ABSTRACT
Skin could protect our body and regenerate itself to against dysfunctional and disfiguring scars when faced with external injury. As wound dressings, hydrogels are biocompatible, hydrophilic and have a 3D structure similar to the extracellular matrix (ECM). In particular, hydrogels with drug-releasing capabilities are in acute wound healing. In this paper, photocrosslinked hydrogels served as wound dressing based on sodium carboxymethylcellulose (CMC) were prepared to promote wound healing. Photocrosslinked hydrogels were prepared by grafting lysine and allyl glycidyl ether (AGE) onto CMC and encapsulating curcumin (Cur). The synthesized hydrogels had the unique 3D porous structure with a swelling ratio up to 1300 % in aqueous solution. The drug release ratios of the hydrogels were 20.8 % in acid environment, and 14.4 % in alkaline environment. Notably, the hydrogels showed good biocompatibility and antibacterial properties and also exhibited the ability to accelerate the process of skin wound healing while prevent inflammation and scar formation when applied to a mouse skin wound model. As a result, the prepared hydrogels Gel-CLA@Cur showed great potential in wound healing.
Subject(s)
Carboxymethylcellulose Sodium , Curcumin , Hydrogels , Wound Healing , Curcumin/pharmacology , Curcumin/chemistry , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Wound Healing/drug effects , Carboxymethylcellulose Sodium/chemistry , Animals , Mice , Drug Liberation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Drug Carriers/chemistry , Cross-Linking Reagents/chemistry , Skin/drug effects , Drug Delivery SystemsABSTRACT
Ischemic stroke (IS) is one of the main causes inducing death and disability in adults. Because of the high recurrence rate of IS, prevention of recurrence is of great significance to this population, for which the evidence-based and effective secondary prevention strategy is an important means, and acupuncture intervention has a positive effect on its risk factors. In the present article, we reviewed the progress of researches on the mechanisms of acupuncture underlying prevention of IS relapse from the perspective of its main risk factors, namely 1) hypertension (preventing and controlling the adverse effects caused by the imbalance of blood pressure level, vascular and other tissue structures, endocrine factors and central nervous system activities in patients with hypertension after IS), 2) hypercholesterolemia (lowering serum total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein cholesterol), 3) diabetes (regulating the secretion function of adipose tissue, activating the insulin signal transduction pathway, protecting the function of pancreatic ß cells, and regulating the central nervous system functions to participate in the secondary prevention of IS), 4) smoking (relieving the symptoms of smoking cessation and reducing the smoker's dependence on smoking by changing the internal environment, lowering the level of blood endorphin and regulating the excitability of central nervous system), 5) sleep apnea syndrome (regulating local muscle function and the excitability of the nervous system, but also affecting some organic changes as reducing tonsil swelling) and 6) obesity (lowering blood glucose and lipid, increasing the ratio of brown/white fat, reducing leptin resistance, and suppressing appetite to induce body weight loss, or directly regulate the changes of fat tissue, etc). Results shows that the acupuncture's regulatory mechanism for IS risk factors is closely related to the neuroendocrine system, and simultaneously involves multiple targets of multiple risk factors. Due to its good efficacy and safety, acupuncture therapy is of great value for clinical promotion as an important intervention for secondary prevention.
Subject(s)
Acupuncture Therapy , Ischemic Stroke , Secondary Prevention , Humans , Animals , Ischemic Stroke/prevention & control , Ischemic Stroke/therapy , Ischemic Stroke/metabolism , Hypertension/therapy , Hypertension/metabolism , Hypertension/prevention & control , Hypertension/physiopathologyABSTRACT
Influenza virus infection is initiated by the attachment of the viral haemagglutinin (HA) protein to sialic acid receptors on the host cell surface. Most virus particles enter cells through clathrin-mediated endocytosis (CME). However, it is unclear how viral binding signals are transmitted through the plasma membrane triggering CME. Here we found that metabotropic glutamate receptor subtype 2 (mGluR2) and potassium calcium-activated channel subfamily M alpha 1 (KCa1.1) are involved in the initiation and completion of CME of influenza virus using an siRNA screen approach. Influenza virus HA directly interacted with mGluR2 and used it as an endocytic receptor to initiate CME. mGluR2 interacted and activated KCa1.1, leading to polymerization of F-actin, maturation of clathrin-coated pits and completion of the CME of influenza virus. Importantly, mGluR2-knockout mice were significantly more resistant to different influenza subtypes than the wild type. Therefore, blocking HA and mGluR2 interaction could be a promising host-directed antiviral strategy.
Subject(s)
Endocytosis , Mice, Knockout , Receptors, Metabotropic Glutamate , Animals , Receptors, Metabotropic Glutamate/metabolism , Receptors, Metabotropic Glutamate/genetics , Mice , Humans , Virus Internalization , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Clathrin/metabolism , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/metabolism , HEK293 Cells , Actins/metabolism , Dogs , Madin Darby Canine Kidney Cells , Receptors, Virus/metabolism , Receptors, Virus/genetics , Influenza, Human/virology , Influenza, Human/metabolism , Orthomyxoviridae/physiology , Orthomyxoviridae/genetics , Orthomyxoviridae/metabolismABSTRACT
This research investigates the recognition of basketball techniques actions through the implementation of three-dimensional (3D) Convolutional Neural Networks (CNNs), aiming to enhance the accurate and automated identification of various actions in basketball games. Initially, basketball action sequences are extracted from publicly available basketball action datasets, followed by data preprocessing, including image sampling, data augmentation, and label processing. Subsequently, a novel action recognition model is proposed, combining 3D convolutions and Long Short-Term Memory (LSTM) networks to model temporal features and capture the spatiotemporal relationships and temporal information of actions. This facilitates the facilitating automatic learning of the spatiotemporal features associated with basketball actions. The model's performance and robustness are further improved through the adoption of optimization algorithms, such as adaptive learning rate adjustment and regularization. The efficacy of the proposed method is verified through experiments conducted on three publicly available basketball action datasets: NTURGB + D, Basketball-Action-Dataset, and B3D Dataset. The results indicate that this approach achieves outstanding performance in basketball technique action recognition tasks across different datasets compared to two common traditional methods. Specifically, when compared to the frame difference-based method, this model exhibits a significant accuracy improvement of 15.1%. When compared to the optical flow-based method, this model demonstrates a substantial accuracy improvement of 12.4%. Moreover, this method showcases strong robustness, accurately recognizing actions under diverse lighting conditions and scenes, achieving an average accuracy of 93.1%. The research demonstrates that the method reported here effectively captures the spatiotemporal relationships of basketball actions, thereby providing reliable technical assessment tools for basketball coaches and players.
Subject(s)
Basketball , Neural Networks, Computer , Pattern Recognition, Automated , Video Recording , Humans , Basketball/classification , Basketball/physiology , Datasets as Topic , Movement , Reproducibility of Results , Pattern Recognition, Automated/methodsABSTRACT
Pregnancy heightens susceptibility to influenza A virus (IAV) infection, thereby increasing the risk of severe pneumonia and maternal mortality. It also raises the chances of adverse outcomes in offspring, such as fetal growth restriction, preterm birth, miscarriage, and stillbirth in offsprings. However, the underlying mechanisms behind these effects remain largely unknown. Syncytiotrophoblast cells, crucial in forming the placental barrier, nutrient exchange and hormone secretion, have not been extensively studied for their responses to IAV. In our experiment, we used Forskolin-treated BeWo cells to mimic syncytiotrophoblast cells in vitro, and infected them with H1N1, H5N1 and H7N9 virus stains. Our results showed that syncytiotrophoblast cells, with their higher intensity of sialic acid receptors, strongly support IAV infection and replication. Notably, high-dose viral infection and prolonged exposure resulted in a significant decrease in fusion index, as well as gene and protein expression levels associated with trophoblast differentiation, ß-human chorionic gonadotropin secretion, estrogen and progesterone biosynthesis, and nutrient transport. In pregnant BALB/c mice infected with the H1N1 virus, we observed significant decreases in trophoblast differentiation and hormone secretion gene expression levels. IAV infection also resulted in preterm labor, fetal growth restriction, and increased maternal and fetal morbidity and mortality. Our findings indicate that IAV infection in syncytiotrophoblastic cells can result in adverse pregnancy outcomes by altering trophoblast differentiation, suppressing of ß-hCG secretion, and disrupting placental barrier function.
Subject(s)
Influenza A Virus, H1N1 Subtype , Mice, Inbred BALB C , Orthomyxoviridae Infections , Pregnancy Outcome , Trophoblasts , Female , Trophoblasts/virology , Pregnancy , Animals , Humans , Influenza A Virus, H1N1 Subtype/physiology , Mice , Orthomyxoviridae Infections/virology , Influenza, Human/virology , Cell Line , Influenza A Virus, H5N1 Subtype/physiology , Influenza A Virus, H7N9 Subtype/physiology , Influenza A Virus, H7N9 Subtype/pathogenicity , Pregnancy Complications, Infectious/virology , Placenta/virology , Virus ReplicationABSTRACT
A 6-year-old male golden retriever presented with swelling of the left upper eyelid of 2 months duration, which did not improve following a course of antibiotics. Routine serum biochemistry, complete blood count and diagnostic imaging identified no clinically significant abnormalities. The mass was surgically excised, and histopathologic examination was performed. Eosinophilic granulocytic sarcoma (GS) was diagnosed based on the results of histopathology and immunohistochemistry. This is the first report of GS affecting the eyelid of a dog.
Subject(s)
Dog Diseases , Sarcoma, Myeloid , Animals , Dogs , Male , Dog Diseases/surgery , Dog Diseases/diagnosis , Dog Diseases/pathology , Sarcoma, Myeloid/veterinary , Sarcoma, Myeloid/diagnosis , Sarcoma, Myeloid/pathology , Sarcoma, Myeloid/surgery , Eyelid Neoplasms/veterinary , Eyelid Neoplasms/surgery , Eyelid Neoplasms/diagnosis , Eyelid Neoplasms/pathologyABSTRACT
Feline calicivirus (FCV) is one of the few members of the Caliciviridae family that grows well in cell lines and, therefore, serves as a surrogate to study the biology of other viruses in the family. Conley et al. (14) demonstrated that upon the receptor engagement to the capsid, FCV VP2 forms a portal-like assembly, which might provide a channel for RNA release. However, the process of calicivirus RNA release is not yet fully understood. Our findings suggest that the separation of the FCV capsid from its genome RNA (gRNA) occurs rapidly in the early endosomes of infected cells. Using a liposome model decorated with the FCV cell receptor fJAM-A, we demonstrate that FCV releases its gRNA into the liposomes by penetrating membranes under low pH conditions. Furthermore, we found that VP2, which is rich in hydrophobic residues at its N-terminus, functions as the pore-forming protein. When we substituted the VP2 N-terminal hydrophobic residues, the gRNA release efficacy of the FCV mutants decreased. In conclusion, our results suggest that in the acidic environment of early endosomes, FCV VP2 functions as the pore-forming protein to mediate gRNA release into the cytoplasm of infected cells. This provides insight into the mechanism of calicivirus genome release.IMPORTANCEResearch on the biology and pathogenicity of certain caliciviruses, such as Norovirus and Sapovirus, is hindered by the lack of easy-to-use cell culture system. Feline calicivirus (FCV), which grows effectively in cell lines, is used as a substitute. At present, there is limited understanding of the genome release mechanism in caliciviruses. Our findings suggest that FCV uses VP2 to pierce the endosome membrane for genome release and provide new insights into the calicivirus gRNA release mechanism.
Subject(s)
Calicivirus, Feline , Capsid Proteins , Endosomes , RNA, Viral , Animals , Cats , Caliciviridae Infections/virology , Caliciviridae Infections/metabolism , Calicivirus, Feline/genetics , Calicivirus, Feline/metabolism , Calicivirus, Feline/physiology , Capsid/metabolism , Capsid Proteins/metabolism , Capsid Proteins/genetics , Cell Line , Endosomes/virology , Endosomes/metabolism , Genome, Viral , Liposomes/metabolism , RNA, Viral/metabolism , RNA, Viral/genetics , Virus ReleaseABSTRACT
Getah virus (GETV) belongs to the Alphavirus genus in the Togaviridae family and is a zoonotic arbovirus causing disease in both humans and animals. The capsid protein (CP) of GETV regulates the viral core assembly, but the mechanism underlying this process is poorly understood. In this study, we demonstrate that CP undergoes liquid-liquid phase separation (LLPS) with the GETV genome RNA (gRNA) in vitro and forms cytoplasmic puncta in cells. Two regions of GETV gRNA (nucleotides 1-4000 and 5000-8000) enhance CP droplet formation in vitro and the lysine-rich Link region of CP is essential for its phase separation. CP(K/R) mutant with all lysines in the Link region replaced by arginines exhibits improved LLPS versus wild type (WT) CP, but CP(K/E) mutant with lysines substituted by glutamic acids virtually loses condensation ability. Consistently, recombinant virus mutant with CP(K/R) possesses significantly higher gRNA binding affinity, virion assembly efficiency and infectivity than the virus with WT-CP. Overall, our findings provide new insights into the understanding of GETV assembly and development of new antiviral drugs against alphaviruses.
Subject(s)
Alphavirus , Animals , Humans , Alphavirus/genetics , Alphavirus/metabolism , Capsid Proteins/genetics , Capsid Proteins/metabolism , RNA, Viral/genetics , RNA, Guide, CRISPR-Cas Systems , Genomics , Virion/geneticsABSTRACT
Developing inexpensive and efficient catalysts for biomass hydrogenation or hydrodeoxygenation (HDO) is essential for efficient energy conversion. Transition metal phosphides (TMPs), with the merits of abundant active sites, unique physicochemical properties, tunable component structures, and excellent catalytic activities, are recognized as promising biomass hydrogenation or HDO catalytic materials. Nevertheless, the biomass hydrogenation or HDO catalytic applications of TMPs are still limited by various complexities and inherent performance bottlenecks, and thus their future development and utilization remain to be systematically sorted out and further explored. This review summarizes the current popular strategies for the preparation of TMPs. Subsequently, based on the structural and electronic properties of TMPs, the catalytic activity origins of TMPs in biomass hydrogenation or HDO is elucidated. Additionally, the application of TMPs in efficient biomass hydrogenation or HDO catalysis, as well as highly targeted multiscale strategies to enhance the catalytic performance of TMPs, are comprehensively described. Finally, large-scale amplification synthesis, rational construction of TMP-based catalysts and in-depth study of the catalytic mechanism are also mentioned as challenges and future directions in this research field. Expectedly, this review can provide professional and targeted guidance for the rational design and practical application of TMPs biomass hydrogenation or HDO catalysts.
ABSTRACT
Species-specific differences in acidic nuclear phosphoprotein 32 family member A (ANP32A) determine the restriction of avian-signature polymerase in mammalian cells. Mutations that evade this restriction, such as PB2-E627K, are frequently acquired when avian influenza A viruses jump from avian hosts to mammalian hosts. However, the mechanism underlying this adaptation process is still unclear. Here, we report that host factor ANP32 proteins can be incorporated into influenza viral particles through combination with the viral RNA polymerase (vPol) and then transferred into targeted cells where they support virus replication. The packaging of the ANP32 proteins into influenza viruses is dependent on their affinity with the vPol. Avian ANP32A (avANP32A) delivered by avian influenza A virions primes early viral replication in mammalian cells, thereby favoring the downstream interspecies transmission event by increasing the total amount of virus carrying adaptive mutations. Our study clarifies one role of avANP32A where it is used by avian influenza virus to help counteract the restriction barrier in mammals.
Subject(s)
Influenza A virus , Influenza in Birds , Animals , Chickens , Mammals , Virus Replication , VirionABSTRACT
Activation of small molecules is considered to be a central concern in the theoretical investigation of environment- and energy-related catalytic conversions. Sub-nanostructured frustrated Lewis pairs (FLPs) have been an emerging research hotspot in recent years due to their advantages in small molecule activation. Although the progress of catalytic applications of FLPs is increasingly reported, the fundamental theories related to the structural formation, site regulation, and catalytic mechanism of FLPs have not yet been fully developed. Given this, it is attempted to demonstrate the underlying theory of FLPs formation, corresponding regulation methods, and its activation mechanism on small molecules using CeO2 as the representative metal oxide. Specifically, this paper presents three fundamental principles for constructing FLPs on CeO2 surfaces, and feasible engineering methods for the regulation of FLPs sites are presented. Furthermore, cases where typical small molecules (e.g., hydrogen, carbon dioxide, methane oxygen, etc.) are activated over FLPs are analyzed. Meanwhile, corresponding future challenges for the development of FLPs-centered theory are presented. The insights presented in this paper may contribute to the theories of FLPs, which can potentially provide inspiration for the development of broader environment- and energy-related catalysis involving small molecule activation.