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Alternative (M2) activation of macrophages driven via the α-chain of the receptor for interleukin 4 (IL-4Rα) is important for immunity to parasites, wound healing, the prevention of atherosclerosis and metabolic homeostasis. M2 polarization is dependent on fatty acid oxidation (FAO), but the source of the fatty acids that support this metabolic program has not been clear. We found that the uptake of triacylglycerol substrates via the scavenger receptor CD36 and their subsequent lipolysis by lysosomal acid lipase (LAL) was important for the engagement of elevated oxidative phosphorylation, enhanced spare respiratory capacity (SRC), prolonged survival and expression of genes that together define M2 activation. Inhibition of lipolysis suppressed M2 activation during infection with a parasitic helminth and blocked protective responses to this pathogen. Our findings delineate a critical role for cell-intrinsic lysosomal lipolysis in M2 activation.
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Antígenos CD36/inmunología , Ácidos Grasos/metabolismo , Interleucina-4/inmunología , Lipólisis/inmunología , Lisosomas/inmunología , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Fosforilación Oxidativa , Transducción de Señal/inmunología , Esterol Esterasa/inmunología , Animales , Respiración de la Célula , Helmintiasis Animal/inmunología , Humanos , Ratones , Consumo de Oxígeno , Receptores de Interleucina-4/inmunología , TranscriptomaRESUMEN
Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.
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Hipoxia/inmunología , Antígenos Comunes de Leucocito/metabolismo , Macrófagos/inmunología , Monoéster Fosfórico Hidrolasas/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Diferenciación Celular , Movimiento Celular , Células Cultivadas , Dimerización , Femenino , Antígenos Comunes de Leucocito/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Células Mieloides/inmunología , Monoéster Fosfórico Hidrolasas/genética , Factor de Transcripción STAT3/genética , Ácidos Siálicos/metabolismo , Microambiente TumoralRESUMEN
Phase transitions in molecular solids involve synergistic changes in chemical and electronic structures, leading to diversification in physical and chemical properties. Despite the pivotal role of hydrogen bonds (H-bonds) in many phase-transition materials, it is rare and challenging to chemically regulate the dynamics and to elucidate the structure-property relationship. Here, four high-spin CoII compounds were isolated and systematically investigated by modifying the ligand terminal groups (X=S, Se) and substituents (Y=Cl, Br). S-Cl and Se-Br undergo a reversible structural phase transition near room temperature, triggering the rotation of 15-crown-5 guests and the swing between syn- and anti-conformation of NCX- ligands, accompanied by switchable magnetism. Conversely, S-Br and Se-Cl retain stability in ordered and disordered phases, respectively. H-bonds geometric analysis and ab initio calculations reveal that the electronegativity of X and Y affects the strength of NY-ap-Hâ â â X interactions. Entropy-driven structural phase transitions occur when the H-bond strength is appropriate; otherwise, the phase stays unchanged if it is too strong or weak. This work highlights a phase transition driven by H-bond strength complementarity - pairing strong acceptor with weak donor and vice versa, which offers a straightforward and effective approach for designing phase-transition molecular solids from a chemical perspective.
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Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures (Tf) were achieved as the chain lengths of the fatty acyl chlorides were reduced. In particular, a cellulose decanoate with a DS of 1.85 and a Tf of 186 °C was achieved by feeding 3 mol of decanoyl chloride per mole anhydroglucose units of cellulose. However, cellulose stearate (DS = 1.53) synthesized by the same protocols cannot melt even at 250 °C. More interestingly, the fatty acyl chlorides with 10 and 12 carbons resulted in FACE with superior toughness (elongation at break up to 94.4%). In contrast, due to their potential crystallization of the fatty acyl groups with 14-18 carbons, the corresponding FACE showed higher tensile strength and Young's modulus than the others. This study provides some theoretical basis for the mechanochemical synthesis of thermoplastic FACE with designated properties.
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Cloruros , Ésteres , Ésteres/química , Estudios de Factibilidad , Esterificación , Celulosa/químicaRESUMEN
Polyoxometalates (POMs) with various coordination fashions are versatile ligands for constructing single-ion magnets (SIMs), but enforcing POM-SIMs with a specific geometry remains a synthetic challenge. Herein, we synthesized a POM-cocrystallized DyIII-SIM [Dy(OPPh3)4(H2O)3][PW12O40]·4EtOH (1Dy) and a POM-ligated DyIII-SIM [{Dy(OPPh3)3(H2O)3}{PW12O40}]·Ph3PO·H2O (2Dy) with pentagonal bipyramidal local coordination geometry. Magnetic measurements indicate that 1Dy displays field-induced single-molecule magnet (SMM) behavior and the relaxation is dominated by under-barrier processes. 2Dy exhibits spin-lattice relaxation at a broader temperature region with a reversal barrier over 300 K. Magneto-structural analysis reveals that the enhancement of SMM behavior originated from the equatorial replacement of Ph3PO by POM, which strengthens the axial anisotropy in 2Dy. Luminescent experiments indicate that the characteristic DyIII emissions of 1Dy are covered up by the strong π-π* emission of Ph3PO at low-temperature regions. As for 2Dy, partial DyIII emission persists thanks to the antenna effect between DyIII and POM.
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Silicon solar cell is the most mature photovoltaic conversion device, and in order to further improve the performance of the device, application of downshifting films has become a research hotspot. In this paper, CsPbBr3perovskite quantum dot/EVA composite adhesive film was prepared by melting method with CsPbBr3perovskite quantum dot film under solution processing as masterbatch and EVA particles as excipient. The effect of synthesis conditions on the luminescence properties of the composite films were thoroughly studied. The optimized CsPbBr3perovskite quantum dot/EVA composite adhesive film has excellent performance, and its light transmission reaches 85%. The CsPbBr3perovskite quantum dot/EVA composite adhesive film absolutely improves the efficiency of silicon solar cells by 1.08%, which is much higher than that of pure EVA adhesive film (0.63%). In addition, the device efficiencies have almost no change after 30 d in the air, maintaining the working stability of the device and contributing to industrial applications. This study provides a novel, industrial and low-cost synthesis route for the synthesis of CsPbBr3perovskite quantum dot/EVA composite adhesive film, which is expected to have broad application.
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BACKGROUND: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). METHODS: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. RESULTS: The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P < 0.05) was significantly lower in the OFA group than in the OBA group. Moreover, the severity of PONV was less severe in the OFA group than in the OBA group in PACU (post-anesthesia care unit) (0 [0, 0] vs. 0 [0, 3], P<0.05 ) and in the ward 24 h postoperatively ( 0 [0, 0] vs. 0 [0, 2.25], P<0.05). Additionally, the OFA group experienced a significantly shorter length of stay in the PACU compared to the OBA group (39.4 ± 6.76 min vs. 48.7 ± 7.90 min, P < 0.001). CONCLUSIONS: Compared to the OBA with propofol-remifentanil, the OFA with esketamine- dexmedetomidine proved to be feasible for shoulder arthroscopy, resulting in a reduced incidence of PONV and a shorter duration of stay in the PACU. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (No: ChiCTR2100047355), 12/06/2021.
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Analgésicos Opioides , Anestésicos Intravenosos , Artroscopía , Dexmedetomidina , Ketamina , Náusea y Vómito Posoperatorios , Propofol , Remifentanilo , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Dexmedetomidina/administración & dosificación , Masculino , Remifentanilo/administración & dosificación , Propofol/administración & dosificación , Femenino , Artroscopía/métodos , Persona de Mediana Edad , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Adulto , Náusea y Vómito Posoperatorios/prevención & control , Náusea y Vómito Posoperatorios/epidemiología , Náusea y Vómito Posoperatorios/etiología , Anestésicos Intravenosos/administración & dosificación , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Dolor Postoperatorio/diagnóstico , Anestesia Intravenosa/métodos , Bloqueo del Plexo Braquial/métodosRESUMEN
Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.
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Antifúngicos , Benzopiranos , Fungicidas Industriales , Nitrilos , Oxindoles , Piperazinas , Compuestos de Espiro , Antifúngicos/química , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Fungicidas Industriales/farmacologíaRESUMEN
Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4) â 4H2O (H2quinha=quinaldichydroxamic acid, HClsal=5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4) â 3H2O (HClsaldt=4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S=0 to high-spin S=1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57â cm-1 to 423â cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2â K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.
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Single-photon devices such as switches, beam splitters, and circulators are fundamental components to construct photonic integrated quantum networks. In this paper, two V-type three-level atoms coupled to a waveguide are proposed to simultaneously realize these functions as a multifunctional and reconfigurable single-photon device. When both the two atoms are driven by the external coherent fields, the difference in the phases of the coherent driving induces the photonic Aharonov-Bohm effect. Based on the photonic Aharonov-Bohm effect and setting the two-atom distance to match the constructive or destructive interference conditions among photons travelling along different paths, a single-photon switch is achieved since the incident single photon can be controlled from complete transmission to complete reflection by adjusting the amplitudes and phases of the driving fields. When properly changing the amplitudes and phases of the driving fields, the incident photons are split equally into multiple components as a beam splitter operated with different frequencies. Meanwhile, the single-photon circulator with reconfigurable circulation directions can also be obtained.
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Self-powered photodetectors that do not require external power support are expected to play a key role in future photodetectors due to their low power characteristics, but achieving high responsivity remains a challenge. 2D van der Waals heterojunctions are a promising technology for high-performance self-powered photodetectors due to their excellent optical and electrical properties. Here, we fabricate a self-powered photodetector based on In2Se3/WSe2/ReS2van der Waals heterojunction self-powered photodetector. Due to the presence of ReS2layer, photocurrent is enhanced as a result of the increase in light absorption efficiency and the effective region for generating photogenerated carriers. The built-in electric field is enhanced by a negative 'back-gate voltage' along the p-n junction vertical direction generated by the electrons in the photo-generated electrons accumulation layer. Accordingly, the optical responsivity and the photoresponse speed of this heterojunction self-powered photodetector are greatly boosted. The proposed self-powered photodetector based on the In2Se3/WSe2/ReS2heterojunction exhibits a high responsivity of 438 mA W-1, which is 17 times higher compared to the In2Se3/WSe2photodetector, a self-powered current (1.1 nA) that is an order of magnitude higher than that of the In2Se3/WSe2photodetector, and a fast response time that is 250% faster. Thus the self-powered photodetector with a stronger built-in electric field and a wider depletion zone can provide a new technological support for the fabrication of high responsivity, low power consumption and high speed self-powered photodetectors based on van der Waals heterojunctions.
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Preserving appropriate function and metabolism in regulatory T (Treg) cells is crucial for controlling immune tolerance and inflammatory responses. Yet how Treg cells coordinate cellular metabolic programs to support their functional specification remains elusive. In this study, we report that BATF couples the TH2-suppressive function and triglyceride (TG) metabolism in Treg cells for controlling allergic airway inflammation and IgE responses. Mice with Treg-specific ablation of BATF developed an inflammatory disorder characterized by TH2-type dominant responses and were predisposed to house dust mite-induced airway inflammation. Loss of BATF enabled Treg cells to acquire TH2 cell-like characteristics. Moreover, BATF-deficient Treg cells displayed elevated levels of cellular TGs, and repressing or elevating TGs, respectively, restored or exacerbated their defects. Mechanistically, TCR/CD28 costimulation enhanced expression and function of BATF, which sustained IRF4 activity to preserve Treg cell functionality. Thus, our studies reveal that BATF links Treg cell functional specification and fitness of cellular TGs to control allergic responses, and suggest that therapeutic targeting of TG metabolism could be used for the treatment of allergic disease.
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Hipersensibilidad , Linfocitos T Reguladores , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Ratones , Ratones Noqueados , Pyroglyphidae , TriglicéridosRESUMEN
PURPOSE: This study aimed to investigate the relevance of cerebral endothelial cell adhesion molecule (CERCAM) expression to head and neck squamous cell carcinoma (HNSCC) prognosis and immune infiltration by macrophage M2 polarization. METHODS: Timer, UALCAN and HPA databases was used to analyze the differences in mRNA and protein levels of CERCAM expression in HNSCC. The Timer database was also applied to analyze the correlation between CERCAM in HNSCC and immune infiltration. TCGA-HNSCC database was applied to analyze the correlation between CERCAM expression levels and clinicopathological features, and its diagnostic and prognostic value in HNSCC was also assessed. The cBioPortal and MethSurv databases were then applied to analyze the genetic variation and methylation status of CERCAM. In vitro cellular assays were performed to provide evidence that CERCAM promotes malignant biological behavior of tumors and promotes macrophage M2 polarization in tumors. Finally, underlying pathophysiological mechanisms of CERCAM involvement in the development of HNSCC were predicted using a bioinformatics approach. RESULTS: CERCAM is significantly overexpressed in HNSCC and correlates with poor prognostic levels and has good performance in predicting survival status in HNSCC patients. Cox regression analysis indicates that CERCAM expression levels are independent risk factors for predicting OS, DSS, and PFI. CERCAM promotes tumor malignant biological behavior and promotes macrophage M2 polarization immune infiltration in HNSCC. In addition, CERCAM promotes tumor cell adhesion in head and neck squamous carcinoma and promotes tumor progression through several oncogenic signaling pathways. CONCLUSION: CERCAM may serve as a new diagnostic and prognostic biomarker in HNSCC and is a promising therapeutic target for HNSCC.
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Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Neoplasias de Cabeza y Cuello/genética , Macrófagos , BiomarcadoresRESUMEN
Spin crossover (SCO) materials with new architectures will expand and enrich the research in the SCO field. Here, we report two metal-organic frameworks (MOFs) containing tetradentate organic ligands and hexatopic linkers [Ag8 X8 (CN)6 ]6- (X=Br and I), which represents the first SCO MOF with clusters as building blocks. The silver halide cluster can be further removed after reacting with lithium tetracyanoquinodimethan (LiTCNQ). Such post-synthetic modification (PSM) is realized via single-crystal to single-crystal (SCSC) transformation from urk to nbo topology. Accordingly, the spin state and fluorescence properties are greatly modified by cluster deconstruction. Therefore, these achievements will provide new ideas for the design of new SCO systems and the development of PSM methods.
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Utilization of proper preclinical models accelerates development of immunotherapeutics and the study of the interplay between human malignant cells and immune cells. Lysosomal acid lipase (LAL) is a critical lipid hydrolase that generates free fatty acids and cholesterol. Ablation of LAL suppresses immune rejection and allows growth of human lung cancer cells in lal-/- mice. In the lal-/- lymph nodes, the percentages of both T- and B-regulatory cells (Tregs and Bregs, respectively) are increased, with elevated expression of programmed death-ligand 1 and IL-10, and decreased expression of interferon-γ. Levels of enzymes in the glucose and glutamine metabolic pathways are elevated in Tregs and Bregs of the lal-/- lymph nodes. Pharmacologic inhibitor of pyruvate dehydrogenase, which controls the transition from glycolysis to the citric acid cycle, effectively reduces Treg and Breg elevation in the lal-/- lymph nodes. Blocking the mammalian target of rapamycin or reactivating peroxisome proliferator-activated receptor γ, an LAL downstream effector, reduces lal-/- Treg and Breg elevation and PD-L1 expression in lal-/- Tregs and Bregs, and improves human cancer cell rejection. Treatment with PD-L1 antibody also reduces Treg and Breg elevation in the lal-/- lymph nodes and improves human cancer cell rejection. These observations conclude that LAL-regulated lipid metabolism is essential to maintain antitumor immunity.
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Linfocitos B Reguladores/inmunología , Neoplasias Experimentales/inmunología , Esterol Esterasa/deficiencia , Linfocitos T Reguladores/inmunología , Escape del Tumor/inmunología , Animales , Modelos Animales de Enfermedad , Xenoinjertos , Homeostasis/inmunología , Humanos , Ganglios Linfáticos/inmunología , Ratones , Ratones Noqueados , Trasplante de Neoplasias , Esterol Esterasa/inmunologíaRESUMEN
Linkage isomers involving changes in the bonding mode of ambidentate ligands have potential applications in data storage, molecular machines, and motors. However, the observation of the cyanide-linkage-isomerism-induced spin change (CLIISC) effect characterized by single-crystal X-ray diffraction remains a considerable challenge. Meanwhile, the high-spin and low-spin states can be reversibly switched in spin-crossover (SCO) compounds, which provide the potential for applications to data storage, switches, and sensors. Here, a new perovskite-type SCO framework (PPN)[Fe{Ag(CN)2}3] (PPN+ = bis(trisphenylphosphine)iminium cation) is synthesized, which displays the unprecedented aging and temperature dependences of hysteretic multistep SCO behaviors near room temperature. Moreover, the thermal-induced cyanide linkage isomerization from FeII-N≡C-AgI to FeII-C≡N-AgI is revealed by single-crystal X-ray diffraction, Raman, and Mössbauer spectra, which is associated with a transition from the mixed spin state to the low-spin state and a dramatic volume shrinkage. Considering the wide use of cyanogen in magnetic systems, the association of CLIISC and SCO opens a new dimension to modulate the spin state and realize a colossal negative thermal expansion.
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OBJECTIVES: To estimate the prevalence of extra-glandular lesions in patients with immunoglobulin G4-related sialadenitis (IgG4-RS). METHODS: Six electronic databases (PubMed, EMBASE, Science Direct, Scopus, Web of Science, and China National Knowledge Infrastructure) were systematically searched from the date of inception of each database to March 2021. The Strengthening the Reporting of Observational Studies in Epidemiology statement was used to conduct methodological quality assessment, and a random-effect meta-analysis model was applied to estimate the prevalence. Publication bias was visually assessed using a funnel plot and calculated via Begg's and Egger's tests. The Stata 15 software was used to perform data analysis. RESULTS: A total of 43 articles comprising 1,864 patients with IgG4-RS were considered to be eligible for this study. The pooled prevalence of extra-salivary gland lesions in IgG4-RS was 76.53% with a confidence interval (CI) of (69.39%, 83.04%). A higher prevalence was associated with studies published before or during 2015 (84.38%, CI [74.23%, 92.58%]) than those published after 2015 (68.55%, CI [58.44%, 77.88%]). Lacrimal gland involvement (54.68%, CI [45.61%, 63.60%]) and lymph node swelling (56.96%, CI [48.16%, 65.56%]) were the most frequent lesions. CONCLUSIONS: Extra-glandular lesions were common in patients with IgG4-RS. More high-quality prospective studies with less heterogeneity are required to determine the accurate prevalence.
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Sialadenitis , Humanos , Inmunoglobulina G , Prevalencia , Estudios Prospectivos , Glándulas Salivales/patología , Sialadenitis/epidemiología , Sialadenitis/patologíaRESUMEN
In real industrial scenarios, intelligent fault diagnosis based on data-driven methods has been widely researched in the past decade. However, data scarcity is widespread in fault diagnosis tasks owning to the difficulties in collecting adequate data. As a result, there is an increasing demand for both researchers and engineers for fault identification with scarce data. To address this issue, an innovative domain-adaptive prototype-recalibrated network (DAPRN) based on a transductive learning paradigm and prototype recalibration strategy (PRS) is proposed, which has the potential to promote the generalization ability from the source domain to target domain in a few-shot fault diagnosis. Within this scheme, the DAPRN is composed of a feature extractor, a domain discriminator, and a label predictor. Concretely, the feature extractor is jointly optimized by the minimization of few-shot classification loss and the maximization of domain-discriminative loss. The cosine similarity-based label predictor, which is promoted by the PRS, is exploited to avoid the bias of naïve prototypes in the metric space and recognize the health conditions of machinery in the meta-testing process. The efficacy and advantage of DAPRN are validated by extensive experiments on bearing and gearbox datasets compared with seven popular and well-established few-shot fault diagnosis methods. In practical application, the proposed DAPRN is expected to solve more challenging few-shot fault diagnosis scenarios and facilitate practical fault identification problems in modern manufacturing.
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Aprendizaje , Aprendizaje Automático , InteligenciaRESUMEN
OBJECTIVE: To design a sitting walking aid with intelligent shock absorption, high safety, alarm and heart rate monitoring device. METHODS: Aluminum alloy bracket is used as the main body of the walker. U-shaped soft arm bracket and L-shaped handle are arranged at the top, and universal wheel and anti-slip floor mat are arranged at the bottom. The shock-absorbing seat is connected to the geared motor through a hydraulic rod, and the seat is equipped with GPS, alarm device and heart rate monitoring device, and the finite element software Abaqus 2021 is used to analyze the force of the shock absorbing seat. RESULTS: The main body of the walker is light and easy to carry, with strong bearing capacity. The U-shaped soft arm rest and L-shaped handle can increase the sense of user experience. The combination of universal wheel and anti-slip floor mat can make the user safe and labor-saving. When the user wants to sit down and rest, the switch can be adjusted to drive the shock absorbing seat to turn over and support the elderly to sit down slowly through the deceleration motor, so as to realize the safe and independent rest, and the shock absorbing seat can withstand the corresponding stress. CONCLUSIONS: The intelligent shock-absorbing sitting and standing walker saves manpower, is safe and reliable, and meets market demand and user needs.
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Fenómenos Mecánicos , Sedestación , Humanos , Anciano , Posición de PieRESUMEN
BACKGROUND: Transforming growth factor beta1 (TGFB1) is a multi-functional cytokine that regulates mammary gland development and cancer progression through endocrine, paracrine and autocrine mechanisms. TGFB1 also plays roles in tumour development and progression, and its increased expression is associated with an increased breast cancer risk. Macrophages are key target cells for TGFB1 action, also playing crucial roles in tumourigenesis. However, the precise role of TGFB-regulated macrophages in the mammary gland is unclear. This study investigated the effect of attenuated TGFB signalling in macrophages on mammary gland development and mammary cancer susceptibility in mice. METHODS: A transgenic mouse model was generated, wherein a dominant negative TGFB receptor is activated in macrophages, in turn attenuating the TGFB signalling pathway specifically in the macrophage population. The mammary glands were assessed for morphological changes through wholemount and H&E analysis, and the abundance and phenotype of macrophages were analysed through immunohistochemistry. Another cohort of mice received carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), and tumour development was monitored weekly. Human non-neoplastic breast tissue was also immunohistochemically assessed for latent TGFB1 and macrophage marker CD68. RESULTS: Attenuation of TGFB signalling resulted in an increase in the percentage of alveolar epithelium in the mammary gland at dioestrus and an increase in macrophage abundance. The phenotype of macrophages was also altered, with inflammatory macrophage markers iNOS and CCR7 increased by 110% and 40%, respectively. A significant decrease in DMBA-induced mammary tumour incidence and prolonged tumour-free survival in mice with attenuated TGFB signalling were observed. In human non-neoplastic breast tissue, there was a significant inverse relationship between latent TGFB1 protein and CD68-positive macrophages. CONCLUSIONS: TGFB acts on macrophage populations in the mammary gland to reduce their abundance and dampen the inflammatory phenotype. TGFB signalling in macrophages increases mammary cancer susceptibility potentially through suppression of immune surveillance activities of macrophages.