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1.
Nat Commun ; 15(1): 3717, 2024 May 02.
Article En | MEDLINE | ID: mdl-38697983

The chiral antiferromagnetic (AFM) materials, which have been widely investigated due to their rich physics, such as non-zero Berry phase and topology, provide a platform for the development of antiferromagnetic spintronics. Here, we find two distinctive anomalous Hall effect (AHE) contributions in the chiral AFM Mn3Pt, originating from a time-reversal symmetry breaking induced intrinsic mechanism and a skew scattering induced topological AHE due to an out-of-plane spin canting with respect to the Kagome plane. We propose a universal AHE scaling law to explain the AHE resistivity ( ρ A H ) in this chiral magnet, with both a scalar spin chirality (SSC)-induced skew scattering topological AHE term, a s k and non-collinear spin-texture induced intrinsic anomalous Hall term, b i n . We found that a s k and b i n can be effectively modulated by the interfacial electron scattering, exhibiting a linear relation with the inverse film thickness. Moreover, the scaling law can explain the anomalous Hall effect in various chiral magnets and has far-reaching implications for chiral-based spintronics devices.

2.
Brain Res ; 1825: 148732, 2024 02 15.
Article En | MEDLINE | ID: mdl-38104922

Trigeminal neuralgia (TN) is a common form of facial pain, which primarily manifests as severe pain similar to facial acupuncture and electric shock. Olfactory ensheathing cells (OECs) are glial cells with high bioactivity; these cells are essential for the periodic regeneration of the olfactory nerve and have been utilized for the repair of nerve injuries. A member of the P2X receptor family, P2X7R, is an ion channel type receptor that has been confirmed to participate in various pain response processes. In this study, we transplanted OECs into trigeminal nerve-model rats with distal infraorbital nerve ligation to observe the therapeutic effect of transplanted OECs in rats. Additionally, we utilized the P2X7R-specific inhibitor brilliant blue G (BBG) to study the therapeutic mechanisms of cell transplantation. The facial mechanical pain threshold of these rats significantly increased following cell transplantation. The immunohistochemistry, immunoblotting, and RT-qPCR results demonstrated that the levels of P2X7R, (NOD)-like receptor protein-3 (NLRP3), nuclear factor-κB (NF-κB), interleukin (IL)-1ß, and IL-18 in the trigeminal ganglion of rats treated with OEC transplantation or BBG treatment were significantly lower than those in the injured group without treatment. Overall, our results demonstrate that OEC transplantation can alleviate TN in rats, and it can reduce the expression of P2X7R related inflammatory factors in TN rats, reducing neuroinflammatory response in TG.


Trigeminal Neuralgia , Rats , Animals , Trigeminal Neuralgia/drug therapy , Trigeminal Neuralgia/metabolism , Rats, Sprague-Dawley , Facial Pain/metabolism , Pain Threshold/physiology , Cell Transplantation/methods , Olfactory Bulb/metabolism
3.
Environ Res ; 239(Pt 1): 117345, 2023 Dec 15.
Article En | MEDLINE | ID: mdl-37821065

Owing to accelerated urbanization and industrialization, many plastic products have been manufactured and discharged into the environment, causing environmental and public health problems. Plastics in environmental media are further degraded by prolonged exposure to light, heat, mechanical friction, and other factors to form new pollutants called microplastics (MPs). Medical plastics have become a crucial source of plastics in environmental media. However, the release profiles of MPs from medical plastics and their potential ecological and health risks remain unclear. We used optical photothermal infrared spectroscopy to explore the release profiles of eight typical disposable medical devices under high-temperature steam disinfection (HSD). We also evaluated the toxicity of disposable medical devices-derived MPs in Caenorhabditis elegans (C. elegans). Our results showed that the changes in the surface morphology and modification of the disposable medical devices were mainly associated with the material. Polypropylene (PP) and polystyrene (PS) materials exhibited high aging phenomena (e.g., bumps, depressions, bulges and cracks), and HSD broke their oxygen-containing functional groups and carbon chains. By contrast, minor changes in the chemical and physical properties were observed in the polyvinyl chloride (PVC)-prepared disposable medical devices under the same conditions. Further physicochemical characterization indicated that the amount of MPs released from PP-prepared disposable medical devices (P4: 1.27 ± 0.34 × 106) was greater than that from PVC-prepared disposable medical devices (P7: 1.08 ± 0.14 × 105). The particle size of the released MPs was the opposite, PVC-prepared disposable medical devices (P7: 11.45 ± 1.79 µm) > PP-prepared disposable medical devices (P4: 7.18 ± 0.52 µm). Toxicity assessment revealed that disposable medical devices-released MPs significantly increased germ cell apoptosisin C. elegans. Moreover, MPs from PP-prepared disposable medical devices disrupted the intestinal barrier of worms, decreasing their lifespan. Our findings provided novel information regarding the profiles and mechanisms of MP release from disposable medical devices and revealed their potential risks to ecological environment.


Microplastics , Plastics , Animals , Microplastics/toxicity , Caenorhabditis elegans , Polypropylenes , Carbon
4.
Ecotoxicol Environ Saf ; 259: 115005, 2023 Jul 01.
Article En | MEDLINE | ID: mdl-37210995

With the rapid development of magnetic technology, the biological effects of moderate static magnetic fields (SMFs) have attracted increasing research interest due to their potential medical diagnosis and treatment application. The present study explored the effects of moderate SMFs on the lipid metabolism of Caenorhabditis elegans (C. elegans) in different genders including male, female, and hermaphrodite. We found that the fat content was significantly decreased by moderate SMFs in wild-type N2 worms, which was associated with their development stages. The diameters of lipid droplets in N2 worms, him-5 worms, and fog-2 worms were greatly decreased by 19.23%, 15.38%, and 23.07% at young adult stage under 0.5 T SMF, respectively. The mRNA levels of lipolysis related genes atgl-1 and nhr-76 were significantly up-regulated by SMF exposure, while the mRNA levels of the lipogenesis related genes fat-6, fat-7, and sbp-1 were down-regulated by SMF, whereas the concentration of ß-oxidase was increased. There was a slight effect of SMF on the mRNA levels of ß-oxidation related genes. Moreover, the insulin and serotonin pathway were regulated by SMF, instead of the TOR pathway. In wild-type worms, we found that their lifespan was prolonged by exposure to 0.5 T SMF. Our data suggested that moderate SMFs could significantly modify the lipogenesis and lipolysis process in C. elegans in a gender and development stage-dependent manner, which could provide a novel insight into understanding the function of moderate SMFs in living organisms.


Caenorhabditis elegans Proteins , Caenorhabditis elegans , Female , Male , Animals , Caenorhabditis elegans/metabolism , Lipolysis , Lipogenesis/genetics , Magnetic Fields , RNA, Messenger/metabolism , Lipase/genetics , Lipase/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism
5.
Int J Nanomedicine ; 18: 1659-1676, 2023.
Article En | MEDLINE | ID: mdl-37020688

Introduction: The increasing use of gold nanoparticles (Au NPs) in the medical field has raised concerns about the potential adverse effect of Au NPs exposure. However, it is difficult to assess the health risks of Au NPs exposure at the individual organ level using current measurement techniques. Methods: The physical and chemical properties of Au NPs were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR), and zeta sizer. The RNA-seq data of Au NPs-exposed worms were analyzed. The food intake was measured by liquid culture and Pharyngeal pumping rate. The function of the smell and taste neurons was evaluated by the chemotaxis and avoidance assay. The activation of ASE neurons was analyzed by calcium imaging. The gene expression of ins-22 and egl-19 was obtained from the C. elegans single cell RNA-seq databases. Results: Our data analysis indicated that 62.8% of the significantly altered genes were functional in the nervous system. Notably, developmental stage analysis demonstrated that exposure to Au NPs interfered with animal development by regulating foraging behavior. Also, our chemotaxis results showed that exposure to Au NPs reduced the sensation of C. elegans to NaCl, which was consistent with the decrease in calcium transit of ASEL. Further studies confirmed that the reduced calcium transit was dependent on voltage-gated calcium channel EGL-19. The neuropeptide INS-22 was partially involved in Au NPs-induced NaCl sensation defect. Therefore, we proposed that Au NPs reduced the calcium transit in the ASEL neuron through egl-19-dependent calcium channels. It was partially regulated by the DAF-16 targeting neuropeptide INS-22. Discussion: Our results demonstrate that Au NPs affect food sensation by reducing the calcium transit in ASEL neurons, which further leads to reduced pharynx pumping and feeding defects. The toxicology studies of Au NPs from worms have great potential to guide the usage of Au NPs in the medical field such as targeted drug delivery.


Calcium Channels , Gold , Metal Nanoparticles , Caenorhabditis elegans , Metal Nanoparticles/adverse effects , Metal Nanoparticles/chemistry , Gold/adverse effects , Gold/chemistry , Calcium Channels/metabolism , Eating/drug effects , Nervous System/drug effects , Animals , Sensation/drug effects
6.
J Environ Manage ; 335: 117547, 2023 Jun 01.
Article En | MEDLINE | ID: mdl-36841002

A low-cost practical technology is urgently needed to minimize cadmium (Cd) pollution in rice in many parts of the world. In the present study, we elucidated the effects and mechanisms of four alkaline compound materials via field experiments in southern China. The results indicated that these two alkaline Si-rich compound materials (AF-SC, alkaline fertilizer compounded with Si-Ca mineral powder; AF-SS, AF compounded with Si-Se mineral powder) could achieve multi-objective gains by simultaneously reducing grain Cd, increasing yield and improving soil quality at a lower cost. The grain Cd content was decreased by an average of about 75% in two field sites, which even ensured safe grain production in areas with medium Cd pollution. The rice yield was increased by a range of 6.7%-21.0% for different varieties and sites. Moreover, the materials abated soil acidification with the increase of 0.36-0.62 pH units, increased the contents of available P and available Si, subsequently reducing available Cd content in soils. Structural equation model and regression analysis showed that the alkaline environment provided by the alkaline components in compound materials effectively inhibited the formation of Fe/Mn plaques on the root surface, reducing the uptake of Cd from the environment. In addition, the decrease in grain Cd was also attributed to the inhibition of Cd translocation from root to stem, mainly caused by the increase of available Si. These findings reveal that the base application of such alkaline Si-rich compound materials is a viable solution for the remediation of Cd-polluted paddy fields in south China.


Oryza , Soil Pollutants , Cadmium/chemistry , Powders/analysis , Soil Pollutants/chemistry , Soil/chemistry , Minerals/analysis , Edible Grain/chemistry , Oryza/chemistry
7.
Front Psychiatry ; 13: 980371, 2022.
Article En | MEDLINE | ID: mdl-36159911

Multiple system atrophy (MSA) is a common atypical parkinsonism, characterized by a varying combination of autonomic, cerebellar, and pyramidal systems. It has been noticed that the patients with MSA can be accompanied by some neuropsychiatric disorders, in particular depression. However, there is limited understanding of MSA-related depression. To bridge existing gaps, we summarized research progress on this topic and provided a new perspective regarding pathological, clinical, and imaging aspects. Firstly, we synthesized corresponding studies in order to investigate the relationship between depression and MSA from a pathological perspective. And then, from a clinical perspective, we focused on the prevalence of depression in MS patients and the comparison with other populations. Furthermore, the associations between depression and some clinical characteristics, such as life quality and gender, have been reported. The available neuroimaging studies were too sparse to draw conclusions about the radiological aspect of depression in MSA patients but we still described them in the presence of paper. Finally, we discussed some limitations and shortcomings existing in the included studies, which call for more high-quality basic research and clinical research in this field.

8.
Front Pharmacol ; 13: 916421, 2022.
Article En | MEDLINE | ID: mdl-36091794

Background: Due to limited time windows and technical requirements, only a small percentage of patients can receive reperfusion therapy for acute ischemic stroke (AIS). Previous studies have shown that LongShengZhi (LSZ) capsule can improve neurological outcomes in patients after AIS, yet those results have not been finally verified through rigorous randomized controlled trials. Thus, this trial was designed to further clarify the efficacy and safety of LSZ capsule for patients with AIS. Methods: LSZ capsule on Functional Recovery after Acute Ischemic Stroke (LONGAN) trial is a prospective, multicenter, randomized, placebo-controlled, double-blind, parallel-group, superiority trial that enrolls patients from stroke and rehabilitation units in China. We will enroll 1,376 patients aged 18 years or older with AIS within 7 days of symptom onset and a National Institute of Health Stroke Scale (NIHSS) score of 4-15. Eligible patients will be randomized to receive either 2 g LSZ capsules three times a day or placebo LSZ capsules for 90 days. The primary outcome is the proportion of patients with favorable outcomes, as measured by the modified Rankin Scale (mRS) 90 days after randomization. The main safety outcome is the proportion of severe adverse events. Conclusion: This study will be the first randomized, double-blind trial to evaluate the efficacy and safety of LSZ capsule in patients with AIS. In order to improve the transparency and reproducibility of the trial, the data will be analyzed in accordance with this pre-specified plan for statistical analysis to reduce bias due to selective analysis and reporting. This trial aims to provide high-quality evidence for the efficacy and safety of LSZ capsule for AIS.

9.
Front Integr Neurosci ; 16: 940265, 2022.
Article En | MEDLINE | ID: mdl-36118114

Mammalian target of rapamycin (mTOR) is an important molecule that regulates cell metabolism, growth, and proliferation in the nervous system. This study aimed to present the current study hot spots and predict the future development trend of the mTOR pathway in neurologic diseases using bibliometrics. We referred to the publications in the Web of Science Core Collection database. VOSviewer and CiteSpace programs were used to evaluate countries/regions, institutions, authors, journals, keywords, and citations showing the current study focus and predicting the future trend of mTOR in neuroscience. The search date ended on 19 June 2022, and there were 3,029 articles on mTOR in neuroscience from 2002 to 2021. Visual analysis showed that although the number of publications declined slightly in some years, the number of publications related to mTOR generally showed an upward trend, reaching its peak in 2021. It had the largest number of publications in the United States. Keywords and literature analysis showed that protein synthesis regulation, ischemia, mitochondrial dysfunction, oxidative stress, and neuroinflammation may be hot spots and future directions of the nervous system in mTOR studies. Recently, the most studied neurological diseases are Alzheimer's disease (AD), tuberous sclerosis complex (TSC), and depression, which are still worthy of further studies by researchers in the future. This can provide a useful reference for future researchers to study mTOR further in the field of neuroscience.

10.
Front Immunol ; 13: 890263, 2022.
Article En | MEDLINE | ID: mdl-36016955

Tembusu virus (TMUV) can result in a severe disease affecting domestic ducks. The role of T cells in protection from TMUV infection and the molecular basis of T cell-mediated protection against TMUV remain largely uncharacterized. Here, we used the high-virulence TMUV strain Y and the low-virulence TMUV strain PS to investigate the protective role for TMUV-specific CD4+ and CD8+ T cells. When tested in a 5-day-old Pekin duck model, Y and PS induced comparable levels of neutralizing antibody, whereas Y elicited significantly stronger cellular immune response relative to PS. Using a duck adoptive transfer model, we showed that both CD4+ and CD8+ T cells provided significant protection from TMUV-related disease, with CD8+ T cell conferring more robust protection to recipient ducklings. For TMUV, CD4+ T cells mainly provided help for neutralizing antibody response, whereas CD8+ T cells mainly mediated viral clearance from infected tissues. The difference in T cell immunity between Y and PS was primarily attributed to CD4+ T cells; adoptive transfer of Y-specific CD4+ T cells resulted in significantly enhanced protective ability, neutralizing antibody response, and viral clearance from the brain relative to PS-specific CD4+ T cells. Further investigations with chimeric viruses, mutant viruses, and their parental viruses identified two mutations (T151A and R304M) in the envelope (E) protein that contributed significantly to TMUV-specific CD4+ T cell-mediated protective ability and neutralizing antibody response, with more beneficial effects being conferred by R304M. These data indicate T cell-mediated immunity is important for protection from disease, for viral clearance from tissues, and for the production of neutralizing antibodies, and that the difference in CD4+T cell immunity between high- and low-virulence TMUV strains is primarily related to residues 151 and 304 in the E protein.


Flavivirus Infections , Flavivirus , Poultry Diseases , Animals , Antibodies, Neutralizing , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Ducks , Virulence
11.
J Immunol ; 209(4): 684-695, 2022 08 15.
Article En | MEDLINE | ID: mdl-35879100

Previous studies identified three neutralizing epitopes on domains I, II, and III of the Tembusu virus (TMUV) envelope (E). More evidence is needed to understand the molecular basis of Ab-mediated neutralization and protection against TMUV. In this study, we observed a neutralizing mAb, 6C8, that neutralized TMUV infection primarily by inhibiting cell attachment. In immunofluorescence assays, 6C8 recognized the premembrane and E proteins coexpressed in HEK-293T cells, but failed to react with premembrane or E expressed individually. Epitope mapping identified nine E protein residues positioned on BC/EF loops and F/G strands in domain III and the first α-helical domain in the stem region. Further investigation with mutant viruses showed that 6C8 pressure resulted in mutations at residues 330 of BC loop and 409 of the first α-helical domain, although 6C8 only exhibited a moderate neutralizing activity in BHK-21 cells and a weak protective activity in BALB/c mice and Shaoxing duck models. Mutations A330S and T409M conferred high- and low-level 6C8 resistance, respectively, whereas the combination of A330S and T409M mutations conferred moderate-level 6C8 resistance. As a result, a quasispecies comprising three groups of antigenic variants appeared in BHK-21 cell-derived viral stocks after repeated passages of TMUV strain Y in the presence of 6C8 treatment. Taken together, these findings have raised a concern about Ab-induced antigenic variations in vivo, and they have revealed information concerning the conformational structure of the 6C8 epitope and its role in constraint on antigenic variations. The present work contributes to a better understanding of the complexity of the TMUV immunogen.


Flavivirus Infections , Flavivirus , Animals , Mice , Antibodies, Neutralizing , Antibodies, Viral , Ducks/virology , Epitopes , Viral Envelope Proteins/genetics , Humans
12.
J Hazard Mater ; 439: 129599, 2022 10 05.
Article En | MEDLINE | ID: mdl-35878496

Cadmium (Cd) contamination in rice grains has become a severe issue worldwide. This study aims to explore feasible technologies applicable to different risk lands and develop a practical solution for safe rice production at a regional scale. Despite inconsistent field conditions in the whole region, various foliar fertilizers could effectively decrease grain Cd content by 20.4-41.6 % and were capable of producing safe grains in low/medium-risk areas. At high-risk sites, foliage dressing coupled with alkaline fertilizers significantly reduced Cd accumulation and increased grain compliance rate to 95.0 %. The cost analysis and questionnaire survey showed the above technologies are low-cost, eco-friendly, and highly acceptable in real-world scenarios. The classification results by conditional inference tree (CIT) for CK and FS scenarios indicated grain Cd content is closely related to the interaction effects of soil Cd and pH. On these bases, the whole area was divided spatially into three different risk zones, and each zone matched a feasible method for safe production, subsequently developing a precise and differentiated solution. The estimation results demonstrate it can effectively improve the precision level of safe utilization of regional polluted lands and save more than half of the total cost, providing a new idea for regional Cd-polluted paddy fields management strategies.


Oryza , Soil Pollutants , Cadmium/chemistry , China , Fertilizers/analysis , Oryza/chemistry , Soil/chemistry , Soil Pollutants/analysis
13.
Brain Sci ; 12(6)2022 May 30.
Article En | MEDLINE | ID: mdl-35741592

Trigeminal neuralgia (TN) is a common facial neuropathic pain that is mainly characterized by spontaneous or induced needling or electric shock pain in the innervation area of the trigeminal nerve. It is also referred to as "the cancer that never dies". The olfactory ensheathing cell (OEC) is a special glial cell in the nervous system that has a strong supportive function in nerve regeneration. Cell transplantation therapy is a useful treatment modality that we believe can be applied in TN management. In this study, OECs were transplanted into the ligation site of the infraorbital nerve of rats. We found that after the OEC transplantation, mechanical pain threshold in the face of the rats was significantly increased. Western blotting, immunofluorescence assay, and reverse transcription-quantitative polymerase chain reaction were performed on the trigeminal ganglia (TG) of model rats. The results revealed a decrease in the expression of P2X7 receptor (P2X7R) in the trigeminal ganglia. Our findings show that OEC transplantation has a good therapeutic effect on TN in rats, and that can reduce the expression of P2X7R in trigeminal ganglia. Therefore, we think that OEC transplantation may be a suitable treatment for TN.

14.
Ecotoxicol Environ Saf ; 240: 113671, 2022 Jul 15.
Article En | MEDLINE | ID: mdl-35653972

With the wide application of static magnetic fields (SMFs), the risk of living organisms exposed to man-made magnetic fields that the intensity is much higher than geomagnetic field has gradually increased. Reproductive system is highly sensitive to environmental stress; however, the influence of high SMFs on reproduction system is still largely unknown. Here we explored the biological responses of SMFs exposure at an intensity of 10 T on the sperms and their offspring in him-5 male mutants of Caenorhabditis elegans (C. elegans). The size of unactivated sperms was deceased by 10 T SMF exposure, instead of the morphology. Exposure to 10 T SMF significantly altered the function of sperms in him-5 worms including the activation of sperms and the non-transferred ratio of sperms. In addition, the brood size assay revealed that 10 T SMF exposure eventually diminished the reproductive capacity of him-5 male worms. The lifespan of outcrossed offspring from exposed him-5 male mutants and unexposed fog-2 female mutants was decreased by 10 T SMF in a time dependent manner. Together, our findings provide novel information regarding the adverse effects of high SMFs on the sperms of C. elegans and their offspring, which can improve our understanding of the fundamental aspects of high SMFs on biological system.


Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/genetics , Female , Humans , Longevity , Magnetic Fields , Male , Reproduction
15.
Arch Virol ; 167(8): 1687-1691, 2022 Aug.
Article En | MEDLINE | ID: mdl-35639191

Earlier studies have shown that Tembusu virus (TMUV) can elicit high levels of neutralizing antibodies, but the ability of antibodies to protect against TMUV-associated disease and to inhibit replication of TMUV in vivo remains to be investigated. Here, we tested the prophylactic efficacy of TMUV immune serum directly using a 2-day-old Pekin duck model. Passive administration of the immune serum prior to challenge protected ducklings against morbidity and mortality, substantially reduced TMUV-caused tissue injury, and significantly decreased TMUV levels in the periphery and central nervous system. These findings demonstrate that antibodies play a dominant protective role in controlling TMUV-associated disease.


Flavivirus Infections , Flavivirus , Poultry Diseases , Animals , Ducks , Immune Sera
16.
Int J Mol Med ; 50(1)2022 Jul.
Article En | MEDLINE | ID: mdl-35593308

Ischemic injuries result from ischemia and hypoxia in cells. Tissues and organs receive an insufficient supply of nutrients and accumulate metabolic waste, which leads to the development of inflammation, fibrosis and a series of other issues. Ischemic injuries in the brain, heart, kidneys, lungs and other organs can cause severe adverse effects. Acute renal ischemia induces acute renal failure, heart ischemia induces myocardial infarction and cerebral ischemia induces cerebrovascular accidents, leading to loss of movement, consciousness and possibly, life­threatening disabilities. Existing evidence suggests that long non­coding RNAs (lncRNAs) are regulatory sequences involved in transcription, post­transcription, epigenetic regulation and multiple physiological processes. lncRNAs have been shown to be differentially expressed following ischemic injury, with the severity of the ischemic injury being affected by the upregulation or downregulation of certain types of lncRNA. The present review article provides an extensive summary of the functional roles of lncRNAs in ischemic injury, with a focus on the brain, heart, kidneys and lungs. The present review mainly summarizes the functional roles of lncRNA MALAT1, lncRNA MEG3, lncRNA H19, lncRNA TUG1, lncRNA NEAT1, lncRNA AK139328 and lncRNA CAREL, among which lncRNA MALAT1, in particular, plays a crucial role in ischemic injury and is currently a hot research topic.


Brain Ischemia , RNA, Long Noncoding , Stroke , Brain Ischemia/genetics , Epigenesis, Genetic , Humans , Ischemia , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Stroke/genetics
17.
Trials ; 23(1): 285, 2022 Apr 11.
Article En | MEDLINE | ID: mdl-35410433

BACKGROUND: Lumbrokinase has been widely used for patients with acute ischemic stroke (AIS) in China; however, because rigorously designed studies are lacking, safety and efficacy of lumbrokinase in the treatment of acute ischemic stroke remains largely unknown. In this multicenter, randomized, and controlled trial, we aim to compare lumbrokinase plus aspirin versus aspirin alone in patients with acute ischemic stroke. METHODS: A total of 220 eligible participants will be randomized to either the intervention or control group with a 1:1 ratio. These participants must be diagnosed with acute ischemic stroke for the first time, whose symptoms appear within 72 h. Their NIHSS score must be greater than 5 and less than 15, and their age must be between 35 and 85 years old. They must have not received intravenous thrombolysis, arterial thrombolysis, or intravascular intervention. Participants in the intervention group will be treated with lumbrokinase plus aspirin for the first 90 days. Participants in the control group will use placebo plus aspirin for the first 90 days. Then, all participants will be treated with aspirin only and followed up for another 90 days (180-day follow-up). The primary outcome is the modified Rankin Scale (mRS) score. The secondary outcomes are National Institutes of Health Stroke Scale (NIHSS) score, Activity of Daily Living (ADL) Scale score, coagulation function, and serum hypersensitive C-reactive protein. The exploratory outcomes are fasting lipid panel, recurrence rate, the occurrence of cardiovascular and cerebrovascular events, and the mortality rate. Safety evaluations include liver function and kidney function, serum fibrinogen, adverse events, serious adverse events, and bleeding events. Adherence of participants will also be assessed. DISCUSSION: This trial will investigate the efficacy and safety of lumbrokinase plus aspirin as compared to aspirin alone in the treatment of acute ischemic stroke. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000032952 . Registered on May 16, 2020.


Aspirin , Endopeptidases , Ischemic Stroke , Adult , Aged , Aged, 80 and over , Aspirin/adverse effects , Aspirin/therapeutic use , Drug Therapy, Combination/adverse effects , Endopeptidases/therapeutic use , Humans , Ischemic Stroke/drug therapy , Middle Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic
18.
Nat Commun ; 13(1): 2353, 2022 04 29.
Article En | MEDLINE | ID: mdl-35487897

Porous liquids with chemical separation properties are quite well-studied in general, but there is only a handful of reports in the context of identification and separation of non-gaseous molecules. Herein, we report a Type II porous ionic liquid composed of coordination cages that exhibits exceptional selectivity towards L-tryptophan (L-Trp) over other aromatic amino acids. A previously known class of anionic organic-inorganic hybrid doughnut-like cage (HD) is dissolved in trihexyltetradecylphosphonium chloride (THTP_Cl). The resulting liquid, HD/THTP_Cl, is thereby composed of common components, facile to prepare, and exhibit room temperature fluidity. The permanent porosity is manifested by the high-pressure isotherm for CH4 and modeling studies. With evidence from time-dependent amino acid uptake, competitive extraction studies and molecular dynamic simulations, HD/THTP_Cl exhibit better selectivity towards L-Trp than other solid state sorbents, and we attribute it to not only the intrinsic porosity of HD but also the host-guest interactions between HD and L-Trp. Specifically, each HD unit is filled with nearly 5 L-Trp molecules, which is higher than the L-Trp occupation in the structure unit of other benchmark metal-organic frameworks.


Ionic Liquids , Amino Acids, Aromatic , Ionic Liquids/chemistry , Metals , Porosity , Tryptophan/chemistry
19.
Environ Sci Pollut Res Int ; 29(28): 43102-43113, 2022 Jun.
Article En | MEDLINE | ID: mdl-35092591

Man-made static magnetic fields (SMFs) widely exist in human life as a physical environmental factor. However, the biological responses to moderate SMFs exposure and their underlying mechanisms are largely unknown. The present study was focused on exploring the nervous responses to moderate-intensity SMFs at 0.5 T and 1 T in Caenorhabditis elegans (C. elegans). We found that SMFs at either 0.5 T or 1 T had no statistically significant effects on the locomotor behaviors, while the 1 T magnetic field increased pharyngeal pumping. The avoidance behavior of the pathogenic Pseudomonas aeruginosa was greatly decreased in either 0.5 T or 1 T SMFs exposed nematodes, and the learning index was reducede from 0.52 ± 0.11 to 0.23 ± 0.17 and 0.16 ± 0.11, respectively. The total serotonin level was increased by 17.08% and 16.45% with the treatment of 0.5 T and 1 T SMF, compared to the control group; however, there were minimal effects of SMFs on other three neurotransmitters including choline, γ-aminobutyric acid (GABA), dopamine. RT-qPCR was used to further investigate the expression of serotonin-related genes, including rate-limiting enzymes, transcription factors and transport receptors. The expression levels of tph-1 and unc-86 genes were increased by SMF exposure, while those of ocr-2, osm-9, ser-1 and mod-1 genes were decreased. With the staining of lipid in either wild-type N2 or tph-1 mutants, we found that 0.5 T and 1 T SMFs decreased fat storage in C. elegans via serotonin pathway. Our study demonstrated that moderate-intensity SMFs induced neurobehavioral disorder and the reduction of fat storage by disturbing the secretion of serotonin in C. elegans, which provided new insights into elucidating nervous responses of C. elegans to moderate-intensity SMFs.


Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Avoidance Learning , Caenorhabditis elegans/physiology , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Dopamine/metabolism , Humans , Magnetic Fields , Serotonin/metabolism
20.
Virus Res ; 306: 198582, 2021 12.
Article En | MEDLINE | ID: mdl-34599934

We recently developed a Tembusu virus (TMUV)-specific monoclonal antibody (MAb) 12F11, which was found to recognize a long amino acid sequence between residues 8 and 77 of domain III of the envelope protein (EDIII). Here, the epitope recognized by MAb 12F11 was mapped using alanine substitutions combined with dissociation constant analysis. The findings, and prediction of tertiary structure of TMUV EDIII, showed that the MAb 12F11 epitope contained one critical residue and 13 peripheral residues. Moreover, the antigenic site was shown to span four loops (N-terminal region, AB, BC, and CD) and three ß-strands (A, B, and D). The present work contributes to the understanding of antigenic structure of TMUV envelope protein.


Antibodies, Neutralizing , Flavivirus , Antibodies, Monoclonal , Antibodies, Viral , Epitope Mapping , Epitopes , Flavivirus/genetics , Viral Envelope Proteins
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