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Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.
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Asma , Medicamentos de Ervas Chinesas , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Inteligência Artificial , Medicina Tradicional Chinesa/métodos , Asma/tratamento farmacológico , Aprendizado de Máquina SupervisionadoRESUMO
Novel evanescently coupled waveguide modified uni-traveling carrier photodiodes (MUTC-PDs) employing a thick multi-layer coupling waveguide are reported. To improve the optical-to-electrical (O/E) conversion efficiency, a thick multi-layer coupling waveguide with a gradually increased refractive index from the bottom layer to the absorption layer is utilized. The refractive index profile facilitates the upward transmission of incident light into the absorption region, thereby enhancing the evanescent coupling efficiency. Meanwhile, the coupling waveguide, with a total thickness of 1.75 µm, expands the mode field diameter, thereby reducing the input coupling loss. Additionally, the top layer of the coupling waveguide also serves as the drift layer. This configuration facilitates efficient light absorption within a short PD length, thus ensuring ultrawide bandwidth and high O/E conversion efficiency simultaneously. Without an additional spot size coupler or anti-reflection coating, the measured responsivity is as high as 0.38 A/W for the PD with an active area of 5 × 6 µm2. Meanwhile, an ultrawide 3-dB bandwidth of 153 GHz has been demonstrated.
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Mueller matrix microscopy can provide comprehensive polarization-related optical and structural information of biomedical samples label-freely. Thus, it is regarded as an emerging powerful tool for pathological diagnosis. However, the staining dyes have different optical properties and staining mechanisms, which can put influence on Mueller matrix microscopic measurement. In this Letter, we quantitatively analyze the polarization enhancement mechanism from hematoxylin and eosin (H&E) staining in multispectral Mueller matrix microscopy. We examine the influence of hematoxylin and eosin dyes on Mueller matrix-derived polarization characteristics of fibrous tissue structures. Combined with Monte Carlo simulations, we explain how the dyes enhance diattenuation and linear retardance as the illumination wavelength changed. In addition, it is demonstrated that by choosing an appropriate incident wavelength, more visual Mueller matrix polarimetric information can be observed of the H&E stained tissue sample. The findings can lay the foundation for the future Mueller matrix-assisted digital pathology.
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Coloração e Rotulagem , Microscopia de Polarização/métodos , Amarelo de Eosina-(YS)/química , Método de Monte Carlo , Hematoxilina , HumanosRESUMO
Flexible engineering of the complex shapes of the surface nanoscale axial photonics (SNAP) bottle microresonators (SBMs) is challenging for future nanophotonic technology applications. Here, we experimentally propose a powerful approach for the one-step fabrication of SBMs with simultaneous negative and positive radius variations, exhibiting a distinctive "bump-well-bump" profile. It is executed by utilizing two focused and symmetrical CO2 laser beams exposed on the fiber surface for only several hundred milliseconds. The spectral characteristics of different eigenmodes are analyzed, providing deep insights into the complex physical processes during the CO2 laser exposure. The shapes of the SBMs can be flexibly adjusted by the exposure time, laser power, and applied pre-strains. As a proof of this technique, the developed approach enables the efficient production of a bat SBM, ensuring a uniform field amplitude of the bat mode over the length exceeding 120â µm with 7% deviation. Our proposed technique provides a powerful technique for the efficient fabrication of SBMs with predetermined shapes, laying the groundwork for its applications on microscale optical signal processing, quantum computing, and so on.
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PURPOSE: Anemia is relatively common in cancer patients, and is associated with poor survival in patients with various malignancies. However, how anemia would affect prognosis and response to neoadjuvant chemotherapy (NAC) in osteosarcoma (OS) is still without substantial evidence. METHODS: We retrospectively analysed 242 patients with stage II OS around the knee joint in our institute. Changed hemoglobin (Hb) levels (before and after NAC) were recorded to assess the prognostic value in DFS (disease-free survival) and tumor response to NAC. Univariate and multivariate analyses were conducted to identify prognostic factors related with outcome in OS patients. RESULTS: The mean Hb level significantly decreased after NAC (134.5 ± 15.3 g/L vs. 117.4 ± 16.3 g/L). The percentage of mild (21%), moderate (4.2%) and severe (0%) anemia patients markedly increased after NAC: 41%, 24% and 4.1% respectively. There was higher percentage of ≥ 5% Hb decline in patients with tumor necrosis rate < 90% (141 out of 161), compared with those with tumor necrosis rate ≥ 90% (59 out of 81). Further univariate and survival analysis demonstrated that Hb decline had a significant role in prediction survival in OS patients. Patients with ≥ 5% Hb decline after NAC had an inferior DFS compared with those with < 5% Hb decline. CONCLUSION: In osteosarcoma, patients with greater Hb decrease during neoadjuvant treatment were shown to have worse DFS and a poorer response to NAC than those without. Attempts to correct anemia and their effects on outcomes for osteosarcoma patients should be explored in future studies.
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Anemia , Neoplasias Ósseas , Hemoglobinas , Articulação do Joelho , Terapia Neoadjuvante , Osteossarcoma , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Terapia Neoadjuvante/métodos , Hemoglobinas/análise , Adulto , Prognóstico , Anemia/etiologia , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Adulto Jovem , Criança , Articulação do Joelho/patologia , Intervalo Livre de Doença , Pessoa de Meia-Idade , Análise Multivariada , Quimioterapia Adjuvante/métodos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Osteoporosis vertebral compression fracture (OVCF) secondary to osteoporosis is a common health problem in the elderly population. Vertebral augmentation (VA) has been widely used as a minimally invasive surgical method. The transpedicle approach is commonly used for VA puncture, but sometimes, it is limited by the anatomy of the vertebral body and can not achieve good surgical results. Therefore, we propose the treatment of OVCF with precise puncture vertebral augmentation (PPVA). This study used finite element analysis to explore the biomechanical properties of PPVA in the treatment of osteoporotic vertebral compression fractures (OVCFs) with wedge, biconcave, and collapse deformities. METHOD: Three-dimensional finite element models of the fractured vertebral body and adjacent superior and inferior vertebral bodies were established using Computed Tomography (CT) data from patients with OVCF, both before and after surgery. Evaluate the stress changes of the wedged deformed vertebral body, biconcave deformed vertebral body, collapsed deformed vertebral body, and adjacent vertebral bodies before and after PPVA. RESULT: In vertebral bodies with wedge deformity and collapsed deformity, PPVA can effectively reduce the stress on the vertebral body but increases the stress on the vertebral body with biconcave deformity. PPVA significantly decreases the stress on the adjacent vertebral bodies of the wedge deformed vertebral body, and decreases the stress on the adjacent superior vertebral body of biconcave deformity and collapsed deformed vertebral bodies, but increases the stress on the adjacent inferior vertebral bodies. PPVA improves the stress distribution of the vertebral body and prevents high-stress areas from being concentrated on one side of the vertebral body. CONCLUSION: PPVA has shown positive surgical outcomes in treating wedge deformed and collapsed deformed vertebral bodies. However, its effectiveness in treating biconcave vertebral body is limited. Furthermore, PPVA has demonstrated favorable results in addressing adjacent superior vertebral body in three types of fractures.
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Análise de Elementos Finitos , Fraturas por Compressão , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Fraturas por Compressão/cirurgia , Fraturas por Compressão/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Idoso , Feminino , Masculino , Tomografia Computadorizada por Raios X , Vertebroplastia/métodos , Idoso de 80 Anos ou mais , Punções , Imageamento Tridimensional , Resultado do Tratamento , Fenômenos Biomecânicos , Corpo Vertebral/cirurgia , Corpo Vertebral/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the biomechanical effects of percutaneous vertebroplasty combined with cement pedicle plasty (PVCPP) on the unstable osteoporotic vertebral fractures (OVFs) through finite element (FE) analysis. The study compares the biomechanical stability of finite element models between percutaneous vertebroplasty (PVP) and percutaneous vertebroplasty combined with cement pedicle plasty. METHODS: Two patients with unstable OVFs underwent computed tomography (CT) examination at the thoracolumbar vertebral body levels, respectively. The CT images were reconstructed into three-dimensional finite element models to simulate stress conditions across six dimensions and to evaluate the vertebral von Mises stress before and after bone cement reinforcement. RESULTS: The study found that stress distribution differed between groups mainly at the pedicle base. In the surgical vertebral bodies, the maximum stress in the PVP group decreased during flexion and left bending, while it increased in other states. In the PVCPP group, all maximum stresses decreased. In the inferior vertebral bodies, the maximum stress in the PVP group generally increased, while it decreased in the PVCPP group. In the superior vertebral bodies, postoperatively, the maximum stress in the PVP group generally increased, while it almost remained unchanged in the PVCPP group. PVP group had higher cement stress and displacement. CONCLUSION: PVCPP is an effective treatment method for patients with unstable OVFs. It can quickly relieve pain and enhance the stability of the three columns, thereby reducing the risk of some complications.
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Cimentos Ósseos , Análise de Elementos Finitos , Vértebras Lombares , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Humanos , Vertebroplastia/métodos , Fenômenos Biomecânicos/fisiologia , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/fisiopatologia , Feminino , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Idoso , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/fisiopatologia , Vértebras Torácicas/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Masculino , Estresse Mecânico , Idoso de 80 Anos ou maisRESUMO
The development of Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors is a hot spot in the research and development of antitumor drugs, which may induce immunomodulatory effects in the tumor microenvironment and participate in anti-tumor immune responses. To date, several SHP2 inhibitors have made remarkable progress and entered clinical trials for the treatment of patients with advanced solid tumors. Multiple compounds derived from natural products have been proved to influence tumor cell proliferation, apoptosis, migration and other cellular functions, modulate cell cycle and immune cell activation by regulating the function of SHP2 and its mutants. However, there is a paucity of information about their diversity, biochemistry, and therapeutic potential of targeting SHP2 in tumors. This review will provide the structure, classification, inhibitory activities, experimental models, and antitumor effects of the natural products. Notably, this review summarizes recent advance in the efficacy and pharmacological mechanism of natural products targeting SHP2 in inhibiting the various signaling pathways that regulate different cancers and thus pave the way for further development of anticancer drugs targeting SHP2.
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Immune checkpoint inhibitors (ICIs) are currently one of the most popular treatment methods for cancers. Several ICIs have been approved in China and the United States. We created a database of approved ICIs by extracting the information of interest from the drug labels and reviewing documents disclosed on the official websites of the US Food and Drug Administration (FDA) and the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) and compared the difference between the marketed ICIs in China and the United States regarding the number of indications, tumor types, review time, treatment setting, and so forth. Until June 30, 2022, 9 and 15 ICIs had been approved for 86 and 58 indications in the United States and China, involving 20 and 14 types of tumors, respectively. The correlation between indications and disease incidence was higher in China (r = 0.64) than in the United States (r = 0.45). About half of the indications were approved as first-line therapies in combination with chemotherapy, target therapy, or immunotherapy. Over 30% of indications were approved under accelerated or conditional approval in the two countries. A shorter regulatory review time was required by the FDA (median:181 days) compared to the NMPA (median: 279 days) for the new indication approval. Five ICIs marketed in China were approved by the FDA before the NMPA, with the median launch delay for the same indication of 344 days in China. A differentiated clinical development program that focuses on meeting unmet needs may bring new success for subsequent ICI products.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Estados Unidos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , China , Imunoterapia/métodosRESUMO
Non-tuberculosis mycobacteria (NTM) is one family of pathogens usually leading to nosocomial infections. Exploration of high-performance biological recognition agent plays a pivotal role for the development of point-of-care testing device and kit for detecting NTM. Mycobacterium smegmatis (M. smegmatis) is a NTM which has been frequently applied as an alternative model for highly pathogenic mycobacteria. Herein, a recombinant tail protein derived from mycobacteriophage SWU1 infecting M. smegmatis was expressed with Escherichia coli system and noted as GP89. It shows a fist-like structure according to the results of homology modeling and ab initio modeling. It is confirmed as a lipoarabinomannan (LAM) binding protein, which can recognize studied NTM genus since abundant LAM constructed with d-mannan and d-arabinan is distributed over the mycobacterial surface. Meanwhile an enhanced green fluorescent protein (eGFP)-fused GP89 protein was acquired with a fusion expression technique. Then GP89 and eGFP-fused GP89 were applied to establish a sensitive and rapid method for fluorescent detection of M. smegmatis with a broad linear range of 1.0 × 102 to 1.0 × 106 CFU mL-1 and a low detection limit of 69 CFU mL-1. Rapid and reliable testing of antimicrobial susceptibility was achieved by the GP89-based fluorescent method. The present work provides a promising recognition agent for studied NTM and opens an avenue for clinical diagnosis of NTM-induced infections.
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Micobacteriófagos , Mycobacterium tuberculosis , Mycobacterium , Proteínas de Transporte , Micobactérias não Tuberculosas , Mycobacterium smegmatisRESUMO
The ultrasensitive and quantitative detection of renal cancer protein biomarkers present at ultralow concentrations for early-stage cancer diagnosis requires a biosensing probe possessing ultrahigh detection sensitivity and remarkable biosensing selectivity. Here, we report an optical microfiber integrated with Ti3C2-supported gold nanorod hybrid nanointerfaces for implementation in ultrasensitive sensing of the carbonic anhydrase IX (CAIX) protein and renal cancer cells. Because the evanescent field of the fiber is strongly coupled with nanointerfaces in the near-infrared region, the proposed optical microfiber biosensor achieves ultrahigh-sensitivity detection of the CAIX protein biomarker with ultralow limits of detection (LODs) of 13.8 zM in pure buffer solution and 0.19 aM in 30% serum solution. In addition, the proposed sensor also successfully and specifically recognizes living renal cancer cells in cell culture media with a LOD of 180 cells/mL. This strategy may serves as a powerful biosensing platform that combines the quantification of protein biomarkers and cancer cells, resulting in a higher accuracy of early-stage renal cancer diagnosis and screenings.
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Técnicas Biossensoriais , Neoplasias Renais , Nanotubos , Humanos , Ouro , Titânio , Técnicas Biossensoriais/métodos , Limite de Detecção , Antígeno Carcinoembrionário , Neoplasias Renais/diagnósticoRESUMO
BACKGROUND: Waterlogging is one of the major abiotic stresses in barley and greatly reduces grain yield and quality. To explore the mechanism controlling waterlogging tolerance in barley, physiological, anatomical and transcriptional analyses were performed in two contrasting barley varieties, viz. Franklin (susceptible) and TX9425 (tolerant). RESULTS: Compared to Franklin, TX9425 had more adventitious roots and aerenchymas and higher antioxidant enzyme activities. A total of 3064 and 5693 differentially expressed genes (DEGs) were identified in TX9425 after 24 h and 72 h of waterlogging treatment, respectively, while 2297 and 8462 DEGs were identified in Franklin. The results suggested that TX9425 was less affected by waterlogging stress after 72 h of treatment. The DEGs were enriched mainly in energy metabolism, hormone regulation, reactive oxygen species (ROS) scavenging, and cell wall-modifying enzymes. Alcohol dehydrogenase (ADH) plays an important role in response to waterlogging stress. We found that HvADH4 was significantly upregulated under waterlogging stress in TX9425. Transgenic Arabidopsis overexpressing HvADH4 displayed higher activity of antioxidant enzymes and was more tolerant to waterlogging than the wild type (WT). CONCLUSIONS: The current results provide valuable information that will be of great value for the exploration of new candidate genes for molecular breeding of waterlogging tolerance in barley.
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Arabidopsis , Hordeum , Hordeum/genética , Arabidopsis/genética , Antioxidantes , Perfilação da Expressão Gênica , Raízes de Plantas/genética , Estresse Fisiológico/genéticaRESUMO
BACKGROUND: Cell-based immunotherapy shows the therapeutic potential in sarcomas, in addition to angiogenesis-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI). Multi-antigen stimulated cell therapy-I (MASCT-I) technology is a sequential immune cell therapy for cancer, which composes of multiple antigen-loaded dendritic cell (DC) vaccines followed by the adoptive transfer of anti-tumor effector T-cells. METHODS: In this phase 1 study, we assessed MASCT-I plus camrelizumab (an ICI against PD-1) and apatinib (a highly selective TKI targeting VEGFR2) in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma after at least one line of prior systemic therapy. One MASCT-I course consisted of 3 DC subcutaneous injections, followed by 3 active T cell infusions administered 18-27 days after each DC injection. In schedule-I group, 3 DC injections were administered with a 28-day interval in all courses; in schedule-II group, 3 DC injections were administered with a 7-day interval in the first course and with a 28-day interval thereafter. All patients received intravenous camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg daily. RESULTS: From October 30, 2019, to August 12, 2021, 19 patients were enrolled and randomly assigned to schedule-I group (n = 9) and schedule-II group (n = 10). Of the 19 patients, 11 (57.9%) experienced grade 3 or 4 treatment-related adverse events. No treatment-related deaths occurred. Patients in schedule-II group showed similar objective response rate (ORR) with those in schedule-I group (30.0% versus 33.3%) but had higher disease control rate (DCR; 90.0% versus 44.4%) and longer median progression-free survival (PFS; 7.7 versus 4.0 months). For the 13 patients with soft-tissue sarcomas, the ORR was 30.8%, DCR was 76.9%, and median PFS was 12.9 months; for the 6 patients with osteosarcomas, the ORR was 33.3%, the DCR was 50.0%, and median PFS was 5.7 months. CONCLUSIONS: Overall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04074564.
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Sarcoma , Humanos , Projetos Piloto , Sarcoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Platinum group metal (PGM)-free M-N-C catalysts have exhibited dramatic electrocatalytic performance and are considered the most promising candidate of the Pt catalysts in oxygen reduction reaction (ORR). However, the electrocatalytic performance of the M-N-C catalysts is still limited by their inferior intrinsic activity and finite active site density. Regulating the coordination environment and increasing the pore structure of the catalyst is an effective strategy to enhance the electrocatalytic performance of the M-N-C catalysts. In this work, the coordination environment and pore structure exquisitely regulated Fe-N-C catalyst exhibit excellent ORR activity and durability. With the enhanced intrinsic activity and increased active site density, the optimized Fe-N/S-C catalyst shows impressive ORR activity (E1/2 = 0.904 V vs reversible hydrogen electrode (RHE)) and superior long-term durability in an alkaline medium. As the advanced physical characterization and theoretical chemistry methods illustrate, the S-modified Fe-Nx (Fe-N3 /S-C) moiety is confirmed as the improved active center for ORR, and the increased active site density further improved ORR efficiency. Based on the Fe-N/S-C cathode, a Zn-air battery is fabricated and shows superior power density (315.4 mW cm-2 ) and long-term discharge stability at 20 mA cm-2 . This work would open a new perspective to design atomically dispersed iron-metal site catalysts for advanced electro-catalysis.
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Oxygen electrocatalysis has aroused considerable interest over the past years because of the new energy technologies boom in hydrogen energy and metal-air battery. However, due to the sluggish kinetic of the four-electron transfer process in oxygen reduction reaction and oxygen evolution reaction, the electro-catalysts are urgently needed to accelerate the oxygen electrocatalysis. Benefit from the high atom utilization efficiency, unprecedentedly high catalytic activity, and selectivity, single-atom catalysts (SACs) are considered the most promising candidate to replace the traditional Pt-group-metal catalysts. Compared with SACs, the dual-atom catalysts (DACs) are attracting more attraction including higher metal loading, more versatile active sites, and excellent catalytic activity. Therefore, it is essential to explore the new universal methods approaching to the preparation, characterization, and to elucidate the catalytic mechanisms of the DACs. In this review, several general synthetic strategies and structural characterization methods of DACs are introduced and the involved oxygen catalytic mechanisms are discussed. Moreover, the state-of-the-art electrocatalytic applications including fuel cells, metal-air batteries, and water splitting have been sorted out at present. The authors hope this review has given some insights and inspiration to the researches about DACs in electro-catalysis.
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Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.
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Remodelação das Vias Aéreas , Asma , Animais , Humanos , Camundongos , Asma/metabolismo , Interleucinas/metabolismo , Pulmão/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Pyroglyphidae , Camundongos Endogâmicos BALB CRESUMO
Novel back-illuminated modified uni-traveling-carrier photodiodes (MUTC-PDs) with wide bandwidth and high saturation power are demonstrated. The effect of cliff layer doping on the electric field distribution is investigated to achieve fast carrier transport. MUTC-PDs with miniaturized device diameter and low contact resistance are fabricated to improve the RC-limited bandwidth. Meanwhile, inductive peaking is implemented to further extend the bandwidth. PDs with 3-µm and 3.6-µm-diameter exhibit a ultrawide bandwidth of 230â GHz and 200â GHz, together with -4.94 dBm and -2.14 dBm saturation power at 220â GHz and 200â GHz, respectively.
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The ray-mapping method has been widely used for designing freeform illumination lenses. However, in non-paraxial or off-axis situations, it remains challenging to obtain an integrable ray-mapping, often requiring a complex iterative correction process for the initial mapping. To address this challenge, we propose an extended ray-mapping method that incorporates differentiable ray-tracing into the design pipeline of the ray-mapping method. This enables accurate surface construction according to ray-mapping and efficient shape correction based on irradiance distribution. The proposed method involves two optimization stages. In the first stage, the freeform surface is preliminarily optimized to closely match the optimal transport mapping. The obtained freeform surface is then further optimized in the second stage to minimize the divergence between the target and simulated irradiance distributions. Additionally, the mean curvature of the freeform surface is also constrained in the second stage to facilitate the fabrication of the final freeform surface. Non-paraxial illumination lenses and off-axis illumination lenses have been designed using the proposed method within ten minutes, and simulations demonstrate that the approach is effective and robust.
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The dispersion characteristics of a microresonator are important for applications in nonlinear optics, and precise measurement of the dispersion profile is crucial to device design and optimization. Here we demonstrate the dispersion measurement of high-quality-factor gallium nitride (GaN) microrings by a single-mode fiber ring, which is simple and convenient to access. Once the dispersion parameters of the fiber ring have been determined by the opto-electric modulation method, the dispersion can be obtained from the microresonator dispersion profile by polynomial fitting. To further verify the accuracy of the proposed method, the dispersion of the GaN microrings is also evaluated with frequency comb-based spectroscopy. Dispersion profiles obtained with both methods are in good agreement with simulations based on the finite element method.
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BACKGROUND: The effect of autologous hematopoietic stem cell transplantation (auto-HSCT) versus conventional chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the survival of patients with advanced follicular lymphoma (FL) is uncertain. OBJECTIVES: To elucidate this, FL and HSCT were used as keywords to search in PubMed, Embase, Web of Science, and Cochrane Library databases. METHOD: After data extraction and quality evaluation, a total of 13 studies were included, seven of which compared auto-HSCT with conventional chemotherapy and the other six compared allo-HSCT with auto-HSCT to the survival of FL patients. RESULTS: The results showed that auto-HSCT improved overall survival (OS), progression-free survival, and event-free survival of FL patients compared with conventional chemotherapy without auto-HSCT. Compared with allo-HSCT, the patients receiving auto-HSCT had longer OS and lower non-recurrent mortality. CONCLUSIONS: Auto-HSCT can provide a survival advantage for patients with FL compared with conventional chemotherapy and allo-HSCT did not result in a survival benefit.