RESUMEN
Spiking neural networks (SNNs) have received increasing attention due to their high biological plausibility and energy efficiency. The binary spike-based information propagation enables efficient sparse computation in event-based and static computer vision applications. However, the weight precision and especially the membrane potential precision remain as high-precision values (e.g., 32 bits) in state-of-the-art SNN algorithms. Each neuron in an SNN stores the membrane potential over time and typically updates its value in every time step. Such frequent read/write operations of high-precision membrane potential incur storage and memory access overhead in SNNs, which undermines the SNNs' compatibility with resource-constrained hardware. To resolve this inefficiency, prior works have explored the time step reduction and low-precision representation of membrane potential at a limited scale and reported significant accuracy drops. Furthermore, while recent advances in on-device AI present pruning and quantization optimization with different architectures and datasets, simultaneous pruning with quantization is highly under-explored in SNNs. In this work, we present SpQuant-SNN, a fully-quantized spiking neural network with ultra-low precision weights, membrane potential, and high spatial-channel sparsity, enabling the end-to-end low precision with significantly reduced operations on SNN. First, we propose an integer-only quantization scheme for the membrane potential with a stacked surrogate gradient function, a simple-yet-effective method that enables the smooth learning process of quantized SNN training. Second, we implement spatial-channel pruning with membrane potential prior, toward reducing the layer-wise computational complexity, and floating-point operations (FLOPs) in SNNs. Finally, to further improve the accuracy of low-precision and sparse SNN, we propose a self-adaptive learnable potential threshold for SNN training. Equipped with high biological adaptiveness, minimal computations, and memory utilization, SpQuant-SNN achieves state-of-the-art performance across multiple SNN models for both event-based and static image datasets, including both image classification and object detection tasks. The proposed SpQuant-SNN achieved up to 13× memory reduction and >4.7× FLOPs reduction with < 1.8% accuracy degradation for both classification and object detection tasks, compared to the SOTA baseline.
RESUMEN
Rheumatoid arthritis (RA) is a complex inflammatory disease of the joints, which is often accompanied by degeneration of articular cartilage and bone erosion, seriously affecting the quality of life and psychological state of patients. RA is difficult to be cured completely, and currently the main purpose of relief is through the use of anti-inflammatory and antirheumatic drugs, hormones, and biological agents. Tofacitib is a new type of small molecule inhibitor, which has a good effect in the treatment of RA. The current direct drug delivery method has serious side effects caused by the systemic distribution of the drug, so there is a need to develop an intelligent drug delivery system to realize precise treatment. In this work, tofacitib, gallic acid, targeted molecule folic acid, and Fe(III) were selected to assemble a novel type of artificial controllable nanodrug GF-TF. The self-photoacoustic/magnetic resonance imaging (self-PA/MRI) monitored the enrichment of GF-TF in the lesion in real-time, and artificially regulated the addition of deferoxamine (DFO) at the optimal enrichment. DFO strongly chelates Fe(III) in GF-TF and causes its structure to disintegrate gradually, and the self-PA/MRI signal of GF-TF became weaker while tofacitib began to be released, thus realizing the precise and artificially controlled release of the drug under the guidance of imaging. This nanodrug not only achieves efficient aggregation of drugs in inflamed joints, but also achieves real-time monitoring and precise control of drug release through self-PA/MRI, providing a new strategy for the precise treatment of RA.
RESUMEN
Coherent control of molecular photodissociation through one-photon transitions has become a topic of interest in physical chemistry. Previous studies have shown that modulating the spectral phase of a single ultrafast laser pulse while keeping its spectral amplitude constant does not affect the dissociation yield of reactions originating from a pure eigenstate of the ground electronic state. Here, we explore the indirect photodissociation reaction of NaI molecules using theoretical and numerical methods. Our findings show that, in contrast to the outcomes achieved with negatively chirped pulses, time-dependent population of the eigenstates of the excited adiabatic potential induced by positively chirped laser pulses, acting as intermediates in the reaction, cannot be periodically restored to that caused by the unchirped pulse. This gives rise to an intriguing phenomenon: the sign of the pulse's chirp rate influences the distribution of dissociation fragments in coordinate and momentum space over extended periods. This work highlights the potential of using spectral-phase modulated pulses to manipulate indirect photodissociation reactions, offering a way to modify the transient photofragment distributions by controlling reaction intermediates.
RESUMEN
Light non-aqueous phase liquids (LNAPLs) that infiltrate into the subsurface are commonly described in two distinct zones: the source zone and the plume zone. A precise differentiation between these zones is essential for constraining further migration and selecting an effective remediation method. In this study, we employ the induced polarization (IP) method to characterize the contaminants. Six time domain IP survey lines were conducted at a former chemical plant contaminated with LNAPLs. Even though the contaminated areas corresponding to BTEX concentration above 180 mg/kg are less than 5 mS/m, the source and plume zones cannot be distinguished by conductivity alone. However, a noticeable difference in phase ( φ ) between the two zones is observed, and the threshold phase value corresponding to a critical concentration of 450 mg/kg is 20 mrad. Moreover, the normalized chargeability ( M n ) threshold for the source zone is 80 mS/m, and the corresponding M n differences between the source and plume zones are more significant than those in φ . These results illustrate that changes in polarization characteristics associated with BTEX concentrations can aid in further distinguishing between the source and plume zones. Ultimately, it is concluded that IP imaging is a well-suited method for LNAPL investigations that permits an improved characterization of different contaminated zones, which can facilitate the optimization of drillings for further site assessment and remediation.
RESUMEN
Background: The incidence rate of thyroid nodules has reached 65%, but only 5-15% of these modules are malignant. Therefore, accurately determining the benign and malignant nature of thyroid nodules can prevent unnecessary treatment. We aimed to develop a deep-learning (DL) radiomics model based on ultrasound (US), explore its diagnostic efficacy for benign and malignant thyroid nodules, and verify whether it improved the diagnostic level of physicians. Methods: We retrospectively included 1,076 thyroid nodules from 817 patients at three institutions. The radiomics and DL features of the US images were extracted and used to construct radiomics signature (Rad_sig) and deep-learning signature (DL_sig). A Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used for feature selection. Clinical US semantic signature (C_US_sig) was constructed based on clinical information and US semantic features. Next, a combined model was constructed based on the above three signatures in the form of a nomogram. The model was constructed using a development set (institution 1: 719 nodules), and the model was evaluated using two external validation sets (institution 2: 74 nodules, and institution 3: 283 nodules). The performance of the model was assessed using decision curve analysis (DCA) and calibration curves. Furthermore, the C_US_sigs of junior physicians, senior physicians, and expers were constructed. The DL radiomics model was used to assist the physicians with different levels of experience in the interpretation of thyroid nodules. Results: In the development and validation sets, the combined model showed the highest performance, with areas under the curve (AUCs) of 0.947, 0.917, and 0.929, respectively. The DCA results showed that the comprehensive nomogram had the best clinical utility. The calibration curves indicated good calibration for all models. The AUCs for distinguishing between benign and malignant thyroid nodules by junior physicians, senior physicians, and experts were 0.714-0.752, 0.740-0.824, and 0.891-0.908, respectively; however, with the assistance of DL radiomics, the AUCs reached 0.858-0.923, 0.888-0.944, and 0.912-0.919, respectively. Conclusions: The nomogram based on DL radiomics had high diagnostic efficacy for thyroid nodules, and DL radiomics could assist physicians with different levels of experience to improve their diagnostic level.
RESUMEN
BACKGROUND: Vascular smooth muscle cell (VSMC) intimal migration, proliferation, and phenotypic transformation from a contractile to a synthetic state are hallmarks of the progression of atherosclerotic plaques. This study aims to explore the effects of exosomes derived from M2 macrophages (ExoM2) on the pathological changes of VSMCs in atherosclerosis (AS). METHODS: Cell Counting Kit-8 (CCK8) and wound healing assays were used to examine the impact of ExoM2 on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, respectively. Western blotting was employed to analyze changes in the expression levels of contractile markers (e.g., alpha-smooth muscle actin [α-SMA]) and synthetic ones (e.g., osteopontin [OPN]) in VSMCs with or without ExoM2 treatment. ApoE-â£/- mice on a high fat diet were utilized to observe the effects of ExoM2 on plaque progression and stability. Serial histopathological analysis was performed to elucidate the cellular mechanisms underlying the atheroprotective effects of ExoM2. RESULTS: Compared with controls, ExoM2 significantly inhibited PDGF-BB-induced VSMC proliferation, migration, and phenotypic transformation in vitro. In ApoE-â£/- mice, ExoM2 treatment led to a marked reduction in plaque size, necrotic core area, the CD68/α-SMA ratio, and matrix metalloproteinase 9 (MMP9) and OPN levels, while enhancing plaque stability. CONCLUSIONS: ExoM2 inhibit AS progression by regulating VSMC proliferation, migration, and phenotypic transformation.
Asunto(s)
Aterosclerosis , Becaplermina , Movimiento Celular , Proliferación Celular , Exosomas , Macrófagos , Músculo Liso Vascular , Miocitos del Músculo Liso , Fenotipo , Animales , Aterosclerosis/patología , Aterosclerosis/metabolismo , Macrófagos/metabolismo , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Exosomas/metabolismo , Músculo Liso Vascular/citología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Becaplermina/metabolismo , Becaplermina/farmacología , Ratones , Masculino , Progresión de la Enfermedad , Ratones Endogámicos C57BL , Placa Aterosclerótica/patología , Placa Aterosclerótica/metabolismo , Células CultivadasRESUMEN
PURPOSE: To investigate the inhibitory effect of sodium cantharidate (SCA) on human tongue squamous cell carcinoma CAL27 cells and its mechanism. METHODS: CAL27 cells were pretreated with different concentrations of SCA. Cell viability was analyzed by CCK-8 method. The migration and invasion of CAL27 cells were measured by scratch test and Transwell chamber, and the apoptosis rate was measured by flow cytometry. p53 protein and its phosphorylation sites Ser33, Ser37, Ser46, expression of BCL-2, BAX, and cleaved caspase 3 in CAL27 cells were detected by Western blot. Statistical analysis was performed with Graphpad Prism 9.0 software package. RESULTS: Compared with the blank control group, the proliferation, migration and invasion of CAL27 cells in sodium cantharidate group were significantly decreased, and the apoptosis rate was significantly increased(Pï¼0.01) in a dose-dependent manner. The expression of p53 protein and its phosphorylation sites Ser33, Ser37, Ser46 protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). The expression of BCL-2 protein was down-regulated and the expression of BAX protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). The ratio of BCL-2/BAX was significantly decreased and the expression of cleaved caspase 3 protein was significantly up-regulated(Pï¼0.05 or Pï¼0.01). CONCLUSIONS: SCA can inhibit the proliferation, migration and invasion of human tongue squamous cell carcinoma CAL27 cells. It also down-regulates the ratio of BCL-2/BAX and up-regulates the expression of cleaved caspase 3 protein by regulating the phosphorylation of p53 protein, which induces apoptosis.
Asunto(s)
Apoptosis , Carcinoma de Células Escamosas , Movimiento Celular , Proliferación Celular , Neoplasias de la Lengua , Proteína p53 Supresora de Tumor , Proteína X Asociada a bcl-2 , Humanos , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/genética , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Fosforilación/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismo , Proteína X Asociada a bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Caspasa 3/metabolismo , Supervivencia Celular/efectos de los fármacos , Invasividad NeoplásicaRESUMEN
ETHNO-PHARMACOLOGICAL RELEVANCE: Huangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear. AIM OF THE STUDY: Following PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE). MATERIALS AND METHODS: To evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed. RESULTS: In mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect. CONCLUSIONS: Our findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.
Asunto(s)
Planta del Astrágalo , Sinergismo Farmacológico , Medicamentos Herbarios Chinos , Isoflavonas , Polisacáridos , Trombosis , Animales , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Isoflavonas/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Masculino , Administración Oral , Trombosis/tratamiento farmacológico , Ratones , Planta del Astrágalo/química , Fibrinolíticos/farmacología , Fibrinolíticos/administración & dosificación , Pueraria/química , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Astragalus propinquus/química , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
Hierarchical porous structures and well-modulated interfacial interactions are essential for the performance of electrode materials. The energy storage performance can be promoted by regulating the diffusion behavior of the electrolyte and constructing a coupled interaction at heterogeneous interfaces. Herein, we have synthesized ultrathin NiO nanosheets anchored to nitrogen-doped hierarchical porous carbon (NiO/N-HPC) and applied it to construct aqueous potassium ion hybrid capacitors (APIHCs). The abundant and interconnected porous architecture promotes electrolyte penetration/diffusion and shortens the ion transport path, thereby accelerating storage reaction kinetics. The nitrogen-doped carbon support can achieve optimized metal oxides-carbon interaction and enhance the adsorption ability for the electrolyte ions, leading to earning higher storage capacity. Consequently, the prepared NiO/N-HPC exhibits a superior capacitance of 126.4 F g-1 at a current density of 0.5 A g-1, and the as-fabricated NiO/N-HPC//N-HPC APIHC achieves an ultra-high capacitance retention of 91.6% over 8000 cycles at a current density of 2 A g-1. Meanwhile, the APIHC device shows an excellent energy density of 21.95 W h kg-1 and a power density of 9000 W kg-1.
RESUMEN
OBJECTIVE: We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. METHODS: A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. RESULTS: Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. CONCLUSIONS: This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD.
Asunto(s)
Diabetes Mellitus Tipo 2 , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Vitamina D , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/patología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Vitamina D/sangre , Vitamina D/análogos & derivados , Persona de Mediana Edad , Cirrosis Hepática/sangre , Cirrosis Hepática/patología , Anciano , Progresión de la Enfermedad , Biomarcadores/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología , Pronóstico , Adulto , Estudios de SeguimientoRESUMEN
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with onset in childhood. The molecular mechanisms underlying ASD have not yet been elucidated completely. Evidence has emerged to support a link between microglial dysfunction and the etiology of ASD. This review summarizes current research on microglial dysfunction in neuroinflammation and synaptic pruning, which are associated with altered transcriptomes and autophagy in ASD. Dysbiosis of gut microbiota in ASD and its correlation with microglial dysfunction are also addressed.
RESUMEN
Backfill mining is an effective way to solve environment pollute, surface subsidence, and groundwater system damage which caused by coal mining. However, the complex underground environment may change the physical and mechanical properties of the backfill body, which poses a risk of strength failure. This paper analyzed the failure of gangue-based cemented backfill body which made up of gangue and fly ash. The results show that physicochemical reactions will generate quartz, kaolinite, and other high-strength substances; hydration reaction between the fine particles will generate hydrocalcium silicate and other C-S-H gels, they wrapped gangues as a whole, which provide a high strength of the cemented backfill body. Several experiments were carried out in order to find the reason for failure in samples under loads. The conclusion drawn as following: (1) When the load is large, the cracks extend from the surface of the samples to the interior, at the same time, the length and width of the cracks increasing obviously and connecting as net. Especially the external load exceeds the peak intensity. (2) The relationship between sample failure and pores is weak, but obvious with crack development, especially the cracks connected as a net. (3) The interface structure formed by gangue is an important source of crack development and, thus, will stimulate the development of cracks.
Asunto(s)
Minas de Carbón , Minas de Carbón/métodos , CaolínRESUMEN
In this paper, we propose a general deep learning training framework XGrad which introduces weight prediction into the popular gradient-based optimizers to boost their convergence and generalization when training the deep neural network (DNN) models. In particular, ahead of each mini-batch training, the future weights are predicted according to the update rule of the used optimizer and are then applied to both the forward pass and backward propagation. In this way, during the whole training period, the optimizer always utilizes the gradients w.r.t. the future weights to update the DNN parameters, making the gradient-based optimizer achieve better convergence and generalization compared to the original optimizer without weight prediction. XGrad is rather straightforward to implement yet pretty effective in boosting the convergence of gradient-based optimizers and the accuracy of DNN models. Empirical results concerning five popular optimizers including SGD with momentum, Adam, AdamW, AdaBelief, and AdaM3 demonstrate the effectiveness of our proposal. The experimental results validate that XGrad can attain higher model accuracy than the baseline optimizers when training the DNN models.
RESUMEN
PURPOSE: Information regarding quantitative flow ratio (QFR) usage in coronary artery bypass grafting (CABG) is lacking. We compared the incidence of postoperative long-term adverse cardiovascular and cerebrovascular events after QFR-guided or coronary angiography-guided adult cardiac surgery with concurrent bypass surgery. MATERIALS AND METHODS: This study included 432 patients who underwent cardiopulmonary bypass (CPB) at our institution with at least 1 angiographical coronary artery lesion (diameter stenosis: 30% to 90%) between January 2015 and January 2016. The QFR of each patient was calculated. Patients who only underwent intraoperative coronary revascularization following the principles of optimal revascularization strategy were assigned to group A. Patients with coronary lesions not meeting the above criteria were placed in group B. RESULTS: The average number of distal anastomoses of patients with combined CABG in group B was similar to that in Group A (1.9±1.0 vs. 1.7±0.9; P =0.081). Group A had a shorter CPB duration (114.4±49.2 vs 135.8±55.2 minutes; P <0.001) and shorter aortic cross-clamping time (83.6±36.2 vs 101.1±40.6 minutes; P <0.001). The rates of perioperative mortality and major complications did not differ between groups. Long-term major adverse cardiovascular and cerebrovascular events (MACCEs) were less common in group A than in group B (14.7% vs 29.5%; P <0.001). CONCLUSIONS: In primary noncoronary cardiac surgery, despite the similar average numbers of distal anastomoses, the group with target vessels treated using an optimal coronary revascularization strategy presented shorter CPB time and aortic cross-clamping time than the other group. Multivariate analyses also showed a lower incidence of long-term MACCEs.
Asunto(s)
Angiografía Coronaria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Angiografía Coronaria/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Complicaciones Posoperatorias/diagnóstico por imagen , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Procedimientos Quirúrgicos Cardíacos/métodos , Puente Cardiopulmonar/métodosRESUMEN
Background and aims: Compulsivity contributes to the development and maintenance of multiple addictive disorders. However, the relationship between compulsivity-related cognitive features and problematic usage of the internet (PUI), an umbrella term for various internet use disorders/interfering behaviors, remains largely unclear, partly due to the multidimensional nature of compulsivity. This scoping review utilized a four-domain framework of compulsivity to consider this topic and aimed to summarize available evidence on compulsivity-related neuropsychological characteristics in PUI based on this framework. Methods: A systematic literature search was conducted by applying the combination of search term to the search engines of PubMed, PsycINFO and Web of Science. A four-domain framework of compulsivity, involving cognitive flexibility, set-shifting, attentional bias, and habit learning, was used to consider its complex structure and frequently used tasks. Main findings in related PUI studies were summarized based on this framework. Our secondary aim was to compare compulsivity-related features between different PUI subtypes. Results: Thirty-four empirical studies were retained, comprising 41 task-results and 35 independent data sets. Overall, individuals with PUI showed more consistent deficits in attentional biases and were relatively intact in set-shifting. Few studies have examined cognitive flexibility and habit learning, and more evidence is thus needed to establish reliable conclusions. Moreover, most studies focused on internet gaming disorder, whereas other PUI sub-types were not sufficiently examined. Conclusion: This systematic review highlights the use of the four-domain framework for advancing understanding of mechanisms underlying compulsivity in PUI. Related therapeutic implications and future directions are discussed.
Asunto(s)
Conducta Compulsiva , Trastorno de Adicción a Internet , Humanos , Conducta Adictiva/psicologíaRESUMEN
BACKGROUND: The differences between existing preclinical models and the tumor microenvironment in vivo are one of the significant challenges hindering cancer therapy development. Patient-derived tumor organoids (PDTO) can highly retain tumor heterogeneity. Thus, it provides a more reliable platform for research in tumor biology, new drug screening, and precision medicine. METHODS: We conducted a systematic review to summarise the characteristics of the existing preclinical models, the advantages of patient-derived tumor organoids in reconstructing the tumor microenvironment, and the latest research progress. Moreover, this study deciphers organoid culture technology in the clinical precision treatment of head and neck cancer to achieve better transformation. Studies were identified through a comprehensive search of Ovid MEDLINE (Wolters Kluwer), PubMed (National Library of Medicine), web of Science (Thomson Reuters) and, Scopus (Elsevier) databases, without publication date or language restrictions. RESULTS: In tumor development, the interaction between cellular and non-cellular components in the tumor microenvironment (TME) has a crucial role. Co-culture, Air-liquid interface culture, microfluidics, and decellularized matrix have depicted great potential in reconstructing the tumor microenvironment and simulating tumor genesis, development, and metastasis. CONCLUSION: An accurate determination of stromal cells, immune cells, and extracellular matrix can be achieved by reconstructing the head and neck cancer tumor microenvironment using the PDTO model. Moreover, the interaction between head and neck cancer cells can also play an essential role in implementing the individualized precision treatment of head and neck cancer.
Asunto(s)
Neoplasias de Cabeza y Cuello , Organoides , Medicina de Precisión , Microambiente Tumoral , Humanos , Organoides/patología , Neoplasias de Cabeza y Cuello/patología , Técnicas de CocultivoRESUMEN
AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. CONCLUSION: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.
Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Humanos , Masculino , Inhibidores de la Dipeptidil-Peptidasa IV/farmacocinética , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Adulto , Biotransformación , Semivida , Heces/química , Adulto Joven , Voluntarios Sanos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/uso terapéutico , Administración OralRESUMEN
BACKGROUND: Short-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment. METHODS: A multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome. RESULTS: Among the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment. CONCLUSIONS: This study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.
Asunto(s)
Periodo Posparto , Útero , Humanos , Femenino , Adulto , Útero/diagnóstico por imagen , Embarazo , Terapia por Ultrasonido/métodos , Hemorragia Posparto/terapia , Resultado del Tratamiento , Contracción Uterina/fisiologíaRESUMEN
PURPOSE: Bioactive magnesium ions were successfully incorporated into the nanoporous titanium base coating by micro-arc oxidation(MAO), and its physical properties and osteogenic effects were explored. METHODS: Non-magnesium-containing and magnesium-containing titanium porous titanium coatings(MAO, MAO-mg) were prepared by changing the composition of MAO electrolyte and controlling the doping of magnesium in porous titanium coatings. The samples were characterized by scanning electron microscope (SEM), roughness, contact angle and energy dispersive X-ray spectrometer (EDS). Mg2+ release ability of magnesium-doped nanoporous titanium coatings was determined by inductively coupled plasma/optical emission spectrometer(ICP-OES). The structure of the cytoskeleton was determined by live/dead double staining, CCK-8 detection of material proliferation-toxicity, and staining of ß-actin using FITC-phalloidin. The effects of the coating on osteogenic differentiation in vitro were determined by alizarin red (ARS), alkaline phosphatase (ALP) staining and real-time polymerase chain reaction (qRT-PCR). SPSS 25.0 software package was used for statistical analysis. RESULTS: The MAO electrolyte with magnesium ions did not change the surface characteristics of the porous titanium coating. Each group prepared by MAO had similar microporous structure(Pï¼0.05). There was no significant difference in surface roughness and contact angle between MAO treatment group (MAO, MAO-mg)(Pï¼0.05), but significantly higher than that of Ti group (Pï¼0.05). With the passage of cell culture time, MAO-mg group promoted cell proliferation (Pï¼0.05). MAO-mg group was significantly higher than other groups in ALP and ARS staining. The expression of Runx2 mRNA (Pï¼0.05), ALP(Pï¼0.05) and osteocalcin OCN(Pï¼0.05) in MAO-mg group was significantly higher than that in Ti and MAO groups. CONCLUSIONS: MAO successfully prepared magnesium-containing nanoporous titanium coating, and showed a significant role in promoting osteogenic differentiation.
Asunto(s)
Nanoporos , Titanio , Titanio/farmacología , Magnesio/química , Magnesio/farmacología , Osteogénesis/genética , Electrólitos/farmacología , Iones/farmacología , Propiedades de Superficie , Materiales Biocompatibles Revestidos/farmacología , Materiales Biocompatibles Revestidos/químicaRESUMEN
A comprehensive analysis and simulation of two memristor-based neuromorphic architectures for nuclear radiation detection is presented. Both scalable architectures retrofit a locally competitive algorithm to solve overcomplete sparse approximation problems by harnessing memristor crossbar execution of vector-matrix multiplications. The proposed systems demonstrate excellent accuracy and throughput while consuming minimal energy for radionuclide detection. To ensure that the simulation results of our proposed hardware are realistic, the memristor parameters are chosen from our own fabricated memristor devices. Based on these results, we conclude that memristor-based computing is the preeminent technology for a radiation detection platform.