Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia.

BACKGROUND: The metalloprotease ADAMTS-7 (a disintegrin and metalloproteinase with thrombospondin type 1 motif 7) is a novel locus associated with human coronary atherosclerosis. ADAMTS-7 deletion protects against atherosclerosis and vascular restenosis in rodents. METHODS: We designed 3 potential vaccines consisting of distinct B cell epitopic peptides derived from ADAMTS-7 and conjugated with the carrier protein KLH (keyhole limpet hemocyanin) as well as aluminum hydroxide as an adjuvant. Arterial ligation or wire injury was used to induce neointima in mice, whereas ApoE-/- and LDLR-/- (LDLR [low-density lipoprotein receptor]) mice fed a high-fat diet were applied to assess atherosclerosis. In addition, coronary stent implantation was performed on vaccine-immunized Bama miniature pigs, followed by optical coherence tomography to evaluate coronary intimal hyperplasia. RESULTS: A vaccine, ATS7vac, was screened out from 3 candidates to effectively inhibit intimal thickening in murine carotid artery ligation models after vaccination. As well, immunization with ATS7vac alleviated neointima formation in murine wire injury models and mitigated atherosclerotic lesions in both hyperlipidemic ApoE-/- and LDLR-/- mice without lowering lipid levels. Preclinically, ATS7vac markedly impeded intimal hyperplasia in swine stented coronary arteries, but without significant immune-related organ injuries. Mechanistically, ATS7vac vaccination produced specific antibodies against ADAMTS-7, which markedly repressed ADAMTS-7-mediated COMP (cartilage oligomeric matrix protein) and TSP-1 (thrombospondin-1) degradation and subsequently inhibited vascular smooth muscle cell migration but promoted re-endothelialization. CONCLUSIONS: ATS7vac is a novel atherosclerosis vaccine that also alleviates in-stent restenosis. The application of ATS7vac would be a complementary therapeutic avenue to the current lipid-lowering strategy for atherosclerotic disease.

Nidogen-2 is a Novel Endogenous Ligand of LGR4 to Inhibit Vascular Calcification.

BACKGROUND: Vascular calcification is closely related to the all-cause mortality of cardiovascular events. Basement membrane protein nidogen-2 is a key component of the vascular extracellular matrix microenvironment and we recently found it is pivotal for the maintenance of contractile phenotype in vascular smooth muscle cells (VSMCs). However, whether nidogen-2 is involved in VSMCs osteochondrogenic transition and vascular calcification remains unclear. METHODS: VSMCs was treated with high-phosphate to study VSMC calcification in vitro. Three different mice models (5/6 nephrectomy-induced chronic renal failure, cholecalciferol-overload, and periadventitially administered with CaCl2) were used to study vascular calcification in vivo. Membrane protein interactome, coimmunoprecipitation, flow cytometric binding assay, surface plasmon resonance, G protein signaling, VSMCs calcium assays were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: Nidogen-2 protein levels were significantly reduced in calcified VSMCs and aortas from mice in different vascular calcification model. Nidogen-2 deficiency exacerbated high-phosphate-induced VSMC calcification, whereas the addition of purified nidogen-2 protein markedly alleviated VSMC calcification in vitro. Nidogen-2-/- mice exhibited aggravated aorta calcification compared to wild-type (WT) mice in response to 5/6 nephrectomy, cholecalciferol-overload, and CaCl2 administration. Further unbiased coimmunoprecipitation and interactome analysis of purified nidogen-2 and membrane protein in VSMCs revealed that nidogen-2 directly binds to LGR4 (leucine-rich repeat G-protein-coupled receptor 4) with KD value 26.77 nM. LGR4 deficiency in VSMCs in vitro or in vivo abolished the protective effect of nidogen-2 on vascular calcification. Of interest, nidogen-2 biased activated LGR4-Gαq-PKCα (protein kinase Cα)-AMPKα1 (AMP-activated protein kinase α1) signaling to counteract VSMCs osteogenic transition and mineralization. CONCLUSIONS: Nidogen-2 is a novel endogenous ligand of LGR4 that biased activated Gαq- PKCα-AMPKα1 signaling and inhibited vascular calcification.

PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing.

BACKGROUND: Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive. METHODS: A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-ß or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-ß and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently, Phb2SMCKO mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with Phb2flox/flox mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2-hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo. CONCLUSIONS: Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.

ADAMTS7-Mediated Complement Factor H Degradation Potentiates Complement Activation to Contributing to Renal Injuries.

BACKGROUND: The dysfunction of complement factor H (CFH), the main soluble complement negative regulator, potentiates various complement-induced renal injuries. However, insights into the underlying mechanism of CFH dysfunction remain limited. In this study, we investigated whether extracellular protease-mediated degradation accounts for CFH dysfunction in complement-mediated renal injuries. METHODS: An unbiased interactome of lupus mice kidneys identified CFH-binding protease. In vitro cleavage assay clarified CFH degradation. Pristane-induced SLE or renal ischemia-reperfusion (I/R) injury models were used in wild-type and ADAMTS7-/- mice. RESULTS: We identified the metalloprotease ADAMTS7 as a CFH-binding protein in lupus kidneys. Moreover, the upregulation of ADAMTS7 correlated with CFH reduction in both lupus mice and patients. Mechanistically, ADAMTS7 is directly bound to CFH complement control protein (CCP) 1-4 domain and degraded CCP 1-7 domain through multiple cleavages. In mice with lupus nephritis or renal I/R injury, ADAMTS7 deficiency alleviated complement activation and related renal pathologies, but without affecting complement-mediated bactericidal activity. Adeno-associated virus-mediated CFH silencing compromised these protective effects of ADAMTS7 knockout against complement-mediated renal injuries in vivo. CONCLUSION: ADAMTS7-mediated CFH degradation potentiates complement activation and related renal injuries. ADAMTS7 would be a promising anticomplement therapeutic target that does not increase bacterial infection risk.

Advances in protein glycosylation and its role in tissue repair and regeneration.

After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function. These events include inter-cell communication, cell proliferation, cell migration, extracellular matrix differentiation, and other critical biological processes. Glycosylation is the crucial conservative and universal post-translational modification in all eukaryotic cells [1], with influential roles in intercellular recognition, regulation, signaling, immune response, cellular transformation, and disease development. Studies have shown that abnormally glycosylation of proteins is a well-recognized feature of cancer cells, and specific glycan structures are considered markers of tumor development. There are many studies on gene expression and regulation during tissue repair and regeneration. Still, there needs to be more knowledge of complex carbohydrates' effects on tissue repair and regeneration, such as glycosylation. Here, we present a review of studies investigating protein glycosylation in the tissue repair and regeneration process.

Crystal Growth, Thermal Treatment, and Characterization of Nonlinear Optical Crystal LiGa0.5In0.5Se2 for Mid-infrared Applications.

LiGa0.5In0.5Se2 is a new quaternary nonlinear optical crystal for the mid-IR application grown as a mixed crystal of the LiGaSe2-LiInSe2 solid-solution system. It is transparent in the 0.47-14 µm range and has an appropriate bandgap and a lower melting point than LiGaSe2 and LiInSe2. It is more technological about the growth process since its homogeneity range is broader in the phase diagram. In this work, we have synthesized the LiGa0.5In0.5Se2 polycrystal by the two-zone temperature method. LiGa0.5In0.5Se2 single crystals (Φ26 mm × 50 mm) were grown through the modified Bridgman method with the c-axis seed crystal which has the smallest thermal expansion coefficient of the three main axes in 293-773 K. The crystal structure was studied by X-ray diffraction and the Rietveld refinement method. Due to the low transmittance of the as-grown crystals, a systematic thermal treatment experiment was carried out. In the annealing experiment, the crystal surface is seriously enriched with selenium due to the thermal diffusion of selenium, resulting in the crystal opacity and cracking, while after vacuum quenching at 873 K, the transmittance of the LiGa0.5In0.5Se2 crystal wafer was greatly improved, the bandgap shows a large increase from 2.13 to 2.51 eV, and the quenched crystal shows strong SHG response (×1.91 LiGaSe2). The chemical states and vibration modes of surface elements for both conditions were characterized by X-ray photoelectron and Raman spectra. Density functional theory calculations were carried out to simulate the phonon spectrum and phonon density of states, which can help to study the phonon vibration modes in the lattice.

Nidogen-2 Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells and Prevents Neointima Formation via Bridging Jagged1-Notch3 Signaling.

BACKGROUND: How the extracellular matrix (ECM) microenvironment modulates the contractile phenotype of vascular smooth muscle cells (VSMCs) and confers vascular homeostasis remains elusive. METHODS: To explore the key ECM proteins in the maintenance of the contractile phenotype of VSMCs, we applied protein-protein interaction network analysis to explore novel ECM proteins associated with the VSMC phenotype. By combining in vitro and in vivo genetic mice vascular injury models, we identified nidogen-2, a basement membrane glycoprotein, as a key ECM protein for maintenance of vascular smooth muscle cell identity. RESULTS: We collected a VSMC phenotype-related gene dataset by using Gene Ontology annotation combined with a literature search. A computational analysis of protein-protein interactions between ECM protein genes and the genes from the VSMC phenotype-related gene dataset revealed the candidate gene nidogen-2, a basement membrane glycoprotein involved in regulation of the VSMC phenotype. Indeed, nidogen-2-deficient VSMCs exhibited loss of contractile phenotype in vitro, and compared with wild-type mice, nidogen-2-/- mice showed aggravated post-wire injury neointima formation of carotid arteries. Further bioinformatics analysis, coimmunoprecipitation assays, and luciferase assays revealed that nidogen-2 specifically interacted with Jagged1, a conventional Notch ligand. Nidogen-2 maintained the VSMC contractile phenotype via Jagged1-Notch3 signaling but not Notch1 or Notch2 signaling. Nidogen-2 enhanced Jagged1 and Notch3 interaction and subsequent Notch3 activation. Reciprocally, Jagged1 and Notch3 interaction, signaling activation, and Jagged1-triggered VSMC differentiation were significantly repressed in nidogen-2-deficient VSMCs. In accordance, the suppressive effect of Jagged1 overexpression on neointima formation was attenuated in nidogen-2-/- mice compared with wild-type mice. CONCLUSIONS: Nidogen-2 maintains the contractile phenotype of VSMCs through Jagged1-Notch3 signaling in vitro and in vivo. Nidogen-2 is required for Jagged1-Notch3 signaling.

Catalyst-Free Oxidation Reactions in a Microwave Plasma Torch-Based Ion/Molecular Reactor: An Approach for Predicting the Atmospheric Oxidation of Pollutants.

The atmospheric oxidation of chemicals has produced many new unpredicted pollutants. A microwave plasma torch-based ion/molecular reactor (MPTIR) interfacing an online mass spectrometer has been developed for creating and monitoring rapid oxidation reactions. Oxygen in the air is activated by the plasma into highly reactive oxygen radicals, thereby achieving oxidation of thioethers, alcohols, and various environmental pollutants on a millisecond scale without the addition of external oxidants or catalysts (6 orders of magnitude faster than bulk). The direct and real-time oxidation products of polycyclic aromatic hydrocarbons and p-phenylenediamines from the MPTIR match those of the long-term multistep environmental oxidative process. Meanwhile, two unreported environmental compounds were identified with an MPTIR and measured in the actual water samples, which demonstrates the considerable significance of the proposed device for both predicting the environmental pollutants (non-target screening) and studying the mechanism of atmospheric oxidative processes.

Distinguishment of Glycan Isomers by Trapped Ion Mobility Spectrometry.

The in-depth study of glycan has drawn large research interests since it is one of the main biopolymers on the earth with a variety of biological functions. However, the distinguishment of glycans is still difficult due to the similarity of the monosaccharide building block, the anomer, and the linkage of glycosidic bonds. In this study, four novel and representative copper-bound diastereoisomeric complex ions were simultaneously detected in a single measurement by trapped ion mobility mass spectrometry, including mononuclear copper-bound dimeric ions [(Cu2+)(A)(l-Ser)-H]+ and [(Cu2+)(A)(l-His)-H]+, the mononuclear copper-bound trimeric ion [(Cu2+)(A)(l-Ser)(l-His)-H]+, and the binuclear copper-bound tetrameric ion [(Cu2+)2(A)(l-Ser)2(l-His)-3H]+ (where A denotes an oligosaccharide, and l-Ser and l-His denote l-serine and l-histidine, respectively). By combining the collision cross sections of complex ions, 23 oligosaccharide isomers were successfully distinguished including two pairs of sialylated glycan linkage isomers. In addition, due to the unique dissociation pathways of the trimeric ion, both the relative and absolute quantification of the individual isomer in the mixture could be determined using a mass spectrometry-based kinetic method. Finally, the method established above was successfully applied to the identification and quantification of glycan isomers in dairy beverages and juice. The method in the present study was sensitive to the fine difference of glycan isomers and might have wide applicability in glycoscience.

Extracellular matrix dynamics in vascular remodeling.

Vascular remodeling is the adaptive response to various physiological and pathophysiological alterations that are closely related to aging and vascular diseases. Understanding the mechanistic regulation of vascular remodeling may be favorable for discovering potential therapeutic targets and strategies. The extracellular matrix (ECM), including matrix proteins and their degradative metalloproteases, serves as the main component of the microenvironment and exhibits dynamic changes during vascular remodeling. This process involves mainly the altered composition of matrix proteins, metalloprotease-mediated degradation, posttranslational modification of ECM proteins, and altered topographical features of the ECM. To date, adequate studies have demonstrated that ECM dynamics also play a critical role in vascular remodeling in various diseases. Here, we review these related studies, summarize how ECM dynamics control vascular remodeling, and further indicate potential diagnostic biomarkers and therapeutic targets in the ECM for corresponding vascular diseases.

M860, a Monoclonal Antibody against Human Lactoferrin, Enhances Tumoricidal Activity of Low Dosage Lactoferrin via Granzyme B Induction.

Lactoferrin (LF) is a soluble glycoprotein of the transferring family found in most biological fluids, functioning as a major first line defense molecule against infection in mammals. It also shows certain anti-tumor activity, but its clinical application in tumor therapy is limited because high dosage is required. In this study, we demonstrate that M860, a monoclonal antibody against human LF (hLF), could significantly increase the anti-tumor potential of low dosage hLF by forming LF-containing immune complex (IC). Human monocytes primed with LF-IC, but not hLF or M860 alone, or control ICs, showed strong tumoricidal activity on leukemia cell lines Jurkat and Raji through induction of secreted Granzyme B (GzB). LF-IC is able to colligate membrane-bound CD14 (a TLR4 co-receptor) and FcγRIIa (a low affinity activating Fcγ receptor) on the surface of human monocytes, thereby triggering the Syk-PI3K-AKT-mTOR pathway leading to GzB production. Our work identifies a novel pathway for LF-mediated tumoricidal activity and may extend the clinical application of LF in tumor therapy.

Synthesis and Characterization of Multiple Stimuli-Responsive Fluorescent Polymer Hydrogels Based on Terpyridine and N-Isopropylacrylamide.

A series of stimuli-responsive fluorescent hydrogels were successfully synthesized via micelle radical copolymerization of hydrophilic acrylamide (AM), hydrophobic chromophore terpyridine-based monomer (TPY), and N-isopropylacrylamide (NIPAM). These hydrogels presented blue emissions (423-440 nm) under room temperature, which is caused by the π-π* transition of the conjugated structures. Once the ambient temperature was increased to 55 °C, the fluorescence color changed from blue (430 nm) to pink (575 nm) within 10 min, subsequently to yellow (535 nm), and eventually back to pink. The thermal-responsive properties are attributed to the transition of the TPY units from unimer to dimer aggregation via the intermolecular charge transfer complex at high temperatures. The hydrogels showed pH-responsive properties. The emission peak of the hydrogel exhibited a blue shift of ~54 nm from neuter conditions to acidic conditions, while a 6 nm red shift to an alkaline environment was observed. The hydrogels demonstrated an obvious change in fluorescence intensity and wavelength upon adding different metal ions, which is caused by the coordination between the terpyridine units incorporated on the backbones and the metal ions. As a consequence, the hydrogels presented a sharp quenching fluorescence interaction with Fe2+, Fe3+, Cu2+, Hg2+, Ni2+, and Co2+, while it exhibited an enhanced fluorescence intensity interaction with Sn2+, Cd2+, and Zn2+. The microstructural, mechanical, and rheological properties of these luminescent hydrogels have been systematically investigated.

Optimizing electrochemical performance of Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure via preparing concentration-gradient particles for sodium-ion batteries.

P2-type layered oxides for rechargeable sodium-ion batteries have drawn a lot of attention because of their excellent electrochemical performance. However, these types of cathodes usually suffer from poor cyclic stability. To overcome this disadvantage, in this work, novel ball-shaped concentration-gradient oxide Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure modified by Mn-rich surface is successfully prepared using co-precipitation method. The concentration of Mn increased from the inner core to the surface, endowing the material with an excellent cyclic stability. The cathode exhibits enhanced electrochemical properties than that of the sample synthesized by solid-state method and concentration-constant material. It shows 143.2 mAh/g initial discharge capacity and retains 131 mAh/g between 2 V and 4.5 V after 100 rounds. The significant improvement in the electrochemical properties of the sample benefits from the unique concentration-gradient structure, and the Mn-rich surface that effectively stabilizes the basic P2 structure. The relatively higher Ni content in the core leads to a slight improvement in the discharge capacity of the sample. This strategy may provide new insights for preparing layered cathodes for sodium-ion batteries with high electrochemical performance.

Quantitative assessment of preoperative brain development in pediatric congenital heart disease patients by synthetic MRI.

OBJECTIVES: This study investigated the quantitative assessment and application of Synthetic MRI (SyMRI) for preoperative brain development in children with congenital heart disease (CHD). METHODS: Forty-three CHD patients aged 2-24 months were prospectively included in the observation group, and 43 healthy infants were included in the control group. The SyMRI scans were processed by postprocessing software to obtain T1, T2, and PD maps. The values of T1, T2, and PD in different brain regions were compared with the scores of the five ability areas of the Gesell Development Scale by Pearson correlation analysis. RESULTS: In the observation group, the T1 values of the posterior limb of the internal capsule (PLIC), Optic radiation (PTR), cerebral peduncle, centrum semiovale, occipital white matter, temporal white matter, and dentate nucleus were greater than those in the control group. In the observation group, the T2 values of the PLIC, PTR, frontal white matter, occipital white matter, temporal white matter, and dentate nucleus were greater than those in the control group. Pearson correlation analysis revealed that the observation group had significantly lower Development Scale scores. In the observation group, the T2 value of the splenium of the corpus callosum was significantly positively correlated with the personal social behavior score. The AUCs for diagnosing preoperative brain developmental abnormalities in children with CHD using T1 values of the temporal white matter and dentate nucleus were both greater than 0.60. CONCLUSIONS: Quantitative assessment using SyMRI can aid in the early detection of preoperative brain development abnormalities in children with CHD. CRITICAL RELEVANCE STATEMENT: T1 and T2 relaxation values from SyMRI can be considered as a quantitative imaging marker to detect abnormalities, allowing for early clinical evaluation and timely intervention, thereby reducing neurodevelopmental disorders in these children. KEY POINTS: T1 and T2 relaxation values by SyMRI are related to myelin development. Evaluated development quotient markers were lower in the observation compared to the control group. SyMRI can act as a reference indicator for brain development in CHD children.

Pickering Emulsion Stabilized by ß-Cyclodextrin and Cinnamaldehyde/ß-Cyclodextrin Composite.

A Pickering emulsion was prepared using ß-cyclodextrin (ß-CD) and a cinnamaldehyde (CA)/ß-CD composite as emulsifiers and corn oil, camellia oil, lard oil, and fish oil as oil phases. It was confirmed that Pickering emulsions prepared with ß-CD and CA/ß-CD had good storage stability. The rheological experiments showed that all emulsions had G' values higher than G″, thus confirming their gel properties. The results of temperature scanning rheology experiments revealed that the Pickering emulsion prepared with ß-CD and CA/ß-CD composites had high stability, in the range of 20-65 °C. The chewing properties of Pickering emulsions prepared by ß-CD and corn oil, camellia oil, lard, and herring oil were 8.02 ± 0.24 N, 7.94 ± 0.16 N, 36.41 ± 1.25 N, and 5.17 ± 0.13 N, respectively. The chewing properties of Pickering emulsions made with the CA/ß-CD composite and corn oil, camellia oil, lard, and herring oil were 2.51 ± 0.05 N, 2.56 ± 0.05 N, 22.67 ± 1.70 N, 3.83 ± 0.29 N, respectively. The texture properties confirmed that the CA/ß-CD-composite-stabilized-emulsion had superior palatability. After 28 days at 50 °C, malondialdehyde (MDA) was detected in the emulsion. Compared with the ß-CD and CA + ß-CD emulsion, the CA/ß-CD composite emulsion had the lowest content of MDA (182.23 ± 8.93 nmol/kg). The in vitro digestion results showed that the free fatty acid (FFA) release rates of the CA/ß-CD composite emulsion (87.49 ± 3.40%) were higher than those of the ß-CD emulsion (74.32 ± 2.11%). This strategy provides ideas for expanding the application range of emulsifier particles and developing food-grade Pickering emulsions with antioxidant capacity.

Collagen hydrogel viscoelasticity regulates MSC chondrogenesis in a ROCK-dependent manner.

Mesenchymal stem cell (MSC) chondrogenesis in three-dimensional (3D) culture involves dynamic changes in cytoskeleton architecture during mesenchymal condensation before morphogenesis. However, the mechanism linking dynamic mechanical properties of matrix to cytoskeletal changes during chondrogenesis remains unclear. Here, we investigated how viscoelasticity, a time-dependent mechanical property of collagen hydrogel, coordinates MSC cytoskeleton changes at different stages of chondrogenesis. The viscoelasticity of collagen hydrogel was modulated by controlling the gelling process without chemical cross-linking. In slower-relaxing hydrogels, although a disordered cortical actin promoted early chondrogenic differentiation, persistent myosin hyperactivation resulted in Rho-associated kinase (ROCK)-dependent apoptosis. Meanwhile, faster-relaxing hydrogels promoted cell-matrix interactions and eventually facilitated long-term chondrogenesis with mitigated myosin hyperactivation and cell apoptosis, similar to the effect of ROCK inhibitors. The current work not only reveals how matrix viscoelasticity coordinates MSC chondrogenesis and survival in a ROCK-dependent manner but also highlights viscoelasticity as a design parameter for biomaterials for chondrogenic 3D culture.

Correlation between preoperative frailty and postoperative delirium in elderly patients undergoing hip arthroplasty.

BACKGROUND: Postoperative delirium (POD) refers to acute brain dysfunction occurring within 7 days after operation or before discharge. Frailty refers to the state that the body's physiological reserve is insufficient, so that the compensative capacity to endogenous and exogenous stress stimuli decreases. The purpose of this study is to explore the association of preoperative frailty (PF) with POD in elderly patients undergoing hip arthroplasty. METHODS: Totally 228 elderly patients (age ≥ 65 years) who received elective hip arthroplasty in the Ningbo No. 6 Hospital between December 2021 and June 2022 were enrolled. One day before surgery, the frailty phenotype scale was adopted for evaluation of patients' frailty. On the 1st-3rd day after operation, the confusion assessment method was adopted for evaluation of delirium, and the patients were grouped into a POD group and non-POD group. Logistic regression was conducted to analyze the correlation between PF and POD. RESULTS: Among the patients, the incidence of PF was 30.70% (70/228), and the incidence of delirium within 3 days after operation was 25.88% (59/228). According to binary logistic regression analysis, PF, age, hypertension, diabetes mellitus, and preoperative sleep disorder were independent risk factors for POD in elderly patients undergoing hip arthroplasty (all P < .05). CONCLUSION: PF is a crucial risk factor for POD in elderly patients undergoing hip arthroplasty.

Impacts of Industrial Modification on the Structure and Gel Features of Soy Protein Isolate and its Composite Gel with Myofibrillar Protein.

Native soy protein isolate (N-SPI) has a low denaturation point and low solubility, limiting its industrial application. The influence of different industrial modification methods (heat (H), alkaline (A), glycosylation (G), and oxidation (O)) on the structure of SPI, the properties of the gel, and the gel properties of soy protein isolate (SPI) in myofibril protein (MP) was evaluated. The study found that four industrial modifications did not influence the subunit composition of SPI. However, the four industrial modifications altered SPI's secondary structure and disulfide bond conformation content. A-SPI exhibits the highest surface hydrophobicity and I850/830 ratio but the lowest thermal stability. G-SPI exhibits the highest disulfide bond content and the best gel properties. Compared with MP gel, the addition of H-SPI, A-SPI, G-SPI, and O-SPI components significantly improved the properties of the gel. Additionally, MP-ASPI gel exhibits the best properties and microstructure. Overall, the four industrial modification effects may impact SPI's structure and gel properties in different ways. A-SPI could be a potential functionality-enhanced soy protein ingredient in comminuted meat products. The present study results will provide a theoretical basis for the industrialized production of SPI.

ADAMTS-7 deficiency attenuates thoracic aortic aneurysm and dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening cardiovascular disease with severe extracellular matrix (ECM) remodeling that lacks efficient early stage diagnosis and nonsurgical therapy. A disintegrin and metalloproteinase with thrombospondin motif 7 (ADAMTS-7) is recognized as a novel locus for human coronary artery atherosclerosis. Previous work by us and others showed that ADAMTS-7 promoted atherosclerosis, postinjury neointima formation, and vascular calcification. However, whether ADAMTS-7 is involved in TAAD pathogenesis is unknown. We aimed to explore the alterations in ADAMTS-7 expression in human and mouse TAAD, and investigate the role of ADAMTS-7 in TAAD formation. A case-control study of TAAD patients (N = 86) and healthy participants (N = 88) was performed. The plasma ADAMTS-7 levels were markedly increased in TAAD patients within 24 h and peaked in 7 days. A TAAD mouse model was induced with 0.5% ß-aminopropionitrile (BAPN) in drinking water. ELISA analysis of mouse plasma, Western blotting, and immunohistochemical staining of aorta showed an increase in ADAMTS-7 in the early stage of TAAD. Moreover, ADAMTS-7-deficient mice exhibited significantly attenuated TAAD formation and TAAD rupture-related mortality in both male and female mice, which was accompanied by reduced artery dilation and inhibited elastin degradation. ADAMTS-7 deficiency caused repressed inflammatory response and complement system activation during TAAD formation. An increase in plasma ADAMTS-7 is a novel biomarker for human TAAD. ADAMTS-7 deficiency attenuates BAPN-induced murine TAAD. ADAMTS-7 is a potential novel target for TAAD diagnosis and therapy. KEY MESSAGES: A case-control study revealed increased plasma ADAMTS-7 is a risk factor for TAAD. ADAMTS-7 was elevated in plasma and aorta at early stage of mouse TAAD. ADAMTS-7 knockout attenuated mouse TAAD formation and mortality in both sexes.

Physicochemical and pozzolanic properties of municipal solid waste incineration fly ash with different pretreatments.

Swelling caused by gas generated from municipal solid waste incineration fly ash (MSWIFA) when it is mixed with alkali limits its uses. Besides, the leaching of anion salts and heavy metals contained in MSWIFA poses a high risk to environment. This study presents the feasibility of a one-step alkaline washing, one-step thermal quenching and two-step combination of alkaline washing and thermal quenching pretreatment methods in altering the key properties of MSWIFA for promoting its reusability. It was found that apart from H2(gas), NH3(gas) was also generated during the alkaline washing of the MSWIFA. Besides, pretreatments led to the reduction in particle size, the increase in pore volume and specific surface area of the MSWIFA, as well as the removal of chloride and sulfate anions. All the pretreatment methods were effective in reducing leaching of heavy metals to below levels of nonhazardous waste except Cd and Pb with alkaline washing. Furthermore, both the chemical Frattini test and the mechanical activity index test showed improvement in pozzolanic activities of the MSWIFA after the pretreatments. Overall, the combined pretreatment method was most effective in eliminating gas emission, and reducing leaching of metal ions and anions from the ash, while enhancing the pozzolanic activity of the ash.