A facile Immunoregulatory Constructional Design by Proanthocyanidin Optimizing Directional Chitosan Microchannel.

Improving the interconnected structure and bioregulatory function of natural chitosan is beneficial for optimizing its performance in bone regeneration. Here, a facile immunoregulatory constructional design is proposed for developing instructive chitosan by directional freezing and alkaline salting out. The molecular dynamics simulation confirmed the assembly kinetics and structural features of various polyphenols and chitosan molecules. Along with the in vitro anti-inflammatory, antioxidative, promoting bone mesenchymal stem cell (BMSC) adhesion and proliferation performance, proanthocyanidin optimizing chitosan (ChiO) scaffold presented an optimal immunoregulatory structure with the directional microchannel. Transcriptome analysis in vitro further revealed the cytoskeleton- and immune-regulation effect of ChiO are the key mechanism of action on BMSC. The rabbit cranial defect model (Φ = 10 mm) after 12 weeks of implantation confirmed the significantly enhanced bone reconstitution. This facile immunoregulatory directional microchannel design provides effective guidance for developing inducible chitosan scaffolds.

A conditional inference tree model for predicting cancer risk of non-mass lesions detected on breast ultrasound.

OBJECTIVES: To generate and validate a prediction model based on imaging features for cancer risk of non-mass lesions (NMLs) detected on breast ultrasound (US). METHODS: In this single-center study, consecutive women with 503 NMLs detected on breast US between 2012 and 2019 were retrospectively identified. The lesions were randomly assigned to the training or testing dataset with a 70/30 split. Age, symptoms, lesion size, and US features were collected. Multivariate analyses were employed to identify risk factors associated with malignancy. The predictive model was developed by using conditional inference trees (CTREE). RESULTS: There were 498 patients (50.9 ± 13.29 years; range, 22-88 years) with 503 NMLs with histopathologic results or > 2-year follow-up, including 224 (44.5%) benign and 279 (55.5%) malignant lesions. At multivariate analysis, age (odds ratio (OR) = 1.08, 95% confidence interval (CI), 1.06-1.11, p < 0.001), NMLs with focal mass effect (OR = 3.03, 95% CI, 1.59-5.81, p = 0.001), indistinct glandular-fat interface (GFI) (OR = 4.23, 95% CI, 2.31-7.73, p < 0.001), geographic (OR = 3.47, 95% CI, 1.20-10.8, p = 0.022) and mottled (OR = 3.67, 95% CI, 1.32-10.21, p = 0.013) patterns, and calcifications (OR = 2.15, 95% CI, 1.16-4.01, p = 0.016) were associated with malignancy. The GFI status, architectural patterns, general morphology, and calcifications were consistently identified as the strongest US predictors of malignancy using CTREE analysis. Based on these factors, individuals were stratified into six risk groups. The predictive model showed an area under the curve of 0.797 in the testing dataset. CONCLUSION: The CTREE model efficiently aids in interpreting and managing ultrasound-detected breast NMLs, overcoming BI-RADS limitations by refining cancer risk stratification. CLINICAL RELEVANCE STATEMENT: The CTREE model allows for the reclassification of BI-RADS categories into subgroups with varying malignancy probabilities, thus providing a valuable enhancement to the BI-RADS assessment for the diagnosis of ultrasound-detected NMLs, with the potential to minimize unnecessary biopsies. KEY POINTS: • The indistinct glandular-fat interface (GFI) status, NML with focal mass effect, geographic or mottled patterns, and calcifications are the strongest imaging predictors of malignant non-mass lesions (NMLs) detected on breast US. • A practical system has been created to categorize NMLs found in breast US; each classification is associated with a degree of diagnostic certainty. • The model may contribute to patient stratification by determining the relative likelihood of malignancy and thus support clinical decision-making and evidence-based management.

Covalently Grafted Biomimetic Matrix Reconstructs the Regenerative Microenvironment of the Porous Gradient Polycaprolactone Scaffold to Accelerate Bone Remodeling.

Integrating a biomimetic extracellular matrix to improve the microenvironment of 3D printing scaffolds is an emerging strategy for bone substitute design. Here, a "soft-hard" bone implant (BM-g-DPCL) consisting of a bioactive matrix chemically integrated on a polydopamine (PDA)-coated porous gradient scaffold by polyphenol groups is constructed. The PDA-coated "hard" scaffolds promoted Ca2+ chelation and mineral deposition; the "soft" bioactive matrix is beneficial to the migration, proliferation, and osteogenic differentiation of stem cells in vitro, accelerated endogenous stem cell recruitment, and initiated rapid angiogenesis in vivo. The results of the rabbit cranial defect model (Φ = 10 mm) confirmed that BM-g-DPCL promoted the integration between bone tissue and implant and induced the deposition of bone matrix. Proteomics confirmed that cytokine adhesion, biomineralization, rapid vascularization, and extracellular matrix formation are major factors that accelerate bone defect healing. This strategy of highly chemically bonded soft-hard components guided the construction of the bioactive regenerative scaffold.

Polysaccharide-Based Composite Hydrogel with Hierarchical Microstructure for Enhanced Vascularization and Skull Regeneration.

Critical-size skull defects caused by trauma, infection, and tumor resection raise great demands for efficient bone substitutes. Herein, a hybrid cross-linked hierarchical microporous hydrogel scaffold (PHCLS) was successfully assembled by a multistep procedure, which involved (i) the preparation of poly(lactic-co-glycolic)/nanohydroxyapatite (PLGA-HAP) porous microspheres, (ii) embedding the spheres in a solution of dopamine-modified hyaluronic acid and collagen I (Col I) and cross-linking via dopamine polyphenols binding to (i) Col I amino groups (via Michael addition) and (ii) PLGA-HAP (via calcium ion chelation). The introduction of PLGA-HAP not only improved the diversity of pore size and pore communication inside the matrix but also greatly enhanced the compressive strength (5.24-fold, 77.5 kPa) and degradation properties to construct a more stable mechanical structure. In particular, the PHCLS (200 mg, nHAP) promoted the proliferation, infiltration, and angiogenic differentiation of bone marrow mesenchymal stem cells in vitro, as well as significant ectopic angiogenesis and mineralization with a storage modulus enhancement of 2.5-fold after 30 days. Meanwhile, the appropriate matrix microenvironment initiated angiogenesis and early osteogenesis by accelerating endogenous stem cell recruitment in situ. Together, the PHCLS allowed substantial skull reconstruction in the rabbit cranial defect model, achieving 85.2% breaking load strength and 84.5% bone volume fractions in comparison to the natural cranium, 12 weeks after implantation. Overall, this study reveals that the hierarchical microporous hydrogel scaffold provides a promising strategy for skull defect treatment.

Automated Breast Volume Scanner Is More Valuable Than Hand-Held Ultrasound in Diagnosis of Small Breast cancer: An Analysis of 725 Patients With 912 Lesions Evaluations.

ABSTRACT: This study aimed to evaluate the clinical value of automated breast volume scanner (ABVS) compared with hand-held ultrasound (HHUS). From January 2015 to May 2019, a total of 912 breast lesions in 725 consecutive patients were included in this study. κ statistics were calculated to identify interobserver agreement of ABVS and HHUS. The diagnostic performance for ABVS and HHUS was expressed as the area under the receiver operating characteristic curve, as well as the corresponding 95% confidence interval, sensitivity, and specificity. The sensitivities of ABVS and HHUS were 95.95% and 93.69%, and the specificities were 85.47% and 81.20%, respectively. A difference that nearly reached statistical significance was observed in sensitivities between ABVS and HHUS (P = 0.0525). The specificity of ABVS was significantly higher than that of HHUS (P = 0.006). When lesions were classified according to their maximum diameter, the sensitivity and specificity of ABVS were significantly higher than HHUS for lesions ≤20 mm, while they made no statistical significance between ABVS and HHUS for lesions >20 mm. The interobserver agreement for ABVS was better than that of HHUS. Automated breast volume scanner was more valuable than HHUS in diagnosing breast cancer, especially for lesions ≤20 mm, and it could be a valuable diagnostic tool for breast cancer.

Hyaluronated nanohydroxyapatite responsively released from injectable hydrogels for targeted therapy of melanoma.

Nanohydroxyapatite (nHAp) has attracted significant attention for its tumor suppression and tumor microenvironment modulation capabilities. However, a strong tendency to aggregate greatly affects its anti-tumor efficiency. To address this issue, a hydrogel platform consisting of thiolated hyaluronic acid (HA-SH) modified nanohydroxyapatite (nHAp-HA) and HA-SH was developed for sustained delivery of nHAp for melanoma therapy. The hydrophilic and negatively charged HA-SH significantly improved the size dispersion and stability of nHAp in aqueous media while conferring nHAp targeting effects. Covalent sulfhydryl self-cross-linking between HA-SH and nHAp-HA groups ensured homogeneous dispersion of nHAp in the matrix material. Meanwhile, the modification of HA-SH conferred the targeting properties of nHAp and enhanced cellular uptake through the HA/CD44 receptor. The hydrogel platform could effectively reduce the aggregation of nHAp and release nHAp in a sustained and orderly manner. Antitumor experiments showed that the modified nHAp-HA retained the tumor cytotoxicity of nHAp in vitro and inhibited the growth of highly malignant melanomas up to 78.6% while being able to induce the differentiation of macrophages to the M1 pro-inflammatory and antitumor phenotype. This study will broaden the application of nanohydroxyapatite in tumor therapy.

An injectable photocuring silk fibroin-based hydrogel for constructing an antioxidant microenvironment for skin repair.

Skin has a protein microenvironment dominated by functional collagen fibers, while oxidative stress caused by injury can greatly slow down the progress of wound healing. Here, methacrylated dopamine was incorporated into methacrylated silk fibroin molecule chains to develop an injectable hydrogel with photocuring properties for constructing an antioxidant skin protein microenvironment. This silk fibroin-based hydrogel (SF-g-SDA) showed good tensile and adhesion properties for adapting to the wound shape and skin movement, exhibited stable mechanical properties, good biodegradability and cytocompatibility, and promoted cell adhesion and vascularization in vitro. In addition, its phenolic hydroxyl-mediated antioxidant properties effectively protected cells from damage caused by oxidative stress and supported normal cellular life activities. In animal experiments, SF-g-SDA achieved better skin repair effects in comparison to commercial Tegaderm™ in vivo, showing its ability to accelerate wound healing, improve collagen deposition and alignment in newly fabricated tissues, and promote neovascularization and hair follicle formation. These experimental results indicated that the SF-g-SDA hydrogel is a promising wound dressing.

Porous gradient hydrogel promotes skin regeneration by angiogenesis.

The skin has a multilayered structure, and deep-seated injuries are exposed to external microbial invasion and in vivo microenvironmental destabilization. Here, a bilayer bionic skin scaffold (Bilayer SF) was developed based on methacrylated sericin protein to mimic the skin's multilayered structure and corresponding functions. The outer layer (SF@TA), which mimics the epidermal layer, was endowed with the function of resisting external bacterial and microbial invasion using a small pore structure and bio-crosslinking with tannic acid (TA). The inner layer (SF@DA@Gel), which mimics the dermal layer, was used to promote cellular growth using a large pore structure and introducing dopamine (DA) to regulate the wound microenvironment. This Bilayer SF showed good mechanical properties and structural stability, satisfactory antioxidant and promote cell proliferation and migration abilities. In vitro studies confirmed the antimicrobial properties of the outer layer and the pro-angiogenic ability of the inner layer. In vivo animal studies demonstrated that the bilayer scaffolds promoted collagen deposition, neovascularization, and marginal hair follicle formation, which might be a promising new bionic skin scaffold.

Cationic Biopolymeric Scaffold of Chelating Nanohydroxyapatite Self-Regulates Intraoral Microenvironment for Periodontal Bone Regeneration.

Periodontal bone defect is a common but longstanding healthcare issue since traditional bone grafts have limited functionalities in regulating complex intraoral microenvironments. Here, a porous cationic biopolymeric scaffold (CSC-g-nHAp) with microenvironment self-regulating ability was synthesized by chitosan-catechol chelating the Ca2+ of nanohydroxyapatite and bonding type I collagen. Chitosan-catechol's inherent antibacterial and antioxidant abilities endowed this scaffold with desirable abilities to eliminate periodontal pathogen infection and maintain homeostatic balances between free radical generation and elimination. Meanwhile, this scaffold promoted rat bone marrow stromal cells' osteogenic differentiation and achieved significant ectopic mineralization after 4 weeks of subcutaneous implantation in nude mice. Moreover, after 8 weeks of implantation in the rat critical-sized periodontal bone defect model, CSC-g-nHAp conferred 5.5-fold greater alveolar bone regeneration than the untreated group. This cationic biopolymeric scaffold could regulate the local microenvironment through the synergistic effects of its antibacterial, antioxidant, and osteoconductive activities to promote solid periodontal bone regeneration.

Nanostructured 3D-Printed Hybrid Scaffold Accelerates Bone Regeneration by Photointegrating Nanohydroxyapatite.

Nanostructured biomaterials that replicate natural bone architecture are expected to facilitate bone regeneration. Here, nanohydroxyapatite (nHAp) with vinyl surface modification is acquired by silicon-based coupling agent and photointegrated with methacrylic anhydride-modified gelatin to manufacture a chemically integrated 3D-printed hybrid bone scaffold (75.6 wt% solid content). This nanostructured procedure significantly increases its storage modulus by 19.43-fold (79.2 kPa) to construct a more stable mechanical structure. Furthermore, biofunctional hydrogel with biomimetic extracellular matrix is anchored onto the filament of 3D-printed hybrid scaffold (HGel-g-nHAp) by polyphenol-mediated multiple chemical reactions, which contributes to initiate early osteogenesis and angiogenesis by recruiting endogenous stem cells in situ. Significant ectopic mineral deposition is also observed in subcutaneously implanted nude mice with storage modulus enhancement of 25.3-fold after 30 days. Meanwhile, HGel-g-nHAp realizes substantial bone reconstruction in the rabbit cranial defect model, achieving 61.3% breaking load strength and 73.1% bone volume fractions in comparison to natural cranium 15 weeks after implantation. This optical integration strategy of vinyl modified nHAp provides a prospective structural design for regenerative 3D-printed bone scaffold.

An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis.

Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca2+ of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to external stress by flexible deformation. Meanwhile, the appropriate matrix microenvironment regulates macrophage M2 polarization and recruits endogenous stem cells. This scaffold promotes the proliferation and osteogenic differentiation of BMSCs in vitro, as well as significant ectopic mineralization and angiogenesis. Transcriptome analysis confirmed the upregulation of relevant genes and signalling pathways was associated with M2 macrophage activation, endogenous stem cell recruitment, angiogenesis and osteogenesis. Together, the scaffold realized 97 and 72% bone cover areas after 12 weeks in cranial defect models of rabbit (Φ = 9 mm) and beagle dog (Φ = 15 mm), respectively.

Cell-mediated injectable blend hydrogel-BCP ceramic scaffold for in situ condylar osteochondral repair.

The existing approaches for healing mandibular condylar osteochondral defects, which are prevalent in temporomandibular joint disorders (TMD), are sparse and not reparative. To address this, regenerative medicine in situ has transpired as a potential therapeutic solution as it can effectively regenerate composite tissues. Herein, injectable self-crosslinking thiolated hyaluronic acid (HA-SH)/type I collagen (Col I) blend hydrogel and BCP ceramics combined with rabbit bone mesenchymal stem cells (rBMSCs)/chondrocytes were used to fabricate a new bi-layer scaffold to simulate specific structure of rabbit condylar osteochondral defects. The in vitro results demonstrated that the blend hydrogel scaffold provided suitable microenvironment for simultaneously realizing proliferation and chondrogenic specific matrix secretion of both rBMSCs and chondrocytes, while BCP ceramics facilitated rBMSCs proliferation and osteogenic differentiation. The in vivo results confirmed that compared with cell-free implant, the rBMSCs/chondrocytes-loaded bi-layer scaffold could effectively promote the regeneration of both fibrocartilage and subchondral bone, suggesting that the bi-layer scaffold presented a promising option for cell-mediated mandibular condylar cartilage regeneration.

Risk factors of ultrasound-detected tophi in patients with gout.

INTRODUCTION: Tophus is a characteristic manifestation of advanced gout, the clinical significance of which is often underestimated. This study aimed to compare the difference of clinical and ultrasound features between gout patients with and without ultrasound-detected tophus and identify risk factors associated with the presence of ultrasonographic tophus in gout patients. MATERIALS AND METHODS: A total of 85 gout patients were divided into tophaceous (n = 54) and non-tophaceous group (n = 31) according to the presence of ultrasound-detected tophus. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joint (MTP1). Clinical information and ultrasound findings were compared between the groups. A multivariate logistic regression analysis to determine possible risk factors is associated with the number of ultrasound-detected tophaceous joints. RESULTS: Older age, longer gout duration, higher gout flare frequency, lower estimated glomerular filtration rate (eGFR), and higher prevalence of hypertension, hyperlipidemia, and ultrasound manifestations including double contour sign (DCS) and erosion were observed in tophaceous patients from the univariate analysis. Multivariable logistic regression analysis showed that eGFR and disease duration were independently associated with the number of tophaceous joints. Lower eGFR and longer course duration were associated with a higher risk of tophi (B = -0.020, 0.141; P = 0.009, 0.010, respectively). CONCLUSIONS: The main factors that may influence the formation of tophi are disease duration and eGFR.Key Points• Lower eGFR and longer course duration are independent risk factors of tophi formation in gout patients.• The incidence of ultrasound manifestations including double contour sign (DCS) and erosion in patients with tophi were higher than those without tophi.

Redox and pH dual-responsive injectable hyaluronan hydrogels with shape-recovery and self-healing properties for protein and cell delivery.

In this work, 3, 3'-dithiobis (propanoic dihydrazide) modified and aldehyde-modified hyaluronic acid were respectively synthesized as precursor solutions to form redox and pH dual-responsive injectable hydrogels through dynamic acylhydrazone and disulfide linkages without exogenous stimulus conditions. The reversible sol-gel transition behavior of hydrogels could be repeated multiple times by adjusting DTT/H2O2 or HCl/TEA. Interestingly, the hydrogels shrank gradually when pH decreased, which improved significantly the storage modulus up to 8.4 times at pH 2. Furthermore, the hydrogel presented acid-switchable shape-recovery characteristics of self-healing by a dynamic recombination of acylhydrazone bonds. Moreover, the osmotic driving force derived from inner and outer concentration difference also affected the characteristic. The controlled release of bovine serum albumin (BSA) encapsulated in this hydrogel could be achieved in vitro under simulated pH/redox intracellular and intercellular microenvironment. This hydrogel could also promote chondrocytes proliferation.

A di-self-crosslinking hyaluronan-based hydrogel combined with type I collagen to construct a biomimetic injectable cartilage-filling scaffold.

Injectable hydrogels have attracted increasing attention because of convenient clinical operation, non-invasive surgical procedure and seamless filling of irregular defects. Here, injectable di-self-crosslinking HSMSSA hydrogel was formed via fast thiol/maleimide click chemistry reaction and thiol oxidation reaction as primary and secondary self-crosslinking network, respectively. Molecular weight and precursor concentration significantly affected physichemical properties and biological functions of hydrogels. Although single HSMSSA gel (0.1 M Da, 10 mg/mL) had moderate injectability, preferable mechanical properties and good proliferative ability of chondrocytes in vitro, and could greatly promote cartilaginous tissue formation in vivo, the lack of adhesion sites resulted in an untenable situation in maintaining effective connections among newborn cell clusters. However, the biomimetic injectable di-self-crosslinking blend hydrogel by combing injectable HSMSSA and bioactive Col I had improved resistance to degradation, chondrocytes adhesion and proliferation, especially for multiples ascending genes expression level associated with hyaline cartilage formation and polyproteoglycan secretion, which might be a potential clinical treatment strategy for constructing injectable cartilage repair filler by combining expanded autologous chondrocytes. STATEMENT OF SIGNIFICANCE: An injectable di-self-crosslinking Hyaluronan-Based hydrogel was formed via fast thiol/maleimide click chemistry reaction and thiol oxidation reaction as primary/secondary self-crosslinking network, respectively. Molecular weight and precursor concentration significantly affected physichemical properties and biological functions of the hydrogels. Although this HSMSSA gel (0.1 M Da, 10 mg/mL) had moderate injectability, preferable mechanical properties, and good proliferative ability of chondrocytes in vitro, and could greatly promote cartilaginous tissue formation in vivo, the lack of adhesion sites resulted in ineffective connections among newborn cell clusters. The biomimetic injectable di-self-crosslinking blend hydrogel improved chondrocyte adhesion and proliferation by combined injectable HSMSSA and bioactive Col I, especially for multiple ascending gene expression levels associated with hyaline cartilage formation and polyproteoglycan secretion.

Bionic composite hydrogel with a hybrid covalent/noncovalent network promoting phenotypic maintenance of hyaline cartilage.

The injectable composite hydrogel based on collagen and hyaluronic acid provided a bionic three-dimensional microenvironment and mimetic natural extracellular matrix (ECM) for the growth of cells in vivo and has been widely researched and developed for cartilage tissue engineering. Here, a novel injectable bionic hydrogel with hybrid covalent/noncovalent network derived from covalent conjugation of HA-SH and noncovalent supramolecular self-assembly of BPAA-AFF-OH short peptide was fabricated to overcome the collagen immunogenicity of animal origin and effectively maintain its biological function. Moreover, through optimizing the network structure and polymer composition, the bionic HS5FFAB5 hydrogel presented a reliable mechanical strength which depended on the highly integrated fiber structure between HA-SH and FFAB-AFF-OH molecules. The results in vitro and in vivo proved that HA-SH could provide a fundamental frame structure, while the supramolecular hydrogels could reinforce this structure via hydrogen bonds and hydrophilic/hydrophobic interactions, and endow bionic hydrogels with more abundant cell adhesion sites. The bionic composite hydrogel could improve the cell adhesion and proliferation when compared to HA-SH hydrogel, and enhanced chondrogenic related gene expression and matrix secretion by three-dimensional co-cultured in vitro and subcutaneous implantation in vivo, which further promoted phenotypic maintenance of hyaline cartilage. This bionic hydrogel with a hybrid covalent/noncovalent network is supposed to have potential application prospects in cartilage regeneration.

A highly interweaved HA-SS-nHAp/collagen hybrid fibering hydrogel enhances osteoinductivity and mineralization.

The combination of bioactive hydroxyapatite (HAp) with biomimetic bone matrix biomaterials as bone filling scaffolds is a promising strategy for bone regeneration, but the undesirable dispersion of HAp and its interfacial interaction result in inefficient mineralization, mechanical instability, incomplete osteointegration, and even repair failure. Herein, the size dispersion and stabilization of nano-hydroxyapatite (nHAp) in aqueous media were obviously improved by hydrophilic solubilisation and strong negatively charged thiolated hyaluronic acid (HA-SH). Furthermore, the highly interweaved HA-SS-nHAp/collagen hybrid fibering hydrogel exhibited significantly improved mechanical properties and structural stability due to its thickened and densified interweaved fiber network, which ensured the homogeneous dispersion of nHAp in the matrix materials and its integration with the hydrogel network structure completely by covalent self-crosslinking among the sulfhydryl groups derived from the free HA-SH polymer and the mercapto functional groups on the surface of nHAp. Compared with the physically combined micro-hydroxyapatite (µHAp) (d≤25 µm) and nHAp (∼530 nm) with injectable bionic HA-SH and collagen type I biopolymers, HA-SS-nHAp/collagen achieved the maximum efficiency in facilitating rabbit bone marrow stromal cell (rBMSC) adhesion, proliferation and osteogenic differentiation in vitro. The in vivo murine dorsal subcutaneous implantation results further confirmed that the interweaved fiber network structure in HA-SS-nHAp/collagen significantly promoted osteoinductivity and mineralization. This work provides novel insights for the development of new low invasive bone filling biomaterials.

The Survival and Reproduction of Rhopalosiphum padi (Hemiptera: Aphididae) on Different Plants: Exploring the Possible Host Range for a Serious Wheat Pest.

Rhopalosiphum padi (L.) is one of the most economically important pests of wheat worldwide; however, the host ranges of R. padi remain unclear. Particularly, it is unknown which plants R. padi can survive and reproduce on after the harvest of crops. The results revealed that the survival, developmental times, longevity, and fecundity of the aphid varied among the 13 Gramineae weeds, with the life-history parameters significantly differing. The virginoparae could survive long-term and reproduce on 11 of the 13 weeds. Gramineae weeds can possibly play a significant role in the buildup of R. padi populations as reservoirs. The virginoparae could survive long term and reproduce on Iris lactea Pall. var. chinensis (Fisch.) Koidz (Liliflorae: Iridaceae), Iris tectorum Maxim. (Liliflorae: Iridaceae), Cyperus rotundus L. (Cyperales: Cyperaceae), and Brassica oleracea L. var. capitata (Rhoeadales: Cruciferae), but not on Fagopyrum esculentum Moench (Polygonales: Polygonaceae), F. tataricum (L.) Gaertn. (Polygonales: Polygonaceae), Chlorophytum comosum (Thunb.) Baker (Liliflorae: Liliaceae), and Ophiopogon japonicas (Thunb.) Ker-Gawl (Liliflorae: Liliaceae). Rhopalosiphum padi can survive and reproduce on non-Gramineae plants of different families. Detailed host range information would be helpful for more effective control of insect pests. The design and implementation of sustainable pest management strategies should consider the aphid population on weeds and other host plants.

BMSCs-assisted injectable Col I hydrogel-regenerated cartilage defect by reconstructing superficial and calcified cartilage.

The self-healing capacity of cartilage was limited due to absence of vascular, nervous and lymphatic systems. Although many clinical treatments have been used in cartilage defect repair and shown a promising repair result in short term, however, regeneration of complete zonal structure with physiological function, reconstruction cartilage homeostasis and maintaining long-term repair was still an unbridgeable chasm. Cartilage has complex zonal structure and multiple physiological functions, especially, superficial and calcified cartilage played an important role in keeping homeostasis. To address this hurdle of regenerating superficial and calcified cartilage, injectable tissue-induced type I collagen (Col I) hydrogel-encapsulated BMSCs was chosen to repair cartilage damage. After 1 month implantation, the results demonstrated that Col I gel was able to induce BMSCs differentiation into chondrocytes, and formed hyaline-like cartilage and the superficial layer with lubrication function. After 3 months post-surgery, chondrocytes at the bottom of the cartilage layer would undergo hypertrophy and promote the regeneration of calcified cartilage. Six months later, a continuous anatomical tidemark and complete calcified interface were restored. The regeneration of neo-hyaline cartilage was similar with adjacent normal tissue on the thickness of the cartilage, matrix secretion, collagen type and arrangement. Complete multilayer zonal structure with physiological function remodeling indicated that BMSCs-assisted injectable Col I hydrogel could reconstruct cartilage homeostasis and maintain long-term therapeutic effect.

Nobiletin Prevents Trimethylamine Oxide-Induced Vascular Inflammation via Inhibition of the NF-κB/MAPK Pathways.

Dietary choline and its containing foods are biotransformed to trimethylamine (TMA) via gut microbial metabolism. Subsequently, as an intermediate molecule, TMA is quickly transported and oxidized in the liver by hepatic flavin monooxygenases to form trimethylamine oxide (TMAO). TMAO was treated as a waste byproduct from choline metabolism, but recent convincing evidence demonstrated the association between the small molecule TMAO and inflammation-related diseases, including blood vessel inflammation and vascular diseases. The scope of this study is to investigate the preventive effect of nobiletin on TMAO-induced blood vessel inflammation. Our results from Western blot showed that the inhibition of TMAO-induced cardiovascular inflammation was correlated with nobiletin-mediated inhibitory effects on NF-κB and MAPK/ERK related pathways. More specifically, nobiletin prevented the oxidative damage of vascular sites (proximal aorta), inhibited the activity of MAPK/ERK, reduced the expression of NF-κB p65 and phospho-NF-κB p65, and consequently decreased the inflammatory response. Flow cytometry analyses showed that nobiletin decreased TMAO-induced apoptosis of HUVEC cells and counteracted TMAO-induced HUVEC cell proliferation. Results from HE staining and immunohistochemical results also showed that nobiletin reduced the degree of inflammation of the proximal aorta in Sprague-Dawley rats. In summary, nobiletin significantly reduced TMAO-induced vascular inflammation via inhibition of the NF-κB/MAPK pathways.