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OBJECTIVES: To observe the effect of electroacupuncture (EA) stimulation of "Jiaji"(EX-B2) on motor function, histomorphology, and expression of NOD-like receptor protein 3 (NLRP3) and N-terminal domain of gasdermin D (GSDMD-N) in the spinal cord tissue of rats with spinal cord injury (SCI), so as to explore its mechanism underlying improvement of SCI. METHODS: Forty eight female SD rats were randomly divided into sham surgery (sham), SCI model (model), EA, and NLRP3 agonist (monosodium urate, MSU) combined with Jiaji EA (MSU+EA) groups, with 12 rats in each group which were further divided into 3 d and 7 d subgroups, with 6 rats at each time point. Two EA groups received EA stimulation of EX-B2 with a frequency of 100 Hz, electrical current of 1-2 mA for 30 min, once a day for 3 or 7 days. After 5 min, 6 h, and 24 h of modeling, rats of the MSU+EA group received intraperitoneal injection of MSU (200 µg/kg, 200 µg/mL) . The motor function was evaluated using Basso-Beattie-Bresnahan (BBB) scale, the morphological structure of rat spinal cord tissue was observed by H.E. staining. The expression of pyroptosis related factors NLRP3, cleaved Caspase-1 and GSDMD-N of the spinal cord was observed by using immunohistochemistry and Western blot separately, the expression and localization of Iba-1 and GSDMD-N in the spinal cord tissue were observed using immunofluorescence double staining method. RESULTS: Compared with the sham group, the BBB scores after modeling and on day 3 and 7 were decreased (P<0.05), while the average OD values (immunoactivity) and expression levels of NLRP3, cleaved Caspase-1 and GSDMD-N proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N (co-expression) of the spinal cord tissues on day 3 and 7 were significantly increased in the model group (P<0.05). In comparison with the model group, the BBB scores on day 3 and 7 were obviously increased (P<0.05), while the immunoactivity and expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins, and the immunofluorescence intensity of Iba-1/GSDMD-N on day 3 and 7 significantly down-regulated in the EA group (P<0.05) but not in the MSU+EA group (P>0.05), suggesting an elimination of the effects of EA after administration of NLRP3 agonist (MSU). H.E. staining showed obvious bleeding area in the spinal cord tissue, loose tissue and inflammatory cell infiltration on day 3 after modeling, and basic absorption of the bleeding, loose tissue, obvious vacuolar changes of the white matter area, loss and contraction of neurons with infiltration of a large number of inflammatory cells, which was milder in the EA group but not in the MSU+EA group. CONCLUSIONS: EA of EX-B2 can improve the motor function of SCI rats, which may be related to its functions in inhibiting pyroptosis of microglia mediated by NLRP3/Caspase-1 signaling pathway.
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Eletroacupuntura , Traumatismos da Medula Espinal , Animais , Feminino , Ratos , Caspase 1 , Caspases , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Piroptose , Ratos Sprague-Dawley , Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapiaRESUMO
Few-shot semantic segmentation aims to segment novel-class objects in a query image with only a few annotated examples in support images. Although progress has been made recently by combining prototype-based metric learning, existing methods still face two main challenges. First, various intra-class objects between the support and query images or semantically similar inter-class objects can seriously harm the segmentation performance due to their poor feature representations. Second, the latent novel classes are treated as the background in most methods, leading to a learning bias, whereby these novel classes are difficult to correctly segment as foreground. To solve these problems, we propose a dual-branch learning method. The class-specific branch encourages representations of objects to be more distinguishable by increasing the inter-class distance while decreasing the intra-class distance. In parallel, the class-agnostic branch focuses on minimizing the foreground class feature distribution and maximizing the features between the foreground and background, thus increasing the generalizability to novel classes in the test stage. Furthermore, to obtain more representative features, pixel-level and prototype-level semantic learning are both involved in the two branches. The method is evaluated on PASCAL- 5i 1 -shot, PASCAL- 5i 5 -shot, COCO- 20i 1 -shot, and COCO- 20i 5 -shot, and extensive experiments show that our approach is effective for few-shot semantic segmentation despite its simplicity.
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Tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) are neuroprotein toxins, with the latter being the most toxic known protein. They are structurally similar and contain three functional domains: an N-terminal catalytic domain (light chain), an internal heavy-chain translocation domain (HN domain), and a C-terminal heavy chain receptor binding domain (Hc domain or RBD). In this study, fusion functional domain molecules consisting of the TeNT RBD (THc) and the BoNT/A RBD (AHc) (i.e., THc-Linker-AHc and AHc-Linker-THc) were designed, prepared, and identified. The interaction of each Hc domain and the ganglioside receptor (GT1b) or the receptor synaptic vesicle glycoprotein 2 (SV2) was explored in vitro. Their immune response characteristics and protective efficacy were investigated in animal models. The recombinant THc-linker-AHc and AHc-linker-THc proteins with the binding activity had the correct size and structure, thus representing novel subunit vaccines. THc-linker-AHc and AHc-linker-THc induced high levels of specific neutralizing antibodies, and showed strong immune protective efficacy against both toxins. The high antibody titers against the two novel fusion domain molecules and against individual THc and AHc suggested that the THc and AHc domains, as antigens in the fusion functional domain molecules, do not interact with each other and retain their full key epitopes responsible for inducing neutralizing antibodies. Thus, the recombinant THc-linker-AHc and AHc-linker-THc molecules are strong and effective bivalent biotoxin vaccines, protecting against two biotoxins simultaneously. Our experimental design will be valuable to develop recombinant double-RBD fusion molecules as potent bivalent subunit vaccines against bio-toxins. KEY POINTS: ⢠Double-RBD fusion molecules from two toxins had the correct structure and activity. ⢠THc-linker-AHc and AHc-linker-THc efficiently protected against both biotoxins. ⢠Such bivalent biotoxin vaccines based on the RBD are a valuable experimental design.
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Toxinas Botulínicas Tipo A , Toxina Tetânica , Animais , Toxina Tetânica/genética , Toxina Tetânica/metabolismo , Toxinas Botulínicas Tipo A/genética , Toxinas Botulínicas Tipo A/metabolismo , Ligação Proteica , Anticorpos Neutralizantes , Vacinas de Subunidades Antigênicas/genéticaRESUMO
OBJECTIVE: To observe the clinical effect and safety of acupuncture in treatment of neck pain due to cervical spondylosis. METHODS: According to the patients' preference and acceptance for the interventions of neck pain induced by cervical spondylosis, an acupuncture group (221 cases) and a non-acupuncture group (251 cases) were divided. After the control of confounding factors with propensity score matching, 218 cases were included in either acupuncture group or non-acupuncture group. In the acupuncture group, acupuncture was applied to Dazhui (GV 14), Baihui (GV 20), ashi points, bilateral neck-Jiaji (EX-B 2), Fengchi (GB 20), Houxi (SI 3), Shenmai (BL 62), etc. The treatment was given once daily, one course of intervention was composed of 5 treatments and 3 courses were included. In the non-acupuncture group, the oral administration of imrecoxib tablets and cobalt tablets was prescribed for 2 weeks. Before and after treatment, the scores of Northwick Park questionnaire (NPQ) and the simplified McGill pain questionnaire (SF-MPQ) were observed, and the safety was assessed in patients of the two groups. RESULTS: After treatment completion, the scores of NPQ and SF-MPQ were all reduced when compared with those before treatment in each group (P<0.001), and the scores of NPQ and SF-MPQ in the acupuncture group were lower than those of the non-acupuncture group (P<0.001). The incidence of adverse reactions was 6.0% (13/218) in the acupuncture group and was 10.1% (22/218) in the non-acupuncture group, without statistical significance in comparison (P>0.05). CONCLUSION: Acupuncture is effective and safe in the relief of neck pain and the improvement of comprehensive quality of life in the patients with cervical spondylosis.
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Terapia por Acupuntura , Espondilose , Humanos , Cervicalgia/terapia , Pontuação de Propensão , Qualidade de Vida , Pontos de Acupuntura , Espondilose/terapia , Resultado do TratamentoRESUMO
Inflammatory reaction after spinal cord injury (SCI) is the main obstacle to the recovery of neural function. In the occurrence and development of SCI, the complex regulatory mechanisms are involved in inflammatory reaction, including the activation of inflammatory cells (e.g.macrophages and microglia), and the release of cytokines (e.g. tumor necrosis factor, interleukin and chemokines). Acupuncture-moxibustion is significantly effective in clinical treatment of SCI, and its mechanism is related to adjusting the function of inflammatory cells after SCI, modulating the expression of cytokines and the activation of NLRP3 inflammatory bodies, as well as the expression of high mobility group protein B1 and calcitonin gene related peptide. This article summarizes the research progress of mechanism of inflammatory reaction after SCI and the effects of acupuncture-moxibustion intervention in recent years so that the new ideas can be provided to clarify the pathogenesis of SCI and the effect of acupuncture-moxibustion intervention.
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Terapia por Acupuntura , Moxibustão , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/terapia , Citocinas/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Inflamação/terapia , Medula EspinalRESUMO
BACKGROUND: New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin (CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects. AIM: To obtain a deeper understanding of CAM, its distribution, metabolism and anti-inflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method. METHODS: In this paper, the content of isovaleryl spiramycin III was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses. RESULTS: The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4 (IL-4) levels in the lung and kidney and especially the liver and spleen; moreover, CAM significantly reduced the IL-1ß levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets, such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases. CONCLUSION: We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.
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Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Animais , Camundongos , Simulação de Acoplamento Molecular , Neoplasias Hepáticas/tratamento farmacológico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêuticoRESUMO
Botulinum neurotoxin (BoNTs; serotypes A, B, E, and F) cause botulism disease in humans, which could be effectively treated using antitoxins. Herein, we established a novel receptor-binding domain (RBD)-based antitoxin using recombinant C terminal heavy chain (Hc) domains of BoNTs as immunogens. Immunization of horses with these recombinant Hc domains allowed the purification and digestion of IgGs from hyper-immune sera to produce high-quality and high-efficiency monovalent botulism antitoxin F(ab')2 against each BoNT (M-BATs). However, these M-BATs could not bind or neutralize other serotypes of BoNTs, and that there were no cross-protective effects among these M-BATs. This suggested the need to prepare tetravalent antitoxins to neutralize the four BoNTs simultaneously. Thus, these M-BATs were formulated into a novel tetravalent botulism antitoxin (T-BAT), in which a 10-ml volume contained 10000 IU of BoNT/A and 5000 IU of BoNT/B, BoNT/E, and BoNT/F antitoxins. The novel antitoxin preparation could prevent and treat the four mixed botulinum neurotoxins simultaneously in vivo, representing strong efficacy in an animal poisoning model. Moreover, these antibodies in T-BAT could bind the RBD, whereas conventional antitoxins based on inactivated toxins mainly bind the light chain or heavy chain translocation domain (HN) and weakly bind the important RBD in current experimental conditions. The high levels of RBD-specific novel antitoxins can efficiently bind the RBD and neutralize natural or recombinant toxins containing this RBD. The findings of the present study experimentally support the use of RBD-specific antitoxins to treat BoNT serotype A, B, E, and F-mediated botulism. This study demonstrated the concept of developing potent novel multivalent antitoxins against all BoNTs or other toxins, using the RBD of these toxins as an alternative antigen to inactivated toxins. KEY POINTS: ⢠Antitoxins based on the receptor-binding domains of botulinum neurotoxins were made. ⢠Novel antitoxin binds RBD; traditional antitoxin mainly binds light chain or HN domain. ⢠A tetravalent antitoxin could prevent and treat the four mixed neurotoxins in vivo.
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Antitoxinas , Toxinas Botulínicas Tipo A , Botulismo , Humanos , Animais , Cavalos , Antitoxina Botulínica , Botulismo/prevenção & controle , Neurotoxinas , ImunizaçãoRESUMO
Tunnel fan is critical fire-fighting equipment, and its safe and stable operation is very important for the efficiency and safety of tunnel traffic. Existing studies commonly train the fault diagnosis methods with the goal of minimizing mean error which ignores the difference between classes in feature distribution. To solve the problem of inaccurate prediction caused by mean error evaluation, this paper presents a non-neural deep learning model, namely hierarchical cascade forest, which has three characteristics: (1) A hierarchical cascade structure is constructed, of which the output comes from each layer; (2) Each fault class is evaluated and recognized independently, the result of fault classes that are easy to distinguish is output earlier; (3) A confidence-based threshold estimate method is proposed in HCF and used to improve the training method to increase the reliability of HCF. Based on these, HCF improves the cascade forest structure and implements the proper matching of different depth of feature and fault patterns. The effect of HCF is verified through experiments based on the tunnel fans testing rig. Experimented results show that, compared to Deep Forest, the accuracy of HCF increases by 0.6% to 10.8%, and the training time of HCF is reduced 33.24%.
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With the popularity of online-shopping, more and more delivery packages have led to stacking at sorting centers. Robotic detection can improve sorting efficiency. Standard datasets in computer vision are crucial for visual detection. A neuromorphic vision (NeuroVI) camera is a bio-inspired camera that can capture dynamic changes of pixels in the environment and filter out redundant background information with low latency. NeuroVI records pixel changes in the environment with the output of event-points, which are very suitable for the detection of delivery packages. However, there is currently no logistics dataset with the sensor, which limits its application prospects. This paper encodes the events stream of delivery packages, and converts the event-points into frame image datasets for recognition. Considering the falling risk during the packages' transportation on the sorting belt, another falling dataset is made for the first time. Finally, we combine different encoding images to enhance the feature-extraction on the YOLO network. The comparative results show that the new datasets and image-confusing network can improve the detection accuracy with the new NeuroVI.
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Background: Macau is a densely populated international tourist city. Compared to most tensely populated countries/territories, the prevalence and mortality of COVID-19 in Macau are lower. The experiences in Macau could be helpful for other areas to combat the COVID-19 pandemic. This article introduced the endeavours and achievements of Macau in combatting the COVID-19 pandemic. Method: Both qualitative and quantitative analysis methods were used to explore the work, measures, and achievements of Macau in dealing with the COVID-19 pandemic. Results: The results revealed that Macau has provided undifferentiated mask purchase reservation services, COVID-19 vaccination services to all residents and non-residents in Macau along with delivering multilingual services, in Chinese, English and Portuguese, to different groups of the population. To facilitate the travels of people, business and trades between Macau and mainland China, the Macau government launched the Macau Health Code System, which uses the health status declaration, residence history declaration, contact history declaration of the declarant to match various relevant backend databases within the health authority and provide a risk-related colour code operations. The Macau Health Code System connects to the Chinese mainland's own propriety health code system seamlessly, whilst effectively protecting the privacy of the residents. Macau has also developed the COVID-19 Vaccination Appointment system, the Nucleic Acid Test Appointment system, the Port and Entry/Exit Quarantine system, the medical and other supporting systems. Conclusion: The efforts in Macau have achieved remarkable results in COVID-19 prevention and control, effectively safeguarding the lives and health of the people and manifesting the core principle of "serving the public". The measures used are sustainable and can serve as an important reference for other countries/regions.
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COVID-19 , Ácidos Nucleicos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Macau/epidemiologia , Pandemias/prevenção & controleRESUMO
An electret-based mechanical antenna (EBMA), which can transmit extremely low frequency (ELF) electromagnetic signals, has the advantages of miniaturization and high transmitting efficiency, with great potential applications in air, underwater, and underground communications. To improve the charge density of the electret, which is a key factor in determining the radiation performance of an EBMA, this work proposes a fluorinated ethylene propylene/terpolymer of tetrafluoroethylene, hexafluoropropylene and vinylidene fluoride (FEP/THV) unipolar electret exhibiting negative polarity, reaching a total charge density up to -0.46 mC/m2 for each layer of electret. Long transmission distances can be achieved in sea water, soil, and air using a 3-layer-FEP/THV-based EBMA with a compact volume of 5 × 10-4 m3. As an application demonstration, binary ASCII-coded ELF information of "BUAA" is successfully transmitted with a power consumption < 5 W.
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OBJECTIVE: To observe the effect of moxibustion at oppositely-located points "Mingmen" (GV 4) and "Shenque" (CV 8) on the motor function of the hind limbs and bladder function in rats with neurogenic bladder after suprasacral spinal cord injury (SCI), so as to explore the effect of this therapy on bladder tissue apoptosis mediated by endoplasmic reticulum stress pathway. METHODS: Twenty-eight female Wistar rats were randomly divided into a sham-operation group (8 rats) and a model establishment group (20 rats). Using the modified Allen's method, the spinal cord of T10 segment was injured to establish a neurogenic bladder model in the model establishment group. Sixteen rats were modeled successfully and then divided into a model group (8 rats) and a moxibustion group (8 rats). In the moxibustion group, 2 h after consciousness regaining from modeling anesthesia, moxibustion was exerted at "Shenque" (CV 8) and "Mingmen" (GV 4), 2 cones at each acupoint in one intervention. The intervention was administered once every two days and 5-time intervention was required totally. After intervention, Basso, Beattie and Bresnahan locomotor rating scale (BBB) score for the motor function of the hind limbs, and the urodynamics indexes (maximum bladder capacity, urine leakage pressure and bladder compliance) were compared among groups. HE staining method was adopted to observe the morphological changes of bladder tissue. With Western blot method and real-time PCR assay, the protein and mRNA expressions of the endoplasmic reticulum stress-related genes (glucose- regulated protein 78 [GRP78], activating transcription factor 4 [ATF4] and cysteinyl aspartate specific proteinase-12 [Caspase-12]) were determined. RESULTS: The transitional epithelial cells were arranged irregularly, the bladder wall was getting thinner, and the cellular vacuolar degeneration and neutrophil infiltration were found in the model group. Whereas, compared with the model group, in the moxibustion group, the arrangement of transitional epithelial cells was clear and continuous in layers, the cellular vacuolar degeneration was mild and the infiltration presented in a small amount of neutrophil granulocytes. Compared with the sham-operation group, in the model group, the BBB score was reduced (P<0.01), the maximum bladder capacity and bladder compliance were increased (P<0.01), and the protein expression levels of GRP78, ATF4 and Caspase-12, as well as mRNA expressions were all increased (P<0.01). In comparison with the model group, in the moxibustion group, BBB score was increased (P<0.01), the maximum bladder capacity and bladder compliance were decreased (P<0.01), and the protein and mRNA expression levels of GRP78, ATF4 and Caspase-12 were all decreased (P<0.01). CONCLUSION: Moxibustion at the "oppositely-located points" improves the urination function, alleviate urine retention in neurogenic bladder rats after spinal cord injury. The underlying mechanism may be related to the down-regulation of the expressions of GRP78, ATF4 and Caspase-12 in the endoplasmic reticulum stress pathway of the bladder tissues, and thus to alleviate the apoptosis of bladder tissue.
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Eletroacupuntura , Moxibustão , Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Animais , Caspase 12/genética , Estresse do Retículo Endoplasmático , Feminino , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Medula Espinal , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/terapia , Bexiga Urinaria Neurogênica/terapiaRESUMO
Botulinum neurotoxins (BoNTs) are the most toxic known proteins. Naturally occurring botulism in humans is caused by botulinum serotypes A, B, E, and F. Vaccination is an effective strategy to prevent botulism. In this study, a tetravalent botulinum vaccine (TBV) that can prevent serotypes A, B, E, and F was developed using the C-terminal receptor-binding domain of BoNT (Hc) as an antigen. To develop a suitable vaccine formulation, in vitro binding experiments of antigens and aluminum adjuvant in different buffers, and in vivo experiments of TBV at different antigen concentrations, were conducted. Our results showed that the optimal vaccine formulation buffer was a pH 6.0 phosphate buffer, and the suitable antigen concentration was 40 or 80 µg/ml of each antigen. A pilot-scale TBV was then prepared and evaluated for immunogenicity and stability. The results showed that TBV could elicit strong protective efficacy against each BoNT in mice, and remain effective after two years of storage at 4ºC, indicating that the preparation was stable and highly effective. Adsorption experiments also showed that the antigens could be well adsorbed by the aluminum adjuvant after 2 years of storage. Our results provide valuable experimental data supporting the development of a tetravalent botulinum vaccine, which is a promising candidate for the prevention of botulinum serotypes A, B, E, and F.
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Toxinas Botulínicas Tipo A , Toxinas Botulínicas , Botulismo , Clostridium botulinum , Alumínio , Animais , Botulismo/prevenção & controle , Clostridium botulinum/metabolismo , Camundongos , Vacinas CombinadasRESUMO
Ruthenium complexes with good biological properties have attracted increasing attention in recent decades. In this work, three ruthenium polypyridine complexes containing 5-fluorouracil derivatives as ligands, [Ru(bpy)2(L)]2+ (Ru1), [Ru(phen)2(L)]2+ (Ru2), [Ru(dip)2(L)]2+ (Ru3) (L = 1-((1,10-phenanthroline-5-amino) pentyl)-5-fluorouracil; bpy = 2,2'-bipyridine; phen =1,10-phenanthroline; dip = 4,7-diphenyl-1,10-phenanthroline), were synthesized and characterized. Based on in vitro cytotoxicity tests, Ru3 (IC50 = 7.35 ± 0.39 µM) showed the best anticancer activity among three compounds in the selected cell lines. It is worth noting that Ru3 also exerts less cytotoxicity on LO2 cell lines, with an IC50 value 5 times higher than that on HeLa cells, indicating its selective activity. Mechanism studies revealed that Ru3 can specifically target lysosomes and induce cell apoptosis in a caspase-dependent manner. Specifically, Ru3 can arrest cell cycle at the G0/G1 phase, increase the intracellular reactive oxygen species (ROS) level, and then damage DNA. In short, Ru3 can eventually cause cell death through the synergy of inducing apoptosis and autophagy, which was further proven by western blot assay results.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Lisossomos/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Fluoruracila/análogos & derivados , Fluoruracila/farmacologia , Fluoruracila/toxicidade , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Ligantes , Piridinas/síntese química , Piridinas/farmacologia , Piridinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Rutênio/químicaRESUMO
Existing deep learning algorithms for point cloud analysis mainly concern discovering semantic patterns from the global configuration of local geometries in a supervised learning manner. However, very few explore geometric properties revealing local surface manifolds embedded in 3-D Euclidean space to discriminate semantic classes or object parts as additional supervision signals. This article is the first attempt to propose a unique multitask geometric learning network to improve semantic analysis by auxiliary geometric learning with local shape properties, which can be either generated via physical computation from point clouds themselves as self-supervision signals or provided as privileged information. Owing to explicitly encoding local shape manifolds in favor of semantic analysis, the proposed geometric self-supervised and privileged learning algorithms can achieve superior performance to their backbone baselines and other state-of-the-art methods, which are verified in the experiments on the popular benchmarks.
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This paper aims to investigate the mechanism by which dark septate endophytes (DSEs) enhance cadmium (Cd) tolerance in there host plants. Maize (Zea mays L.) was inoculated with a DSE, Exophiala pisciphila, under Cd stress at different concentrations (0, 5, 10, and 20 mg·kg-1). The results show that, under 20 mg/kg Cd stress, DSE significantly increased maize biomass and plant height, indicating that DSE colonization can be utilized to increase the Cd tolerance of host plants. More Cd was retained in DSE-inoculated roots, especially that fixed in the root cell wall (RCW). The capability of DSE to induce a higher Cd holding capacity in the RCW is caused by modulation of the total sugar and uronic acid of DSE-colonized RCW, mainly the pectin and hemicellulose fractions. The fourier-transform spectroscopy analysis results show that carboxyl, hydroxyl, and acidic groups are involved in Cd retention in the DSE-inoculated RCW. The promotion of the growth of maize and improvement in its tolerance to Cd due to DSEs are related to restriction of the translocation of Cd from roots to shoots; resistance of Cd uptake Cd inside cells; and the increase in RCW-integrated Cd through modulating RCW polysaccharide components.
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A single-pixel neural network object classification scenario in the sub-Nyquist ghost imaging system is proposed. Based on the neural network, objects are classified directly by bucket measurements without reconstructing images. Classification accuracy can still be maintained at 94.23% even with only 16 measurements (less than the Nyquist limit of 1.56%). A parallel computing scheme is applied in data processing to reduce the object acquisition time significantly. Random patterns are used as illumination patterns to illuminate objects. The proposed method performs much better than existing methods for both binary and grayscale images in the sub-Nyquist condition, which is also robust to environment noise turbulence. Benefiting from advantages of ghost imaging, it may find applications for target recognition in the fields of remote sensing, military defense, and so on.
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BACKGROUND: Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM: To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS: NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS: The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION: Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.
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Antineoplásicos , Neoplasias Hepáticas , Estruturas Metalorgânicas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/uso terapêutico , Camundongos , TemperaturaRESUMO
Botulinum neurotoxin (BoNT) is a neurotoxin produced by Clostridium botulinum in an anaerobic environment. BoNT is the most toxic protein among bacteria, animals, plants, and chemical substances reported to date. BoNTs are 150 kDa proteins composed of three major functional domains: catalytic (L domain, 50 kDa), translocation (HN domain, 50 kDa), and receptor-binding (Hc domain, 50 kDa) domains. Most studies have focused on the use of the Hc domain as an antigen because it is capable of generating robust protective immunity and contains some functional neutralizing epitopes. In the present study, we produced and characterized a recombinant L-HN fusion fragment of the parent BoNT/B (BL-HN) composed of L and HN domains with a deletion in the Hc domain (BHc). When the BL-HN protein was expressed in E. coli, it retained its stable structure and antigenicity. As a vaccine antigen, the recombinant BL-HN protein was found to induce sufficient protection against native BoNT/B in a mouse model. The BL-HN subunit vaccine could also induce a strong humoral immune response and generate sufficient neutralizing antibodies in immunized mice. Therefore, BL-HN may retain the native neurotoxin structure and critical epitopes responsible for inducing serum neutralizing antibodies. Studies of the dose-dependent immunoprotective effects further confirmed that the BL-HN antigen could provide potent protective immunity. This finding suggests that BL-HN can play an important role in immune protection against BoNT/B. Therefore, the BL-HN fusion fragment provides an excellent platform for the design of recombinant botulinum vaccines and neutralizing antibodies.
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Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Toxinas Botulínicas Tipo A/administração & dosagem , Vacinação/métodos , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Toxinas Botulínicas Tipo A/imunologia , Relação Dose-Resposta Imunológica , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologiaRESUMO
Tetanus is an acute, fatal disease caused by exotoxin produced by Clostridium tetani. The current vaccine against tetanus is based on inactivated tetanus toxin (TeNT). To develop a recombinant TeNT vaccine suitable for replacement of full-length tetanus toxoid (TT) vaccine for use in humans, a recombinant non-tagged isoform of the Hc domain of the tetanus toxin (THc) was expressed in Escherichia coli and purified by sequential chromatography steps. The immunogenicity and protective effect of the THc antigen were explored and compared with those of TT in Balb/c mice. The THc-based subunit vaccine provided complete protection against TeNT challenge following a high dosage as a toxoid vaccine. While the anti-THc and neutralising antibody titres were higher for the THc-based vaccine than the TT vaccine because protective epitopes are located on the THc domain. Frequency- and dose-dependent immunoprotection were also observed in THc-immunised mice. Mice immunised with one injection of 1 µg or 4 µg THc antigen were completely protected against 102 or 103 50% mouse lethal dose (LD50) of TeNT, respectively. Furthermore, the THc protein was found to recognise and bind to ganglioside GT1b in a dose-dependent manner, and anti-THc sera antibodies also inhibited binding between THc and GT1b. Antigen on the form of recombinant non-tagged THc domain expressed in E. coli achieved strong immunoprotective potency, suggesting that it could be developed into a candidate subunit vaccine against tetanus as an alternative to the current TT vaccine.