ABSTRACT
Dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, is often used to treat lactic acidosis and malignant tumors. Increasing studies have shown that DCA has neuroprotective effects. Here, we explored the role and mechanism of DCA in Sepsis associated encephalopathy (SAE). Single-cell analysis was used to determine the important role of PDK4 in SAE and identify the cell type. GO and GSEA analysis were used to determine the correlation between DCA and pyroptosis. Through LPS + ATP stimulation, a microglia pyroptosis model was established to observe the expression level of intracellular pyroptosis-related proteins under DCA intervention, and further detect the changes in intracellular ROS and JC-1. Additionally, a co-culture environment of microglia and neuron was simply constructed to evaluate the effect of DCA on activated microglia-mediated neuronal apoptosis. Finally, Novel object recognition test and the Morris water maze were used to explore the effect of DCA on cognitive function in mice from different groups after intervention. Based on the above experiments, this study concludes that DCA can improve the ratio of peripheral and central M1 macrophages, inhibit NLRP3-mediated pyroptosis through ROS and mitochondrial membrane potential (MMP). DCA can reduce neuron death caused by SAE and improve cognitive function in LPS mice. In SAE, DCA may be a potential candidate drug for the treatment of microglia-mediated neuroinflammation.
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Objective: This study aimed to compare the outcomes of unilateral biportal endoscopy, unilateral laminectomy bilateral decompression (UBE-ULBD), and open lumbar decompression (OLD) in patients with lumbar epidural lipomatosis (LEL). Methods: This prospective observational study was conducted from March 2019 to May 2022 and encompassed 33 patients with LEL who underwent lumbar decompression. The study included 15 cases of UBE-ULBD decompression and 18 cases of open decompression, which were followed up for 1 year. The baseline characteristics, initial clinical manifestations, and surgical details [including estimated blood loss (EBL) and preoperative complications] of all patients were recorded. Radiographic evaluation included the cross-sectional area (CSA) of the thecal sac and paraspinal muscles on MRI. Clinical results were analyzed using the Short Form-36 Score (SF-36), the Numeric Pain Rating Scale (NRS) for lumbar and leg pain, creatine kinase, the Roland and Morris Disability Questionnaire (RMDQ), and the Oswestry Disability Index (ODI). Results: The dural sac CSA increased considerably at the 1-year postoperative follow-up in both groups (p < 0.001). The operative duration in the OLD group (48.2 ± 7.2 min) was shorter than that in the UBE-ULBD group (67.7 ± 6.3 min, p < 0.001). The OLD group (97.2 ± 19.8 mL) was associated with more EBL than the UBE-ULBD group (40.6 ± 13.6 mL, p < 0.001). The duration of hospitalization in the OLD group (5.4 ± 1.3 days) was significantly longer compared with the UBE-ULBD group (3.5 ± 1.2 days, p < 0.01). The SF-36, NRS, RMDQ, and ODI scores improved in both groups postoperatively (p < 0.001). Serum creatine kinase values in the UBE-ULBD group (101.7 ± 15.5) were significantly lower than those in the OLD group (330.8 ± 28.1 U/L) 1 day after surgery (p < 0.001). The degree of paraspinal muscle atrophy in the UBE-ULBD group (4.81 ± 1.94) was significantly lower than that in the OLD group (12.15 ± 6.99) at 1 year (p < 0.001). Conclusion: UBE-ULBD and OLD demonstrated comparable clinical outcomes in treating LEL. However, UBE-ULBD surgery was associated with shorter hospital stays, lower rates of incision infection, lighter paravertebral muscle injury, and lower EBL than OLD surgery. Consequently, UBE-ULBD can be recommended in patients with LEL if conservative treatment fails.
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ETHNOPHARMACOLOGICAL RELEVANCE: The Gu Yan Xiao tincture, a blend of traditional Chinese herbs, is traditionally used for osteoarthritis and related pain. This study investigated its mechanism of action in order to rationalize and validate its therapeutic use. AIM OF THE STUDY: This study analyzed, in a rabbit model of knee osteoarthritis, whether and how Gu Yan Xiao tincture exerts therapeutic benefits by modulating chondrocyte autophagy. MATERIALS AND METHODS: The active constituents within the GYX tincture were identified using liquid chromatography-mass spectrometry. The rabbit model was established by injecting animals with type II collagenase intra-articularly, and the effects of topically applied tincture were examined on osteoarthritis lesions of the knee using histopathology, micro-computed tomography and x-ray imaging. Effects of the tincture were also evaluated on levels of inflammatory cytokines, matrix metalloproteases, and autophagy in chondrocytes. As a positive control, animals were treated with sodium diclofenac. RESULTS: The tincture mitigated the reduction in joint space, hyperplasia of the synovium and matrix metalloproteases in serum that occurred after injection of type II collagenase in rabbits. These therapeutic effects were associated with inhibition of mTOR and activation of autophagy in articular chondrocytes. Inhibiting mTOR with rapamycin potentiated the therapeutic effects of the tincture, while inhibiting autophagy with 3-methyladenine antagonized them. CONCLUSIONS: Gu Yan Xiao tincture mitigates tissue injury in a rabbit model of osteoarthritis, at least in part by inhibiting mTOR and thereby promoting autophagy in chondrocytes. These results rationalize the use of the tincture not only against osteoarthritis but also potentially other diseases involving inhibition of autophagy in bones and joints.
Subject(s)
Cartilage, Articular , Osteoarthritis, Knee , Animals , Rabbits , Chondrocytes , X-Ray Microtomography , TOR Serine-Threonine Kinases , Osteoarthritis, Knee/drug therapy , Osteoarthritis, Knee/pathology , Metalloproteases/pharmacology , Metalloproteases/therapeutic use , Autophagy , CollagenasesABSTRACT
Single-molecule catalysis reflects the heterogeneity of each molecule, providing a unique insight into the complex catalytic mechanism through the statistics of stochastic individuals. However, the present study methods for single-molecule catalysis are either complicated or have low throughput, limiting their rapid acquisition of single-molecule reaction kinetics with statistical significance. Here, a label-free imaging method is developed for the study of single-molecule catalysis in microdroplets with high throughput based on the absorption of the reaction molecules. A wide distribution of the catalytic reaction rate constant value of 238-2026 molecules s-1 is observed from 68 single enzymes. Interestingly, an exponential decayed distribution of the enzyme activity can be clearly observed due to the rapid denaturation of the enzymes. The denaturation mechanism of the Horse Radish Peroxidase (HRP) enzyme is clarified. It is revealed that the denaturation of each enzyme goes through a gradual decay rather than a truncated turn-off process from a single molecule point of view. This absorption-based method can be applied to most of the catalytic reactions with high throughput, which offers an indispensable route for the rapid statistical analysis of various single-molecule catalytic reactions, making it particularly suitable for the acquisition of catalytic kinetics from highly unstable enzymes.
Subject(s)
Horseradish Peroxidase , Kinetics , Horseradish Peroxidase/chemistry , Horseradish Peroxidase/metabolism , Catalysis , Enzymes/chemistry , Enzymes/metabolismABSTRACT
Principal component analysis (PCA) has been applied in many aspects. To address the problem of measuring water content in soil, this paper proposes a method to measure soil water content based on the PCA. We used PCA to reduce the dimension of the data and processed the soil amplitude ratio frequency response spectra. First, we designed the measuring device and measured the soil amplitude ratio frequency response data of different water content, then we used the PCA to extract features from the frequency response spectra of different water contents, established a relationship model of soil water content, and finally, we solved the model, the maximum error between the calculation results and the actual water content was no more than 0.85%. Subsequently, we carried out experimental verification, and we measured six kinds of soil with known water content by this method. The experimental results showed that the maximum error did not exceed 1.16%, and the average error was 0.71%. Thus, the proposed method can provide a useful way of measuring soil water content.
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BACKGROUND: Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism. METHODS: SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined. RESULTS: Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8. CONCLUSION: TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis.
Subject(s)
Pyroptosis , Sepsis-Associated Encephalopathy , Animals , Humans , Mice , Cytokines/genetics , Inflammasomes , Leukocytes, Mononuclear , Lipopolysaccharides , Microglia , Neuroinflammatory Diseases , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Reactive Oxygen Species , Repressor Proteins , RNA, Messenger , RNA, Small InterferingABSTRACT
Envy has been widely discussed as a type of consumption motivation and a consumer attitude towards specific consumer goods in the context of social media. However, research on envy in tourism consumption decision-making is still relatively scarce. Accordingly, adopting social cognitive theory while considering benign envy, this study discusses the impact of social media content on consumers' destination envy and behavioural intention during the COVID-19 pandemic. Using a survey of 320 Chinese tourists who travelled to Macao, this paper develops and tests a conceptual framework. The results show that destination envy plays an intermediary role between social media content and consumer behavioural intention. Our findings thus integrate disparate literature streams while shedding light on the impacts of social media content on tourism consumers' travel decisions during the COVID-19 era.
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Ever-growing evidence has revealed that group 2 innate lymphoid cells (ILC2s) exhibit pleiotropic effects in antihelminth immunity, allergy, tissue protection, and cancer. Currently, the role of ILC2s in cancer is highly controversial regarding the intricate tumor microenvironment (TME), and the tumor-promoting or antitumor immunological mechanisms of ILC2s remain largely unknown. In this study, we report that dopamine receptor 1 (DRD1) restrains ILC2 activity in the TME. DRD1 deficiency promotes ILC2 activation, which irritates eosinophil recruitment and cytotoxic CD8+ T cell expansion during ongoing malignancy. Consequently, DRD1-deficient mice exhibit delayed tumor growth and reduced tumor progression. Furthermore, fenoldopam, a selective DRD1 agonist, restrains the ILC2 response in the TME and aggravates tumor burden in mice. Taken together, our data elaborate that the DRD1 signal acts as an excitatory rheostat in regulating ILC2-dependent antitumor immunity.
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In this paper, we report on a high-power and widely tunable thulium-doped fiber laser (TDFL) based on a monolithic master oscillator power amplifier (MOPA) system. The master oscillator is a Tm fiber ring laser incorporating a tunable bandpass filter to realize narrow linewidth and wavelength tunable operation. The MOPA generated 1010 W â¼1039 W of output power over a tuning range of 107â nm from 1943 to 2050nm with slope efficiencies of more than 51% and spectra linewidth of â¼0.5â nm. Power stability (RMS) in â¼10 min scale is measured to be â¼0.52%. A diffraction-limited beam quality factor M2 of â¼1.18 is measured at 920 W of laser output. Output power is pump-limited without the onset of parasitic oscillation or amplified spontaneous emission (ASE) even at the maximum power level. This is the first demonstration, to the best of our knowledge, on an all-fiber integrated wavelength-tunable TDFL at 2 µm with output power exceeding 1â kW.
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Cd2+ is one of the most toxic heavy metal ions that can be easily accumulated in human body via food chain. Thus, the onsite detection of Cd2+ in food is very important. However, present methods for Cd2+ detection either require the use of large equipment, or suffer from the severe interference from other analogical metal ions. This work establishes a facile Cd2+ mediated turn-on ECL method for highly selective detection of Cd2+ via cation exchanging with the nontoxic ZnS nanoparticles, owing to the unique surface-state ECL properties of CdS nanomaterials. The linear range of the calibration curve is from 7.0 × 10-8 to 1.0 × 10-6 M, while other analogical metal ions do not interfere, facilitating the selective detection of Cd2+ in oyster samples. The result agrees well with that obtained using atomic emission spectroscopy, indicating the potential for wider application of this approach.
Subject(s)
Cadmium , Nanoparticles , Humans , Luminescence , Nanoparticles/chemistry , Sulfides/chemistry , IonsABSTRACT
Neuronal signals have emerged as pivotal regulators of group 2 innate lymphoid cells (ILC2s) that regulate tissue homeostasis and allergic inflammation. The molecular pathways underlying the neuronal regulation of ILC2 responses in lungs remain to be fully elucidated. Here, we found that the abundance of neurotransmitter dopamine was negatively correlated with circulating ILC2 numbers and positively associated with pulmonary function in humans. Dopamine potently suppressed lung ILC2 responses in a DRD1-receptor-dependent manner. Genetic deletion of Drd1 or local ablation of dopaminergic neurons augmented ILC2 responses and allergic lung inflammation. Transcriptome and metabolic analyses revealed that dopamine impaired the mitochondrial oxidative phosphorylation (OXPHOS) pathway in ILC2s. Augmentation of OXPHOS activity with oltipraz antagonized the inhibitory effect of dopamine. Local administration of dopamine alleviated allergen-induced ILC2 responses and airway inflammation. These findings demonstrate that dopamine represents an inhibitory regulator of ILC2 responses in allergic airway inflammation.
Subject(s)
Immunity, Innate , Pneumonia , Humans , Dopamine/metabolism , Lymphocytes , Lung/metabolism , Pneumonia/metabolism , Inflammation/metabolism , Interleukin-33/metabolismABSTRACT
A 4D dual-mode staring hyperspectral-depth imager (DSHI), which acquire reflectance spectra, fluorescence spectra, and 3D structural information by combining a staring hyperspectral scanner and a binocular line laser stereo vision system, is introduced. A 405â nm laser line generated by a focal laser line generation module is used for both fluorescence excitation and binocular stereo matching of the irradiated line region. Under the configuration, the two kinds of hyperspectral data collected by the hyperspectral scanner can be merged into the corresponding points in the 3D model, forming a dual-mode 4D model. The DSHI shows excellent performance with spectral resolution of 3â nm, depth accuracy of 26.2â µm. Sample experiments on a fluorescent figurine, real and plastic sunflowers and a clam are presented to demonstrate system's with potential within a broad range of applications such as, e.g., digital documentation, plant phenotyping, and biological analysis.
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Rapid detection of pathogenic bacteria within a few minutes is the key to control infectious disease. However, rapid detection of pathogenic bacteria in clinical samples is quite a challenging task due to the complex matrix, as well as the low abundance of bacteria in real samples. Herein, we employ a label-free single-particle imaging approach to address this challenge. By tracking the scattering intensity variation of single particles in free solution, the morphological heterogeneity can be well identified with particle size smaller than the diffraction limit, facilitating the morphological identification of single bacteria from a complex matrix in a label-free manner. Furthermore, the manipulation of convection in free solution enables the rapid screening of low-abundance bacteria in a small field of view, which significantly improves the sensitivity of single-particle detection. As a proof of concept demonstration, we are able to differentiate the group B streptococci (GBS)-positive samples within 10 min from vaginal swabs without using any biological reagents. This is the most rapid and low-cost method to the best of our knowledge. We believe that such a single-particle imaging approach will find wider applications in clinical diagnosis and disease control due to its high sensitivity, rapidity, simplicity, and low cost.
Subject(s)
Bacteria , Communicable Diseases , Single-Cell Analysis , Bacteria/isolation & purification , Bacteria/pathogenicity , Communicable Diseases/diagnostic imaging , Female , Humans , Particle Size , Single-Cell Analysis/methods , Vaginal SmearsABSTRACT
Infection is one of the most serious complications harmful to human health, which brings a huge burden to human health. Bone infection is one of the most common and serious complications of fracture and orthopaedic surgery. Antibacterial treatment is the premise of bone defect healing. Among all the antibacterial strategies, irritant antibacterial materials have unique advantages and the ability of targeted therapy. In this review, we focus on the research progress of irritating materials, the development of antibacterial materials and their advantages and disadvantages potential applications in bone infection.
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Advanced drug carriers for the controlled release of chemotherapeutics in the treatment of malignant tumors have drawn significant notice in recent years. In the current study, microspheres (MPs) loaded with docetaxel (DTX) were prepared using polylactic-co-glycolic acid copolymer (PLGA). The double emulsion solvent evaporation method is simple to perform, and results in high encapsulation efficiency. Electron micrographs of the MPs showed that controlling the shear rate can effectively control the size of the MPs. At present, most DTX sustained-release carriers cannot maintain stable and long-term local drug release. The 1.68 µm DTX-loaded microspheres (MP/DTX) with elastase was completely degraded in 14 d. This controlled degradation period is similar to a course of treatment for most cancers. The drug release profile of all kinds of MP/DTX demonstrated an initial rapid release, then slower and stable release to the end. The current study demonstrates that it is possible to create drug-loaded MPs with specific degradation times and drug release curves, which may be useful in achieving optimal treatment times and drug release rates for different diseases, and different drug delivery routes. The initial burst release reaches the effective concentration of the drug at the beginning of release, and then the drug concentration is maintained by stable release to reduce the number of injections and improve patient compliance.
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Titanium alloy prostheses have been widely used for the treatment of orthopedic diseases, in which the interconnected porosity and appropriate pore size are crucial for the osseointegration capacity. Three-dimensional (3D) printing technology provides an efficient method to construct prosthesis scaffolds with controllable internal and surface structure, but printing high-porosity (>60%) scaffolds with pore diameters below 300 µm as implants structures has not yet been studied. In this work, four types of titanium alloy scaffolds with interconnected porosity more than 70% were successfully prepared by selective laser melting (SLM). The actual mean pore sizes of cylindrical scaffolds are 542, 366, 202, and 134 µm. Through the in vitro characterization of the scaffolds, in vivo experiments, and mechanical experiments, it is concluded that as the scaffold pore diameter decreases, the titanium alloy scaffold with diameter of 202 µm has the strongest osseointegration ability and is also the most stable one with the surrounding bone. These findings provide a reference for the clinical pore-size design of porous scaffolds with optimal bone growth stability on the surface of the titanium alloy implant.
Subject(s)
Osseointegration , Titanium , Alloys , Porosity , Printing, Three-Dimensional , Prostheses and ImplantsABSTRACT
Since the Gravity Recovery and Climate Experiment (GRACE) satellite mission was started in 2002, a variety of spatial products have been made available to further understanding of mass redistribution in the Earth system. Two such mascon (mass concentration) solutions were developed by the Center for Space Research (CSR-M) and the NASA Jet Propulsion Laboratory (JPL-M), which offers significantly improved spatial localization and more accurate amplitude measurements of changes in recovered terrestrial Total Water Storage (TWS). However, it is difficult to validate GRACE-derived TWS mascons due to the lack of independent measurements of water storage in various forms at larger scales.In this study, we present a simple framework to evaluate GRACE mascon products based on in-situ GPS measurements from the Yangtze River Basin (YRB) in China. We found that the mascons show a more pronounced spatial difference in TWS distribution and highlight more details as compared to smoother results from empirical post-processing filtering applied to spherical harmonics (SH) data. The prediction of vertical displacements from CSR-M and JLP-M is closer to GPS than that from SH. The residual analysis showed the reductions in WRMS (weighted root-mean-squares) from the GPS minus the CSR-M average were greater than those for JPL-M in 41 GPS stations, and the scaling factors from CLM4.0 used in JPL-M-sf had few improvements with respect to agreement with GPS measurements. Our findings indicated CSR-M solutions were more consistent with in-situ observations and more in line with actual surface mass transport in the YRB. These findings also suggested that when using GRACE mascons to detect local TWS changes or when combining GRACE-derived data with GPS-observed displacement to estimate crustal response to loadings, users should note the contributions from effects of load signal sources from atmospheric, non-tidal ocean, and difference sensitivity kernels on differences between TWS from satellite-based and in-situ observations.
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Subterranean predatory mites are important biological control agents of pests in soil. In order to understand the population characteristics of two predatory mites, Macrocheles glaber Müller and Stratiolaelaps scimitus Womersley, we studied their development, survival and fecundity data under laboratory conditions using Coboldia fuscipes Meigen as a food source and analyzed them with the age-stage, two-sex life table. Macrocheles glaber had a significantly shorter developmental time, oviposition period, longevity and lower fecundity than those of S. scimitus. The intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0 ), net predation rate (C0 ), and finite predation rate (ω) of M. glaber were significantly lower than those of S. scimitus. Both population parameters and computer simulation implied that S. scimitus is a potential powerful biocontrol agent compared to M. glaber.
Subject(s)
Diptera , Mites/growth & development , Pest Control, Biological/methods , Predatory Behavior , Agrocybe , Animals , Female , Larva , MaleABSTRACT
INTRODUCTION: Periprosthetic femoral fractures (PFF) around tumor prosthesis of knee are stubborn problems for surgeons, huge bone defect and inappropriate biomechanics of the revision implant design can be disaster for reconstruction. With the development of three-dimensional (3D) printing technology, surgeons participate more in precise preoperative design and simulation for treatment of such fractures. In this study we explored an accurate and feasible way to restore normal anatomy and function of the knee joint with 3D printing technology. CASE PRESENTATION: Rationale: This report explored an accurate and feasible way to treat PFF around tumor knee prosthesis in a 32 years old women with 3D printing technology, which restored normal anatomy and function of the knee joint. Patient concerns: Pain in left thigh lasted for 10 months after resection of left femoral chondroma and knee joint replacement four years ago. Diagnoses: periprosthetic femoral fractures (PFF) around tumor knee prosthesis. INTERVENTIONS: CT images of the patient were collected and reconstructed. Parameters of bilateral femurs were virtually sliced and measured. Novel femoral stem and nail paths were specially designed by doctors according to these parameters. The prosthetic femoral stem components and navigator were customized by engineers according to the doctor's design. The residual femoral resin model, customized components and navigator were printed with Stereo Lithography Apparatus 3D printer. The shape-preconcerted allograft bone was selected as patch for the bone defect before operation with the printed bone model. All the steps were simulated preoperatively with the models printed, and then the operation was carried out. OUTCOMES: The operation was successfully performed. The postoperative x-ray image, MSTS93 scores were examined and the function restoration sustained well in the follow-up period from 1 month to 27 months. LESSONS: 3D printing and medical interaction are key points in complex PFF cases. CONCLUSION: As for PFF of the complex tumor of knee, preoperative design and simulation with 3D printing technology may provide more accurate and effective operative outcome than traditional methods, which might be considered as a method suitable for popularization in complex and severe cases.