structural and regulatory genes related to important horticultural traits. Perspectives pertaining to the resource protection and utilization, breeding and industrialization of Paeonia in the future are also briefly discussed.

Hierarchical Design of Mn2P Nanoparticles Embedded in N,P-Codoped Porous Carbon Nanosheets Enables Highly Durable Lithium Storage.

Although transition metal phosphide anodes possess high theoretical capacities, their inferior electronic conductivities and drastic volume variations during cycling lead to poor rate capability and rapid capacity fading. To simultaneously overcome these issues, we report a hierarchical heterostructure consisting of isolated Mn2P nanoparticles embedded into nitrogen- and phosphorus-codoped porous carbon nanosheets (denoted as Mn2P@NPC) as a viable anode for lithium-ion batteries (LIBs). The resulting Mn2P@NPC design manifests outstanding electrochemical performances, namely, high reversible capacity (598 mA h g-1 after 300 cycles at 0.1 A g-1 ), exceptional rate capability (347 mA h g-1 at 4 A g-1), and excellent cycling stability (99% capacity retention at 4 A g-1 after 2000 cycles). The robust structure stability of Mn2P@NPC electrode during cycling has been revealed by the in situ and ex situ transmission electron microscopy (TEM) characterizations, giving rise to long-term cyclability. Using in situ selected area electron diffraction and ex situ high-resolution TEM studies, we have unraveled the dominant lithium storage mechanism and confirmed that the superior lithium storage performance of Mn2P@NPC originated from the reversible conversion reaction. Furthermore, the prelithiated Mn2P@NPC∥LiFePO4 full cell exhibits impressive rate capability and cycling stability. This work introduces the potential for engineering high-performance anodes for next-generation high-energy-density LIBs.

Prognostic value of microRNA-451 in various cancers: A meta-analysis.

BACKGROUND: Increasing evidence shows microRNA-451 plays a crucial role in various tumors, but there is inconsistency. The aim of this study was to explore the prognostic role of miR-451 in various tumors. METHODS: Online PubMed, EMBASE, Web of Science, and the Cochrane library database were searched through February 2019. Hazard ratios (HRs) were extracted and used to describe the association between expression of microRNA-451 and survival outcome, and the correlation between microRNA-451 and clinicopathologic features were described by pooled odds ratios (ORs). RESULTS: Sixteen retrospective studies containing 2122 patients were incorporated in this meta-analysis. High expression of miR-451 was considered statistically associated with prolonged overall survival (OS) (HR = 0.62, 95% CI 0.49-0.80, p < 0.001) as well as RFS/DFS (HR = 0.55, 95% CI 0.42-0.71, p < 0.001) compared with low expression of miR-451. Besides, the pooled ORs revealed significant association between high expression of miR-451 with lymph node invasion (yes vs. no) (OR = 0.64, 95% CI 0.46-0.90, P = 0.01), tumor diameter (big vs. small) (OR = 0.77, 95% CI 0.60-0.97, P = 0.028) and tumor stage (III + IV vs. I + II) (OR = 0.62, 95% CI 0.42-0.93, P = 0.019). CONCLUSION: MicroRNA-451 may serve as a promising clinical prognostic biomarker in various carcinomas.