Multicomponent, Multicavity Metallacages That Contain Different Binding Sites for Allosteric Recognition.

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

Highly Efficient Self-Assembly of Heterometallic [2]Catenanes and Cyclic Bis[2]catenanes via Orthogonal Metal-Coordination Interactions.

Although catenated cages have been widely constructed due to their unique and elegant topological structures, cyclic catenanes formed by the connection of multiple catenane units have been rarely reported. Herein, based on the orthogonal metal-coordination-driven self-assembly, we prepare a series of heterometallic [2]catenanes and cyclic bis[2]catenanes, whose structures are clearly evidenced by single-crystal X-ray analysis. Owing to the multiple positively charged nature, as well as the potential synergistic effect of the Cu(I) and Pt(II) metal ions, the cyclic bis[2]catenanes display broad-spectrum antibacterial activity. This work not only provides an efficient strategy for the construction of heterometallic [2]catenanes and cyclic bis[2]catenanes but also explores their applications as superior antibacterial agents, which will promote the construction of advanced supramolecular structures for biomedical applications.

LLPS of FXR proteins drives replication organelle clustering for ß-coronaviral proliferation.

ß-Coronaviruses remodel host endomembranes to form double-membrane vesicles (DMVs) as replication organelles (ROs) that provide a shielded microenvironment for viral RNA synthesis in infected cells. DMVs are clustered, but the molecular underpinnings and pathophysiological functions remain unknown. Here, we reveal that host fragile X-related (FXR) family proteins (FXR1/FXR2/FMR1) are required for DMV clustering induced by expression of viral non-structural proteins (Nsps) Nsp3 and Nsp4. Depleting FXRs results in DMV dispersion in the cytoplasm. FXR1/2 and FMR1 are recruited to DMV sites via specific interaction with Nsp3. FXRs form condensates driven by liquid-liquid phase separation, which is required for DMV clustering. FXR1 liquid droplets concentrate Nsp3 and Nsp3-decorated liposomes in vitro. FXR droplets facilitate recruitment of translation machinery for efficient translation surrounding DMVs. In cells depleted of FXRs, SARS-CoV-2 replication is significantly attenuated. Thus, SARS-CoV-2 exploits host FXR proteins to cluster viral DMVs via phase separation for efficient viral replication.

Long-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study.

There have been reports of long coronavirus disease (long COVID) and breakthrough infections (BTIs); however, the mechanisms and pathological features of long COVID after Omicron BTIs remain unclear. Assessing long-term effects of COVID-19 and immune recovery after Omicron BTIs is crucial for understanding the disease and managing new-generation vaccines. Here, we followed up mild BA.2 BTI convalescents for six-month with routine blood tests, proteomic analysis and single-cell RNA sequencing (scRNA-seq). We found that major organs exhibited ephemeral dysfunction and recovered to normal in approximately six-month after BA.2 BTI. We also observed durable and potent levels of neutralizing antibodies against major circulating sub-variants, indicating that hybrid humoral immunity stays active. However, platelets may take longer to recover based on proteomic analyses, which also shows coagulation disorder and an imbalance between anti-pathogen immunity and metabolism six-month after BA.2 BTI. The immunity-metabolism imbalance was then confirmed with retrospective analysis of abnormal levels of hormones, low blood glucose level and coagulation profile. The long-term malfunctional coagulation and imbalance in the material metabolism and immunity may contribute to the development of long COVID and act as useful indicator for assessing recovery and the long-term impacts after Omicron sub-variant BTIs.

Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines.

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

A compendium of genetic regulatory effects across pig tissues.

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.

Integrated machine learning methods with oversampling technique for regional suitability prediction of waste-to-energy incineration projects.

China's tiered strategy to enhance county-level waste incineration for energy aligns with the sustainable development goals (SDGs), emphasizing the need for comprehensive assessments of waste-to-energy (WtE) plant suitability. Traditional assessment methodologies face challenges, particularly in suggesting innovative site alternatives, adapting to new data sets, and their dependence on strict assumptions. This study introduced enhancements in three pivotal dimensions. Methodologically, it leverages data-driven machine learning (ML) approaches to capture the complex relationships essential for site selection, reducing dependency on strict assumptions. In terms of predictive performance, the integration of oversampling with stacked ensemble models enhances the diversity and generalizability of ML models. The area under curve (AUC) scores from four ML models, enhanced by the oversampled dataset, demonstrated significant improvements compared to the original dataset. The stacking model excelled, achieving a score of 92%. It also led in overall Precision and Recall, reaching 85.2% and 85.08% respectively. Nevertheless, a noticeable discrepancy existed in Precision and Recall for positive classes. The stacking model topped Precision scores at 83.1%, followed by eXtreme Gradient Boosting (XGBoost) (82.61%). In terms of Recall, XGBoost recorded the lowest at 85.07%, while the other three classifiers all marked 88.06%. From an industry applicability standpoint, the stacking model provides innovative location alternatives and demonstrates adaptability in Hunan province, offering a reusable tool for WtE location. In conclusion, this study not only enhances the methodological aspects of WtE site selection but also provides practical and adaptable solutions, contributing positively to sustainable waste management practices.

An ECM-mimicking assembled gelatin/hyaluronic acid hydrogel with antibacterial and radical scavenging functions for accelerating open wound healing.

A multifunctional hydrogel dressing with hemostatic, antibacterial, and reactive oxygen species (ROS)-removing properties is highly desirable for the clinical treatment of open wounds. Although many wound dressings have been prepared, the modification of polymers is often involved in the preparation process, and the uncertainty of biological safety and stability of modified polymers hinders the clinical application of products. In this study, inspired by the composition and crosslinking pattern of extracellular matrix (ECM), a deeply ECM-mimicking multifunctional hydrogel dressing is created. Tannic acid (TA) and poly-ϵ-lysine (EPL) are added into a gelatin/hyaluronic acid (Gel/HA) matrix, and a stable hydrogel is formed due to the formation of the triple helix bundles of gelatin and hydrogen bonds between polymers. The introduction of TA and EPL endows the ECM-mimicking hydrogel with stable rheological properties, as well as antibacterial and hemostatic functions. The as-produced hydrogels have suitable swelling ratio, enzyme degradability, and good biocompatibility. In addition, it also shows a significant ability to eliminate ROS, which is confirmed by the elimination of 2,2-diphenyl-1-picrylhydrazyl free radical. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed ECM-mimicking Gel/HA hydrogels have a prominent effect on ECM formation and promotion of wound closure. Taken together, these findings suggest that the multifunctional hydrogels deeply mimicking the ECM are promising candidates for the clinical treatment of open wounds.

A New Function of MbIAA19 Identified to Modulate Malus Plants Dwarfing Growth.

The primary determinants of apple (Malus) tree architecture include plant height and internode length, which are the significant criteria for evaluating apple dwarf rootstocks. Plant height and internode length are predominantly governed by phytohormones. In this study, we aimed to assess the mechanisms underlying dwarfism in a mutant of Malus baccata. M. baccata dwarf mutant (Dwf) was previously obtained through natural mutation. It has considerably reduced plant height and internode length. A comparative transcriptome analysis of wild-type (WT) and Dwf mutant was performed to identify and annotate the differentially expressed genes responsible for the Dwf phenotype using RNA-seq and GO and KEGG pathway enrichment analyses. Multiple DEGs involved in hormone signaling pathways, particularly auxin signaling pathways, were identified. Moreover, the levels of endogenous indole-3-acetic acid (IAA) were lower in Dwf mutant than in WT. The Aux/IAA transcription factor gene MbIAA19 was downregulated in Dwf mutant due to a single nucleotide sequence change in its promoter. Genetic transformation assay demonstrated strong association between MbIAA19 and the dwarf phenotype. RNAi-IAA19 lines clearly exhibited reduced plant height, internode length, and endogenous IAA levels. Our study revealed that MbIAA19 plays a role in the regulation of dwarfism and endogenous IAA levels in M. baccata.

Isoreticular Preparation of Tetraphenylethylene-based Multicomponent Metallacages towards Light-Driven Hydrogen Production.

Multicomponent metallacages can integrate the functions of their different building blocks to achieve synergetic effects for advanced applications. Herein, based on metal-coordination-driven self-assembly, we report the preparation of a series of isoreticular tetraphenylethylene-based metallacages, which are well characterized by multinuclear NMR, ESI-TOF-MS and single-crystal X-ray diffraction techniques. The suitable integration of photosensitizing tetraphenylethylene units as faces and Re catalytic complexes as the pillars into a single metallacage offers a high photocatalytic hydrogen production rate of 1707 µmol g-1 h-1 , which is one of the highest values among reported metallacages. Femtosecond transient absorption and DFT calculations reveal that the metallacage can serve as a platform for the precise and organized arrangement of the two building blocks, enabling efficient and directional electron transfer for highly efficient photocatalytic performance. This study provides a general strategy to integrate multifunctional ligands into a certain metallacage to improve the efficiency of photocatalytic hydrogen production, which will guide the future design of metallacages towards photocatalysis.

Transmembrane Transporter Constructed from PlatinumMetal-organic Cage.

A perylene diimide-based metal-organic cage (MOC4c) was found to be an efficient transmembrane transporter for ions and small molecules through the internal cavity of the cage. MOC4c could selectively transport different anions, as evidenced by vesicle-based fluorescenceassays and planar lipid bilayer-based current recordings.Furthermore, MOC4c appears tofacilitate calcein transport across the lipid bilayer membrane of a livingcell, suggesting that MOC4c could be used as a biologicaltool for small molecule drugstransmembrane transportation.

Effect of tumor-stromal fibroblasts on the biological behavior of salivary gland pleomorphic adenoma cells in vitro.

OBJECTIVES: This study aims to investigate the effects of tumor-stromal fibroblasts (TSFs) on the proliferation, invasion, and migration of salivary gland pleomorphic adenoma (SPA) cells in vitro. METHODS: Salivary gland pleomorphic adenoma cells (SPACs), TSFs, and peri-tumorous normal fibroblasts (NFs) were obtained by tissue primary culture and identified by immunocytochemical staining. The conditioned medium was obtained from TSF and NF in logarithmic phase. SPACs were cultured by conditioned medium and treated by TSF (group TSF-SPAC) and NF (group NF-SPAC). SPACs were used as the control group. The proliferation, invasion, and migration of the three groups of cells were detected by MTT, transwell, and scratch assays, respectively. The expression of vascular endothelial growth factor (VEGF) in the three groups was tested by enzyme linked immunosorbent assay (ELISA). RESULTS: Immunocytochemical staining showed positive vimentin expression in NF and TSF. Results also indicated the weak positive expression of α-smooth muscle actin (SMA) and fibroblast activation protein (FAP) in TSFs and the negative expression of α-SMA and FAP in NFs. MTT assay showed that cell proliferation in the TSF-SPAC group was significantly different from that in the NF-SPAC and SPAC groups (P<0.05). Cell proliferation was not different between the NF-SPAC and SPAC groups (P>0.05). Transwell and scratch assays showed no difference in cell invasion and migration among the groups (P>0.05). ELISA showed that no significant difference in VEGF expression among the three groups (P>0.05). CONCLUSIONS: TSFs may be involved in SPA biological behavior by promoting the proliferation of SPACs but has no effect on the invasion and migration of SPACs in vitro. Hence, TSF may be a new therapeutic target in SPA treatment.

A proteomics study to explore differential proteins associated with the pathogenesis of ameloblastoma.

BACKGROUND: Reports on the proteomic studies of ameloblastoma and other common odontogenic lesions are limited. We thus explored the differential proteins among ameloblastoma, odontogenic keratocyst, dentigerous cyst, and normal gingival tissue using proteomics and identified hub proteins involved in the local aggressiveness and recurrence of ameloblastoma. METHODS: Samples were obtained from 14 patients with ameloblastoma, 6 with odontogenic keratocyst, 9 with a dentigerous cyst, and 5 with normal gingival tissue. Proteins were then extracted, purified, quantified, and analysed using Easy-nLC chromatography and mass spectrometry. Further functional annotation and enrichment analyses were performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes on the target protein collection. Protein clustering and protein-protein interaction network analyses were used to screen the hub proteins. Proteins with significant interactions were screened according to their degree index. These results were verified by immunohistochemical staining. Proteins meeting the screening criteria of expression difference ploidy >1.2-fold (upregulation and downregulation) and p < 0.05 were considered differential proteins. RESULTS: In ameloblastoma, 808 differential proteins were upregulated and 505 were downregulated compared with those in odontogenic keratocyst; 309 were upregulated and 453 were downregulated compared with those in dentigerous cyst; and 2210 were upregulated and 829 were downregulated compared with those in normal gingival tissue. The three groups of differential proteins were associated with cellular exosomes, antigen binding, complement activation, human papillomavirus infection, focal adhesion, cell adhesion molecules, and metabolic pathways. CONCLUSION: CDH3 is associated with the local aggressiveness and recurrence of ameloblastoma and is a potential therapeutic target.

The significance of spread through air spaces in the prognostic assessment model of stage I lung adenocarcinoma and the exploration of its invasion mechanism.

PURPOSE: Spread through air spaces (STAS) is a crucial invasive mode of lung cancer and has been shown to be associated with early recurrence and metastasis. We aimed to develop a prognostic risk assessment model for stage I lung adenocarcinoma based on STAS and other pathological features and to explore the potential relationship between CXCL-8, Smad2, Snail, and STAS. METHODS: 312 patients who underwent surgery at Harbin Medical University Cancer Hospital with pathologically diagnosed stage I lung adenocarcinoma were reviewed in the study. STAS and other pathological features were identified by H&E staining, and a prognostic risk assessment model was established. The expression levels of CXCL8, Smad2, and Snail were determined by immunohistochemistry. RESULTS: The nomogram was established based on age, smoking history, STAS, tumor lymphocyte infiltration, tissue subtype, nuclear grade, and tumor size. The C-index for DFS was (training set 0.84 vs validation set 0.77) and for OS was (training set 0.83 vs validation set 0.78). Decision curve analysis showed that the model constructed has a better net benefit than traditional reporting. The prognostic risk score validated the risk stratification value for stage I lung adenocarcinoma. STAS was an important prognostic factor associated with stronger invasiveness and higher expression of CXCL8, Smad2, and Snail. CXCL8 was associated with poorer DFS and OS. CONCLUSIONS: We developed and validated a survival risk assessment model and the prognostic risk score formula for stage I lung adenocarcinoma. Additionally, we found that CXCL8 could be used as a potential biomarker for STAS and poor prognosis, and its mechanism may be related to EMT.

Potential involvement of polycystins in the pathogenesis of ameloblastomas: Analysis based on bioinformatics and immunohistochemistry.

OBJECTIVE: To perform an integrated analysis in identifying novel hub genes that could facilitate the diagnosis and targeted therapy of ameloblastoma. DESIGN: The expression profiling dataset, GSE38494, was obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified through GEO2R online tool and characterised via Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The protein-protein interaction network and hub genes were screened using the STRING database and Cytoscape software. Subsequently, an upregulated gene was selected for further validation using the GSE132472 dataset. Further, immunohistochemistry was performed to assess the expression of the selected gene in ameloblastomas, odontogenic keratocysts, dentigerous cysts, and gingival tissues. The diagnostic and therapeutic utility of the selected hub genes were further verified by receiver operating characteristic analysis and the DGIdb database. RESULTS: We identified six hub genes in ameloblastoma, among which the upregulated gene PKD2 and its related gene PKD1 were further validated. GO functional annotation revealed that PKD2 is involved in cell-cell junction, extracellular exosome, cytoplasm, endoplasmic reticulum, and calcium ion transport. The immunohistochemical analysis showed that the expression of polycystin-1 and polycystin-2, encoded by the PKD1 and PKD2 genes, respectively, was upregulated in ameloblastoma. PKD1 and PKD2 had a high diagnostic utility for ameloblastoma, and allopurinol interacted with the PKD2 gene. CONCLUSION: Our research indicates that polycystins are highly expressed in ameloblastoma and might be involved in the oncogenesis of ameloblastoma, thus offering a new perspective on the molecular mechanisms and targeted therapies on ameloblastoma.

Untargeted metabolomics reveals the preventive effect of quercetin on nephrotoxicity induced by four organophosphorus pesticide mixtures.

This research aimed to explore the protective effect of quercetin against nephrotoxicity induced by four organophosphate pesticide mixtures (PM) using untargeted metabolomics technology in rat kidneys. Sixty male Wistar rats were randomly divided into six groups: control, low-dose quercetin treated (10 mg/kg bw), high-dose quercetin treated (50 mg/kg bw), PM-treated, and two dosages of quercetin + PM-treated. Metabolomics results showed that 17 differential metabolites were identified in the PM-treated group, and pathway analysis revealed that renal metabolic disorders include purine metabolism, glycerophospholipid metabolism, and vitamin B6 metabolism. When high-dose quercetin and PM-treated were administered to rats concurrently, the intensities of differential metabolites were substantially restored (p < 0.01), suggesting that quercetin can improve renal metabolic disorders caused by organophosphate pesticides (OPs). Mechanistically, quercetin could regulate the purine metabolism disorder and endoplasmic reticulum stress (ERS)-mediated autophagy induced by OPs by inhibiting XOD activity. Moreover, quercetin inhibits PLA2 activity to regulate glycerophospholipid metabolism and it could also exert antioxidant and anti-inflammatory effects to correct vitamin B6 metabolism in rat kidneys. Taken together, the high dose of quercetin (50 mg/kg. bw) has a certain protective effect on OPs-induced nephrotoxicity in rats, which provides a theoretical basis for quercetin against nephrotoxicity caused by OPs.

Big data and artificial intelligence application in energy field: a bibliometric analysis.

This paper uses bibliometrics to characterize the knowledge systems of big data, artificial intelligence (AI), and energy based on the Science Citation Index Extension (SCI-E) and Social Science Citation Index (SSCI) of the Web of Science from 2001 to 2020. Results show that China is the country with the highest number of publications (1115), accounting for 29% of the total; however, the most influential country in the field is the USA, with an h-index of 75. The Chinese Academy of Sciences publishes the largest number of papers (104) and plays a vital role in the collaboration network. The study also reveals that the IEEE Access is the most productive journal (195) in terms of the number of publications, and engineering is the most popular discipline (1526). The key theoretical foundation includes deep learning (293), big data (105), energy consumption (79), and reinforcement learning (40). The application of big data and AI in the field of energy focuses on smart grid, energy consumption, and renewable energy. Early research frontiers involve optimization and prediction of energy-related problems using the genetic algorithm and neural networks. Since 2013, energy big data have gained prominence. At present, machine learning, deep learning, and fog computing are frequently combined with energy saving. In the future, big data and AI will be utilized to promote the application of renewable energy and energy-saving renovation of buildings. These findings can help researchers understand the developmental trends and correctly grasp the research direction and method of the emerging interdisciplinary field.

Flavonoids for depression and anxiety: a systematic review and meta-analysis.

Natural flavonoids are the most plentiful form of polyphenols. Given the anti-inflammatory and antioxidant properties of flavonoids, researchers discovered that it might be effective in treating depression and anxiety. The effect of flavonoids on depression and anxiety was investigated by a meta-analysis and systematic review. We searched PubMed, Embase, and Medline databases up to October 15, 2021. We selected 11 studies, among them, 10 studies were chosen to evaluate the depression effects of flavonoids and 7 studies were used to assess anxiety disorder. The meta-analysis showed that flavonoids have an overall significant effect on depression (p = 0.004, Hedge's g = -0.487, 95% CI -0.814 to -0.160) and anxiety (p = 0.006, Hedge's g = -0.741, 95% CI -1.266 to -0.217). Subgroup analysis indicated that the symptoms of depression were significantly improved in the studies when the dose of flavonoids was 50-100mg/day or the treatment duration was ≥8weeks. Anxiety symptoms were improved in the studies with the dose of flavonoids was ≥50mg/day. There was no evidence of publication bias. Our findings suggest that flavonoids might improve symptoms of depression and anxiety. However, a small number of participants and studies were included in this meta-analysis. Therefore, the results should be interpreted with caution.

Protein disulfide isomerase A1 as a novel redox sensor in VEGFR2 signaling and angiogenesis.

VEGFR2 signaling in endothelial cells (ECs) is regulated by reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) and mitochondria, which plays an important role in postnatal angiogenesis. However, it remains unclear how highly diffusible ROS signal enhances VEGFR2 signaling and reparative angiogenesis. Protein disulfide isomerase A1 (PDIA1) functions as an oxidoreductase depending on the redox environment. We hypothesized that PDIA1 functions as a redox sensor to enhance angiogenesis. Here we showed that PDIA1 co-immunoprecipitated with VEGFR2 or colocalized with either VEGFR2 or an early endosome marker Rab5 at the perinuclear region upon stimulation of human ECs with VEGF. PDIA1 silencing significantly reduced VEGF-induced EC migration, proliferation and spheroid sprouting via inhibiting VEGFR2 signaling. Mechanistically, VEGF stimulation rapidly increased Cys-OH formation of PDIA1 via the NOX4-mitochondrial ROS axis. Overexpression of "redox-dead" mutant PDIA1 with replacement of the active four Cys residues with Ser significantly inhibited VEGF-induced PDIA1-CysOH formation and angiogenic responses via reducing VEGFR2 phosphorylation. Pdia1+/- mice showed impaired angiogenesis in developmental retina and Matrigel plug models as well as ex vivo aortic ring sprouting model. Study using hindlimb ischemia model revealed that PDIA1 expression was markedly increased in angiogenic ECs of ischemic muscles, and that ischemia-induced limb perfusion recovery and neovascularization were impaired in EC-specific Pdia1 conditional knockout mice. These results suggest that PDIA1 can sense VEGF-induced H2O2 signal via CysOH formation to promote VEGFR2 signaling and angiogenesis in ECs, thereby enhancing postnatal angiogenesis. The oxidized PDIA1 is a potential therapeutic target for treatment of ischemic vascular diseases.

Emissive Metallacage-Cored Polyurethanes with Self-Healing and Shape Memory Properties.

The structures of the crosslinks in supramolecular polymer networks play an important role on their properties and functions. Herein, emissive metallacages are used as crosslinks to prepare metallacage-cored polyurethanes. The mechanical properties including storage modulus, toughness, Young's modulus and breaking strength of polymers are greatly enhanced with the increase of crosslinking densities. Moreover, such polymers not only exhibit good fluorescence in the solid state, but also show self-healing and shape memory properties owing to the dynamic reversible non-covalent bonds in their structures. This study not only offers a convenient strategy to prepare metallacage-crosslinked networks, but also explores their applications as self-healing and shape memory materials, which will promote the study of metallacage-cored supramolecular networks as smart materials.