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A general approach for the α-arylation of heteroarenes with nitroarenes via denitrative coupling is reported for the first time. Various heteroarenes, including derivatives of furan, benzofuran, pyrrole, indole, thiophene, and benzothiophene, can be arylated at the α-position in moderate to good yields. Mechanistic studies demonstrate that the reaction proceeds via a CMD pathway, with C-H bond activation as the rate-determining step. Furthermore, the scalability and applicability in the synthesis of a drug molecule exemplify the utility of this protocol.
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The urgent need to develop efficient, durable, and cost-effective oxygen evolution reaction (OER) catalysts for energy conversion and storage has prompted extensive research. Currently available commercial noble metal-based OER catalysts are expensive and exhibit limited long-term stability. In this study, boron-doped diamond composites (BDDCs) consisting of CoFe and CoFe2C nanoparticles supported by boron-doped diamond (BDD) particles have been prepared. The BDDC catalyst, prepared through a straightforward annealing process, exhibits exceptional durability (up to 72 h at 10 mA cm-2), a low overpotential (306 mV at 10 mA cm-2), and modest Tafel slope (58 mV dec-1). The coherent interfaces between CoFe/CoFe2C nanoparticles and the BDD substrate are essential for enhancing the OER performance. The fabrication method and composite structures presented in this study may facilitate the design and production of promising catalysts.
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Sensitive, flexible, and low false alarm rate X-ray detector is crucial for medical diagnosis, industrial inspection, and scientific research. However, most semiconductors for X-ray detectors are susceptible to interference from ambient light, and their high thickness hinders their application in wearable electronics. Herein, a flexible visible-blind and ultraviolet-blind X-ray detector based on Indium-doped Gallium oxide (Ga2O3:In) single microwire is prepared. Joint experiment-theory characterizations reveal that the Ga2O3:In microwire possess a high crystal quality, large band gap, and satisfactory stability, and reliability. On this basis, an extraordinary sensitivity of 5.9 × 105 µC Gyair -1 cm-2 and a low detection limit of 67.4 nGyair s-1 are achieved based on the prepared Ag/Ga2O3:In/Ag device, which has outstanding operation stability and excellent high temperature stability. Taking advantage of the flexible properties of the single microwire, a portable X-ray detection system is demonstrated that shows the potential to adapt to flexible and lightweight formats. The proposed X-ray detection system enables real-time monitor for X-rays, which can be displayed on the user interface. More importantly, it has excellent resistance to natural light interference, showing a low false alarm rate. This work provides a feasible method for exploring high-performance flexible integrated micro/nano X-ray detection devices.
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Physical unclonable functions (PUFs) have emerged as an unprecedented solution for modern information security and anticounterfeiting by virtue of their inherent unclonable nature derived from distinctive, randomly generated physical patterns that defy replication. However, the creation of traceable optical PUF tags remains a formidable challenge. Here, we demonstrate a traceable PUF system whose unclonability arises from the random distribution of diamonds and the random intensity of the narrow emission from germanium vacancies (GeV) within the diamonds. Tamper-resistant PUF labels can be manufactured on diverse and intricate structural surfaces by blending diamond particles into polydimethylsiloxane (PDMS) and strategically depositing them onto the surface of objects. The resulting PUF codes exhibit essentially perfect uniformity, uniqueness, reproducibility, and substantial encoding capacity, making them applicable as a private key to fulfill the customization demands of circulating commodities. Through integration of a digitized "challenge-response" protocol, a traceable and highly secure PUF system can be established, which is seamlessly compatible with contemporary digital information technology. Thus, the GeV-PUF system holds significant promise for applications in data security and blockchain anticounterfeiting, providing robust and adaptive solutions to address the dynamic demands of these domains.
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AIMS: Although static abnormalities of functional brain networks have been observed in patients with social anxiety disorder (SAD), the brain connectome dynamics at the macroscale network level remain obscure. We therefore used a multivariate data-driven method to search for dynamic functional network connectivity (dFNC) alterations in SAD. METHODS: We conducted spatial independent component analysis, and used a sliding-window approach with a k-means clustering algorithm, to characterize the recurring states of brain resting-state networks; then state transition metrics and FNC strength in the different states were compared between SAD patients and healthy controls (HC), and the relationship to SAD clinical characteristics was explored. RESULTS: Four distinct recurring states were identified. Compared with HC, SAD patients demonstrated higher fractional windows and mean dwelling time in the highest-frequency State 3, representing "widely weaker" FNC, but lower in States 2 and 4, representing "locally stronger" and "widely stronger" FNC, respectively. In State 1, representing "widely moderate" FNC, SAD patients showed decreased FNC mainly between the default mode network and the attention and perceptual networks. Some aberrant dFNC signatures correlated with illness duration. CONCLUSION: These aberrant patterns of brain functional synchronization dynamics among large-scale resting-state networks may provide new insights into the neuro-functional underpinnings of SAD.
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Encéfalo , Conectoma , Imageamento por Ressonância Magnética , Rede Nervosa , Fobia Social , Humanos , Masculino , Feminino , Adulto , Fobia Social/fisiopatologia , Fobia Social/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Adulto JovemRESUMO
At present, there are still challenges in developing highly efficient and thermally stable phosphors for ultraviolet/near ultraviolet-white light emitting diodes (UV/NUV-WLEDs). Herein, we use traditional high-temperature solid-state reactions to prepare blue-emitting phosphors Lu5-xBa6B9O27:xCe3+ (0.1% ≤ x ≤ 3.0%) and Lu4.975Ba6-ySryB9O27:0.5%Ce3+ (0% ≤ y ≤ 20%), and green-emitting phosphors Lu4.975-zBa6B9O27:0.5%Ce3+,zTb3+ (0% ≤ z ≤ 16%), abbreviated as LBB:xCe3+, LBB:0.5%Ce3+,ySr2+ and LBB:0.5%Ce3+,zTb3+, respectively. Upon 340 nm excitation, LBB:Ce3+ exhibits an asymmetric blue emission ranging from 360 nm to 480 nm. Furthermore, the emission intensity of LBB:0.5%Ce3+ increased 4.8-fold without a spectral shift through the partial substitution of Sr2+ for Ba2+. Through constructing the Ce3+ â Tb3+ energy transfer in the LBB structure, the temperature-dependent integral emission intensity at 483 K improved from only 25% to 68% of the intensity at 303 K due to the existence of fast energy transfer from Ce3+ to Tb3+. The related results indicate that LBB:xCe3+, LBB:0.5%Ce3+,ySr2+ and LBB:0.5%Ce3+,zTb3+ phosphors can be used for UV/NUV-WLEDs.
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Background: To investigate the relationship between the Scottish inflammatory prognostic score (SIPS), treatment-related adverse events (TRAEs), and prognostication in patients with neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESCC). Methods: A retrospective investigation was carried out on 208 ESCC patients treated with NICT. The relationships between the SIPS, TRAEs, and prognosis [disease-free survival (DFS) and overall survival (OS)] were analyzed. Results: The patients, comprising 62 (29.8%) cases of SIPS0, 103 (49.5%) cases of SIPS1, and 43 (20.7%) cases of SIPS2, were categorized into three groups based on SIPS. Among patients with SIPS2, the oldest age (P=0.006), lowest BMI (P=0.001), longest tumor length (P=0.001), most advanced ypT stage (P=0.014), and ypN stage (P<0.001) were identified. Pathological complete response (PCR) rates showed statistically significant variations between the three groups (SIPS0: 45.2%, SIPS1: 27.2%, SIPS2: 16.3%, P=0.004). All TRAEs were found in 63.9% (133 cases) of the cases, with serious TRAEs (grade 3-4) accounting for 13.9% (29 cases). TRAEs themselves were not linked with SIPS (P=0.668), while serious TRAEs had a significant correlation with SIPS (P=0.002). Multivariate logistic analysis showed that SIPS2 seemed to confer serious TRAEs [odds radio (OR)=4.044; 95% CI: 1.395-11.722; P=0.010]. For patients classified as SIPS0, 1, or 2, the 3-year DFS was 83.9%, 58.3%, and 39.5% (P<0.001). The 3-year OS for those with SIPS0, 1, or 2 was 88.7%, 72.8%, and 53.5%, respectively (P<0.001). SIPS was substantially correlated with DFS (but not with OS) and could be utilized as an independent predictor [SIPS2: hazard ratio (HR)=3.743, 95% CI: 1.770-7.914, P=0.001; SIPS1: HR=2.303, 95% CI: 1.149-4.616, P=0.019]. Conclusion: The SIPS is associated with serious TRAEs and can be used as a predictor of serious TRAEs in ESCC receiving NICT. SIPS may be employed for pretreatment assessment since it was found to be substantially correlated with DFS.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Masculino , Feminino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Terapia Neoadjuvante/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Adulto , Resultado do Tratamento , Estadiamento de Neoplasias , Inflamação/etiologiaRESUMO
The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.
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Background: For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. Methods: This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. Results: The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. Conclusion: In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.
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Carcinoma Hepatocelular , Progressão da Doença , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , China , Idoso , Adulto , Estadiamento de Neoplasias , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/análise , Resultado do Tratamento , População do Leste AsiáticoRESUMO
Rapid, portable, and accurate detection tools for monitoring ochratoxin A (OTA) in food are essential for the guarantee of food safety and human health. Herein, as a proof-of-concept, this study proposed a ratiometric bioluminescence immunosensor (RBL-immunosensor) for homogeneous detection of OTA in pepper. The construct of the RBL-immunosensor consists of three components, including the large fragment of the split nanoluciferase (NanoLuc)-tagged nanobody (NLg), the small fragment of the split NanoLuc-tagged mimotope peptide heptamer (MPSm), and the calibrator luciferase (GeNL). The specific nanobody-mimotope peptide interaction between NLg and MPSm induces the reconstitution of the NanoLuc, which catalyzes the Nano-Glo substrate and produces a blue emission peak at 458 nm. Meanwhile, GeNL can produce a green emission peak at 518 nm upon substrate conversion via bioluminescent resonance energy transfer (BRET). Therefore, the concentration of OTA can be linked to the variation of the bioluminescence signal (λ458/λ518) measured by microplate reader and the variation of the blue/green ratio measured by smartphone via the competitive immunoreaction where OTA competes with MPSm to bind NLg. The immunosensor is ready-to-use and works by simply mixing the components in a one-step incubation of 10 min for readout. It has a limit of detection (LOD) of 0.98 ng/mL by a microplate reader and an LOD of 1.89 ng/mL by a smartphone. Good selectivity and accuracy were confirmed for the immunosensor by cross-reaction analysis and recovery experiments. The contents of OTA in 10 commercial pepper powder samples were tested by the RBL-immunosensor and validated by high-performance liquid chromatography. Hence, the ready-to-use RBL-immunosensor was demonstrated as a highly reliable tool for detection of OTA in food.
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Técnicas Biossensoriais , Capsicum , Contaminação de Alimentos , Limite de Detecção , Medições Luminescentes , Ocratoxinas , Ocratoxinas/análise , Técnicas Biossensoriais/métodos , Contaminação de Alimentos/análise , Medições Luminescentes/métodos , Imunoensaio/métodos , Capsicum/química , HumanosRESUMO
Physical unclonable functions (PUFs) have emerged as a promising encryption technology, utilizing intrinsic physical identifiers that offer enhanced security and tamper resistance. Multi-level PUFs boost system complexity, thereby improving system reliability and fault tolerance. However, crosstalk-free multi-level PUFs remain a persistent challenge. In this study, a hierarchical PUF system that harnesses the spontaneous phase separation of silk fibroin /PVA blend and the random distribution of silicon-vacancy diamonds within the blend is presented. The thermodynamic instability of phase separation and inherent unpredictability of diamond dispersion gives rise to intricate random patterns at two distinct scales, enabling time-efficient hierarchical authentication for cryptographic keys. These patterns are complementary yet independent, inherently resistant to replication and damage thus affording robust security and reliability to the proposed system. Furthermore, customized authentication algorithms are constructed: visual PUFs authentication utilizes neural network combined structural similarity index measure, while spectral PUFs authentication employs Hamming distance and cross-correlation bit operation. This hierarchical PUF system attains a high recognition rate without interscale crosstalk. Additionally, the coding capacity is exponentially enhanced using M-ary encoding to reinforce multi-level encryption. Hierarchical PUFs hold significant potential for immediate application, offering unprecedented data protection and cryptographic key authentication capabilities.
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OBJECTIVE: The geriatric nutritional risk index (GNRI) is a novel nutrition-related indicator designed to predict the risk of clinical outcomes in various cancers. The clinical significance of risk assessment, therapeutic response, and prognostic prediction of GNRI in esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunochemotherapy (NICT), a hot point of treatment these days, have not been documented in any research. METHODS: Two hundred and twenty-four cases with ESCC who underwent radical resection after NICT were retrospectively recruited. Using the calculation formula of GNRI (1.489 × albumin (g/L) + 41.7 × current weight/ideal weight), the cases were split into two cohorts. Analysis was done on the connections between GNRI and clinical outcomes, such as clinical features, postoperative complications, and pathological complete response (pCR). Prognostic factors of overall survival (OS) and disease-free survival (DFS) were also performed. RESULTS: Patients were then categorized as low (n = 139) or high (n = 85) group based on the threshold. After radical surgery, 67 patients achieved pCR (29.9%). Higher pCR rates were attained by patients in the high GNRI group (41.2% vs. 23.0%, P = 0.004). Lower GNRI patients experienced a considerably higher severe morbidity (36.7% vs. 23.5%, P = 0.040), particularly in the case of respiratory complications (28.8% vs. 14.1%, P = 0.012). Compared to high GNRI patients, lower GNRI cases had inferior 3-year OS (68.5% vs. 87.3%, P = 0.003) and DFS (64.8% vs. 81.5%, P = 0.002). It was also discovered that GNRI was a significant independent variable of both DFS [hazard ratios (HR) = 0.436, P = 0.009] and OS (HR = 0.294, P = 0.012). CONCLUSION: The GNRI, based on nutrition-related indicators, was independently related to postoperative complications, pCR prediction, and prognostication in ESCC receiving NICT.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Avaliação Geriátrica , Terapia Neoadjuvante , Avaliação Nutricional , Humanos , Masculino , Feminino , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Medição de Risco , Estado Nutricional , Esofagectomia , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Imunoterapia/métodos , Intervalo Livre de Doença , Taxa de Sobrevida , Relevância ClínicaRESUMO
Concurrently achieving high growth rate and high quality in single-crystal diamonds (SCDs) is significantly challenging. The growth rate of SCDs synthesized by microwave plasma chemical vapor deposition (MPCVD) was enhanced by introducing N2 into the typical CH4-H2 gas mixtures. The impact of nitrogen vacancy (NV) center concentration on growth rate, surface morphology, and lattice binding structure was investigated. The SCDs were characterized through Raman spectroscopy, photoluminescence (PL) spectroscopy, and X-ray photoelectron spectroscopy. It was found that the saturation growth rate was increased up to 45 µm/h by incorporating 0.8-1.2% N2 into the gas atmosphere, which is 4.5 times higher than the case without nitrogen addition. Nitrogen addition altered the growth mode from step-flow to bidimensional nucleation, leading to clustered steps and a rough surface morphology, followed by macroscopically pyramidal hillock formation. The elevation of nitrogen content results in a simultaneous escalation of internal stress and defects. XPS analysis confirmed chemical bonding between nitrogen and carbon, as well as non-diamond carbon phase formation at 0.8% of nitrogen doping. Furthermore, the emission intensity of NV-related defects from PL spectra changed synchronously with N2 concentrations (0-1.5%) during diamond growth, indicating that the formation of NV centers activated the diamond lattice and facilitated nitrogen incorporation into it, thereby accelerating chemical reaction rates for achieving high-growth-rate SCDs.
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The quest for solar-blind photodetectors (SBPDs) with exceptional optoelectronic properties for imaging applications has prompted the investigation of SBPD arrays. Ga2O3, characterized by its ultrawide bandgap and low growth cost, has emerged as a promising material for solar-blind detection. In this study, SBPD arrays were fabricated by weaving Sn-doped ß-Ga2O3 microbelts (MBs). These MBs, which have a conductive core surrounded by a high-resistivity depletion surface layer resulting from the segregation of Sn and oxygen, are woven into a grid structure. Each intersection of the MBs functions as a photodetector pixel, with the intersecting MBs serving as the output electrodes of the pixel. This design simplifies the readout circuit for the photodetector array. The solar-blind photodetector array demonstrates superior solar-blind detection performance, including a dark current of 0.5 pA, a response time of 38.8 µs, a light/dark current ratio of 108, and a responsivity of 300 A/W. This research may provide a feasible strategy for the fabrication of photodetector arrays, thus pushing forward the application of photodetectors in imaging.
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Regeneration of the architecturally complex blood vascular system requires precise temporal and spatial control of cell behaviours. Additional components must be integrated into the structure to achieve clinical success for in situ tissue engineering. Consequently, this study proposed a universal method for including any substrate type in vascular cell extracellular matrices (VCEM) via regulating selective adhesion to promote vascular tissue regeneration. The results uncovered that the VCEM worked as cell adhesion substrates, exhibited cell type specificity, and functioned as an address signal for recognition by vascular cells, which resulted in matching with the determined cells. The qPCR and immunofluorescence results revealed that a cell type-specific VCEM could be designed to promote or inhibit cell adhesion, consistenting with the expression patterns of eyes absent 3 (Eya3). In addition, a 3D vascular graft combined with VCEM which could recapitulate the vascular cell-like microenvironment was fabricated. The vascular graft revealed a prospective role for cellular microenvironment in the establishment of vascular cell distribution and tissue architecture, and potentiated the orderly regeneration and functional recovery of vascular tissues in vivo. The findings demonstrate that differential adhesion between cell types due to the cellular microenvironment is sufficient to drive the complex assembly of engineered blood vessel functional units, and underlies hierarchical organization during vascular regeneration.
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There is currently an urgent need to develop engineered scaffolds to support new adipose tissue formation and facilitate long-term maintenance of function and defect repair to further generate prospective bioactive filler materials capable of fulfilling surgical needs. Herein, adipose regeneration methods were optimized and decellularized adipose tissue (DAT) scaffolds with good biocompatibility were fabricated. Adipose-like tissues were reconstructed using the DAT and 3T3-L1 preadipocytes, which have certain differentiation potential, and the regenerative effects of the engineered adipose tissuesin vitroandin vivowere explored. The method improved the efficiency of adipose removal from tissues, and significantly shortened the time for degreasing. Thus, the DAT not only provided a suitable space for cell growth but also promoted the proliferation, migration, and differentiation of preadipocytes within it. Following implantation of the constructed adipose tissuesin vivo, the DAT showed gradual degradation and integration with surrounding tissues, accompanied by the generation of new adipose tissue analogs. Overall, the combination of adipose-derived extracellular matrix and preadipocytes for adipose tissue reconstruction will be of benefit in the artificial construction of biomimetic implant structures for adipose tissue reconstruction, providing a practical guideline for the initial integration of adipose tissue engineering into clinical medicine.
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Tecido Adiposo , Alicerces Teciduais , Alicerces Teciduais/química , Estudos Prospectivos , Matriz Extracelular/metabolismo , Diferenciação Celular , Engenharia TecidualRESUMO
Along with the increasing integration density and decreased feature size of current semiconductor technology, heterointegration of the Si-based devices with diamond has acted as a promising strategy to relieve the existing heat dissipation problem. As one of the heterointegration methods, the microwave plasma chemical vapor deposition (MPCVD) method is utilized to synthesize large-scale diamond films on a Si substrate, while distinct structures appear at the Si-diamond interface. Investigation of the formation mechanisms and modulation strategies of the interface is crucial to optimize the heat dissipation behaviors. By taking advantage of electron microscopy, the formation of the epitaxial ß-SiC interlayer is found to be caused by the interaction between the anisotropically sputtered Si and the deposited amorphous carbon. Compared with the randomly oriented ß-SiC interlayer, larger diamond grain sizes can be obtained on the epitaxial ß-SiC interlayer under the same synthesis condition. Moreover, due to the competitive interfacial reactions, the epitaxial ß-SiC interlayer thickness can be reduced by increasing the CH4/H2 ratio (from 3% to 10%), while further increase in the ratio (to 20%) can lead to the broken of the epitaxial relationship. The above findings are expected to provide interfacial design strategies for multiple large-scale diamond applications.
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OBJECTIVE: First, the efficacy and safety of aspirin-ticagrelor after cerebral artery stenting in ischemic stroke patients is controversial. Second, there is a gap in the research on guiding two antiplatelet therapy (DAPT) after stenting based on the CYP2C19 genotype. METHODS: This retrospective study included patients who underwent cerebral artery stenting at the First Affiliated Hospital of Chongqing Medical University from January 2019 to February 2023. We divided them into the aspirin-clopidogrel group and aspirin-ticagrelor group and carefully collected baseline information laboratory data and imaging results from the patients. The efficacy outcomes were 30 days recurrent stroke, 90 days recurrent stroke, and 180 days recurrent stroke, and the safety outcome was intracranial hemorrhage. T-tests or Fisher's tests were performed for study outcomes in both groups of patients. OUTCOME: A total of 372 patients were included. For efficacy outcomes, aspirin-ticagrelor was associated with a reduced risk of 180 days recurrent stroke, in patients with CYP2C19 LOF allele (OR = 0.426, CI = 0.184-0.986, P = 0.042) and CYP2C19 intermediate metabolic genotype (OR = 0.237, CI = 0.026-1.034, P = 0.044), compared with aspirin-clopidogrel. There was no significant difference in the rate of intracranial hemorrhage (ICH) between patients with aspirin-clopidogrel and aspirin-ticagrelor, regardless of overall (OR = 1.221, CI = 0.115-7.245, P = 0.683), CYP2C19 LOF allele carriers (OR = 1.226, CI = 0.411-3.658, P = 0.715), or CYP2C19 intermediate metabolizer (OR = 1.221, CI = 0.115-7.245, P = 0.683). No significant differences were found between the two DAPTs on other efficacy and safety outcomes. CONCLUSION: A cohort study found that aspirin-ticagrelor was significantly superior to aspirin-clopidogrel in reducing 180 days recurrent stroke in CYP2C19 LOF allele carriers and CYP2C19 intermediate metabolizers. There was no significant difference between aspirin-ticagrelor and aspirin-clopidogrel in the risk of intracranial hemorrhage in terms of ICH rates.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Clopidogrel/uso terapêutico , Ticagrelor/efeitos adversos , Aspirina/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Estudos de Coortes , Estudos Retrospectivos , Hemorragias Intracranianas/induzido quimicamente , Artérias Cerebrais , Acidente Vascular Cerebral/genética , Resultado do TratamentoRESUMO
Background: Potentially substantial impacts on the prognosis have been observed in individuals undergoing endovascular treatment due to cytochrome P450 2c19 (CYP2C19) polymorphism. In an attempt to improve prognosis and lower the recurrence rate, this study investigated the CYP2C19 polymorphism in acute ischemic stroke patients. Materials and Methods: A retrospective analysis was performed on 292 patients with cerebral infarction who had acute endovascular recanalization at the Department of Neurology of Chongqing Hospital of Traditional Chinese Medicine between May 2017 and 2019. The patients were categorized into rapid-, medium-, and slow-metabolism groups based on CYP2C19 gene polymorphism, and their prognosis was monitored. In addition, the prognosis of 188 patients selectively receiving carotid artery stenting at a selected time was also observed. Results: Among the 292 cerebral infarction cases receiving acute endovascular recanalization, the patients in the CYP2C19 rapid-metabolism group regularly took clopidogrel and aspirin combined with antiplatelet therapy and suffered from reoccurrence of apoplexy and cerebral hemorrhage; the 90-day good prognosis had a statistical difference (P < 0.05, prognostic assessment includes hospitalization and 6 months after discharge) and the other adverse events had no statistical difference (including mortality). The 188 patients selectively receiving carotid artery stenting had a recurrence of apoplexy, cerebral hemorrhage, and restenosis rate with a statistical difference (P < 0.05), and the other adverse events had no statistical difference. Conclusions: In conclusion, the findings of the current study indicate that irrespective of whether patients are undergoing selective carotid artery stenting or acute endovascular recanalization, those with rapid CYP2C19 metabolism have a significantly lower likelihood of experiencing adverse prognostic events compared to those with intermediate and slow metabolism. Furthermore, this group also has a more favorable prognosis than the other two groups.