Molybdesum selenide-based platelet-rich plasma containing carboxymethyl chitosan/polyvinyl pyrrolidone composite antioxidant hydrogels dressing promotes the wound healing.

Excess free radicals at the wound site can cause an inflammatory response, which is not conducive to wound healing. Hydrogels with antioxidant properties can prevent inflammatory storms by scavenging free radicals from the wound site and inhibiting the release of inflammatory factors. In this study, we prepared the carboxymethyl chitosan (CMCS)/polyvinyl pyrrolidone (PVP)/Molybdenum (IV) Selenide (MoSe2), and platelet-rich plasma (PRP) (CMCS/PVP/MoSe2/PRP) hydrogels for accelerating the repair of wounds. In the hydrogels, the MoSe2 can scavenge various free radicals to reduce oxidative stress at the site of inflammation, endowed the hydrogels with antioxidant properties. Interestingly, growth factors released by PRP assisted the tissue repair by promoting the formation of new capillaries. CMCS as a backbone not only showed good biocompatibility and biodegradability but also played a significant role in maintaining the sustained release of growth factors. In addition, incorporating PVP enhanced the tissue adhesion and mechanical properties. The multifunctional composite antioxidant hydrogels have good swelling properties and biodegradability, which is completely degraded within 28 days. Thus, the antioxidant CMCS/PVP/MoSe2/PRP hydrogels provide a new idea for designing ideal multifunctional wound dressings.

Macroscopic laser pulling based on the Knudsen force in rarefied gas.

Optical pulling is an attractive concept due to the counterintuitive feature, the profound mechanism underneath and promising applications. In recent ten years, optical pulling of micro-nano objects have been fully demonstrated. However, optical pulling of a macroscopic object is challenging. Herein, laser pulling of a macroscopic object is presented in rarefied gas. The pulling force is originated from the Kundsen force when a gauss laser beam irradiates a macroscopic structure composed of the absorptive bulk cross-linked graphene material and a SiO2 layer. A torsional pendulum device qualitatively presents the laser pulling phenomenon. A gravity pendulum device was used to further measure the pulling force that is more than three orders of magnitudes larger than the radiation pressure. This work expands the scope of optical pulling from microscale to macroscale and provides an effective technique approach for macroscopic optical manipulations.

Massive laser pulling of graphene nanosheets in water.

Light manipulation of graphene-based materials attracts much attentions. As a new light manipulation concept, optical pulling develops rapidly in the past decade. However, optical pulling of graphene in liquid is rarely reported. In this work, laser pulling of graphene nanosheets (GN) in pure water by using common gauss beams is presented. This phenomenon holds for multiple incident laser wavelengths including 405 nm, 488 nm, 532 nm and 650 nm. A particle image velocimetry software PIVlab is adopted to analyze the velocity field information of GN. The laser pulling velocity of the GN is approximately ∼ 0.5 mm/s corresponding to ∼ 103 body length/s, which increases with an increase of the incident laser energy. This work presents a contactless mothed to massively pull microscale graphene materials in simple liquid, which supplies a potential manipulation technique for micro-nanofluidic devices and also provides a platform to investigate laser-graphene interaction in a simple liquid phase medium.

Preparation of Biocompatible Manganese Selenium-Based Nanoparticles with Antioxidant and Catalytic Functions.

The specificity of the tumor microenvironment (TME) severely limits the effectiveness of tumor treatment. In this study, we prepared a composite nanoparticle of manganese dioxide and selenite by a one-step redox method, and their stability under physiological conditions was improved with a bovine serum protein modification to obtain MnO2/Se-BSA nanoparticles (SMB NPs). In the SMB NPs, manganese dioxide and selenite endowed the SMB NPs with acid-responsive and catalytic, and antioxidant properties, respectively. The weak acid response, catalytic activity, and antioxidant properties of composite nanoparticles were verified experimentally. Moreover, in an in vitro hemolysis assay, different concentrations of nanoparticles were incubated with mouse erythrocytes, and the hemolysis ratio was less than 5%. In the cell safety assay, the cell survival ratio was as high as 95.97% after the co-culture with L929 cells at different concentrations for 24 h. In addition, the good biosafety of composite nanoparticles was verified at the animal level. Thus, this study helps to design high-performance and comprehensive therapeutic reagents that are responsive to the hypoxia, weak acidity, hydrogen peroxide overexpression nature of TME and overcome the limitations of TME.

Chitosan-Based Hemostatic Hydrogels: The Concept, Mechanism, Application, and Prospects.

The design of new hemostatic materials to mitigate uncontrolled bleeding in emergencies is challenging. Chitosan-based hemostatic hydrogels have frequently been used for hemostasis due to their unique biocompatibility, tunable mechanical properties, injectability, and ease of handling. Moreover, chitosan (CS) absorbs red blood cells and activates platelets to promote hemostasis. Benefiting from these desired properties, the hemostatic application of CS hydrogels is attracting ever-increasing research attention. This paper reviews the recent research progress of CS-based hemostatic hydrogels and their advantageous characteristics compared to traditional hemostatic materials. The effects of the hemostatic mechanism, effects of deacetylation degree, relative molecular mass, and chemical modification on the hemostatic performance of CS hydrogels are summarized. Meanwhile, some typical applications of CS hydrogels are introduced to provide references for the preparation of efficient hemostatic hydrogels. Finally, the future perspectives of CS-based hemostatic hydrogels are presented.

TMEM151A Variants Cause Paroxysmal Kinesigenic Dyskinesia: A Large-Sample Study.

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.

Biodegradable MoSe2-polyvinylpyrrolidone nanoparticles with multi-enzyme activity for ameliorating acute pancreatitis.

Exogenous antioxidant materials mimicking endogenous antioxidant systems are commonly used for the treatment of oxidative stress-induced injuries. Thus, artificial enzymes have emerged as promising candidates for balancing and treating the dysregulation of redox homeostasis in vivo. Herein, a one-pot hydrothermal strategy for the facile preparation of MoSe2-polyvinylpyrrolidone (PVP) nanoparticles (NPs) is reported. The synthesized NPs were biodegradable due to their exposure to oxygen and exhibited high stability. Moreover, they effectively mimicked various naturally occurring enzymes (including catalase, superoxide dismutase, peroxidase, and glutathione peroxidase) and scavenged free radicals, such as 3-ethylbenzothiazoline-6-sulfonic acid, ·OH, ·O2-, and 1,1-diphenyl-2-picrylhydrazyl radical. Further apoptosis detection studies revealed that MoSe2-PVP NPs significantly increased the cell survival probability in H2O2 in a concentration-dependent manner. The cytoprotective effect of MoSe2-PVP NPs was explored for an animal model of acute pancreatitis, which confirmed its remarkable therapeutic efficacy. Owing to the biodegradable and biocompatible nature of MoSe2-PVP NPs, the findings of this work can stimulate the development of other artificial nanoenzymes for antioxidant therapies.

Research Progress of Antioxidant Nanomaterials for Acute Pancreatitis.

Acute pancreatitis (AP) is a complex inflammatory disease caused by multiple etiologies, the pathogenesis of which has not been fully elucidated. Oxidative stress is important for the regulation of inflammation-related signaling pathways, the recruitment of inflammatory cells, the release of inflammatory factors, and other processes, and plays a key role in the occurrence and development of AP. In recent years, antioxidant therapy that suppresses oxidative stress by scavenging reactive oxygen species has become a research highlight of AP. However, traditional antioxidant drugs have problems such as poor drug stability and low delivery efficiency, which limit their clinical translation and applications. Nanomaterials bring a brand-new opportunity for the antioxidant treatment of AP. This review focuses on the multiple advantages of nanomaterials, including small size, good stability, high permeability, and long retention effect, which can be used not only as effective carriers of traditional antioxidant drugs but also directly as antioxidants. In this review, after first discussing the association between oxidative stress and AP, we focused on summarizing the literature related to antioxidant nanomaterials for the treatment of AP and highlighting the effects of these nanomaterials on the indicators related to oxidative stress in pathological states, aiming to provide references for follow-up research and promote clinical application.

Magnetic mesoporous nanomaterials with AIE properties for selective detection and removal of CN- from water under magnetic conditions.

We have prepared a type of magnetic mesoporous nanomaterial with aggregation-induced emission properties (Fe3O4@mSiO2@TPA@BA, hence abbr. FSTB) to detect and remove cyanide ions (CN-) under magnetic conditions. FSTB has a large specific surface area and improved fluorescence performance to identify CN-, and its superparamagnetic behavior plays an important role in removing CN-. The magnetic sensor FSTB shows excellent selectivity and anti-interference for the detection of CN- in aqueous solutions. It is obvious from the equation LOD = 3δ/S that the limit of detection (LOD) of FSTB for CN- is significantly lower than the permissible level of CN- in drinkable water recommended by the World Health Organization. Therefore, the magnetic sensor FSTB has a wide range of applications for detecting and removing harmful CN-.

2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Synthesis of iridium-based nanocomposite with catalase activity for cancer phototherapy.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted attention due to its enhanced tumor therapy effect. This study proposes a novel nanoenzyme-based theranostic nanoplatform, IrO2@MSN@PDA-BSA(Ce6), for the combined PTT and PDT of tumors. IrO2 was prepared by a simple hydrolysis method and coated with a thin layer of mesoporous silica (MSN) to facilitate the physical adsorption of Chlorin e6 (Ce6). The PDA coating and IrO2 NPs of the nanoplatform demonstrated an improved photothermal conversion efficiency of 29.8% under NIR irradiation. Further, the Ce6 loading imparts materials with the ability to produce reactive oxygen species (ROS) under 660 nm NIR laser irradiation. It was also proved that the IrO2 NPs could catalyze the hydrogen peroxide (H2O2) in the tumor microenvironment (TME) to generate endogenous oxygen (O2), thereby enhancing the efficiency of PDT. The in vitro and in vivo experiments indicated that the nanocomposite was highly biocompatible and could produce a satisfactory tumor therapeutic effect. Thus, the findings of the present study demonstrate the viability of using theranostic nanoenzymes for translational medicine.

Advances in hyperekplexia and other startle syndromes.

Startle, a basic alerting reaction common to all mammals, is described as a sudden involuntary movement of the body evoked by all kinds of sudden and unexpected stimulus. Startle syndromes are heterogeneous groups of disorders with abnormal and exaggerated responses to startling events, including hyperekplexia, stimulus-induced disorders, and neuropsychiatric startle syndromes. Hyperekplexia can be attributed to a genetic, idiopathic, or symptomatic cause. Excluding secondary factors, hereditary hyperekplexia, a rare neurogenetic disorder with highly genetic heterogeneity, is characterized by neonatal hypertonia, exaggerated startle response provoked by the sudden external stimuli, and followed by a short period of general stiffness. It mainly arises from defects of inhibitory glycinergic neurotransmission. GLRA1 is the major pathogenic gene of hereditary hyperekplexia, along with many other genes involved in the function of glycinergic inhibitory synapses. While about 40% of patients remain negative genetic findings. Clonazepam, which can specifically upgrade the GABARA1 chloride channels, is the main and most effective administration for hereditary hyperekplexia patients. In this review, with the aim at enhancing the recognition and prompting potential treatment for hyperekplexia, we focused on discussing the advances in hereditary hyperekplexia genetics and the expound progress in pathogenic mechanisms of the glycinergic-synapse-related pathway and then followed by a brief overview of other common startle syndromes.

Injectable Ovalbumin-Based Composite Implant for Photothermal Tumor Therapy.

Polymeric hydrogels with three-dimensional network structures have found tremendous applications in biomedicine. Herein, we report the synthesis of a multifunctional implant based on ovalbumin (OVA) as a carrier capable of synergistically delivering a photothermal transducing agent (polydopamine, PDA) to tumors. The formation of PDA was achieved by utilizing the basicity of OVA, whereas the formation of the hydrogel implant was achieved through the in vitro/in vivo near-infrared (NIR) laser-induced hyperthermia of PDA. The as-prepared PDA@OVA implant exhibits high photothermal conversion efficiency (38.7 %). Once implanted in vivo, the OVA-based implant shows great versatility in the treatment of malignant tumors. Furthermore, a chemotherapeutic (doxorubicin, DOX) and a contrast agent (iohexol), dispersed in the OVA solution in advance, can also be firmly entrapped in the hydrogel along with the hydrogel formation. It is anticipated that the multifunctional OVA-based implant, not showing any obvious toxicity to healthy tissue, could be a promising system for synergistic cancer treatment.

The Phenotypic and Genetic Spectrum of Paroxysmal Kinesigenic Dyskinesia in China.

BACKGROUND: Paroxysmal kinesigenic dyskinesia is a spectrum of involuntary dyskinetic disorders with high clinical and genetic heterogeneity. Mutations in proline-rich transmembrane protein 2 have been identified as the major pathogenic factor. OBJECTIVES: We analyzed 600 paroxysmal kinesigenic dyskinesia patients nationwide who were identified by the China Paroxysmal Dyskinesia Collaborative Group to summarize the clinical phenotypes and genetic features of paroxysmal kinesigenic dyskinesia in China and to provide new thoughts on diagnosis and therapy. METHODS: The China Paroxysmal Dyskinesia Collaborative Group was composed of departments of neurology from 22 hospitals. Clinical manifestations and proline-rich transmembrane protein 2 screening results were recorded using unified paroxysmal kinesigenic dyskinesia registration forms. Genotype-phenotype correlation analyses were conducted in patients with and without proline-rich transmembrane protein 2 mutations. High-knee exercises were applied in partial patients as a new diagnostic test to induce attacks. RESULTS: Kinesigenic triggers, male predilection, dystonic attacks, aura, complicated forms of paroxysmal kinesigenic dyskinesia, clustering in patients with family history, and dramatic responses to antiepileptic treatment were the prominent features in this multicenter study. Clinical analysis showed that proline-rich transmembrane protein 2 mutation carriers were prone to present at a younger age and have longer attack duration, bilateral limb involvement, choreic attacks, a complicated form of paroxysmal kinesigenic dyskinesia, family history, and more forms of dyskinesia. The new high-knee-exercise test efficiently induced attacks and could assist in diagnosis. CONCLUSIONS: We propose recommendations regarding diagnostic criteria for paroxysmal kinesigenic dyskinesia based on this large clinical study of paroxysmal kinesigenic dyskinesia. The findings offered some new insights into the diagnosis and treatment of paroxysmal kinesigenic dyskinesia and might help in building standardized paroxysmal kinesigenic dyskinesia clinical evaluations and therapies. © 2020 International Parkinson and Movement Disorder Society.

Correction: Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

Correction for 'Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy' by Yangjie Xu et al., Soft Matter, 2020, 16, 132-141.

Preparation of electrospray ALG/PDA-PVP nanocomposites and their application in cancer therapy.

In this study, sodium alginate (ALG)/poly dopamine (PDA)-polyvinylpyrrolidone (PVP) nanocomposites was synthesized via a one-step electrostatic spraying method. The spinning solution of ALG and dopamine was electrostatically sprayed into an alkaline solution of PVP, calcium chloride and tris buffer (pH = 8.5), in which the gelation of ALG and the polymerization of dopamine could be simultaneously triggered. PDA hence produced possesses a high photothermal conversion efficiency, while the PVP that was facilely conjugated onto the surface of nanocomposites improves the colloidal stability and compatibility of the material. Moreover, the ALG renders the nanocomposite excellent drug (doxorubicine, DOX) loading capacity. Promisingly, the temperature increment during the PTT process could promote the DOX release, thus enhancing its therapeutic effect. The in vitro/in vivo biosafety and tumor treatment experiments further corroborate that the ALG/PDA-PVP nanocomposites have remarkable biocompatibility and synergism for tumor hyperthermia and chemotherapy. Consequently, such a one-step electrospray strategy provides a new way for designing nanomaterials and is expected to significantly promote the development of organic photothermal therapeutic agents with excellent bio-compatibility.

Preparation of silica microspheres with a broad pore size distribution and their use as the support for a coated cellulose derivative chiral stationary phase.

A templating strategy using crosslinked and functionalized polymeric beads to synthesize silica microspheres with a broad pore size distribution has been developed. The polymer/silica hybrid microspheres were prepared by utilizing the combination of a templating weak cation exchange resin, a structure-directing agent N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride, and a silica precursor tetraethyl orthosilicate. The silica microspheres were then obtained after calcinating the hybrid microspheres. The as-prepared materials were characterized by scanning electron microscopy, mercury intrusion porosimeter, and thermal gravimetric analysis. The results showed that the starting templating beads were about 5 µm in diameter and the formed silica microspheres were less than 3 µm with a pore size range of 10-150 nm, some pores were even extended to beyond 250 nm. It was demonstrated that cellulose tris(3,5-dimethylphenylcarbamate) was readily coated onto the surface of the as-synthesized silica microspheres without any additional surface pretreatment. The coated silica microspheres were uniformly dispersed even with high loading of the chiral stationary phase, which exhibited high resolution chiral separations in high-performance liquid chromatography.

Design of electrospun nanofibrous mats for osteogenic differentiation of mesenchymal stem cells.

The clinical translation potential of mesenchymal stem cells (MSCs) in regenerative medicine has been greatly exploited. With the merits of high surface area to volume ratio, facile control of components, well retained topography, and the capacity to mimic the native extracellular matrix (ECM), nanofibers have received a great deal of attention as bone tissue engineering scaffolds. Electrospinning has been considered as an efficient approach for scale-up fabrication of nanofibrous materials. Electrospun nanofibers are capable of stimulating cell-matrix interaction to form a cell niche, directing cellular behavior, and promoting the MSCs adhesion and proliferation. In this review, we give a comprehensive literature survey on the mechanisms of electrospun nanofibers in supporting the MSCs differentiation. Specifically, the influences of biological and physical osteogenic inductive cues on the MSCs osteogenic differentiation are reviewed. Along with the significant advances in the field, current research challenges and future perspectives are also discussed.

Dendritic Mesoporous Silica Nanospheres Synthesized by a Novel Dual-Templating Micelle System for the Preparation of Functional Nanomaterials.

Highly monodisperse, dendritic, and functionalized mesoporous silica nanospheres (MSNs) with sub-200 nm size were synthesized in a one-pot sol-gel reaction, by a dual-templating micelle system consisting of a partially fluorinated short-chain anionic fluorocarbon surfactant and cetyltrimethylammonium bromide. This kind of anionic fluorocarbon surfactant works simultaneously as a swelling agent to enlarge the pore of the MSNs, an ion-pair agent to the structure-directing silane in the preparation of amine-functionalized MSNs, and a surface tension reducing agent to make the system thermodynamically more stable for producing more uniform MSNs. The particle size and the morphology of the resultant MSNs can be fine-tuned by changing the amount of the fluorocarbon surfactant added and the ratio of the functional group containing organosilane to tetraethoxysilane. Subsequently, the as-prepared MSNs were used as base materials for the preparation of drug delivery nanomaterials through the surface grafting of a pH-sensitive drug-conjugated polymer and fluorescent nanomaterials through the embedding of europium(III) complex or the immobilization of large molecule fluorescein isothiocyanate-bovine serum albumin.

Partially Acetylated Dendrimer-Entrapped Gold Nanoparticles with Reduced Cytotoxicity for Gene Delivery Applications.

Gene therapy has been concerned to be one of the most promising strategies to treat many diseases such as genetic disorders and cancer. However, design of safe and highly efficient gene delivery vectors still remains a great challenge. In this work, we report the use of partially acetylated dendrimer-entrapped gold nanoparticles (Au DENPs) for gene delivery applications. First, partially acetylated generation 5 poly(amidoamine) dendrimers with different acetylation degrees were used as templates to synthesize Au DENPs. The formed Au DENPs were characterized via different techniques and were used to complex two different pDNAs encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The Au DENPs/pDNA polyplexes with different N/P ratios were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements, and the gene transfection efficiency was evaluated by Luc assay and fluorescence microscopic imaging of the EGFP expression, respectively. We show that despite the partial acetylation (5, 10, 20, and 30 acetyl groups per G5 dendrimer according to the molar feeding ratio), all acetylated Au DENPs are able to effectively compact the pDNA and transfect genes to the model cell line with high efficiency comparable to the Au DENPs without acetylation. With the proven less cytotoxicity of the partially acetylated Au DENPs than that of non-acetylated Au DENPs by cell viability assay, the developed partially acetylated Au DENPs may serve as promising vectors for safe gene delivery applications with non-compromised gene transfection efficiency.