Progress in Stimuli-Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases.

Cardiovascular and cerebrovascular diseases (CCVDs) describe abnormal vascular system conditions affecting the brain and heart. Among these, ischemic heart disease and ischemic stroke are the leading causes of death worldwide, resulting in 16% and 11% of deaths globally. Although several therapeutic approaches are presented over the years, the continuously increasing mortality rates suggest the need for more advanced strategies for their treatment. One of these strategies lies in the use of stimuli-responsive biomaterials. These "smart" biomaterials can specifically target the diseased tissue, and after "reading" the altered environmental cues, they can respond by altering their physicochemical properties and/or their morphology. In this review, the progress in the field of stimuli-responsive biomaterials for CCVDs in the last five years, aiming at highlighting their potential as early-stage therapeutics in the preclinical scenery, is described.

The Class II KNOX family members KNAT3 and KNAT7 redundantly participate in Arabidopsis seed coat mucilage biosynthesis.

The production of Arabidopsis seed mucilage involves complex polysaccharide biosynthetic pathways and developmental processes in seed epidermal cells. Although the polysaccharide components of Arabidopsis seed mucilage have been identified, their regulatory mechanism requires further investigation. Here, we show that Class II KNOX gene family members KNAT3 and KNAT7 play an essential role in regulating mucilage production in the early developmental stages of Arabidopsis seeds. Double mutant knat3knat7 resulted in defective seed mucilage production and columellae formation, whereas knat3 showed a normal phenotype compared with wild type, and the mucilage thickness in knat7 was slightly disturbed. Rhamnogalacturonan I (RG-I) and its biosynthetic substrates galacturonic acid and rhamnose were reduced in both the adherent and soluble mucilage of knat3knat7. Comparative transcriptome analysis on whole seeds suggested that polysaccharide, glucosinolate and anthocyanin biosynthetic pathways were specifically repressed in knat3knat7. Transient co-expression of KNAT3 and KNAT7 with promoter regions of candidate genes in Arabidopsis protoplasts revealed that both KNAT3 and KNAT7 act as positive regulators of the RG-I biosynthetic gene MUCILAGE-MODIFIED 4 (MUM4, AT1G53500). Collectively, our results demonstrate that KNAT3 and KNAT7 are multifunctional transcription factors in secondary cell wall development and redundantly modulate mucilage biosynthesis in Arabidopsis seeds.

Insight into the Role of Psychological Factors in Oral Mucosa Diseases.

With the development of psychology and medicine, more and more diseases have found their psychological origins and associations, especially ulceration and other mucosal injuries, within the digestive system. However, the association of psychological factors with lesions of the oral mucosa, including oral squamous cell carcinoma (OSCC), burning mouth syndrome (BMS), and recurrent aphthous stomatitis (RAS), have not been fully characterized. In this review, after introducing the association between psychological and nervous factors and diseases, we provide detailed descriptions of the psychology and nerve fibers involved in the pathology of OSCC, BMS, and RAS, pointing out the underlying mechanisms and suggesting the clinical indications.

Outbreak of febrile illness caused by coxsackievirus A4 in a nursery school in Beijing, China.

BACKGROUND: Coxsackievirus A4 (CV-A4) is classified as human enterovirus A according to its serotype. CV-A4, an etiological agent of hand, foot, and mouth disease, affects children worldwide and can circulate in closed environments such as schools and hospitals for long periods. FINDINGS: An outbreak of febrile illness at a nursery school in Beijing, China, was confirmed to be caused by CV-A4. Phylogenetic analysis of the complete genome of the isolated strain showed that the virus belongs to the same cluster as the predominant CV-A4 strain in China. This outbreak was controlled by effective measures. CONCLUSIONS: The early identification of the pathogen and timely intervention may be the most critical factors in controlling an outbreak caused by CV-A4 in a preschool.

Time-programmed release of curcumin and Zn2+ from multi-layered RSF coating modified PET graft for improvement of graft-host integration.

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ on the surface of the PET grafts (Cur@Zn2+@PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ from the Cur@Zn2+@PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1ß. Meanwhile, a significant release of Zn2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

High-strength fibrous sensors with an enhanced aggregate state for biomechanical monitoring of the Achilles tendon.

Continuous monitoring of biomechanical signals generated from the injured Achilles tendon is essential for the deep understanding of the recovery or rehabilitation process, thus decreasing the risk of secondary injuries. With tissue-like components and adjustable properties, hydrogel-based biomechanical sensors are considered promising materials for human motion detection. However, existing hydrogels are characterized by inferior mechanical properties with strength and modulus typically lower than 1 MPa, as well as poor stability under physiological conditions, which hampers their applications in implantable devices. Moreover, acquiring the stress signal from collected electrical signals remains challenging. Herein, based on the regulation of polymer aggregation, a high-strength fibrous sensor composed of polyvinyl alcohol (PVA) and reduced graphene oxide (rGO) for in vivo monitoring is prepared through a two-step procedure, including freeze-thaw and freeze-soak. Benefiting from the synergy of crystallization, Hofmeister effect and nanocomposite, the hydrogel fibers feature high tensile strength (8.34 ± 0.66 MPa) and elastic modulus (1.15 ± 0.10 MPa). Meanwhile, the removal of salt ions during fabrication improves the water content (69.18 ± 1.47%) and anti-swelling performance of such fibers and minimizes side effects after implantation. It is demonstrated that the fibrous sensor could record the relative resistance changes upon stretching with ideal sensitivity (GF = 1.57) and convert them into bearing stress through formula derivation and calculations. In vitro and in vivo assays further confirm its feasibility for real-time monitoring of joint motion, providing important references for medical diagnosis and treatment.

Electrochemical Visualization of an Ion-Selective Membrane Using a Carbon Nanoelectrode.

Molecular and physical probes have been widely employed to investigate physicochemical properties and mechanisms of interfaces due to their ability to provide accurate measurements with temporal and spatial resolution. However, the direct measurement of electroactive species diffusion in ion-selective electrode (ISE) membranes and quantification of the water layer have been challenging due to the high impedance and optical opacity of polymer membranes. In the present work, carbon nanoelectrodes with ultrathin insulating encapsulation and good geometrical structure are reported as physical probes for direct electrochemical measurement of the water layer. The scanning electrochemical microscopy experiment exhibits positive feedback at the interface of the fresh ISE, and negative feedback after conditioning for 3 h. The thickness of the water layer was estimated to be ca. 13 nm. For the first time, we provide direct evidence that, during conditioning, the water molecules diffuse through the chloride ion selective membrane (Cl-ISM) until a water layer establishes at almost 3 h. Furthermore, the diffusion coefficient and concentration of oxygen molecules in the Cl-ISM are also directly electrochemical measured by introducing ferrocene (Fc) as a redox molecule probe. The oxygen concentration in the Cl-ISM decreases during conditioning, suggesting the diffusion of oxygen from ISM to the water layer. The proposed method can be used for the electrochemical measurement of solid contact, providing theoretical guidance and advice for the performance optimization of ISEs.

Sequential intervention of anti-inflammatory and osteogenesis with silk fibroin coated polyethylene terephthalate artificial ligaments for anterior cruciate ligament reconstruction.

Graft-host integration after the anterior cruciate ligament (ACL) reconstruction sequentially follows the prognosis from the inflammation period to the regeneration period. However, due to insufficient bioactivity, polyethylene terephthalate (PET) artificial ligaments often require a long period for graft-host integration. To improve graft-host integration, sequential therapy targeting multifactor is widely advocated. In this study, a multilayer regenerated silk fibroin (RSF) coating loaded with heparin and bone morphogenetic protein binding peptide (BBP) for differentiated release was introduced on the surface of the PET artificial ligament by a stepwise deposition method. The drug release profiles of heparin and BBP on the coated PET artificial ligament indicated the features of differential drug release, i.e., with heparin in the outermost layer releasing a significant amount (more than 60%) during the first 5 days while BBP in the inner layer only releasing a small amount (ca. 30%) within 1 week without burst release. Based on the isometric ACL reconstruction model of rabbits, such drug-loaded RSF coating was verified to be able to modulate the early inflammatory response and promote the maturation of the graft in the articular cavity, meanwhile, it provided a continuous and stable signal of osteogenic induction to improve graft-bone integration. Thus, sequential intervention with heparin and BBP proved to be a reliable combination, and multifunctional RSF-coated PET artificial ligaments hold great potential for improving the clinical efficacy of ACL reconstruction.

Insight into the Relationship between Oral Microbiota and the Inflammatory Bowel Disease.

Inflammatory bowel disease has been a growing concern of lots of people globally, including both adults and children. As a chronic inflammatory disease of the intestine, even though the etiology of inflammatory bowel disease is still unclear, the available evidence from clinic observations has suggested a close association with microorganisms. The oral microbiota possesses the characteristics of a large number and abundant species, second only to the intestinal microbiota in the human body; as a result, it successfully attracts the attention of researchers. The highly diverse commensal oral microbiota is not only a normal part of the oral cavity but also has a pronounced impact on the pathophysiology of general health. Numerous studies have shown the potential associations between the oral microbiota and inflammatory bowel disease. Inflammatory bowel disease can affect the composition of the oral microbiota and lead to a range of oral pathologies. In turn, there are a variety of oral microorganisms involved in the development and progression of inflammatory bowel disease, including Streptococcus spp., Fusobacterium nucleatum, Porphyromonas gingivalis, Campylobacter concisus, Klebsiella pneumoniae, Saccharibacteria (TM7), and Candida albicans. Based on the above analysis, the purpose of this review is to summarize this relationship of mutual influence and give further insight into the detection of flora as a target for the diagnosis and treatment of inflammatory bowel disease to open up a novel approach in future clinical practice.

Comprehensive phylogeographic and phylodynamic analyses of global Senecavirus A.

Senecavirus A (SVA) is a member of the genus Senecavirus in the family Picornaviridae that infects pigs and shows symptoms similar to foot and mouth diseases and other vesicular diseases. It is difficult to prevent, thus, causing tremendous economic loss to the pig industry. However, the global transmission routes of SVA and its natural origins remain unclear. In this study, we processed representative SVA sequences from the GenBank database along with 10 newly isolated SVA strains from the field samples collected from our lab to explore the origins, population characteristics, and transmission patterns of SVA. The SVA strains were firstly systematically divided into eight clades including Clade I-VII and Clade Ancestor based on the maximum likelihood phylogenetic inference. Phylogeographic and phylodynamics analysis within the Bayesian statistical framework revealed that SVA originated in the United States in the 1980s and afterward spread to different countries and regions. Our analysis of viral transmission routes also revealed its historical spread from the United States and the risk of the global virus prevalence. Overall, our study provided a comprehensive assessment of the phylogenetic characteristics, origins, history, and geographical evolution of SVA on a global scale, unlocking insights into developing efficient disease management strategies.

High-Performance Flexible Pressure Sensor with a Self-Healing Function for Tactile Feedback.

High-performance flexible pressure sensors have attracted a great deal of attention, owing to its potential applications such as human activity monitoring, man-machine interaction, and robotics. However, most high-performance flexible pressure sensors are complex and costly to manufacture. These sensors cannot be repaired after external mechanical damage and lack of tactile feedback applications. Herein, a high-performance flexible pressure sensor based on MXene/polyurethane (PU)/interdigital electrodes is fabricated by using a low-cost and universal spray method. The sprayed MXene on the spinosum structure PU and other arbitrary flexible substrates (represented by polyimide and membrane filter) act as the sensitive layer and the interdigital electrodes, respectively. The sensor shows an ultrahigh sensitivity (up to 509.8 kPa-1 ), extremely fast response speed (67.3 ms), recovery speed (44.8 ms), and good stability (10 000 cycles) due to the interaction between the sensitive layer and the interdigital electrodes. In addition, the hydrogen bond of PU endows the device with the self-healing function. The sensor can also be integrated with a circuit, which can realize tactile feedback function. This MXene-based high-performance pressure sensor, along with its designing/fabrication, is expected to be widely used in human activity detection, electronic skin, intelligent robots, and many other aspects.

A pH-Responsive Cluster Metal-Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect.

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, metal-organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap-ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.

Unusual clinical and histologic findings in a child with mixed dentition with hereditary gingival fibromatosis: a case report.

Hereditary gingival fibromatosis (HGF) is characterized by an accumulation of extracellular matrix resulting in a fibrotic enlargement of keratinized gingiva. The goal of this article is to describe one kindred affected with HGF and discuss the diagnosis, treatment, recurrence risk and histopathology features of the proband with mixed dentition. An 8-year-old boy reported with a chief complaint of gingival enlargement. A series of examinations were performed to make a diagnosis and family histories of the patient were recorded. Surgical therapy included gingivectomy and gingivoplasty technique were performed for the proband to remove excess gingiva. Collagen bundles in the permanent incisors area were prevalently significantly bulkier than that of the deciduous teeth area and the arrangement was much more regular. Microscopic evaluation revealed that epithelial hyperplasia was severe in tissue with intense inflammation, whereas tissue with mild inflammation showed only long and deep epithelial papillae. The patient was placed on a 3-month recall schedule and didn't demonstrate any recurrence of gingival overgrowth over a 1-year follow-up period. The study revealed that the eruption of permanent teeth played an important role in accelerating gingival hyperplasia. For the first time, it was confirmed from histological perspective that inflammation in gingival tissue was crucial to the gingival overgrowth of HGF.

Integrating the Polydopamine Nanosphere/Aptamers Nanoplatform with a DNase-I-Assisted Recycling Amplification Strategy for Simultaneous Detection of MMP-9 and MMP-2 during Renal Interstitial Fibrosis.

Matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) play important roles in the progression of renal interstitial fibrosis (RIF). There is an increasing demand to construct a novel method for the simultaneous detection of MMP-9 and MMP-2 to monitor the progression of RIF. Herein, a strategy based on the nanoplatform composed of the polydopamine nanosphere and fluorescence-labeled aptamers is developed to simultaneously detect MMP-9 and MMP-2 with DNase-I-assisted recycling signal amplification. In the light of tracing the recovered fluorescence intensity at 520 and 610 nm upon adding MMP-9 and MMP-2, the increased fluorescence intensity is linear to the different concentrations of MMP-9 and MMP-2 with the detection limits of 9.6 and 25.6 pg/mL for MMP-9 and MMP-2, respectively. More intriguingly, the results of unilateral ureteral obstruction mice show that the concentration of MMP-9 in urine is increased with the extension of ligation time while the concentration of MMP-2 is reversed, indicating that the ratio of MMP-9 to MMP-2 could be considered as the potential urinary biomarker to evaluate the progress of RIF and the therapeutic effect of Huangkui capsule on RIF. Therefore, this study provides a paradigmatic strategy for the simultaneous detection of the dual markers of RIF, which is promising for the auxiliary clinical diagnosis and assessment of the prognosis of chronic kidney disease.

Stafne's bone defect: a case report and review of literatures.

Stafne's bone defect (SBD) or Stafne's bone cavity (SBC) is an uncommon bony defect occurred especially only at the lingual cortex of mandible. Clinically, patients with SBD are usually asymptomatic. In most cases, the defect is observed accidentally via X-ray panorama during other dental treatments. Here we presented a female with SBD and we reviewed relevant literatures on SBD, summarized the clinical characteristic and radiographic features with our experiences.

A novel thermosensitive in-situ gel of gabexate mesilate for treatment of traumatic pancreatitis: An experimental study.

Gabexate mesilate (GM) is a trypsin inhibitor, and mainly used for treatment of various acute pancreatitis, including traumatic pancreatitis (TP), edematous pancreatitis, and acute necrotizing pancreatitis. However, due to the characteristics of pharmacokinetics, the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration, which is difficult to manage. Specially, when the blood supply of pancreas is directly damaged, intravenous administration is difficult to exert the optimum therapy effect. To address it, a novel thermosensitive in-situ gel of gabexate mesilate (GMTI) was developed, and the optimum formulation of GMTI containing 20.6% (w/w) P-407 and 5.79% (w/w) P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro, and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin (HE) staining, and its curative effect on grade II pancreas injury was also evaluated by testing amylase (AMS), C-reactive protein (CRP) and trypsinogen activation peptide (TAP), and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/mL in GM group and GMTI group, respectively (P<0.05 vs. P-407), and completely inhibited at 10.0 and 20.0 mg/mL (P<0.01 vs. P-407). After local injection of 10 mg/mL GMTI to rat leg muscular tissue, muscle fiber texture was normal, and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore, the expression of AMS, CRP and TAP was significantly increased in TP group as compared with control group (P<0.01), and significantly decreased in GM group as compared with TP group (P<0.01), and also slightly inhibited after 1.0 and 5.0 mg/mL GMTI treatment as compared with TP group (P<0.05), and significantly inhibited after 10.0 and 20.0 mg/mL GMTI treatment as compared with TP group (P<0.01). HE staining results demonstrated that pancreas cells were uniformly distributed in control group, and they were loosely arranged, partially dissolved, with deeply stained nuclei in TP group. Expectedly, after gradient GMTI treatment, pancreas cells were gradually restored to tight distribution, with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes, and alleviate the severity of trauma-induced pancreatitis, and had a potential drug developing and clinic application value.

High-strength hydrogel as a reusable adsorbent of copper ions.

A mechanically strong hydrogel was prepared by photoinitiated polymerization of oligo(ethylene glycol) methacrylate (OEGMA), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT) and cross-linker N,N'-methylenebisacrylamide (MBAA). Introduction of the monomer VDT considerably strengthened the mechanical properties of the hydrogel by self-hydrogen bonding of diaminotriazine, and enhanced the adsorption of copper ion onto the hydrogel by chelation between amino groups and metal ion. Adsorption studies were carried out by varying the OEGMA/VDT ratio, contact time, pH value, counterion and initial concentration of Cu(2+) ions. The evaluation of adsorption properties showed that the hydrogel exhibited better correlation with Langmuir isotherm model. This adsorbent could be used repeatedly with little loss in adsorption capacity.