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Group 2 innate lymphoid cells (ILC2s) are a type of innate immune cells that produce a large amount of IL-5 and IL-13 and two cytokines that are crucial for various processes such as allergic airway inflammation, tissue repair and tissue homeostasis. It is known that damaged epithelial-derived alarmins, such as IL-33, IL-25 and thymic stromal lymphopoietin (TSLP), are the predominant ILC2 activators that mediate the production of type 2 cytokines. In recent years, abundant studies have found that many factors can regulate ILC2 development and function. Hormones synthesized by the body's endocrine glands or cells play an important role in immune response. Notably, ILC2s express hormone receptors and their proliferation and function can be modulated by multiple hormones during allergic airway inflammation. Here, we summarize the effects of multiple hormones on ILC2-driven allergic airway inflammation and discuss the underlying mechanisms and potential therapeutic significance.
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Citocinas , Inmunidad Innata , Linfocitos , Humanos , Inmunidad Innata/inmunología , Animales , Linfocitos/inmunología , Linfocitos/metabolismo , Citocinas/metabolismo , Citocinas/inmunología , Hormonas/metabolismo , Hormonas/inmunología , Inflamación/inmunología , Asma/inmunologíaRESUMEN
OBJECTIVE: The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP. METHODS: We assessed the expression of INPP4A in human and mouse nasal mucosal tissues via immunofluorescence staining. THP-1 cells were cultured and exposed to various cytokines to investigate the regulation of INPP4A expression and its functional role. Additionally, we established a murine nasal polyp (NP) model and administrated an INPP4A-overexpressing lentivirus evaluate its impact on NP. RESULTS: The percentage of INPP4A + CD68 + macrophages among total macrophages decreased in the E-CRSwNP group compared to the control and the non-eosinophilic CRSwNP (NE-CRSwNP) groups, exhibiting an inverse correlation with an increased percentage of CD206 + CD68 + M2 macrophages among total macrophages. Overexpression of INPP4A led to a reduced percentage of THP-1 cells polarizing towards the M2 phenotype, accompanied by decreased levels of associated chemotactic factors including CCL18, CCL22, CCL24, and CCL26. We also validated the involvement of the PI3K-AKT pathway in the function of INPP4A in vitro. Furthermore, INPP4A overexpression in the murine NP model resulted in the attenuation of eosinophilic inflammation in the nasal mucosa. CONCLUSIONS: INPP4A deficiency promotes macrophage polarization towards the M2 phenotype, leading to the secretion of chemokines that recruit eosinophils and Th2 cells, thereby amplifying eosinophilic inflammation in E-CRSwNP. INPP4A may exert a suppressive role in eosinophilic inflammation and could potentially serve as a novel therapeutic strategy.
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Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Animales , Ratones , Fosfatidilinositol 3-Quinasas , Macrófagos , Eosinófilos , Inflamación/complicaciones , Monoéster Fosfórico Hidrolasas/genética , Enfermedad CrónicaRESUMEN
AIMS: Orthodontic treatment commonly results in orthodontically induced inflammatory root resorption (OIIRR). This condition arises from excessive orthodontic force, which triggerslocal inflammatory responses and impedes cementoblasts' mineralization capacity. Low-intensity pulsed ultrasound (LIPUS) shows potential in reducing OIIRR. However, the precise mechanisms through which LIPUS reduces OIIRR remain unclear. This study aimed to explore the effects and mechanisms of LIPUS on the mineralization of force-treated cementoblasts and its impact on OIIRR. METHODS: We established a rat OIIRR model and locally administered LIPUS stimulation for 7 and 14 days. We analyzed root resorption volume, osteoclast differentiation, and the expression of osteocalcin and yes-associated protein 1 (YAP1) using micro-computed tomography (micro-CT), hematoxylin and eosin, tartrate-resistant acid phosphatase, immunofluorescence and immunohistochemistry staining. In vitro, we applied compressive force and LIPUS to the immortalized mouse cementoblasts (OCCM30). We assessed mineralization using alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction, Western blotting and immunofluorescence staining. RESULTS: In rats, LIPUS reduced OIIRR, as evidenced by micro-CT analysis and histological staining. In vitro, LIPUS enhanced mineralization of force-treated OCCM30 cells, as indicated by ALP and alizarin red staining, upregulated mRNA expression of mineralization-related genes, and increased protein expression of mineralization markers. Mechanistically, LIPUS activated YAP1 signaling via the cytoskeleton-Lamin A/C pathway, supported by immunofluorescence and Western blot analysis. CONCLUSION: This study demonstrates that LIPUS promotes mineralization in force-treated cementoblasts and reduces OIIRR by activating YAP1 through the cytoskeletal-Lamin A/C signaling pathway. These findings provide fresh insights into how LIPUS benefits orthodontic treatment and suggest potential strategies for preventing and treating OIIRR.
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Coded aperture compressive temporal imaging (CACTI) utilizes compressive sensing (CS) theory to compress three dimensional (3D) signals into 2D measurements for sampling in a single snapshot measurement, which in turn acquires high-dimensional (HD) visual signals. To solve the problems of low quality and slow runtime often encountered in reconstruction, deep learning has become the mainstream for signal reconstruction and has shown superior performance. Currently, however, impressive networks are typically supervised networks with large-sized models and require vast training sets that can be difficult to obtain or expensive. This limits their application in real optical imaging systems. In this paper, we propose a lightweight reconstruction network that recovers HD signals only from compressed measurements with noise and design a block consisting of convolution to extract and fuse local and global features, stacking multiple features to form a lightweight architecture. In addition, we also obtain unsupervised loss functions based on the geometric characteristics of the signal to guarantee the powerful generalization capability of the network in order to approximate the reconstruction process of real optical systems. Experimental results show that our proposed network significantly reduces the model size and not only has high performance in recovering dynamic scenes, but the unsupervised video reconstruction network can approximate its supervised version in terms of reconstruction performance.
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In the present study, we aimed to investigate the different impacts of temporal processing on reading by Chinese children with and without dyslexia. In total, 27 children with dyslexia who had a deficit in rapid automatized naming (RAN) (D_R), 37 children with dyslexia who had deficits in both RAN and phonological awareness (PA) (D_RP), and 40 typically developing children (TD) were recruited in Taiwan. The children were asked to complete non-verbal intelligence, PA, RAN, Chinese character reading tasks and an auditory temporal order judgement (ATOJ) task. Our results of a multiple regression model showed that the ATOJ accounted for unique variances in the reading differences between the children in the D_R and TD groups; performance was controlled for non-verbal intelligence, PA and RAN tasks. Theoretically, we provide possible explanations for the controversial findings in the field of Chinese children with dyslexia and, practically, suggest different interventions should be provided for children with dyslexia with different underlying impairments.
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Dislexia , Lectura , Humanos , Dislexia/fisiopatología , Niño , Masculino , Femenino , Fonética , Taiwán , Percepción del Tiempo/fisiologíaRESUMEN
Grit, defined as passion and perseverance to achieve long-term goals, has been associated with adolescents' optimal academic and psychological functioning. However, the role of grit in adolescents' positive youth development (PYD)-characterized by the 5Cs known as competence, confidence, connection, character, and caring-remains unknown. Using latent cross-lagged panel modeling, this study examined the longitudinal relations between the triarchic model of grit (TMG) dimensions (i.e., perseverance of effort, consistency of interest, and adaptability to situations), and the 5Cs of PYD while controlling for specific socio-demographic covariates (gender, age, SES, and school type). Data were obtained from 1620 Filipino adolescents (Mage = 17.15; SDage = 1.00) in November 2021 and May 2022. Results show that grit dimensions predicted subsequent PYD dimensions, but not vice versa. Specifically, while perseverance and adaptability were linked to higher levels of competence, confidence, and character, consistency was associated with lower levels of competence and confidence six months later. Results highlight the importance of grit's dimensions in facilitating PYD characteristics among adolescents, especially efficacy-related Cs (competence and confidence). Theoretical and practical implications in promoting adolescent thriving and well-being are discussed.
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Methods that allow versatile manipulation of metastable centers in semiconductors are highly important owing to their potential for quantum information processing and computations. In this study, we demonstrate that the electron-phonon interaction enables phonon participation to promote relaxation of metastable centers in ZnO, which is known for its persistent photoconductivity (PPC) effect. Experimentally, we show that continuous infrared (IR) radiation (1064 nm, â¼30 mW/cm2) promotes longitudinal optical phonons via the Fröhlich interaction and increases the PPC relaxation rate by â¼4 folds. More importantly, we discover that coherent phonons activated by an ultrashort pulse IR laser of the same power increased the relaxation rate by â¼1200-fold, as confirmed by ultrafast transient spectroscopy to be correlated to the excitation of coherent acoustic phonons via the inverse piezoelectric effect. We expect this study to provide valuable guidance for the development of novel quantum and photoactive devices.
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Carbon dioxide (CO2) released by plants can serve as a cue for regulating insect behaviors. Hyphantria cunea is a widely distributed forestry pest that may use CO2 as a cue for foraging and oviposition. However, the molecular mechanism underlying its ability to sense CO2 has not been elucidated. Our initial study showed that CO2 is significantly attractive to H. cunea adults. Subsequently, 44 H. cunea gustatory receptors (GRs) were identified using transcriptome data, and 3 candidate CO2 receptors that are specifically expressed in the labial palps were identified. In vivo electrophysiological assays revealed that the labial palp is the primary organ for CO2 perception in H. cunea, which is similar to findings in other lepidopteran species. By using the Xenopus oocyte expression system, we showed that the HcunGR1 and HcunGR3 co-expressions produced a robust response to CO2, but HcunGR2 had an inhibitory effect on CO2 perception. Finally, immunohistochemical staining revealed sexual dimorphism in the CO2-sensitive labial pit organ glomerulus (LPOG). Taken together, our results clarified the mechanism by which H. cunea sense CO2, laying the foundation for further investigations into the role of CO2 in the rapid spread of H. cunea.
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Dióxido de Carbono , Animales , Dióxido de Carbono/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Femenino , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética , Masculino , Mariposas Nocturnas/metabolismo , Mariposas Nocturnas/genética , Transcriptoma , Oocitos/metabolismo , FilogeniaRESUMEN
A rating of body-object interactions (BOIs) reflects the ease with which a human body can interact physically with a word's referent. Studies with adults have demonstrated a facilitating BOI effect in language tasks, with faster and more accurate responses for high BOI words (e.g., cup) than low BOI words (e.g., coal). A few studies have explored the BOI effect in children. However, these studies have all adopted adult-rated BOIs, which may differ from children's. Using child-rated BOIs, the present study investigated the BOI effect in Chinese children and its relationship with age, as well as whether there was a community difference in the BOI effect. Children (aged 7-8) from Mainland China (N = 100) and Hong Kong SAR (HK; N = 90) completed a lexical decision task used to measure the BOI effect. The children were asked to judge whether each item was a real Chinese word; each real word was assigned a child-rated BOI score. After controlling nonverbal intelligence, gender, working memory, and Chinese character reading, a significant BOI effect was observed at the response accuracy and speed levels. The accuracy and latency analyses illustrated a community difference; the BOI effect was smaller in the HK children. This study suggests that BOI measures may be sensitive to the ecological differences between tested communities. The findings support the need for further investigations into the BOI effect across Chinese communities, particularly those in Mainland China.
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Formación de Concepto , Humanos , Masculino , Femenino , Niño , China , Formación de Concepto/fisiología , Tiempo de Reacción/fisiología , Cuerpo Humano , Hong KongRESUMEN
A large proportion of the heritability of pancreatic cancer risk remains elusive, and the contribution of specific mRNA splicing events to pancreatic cancer susceptibility has not been systematically evaluated. In this study, we performed a large splicing transcriptome-wide association study (spTWAS) using three modeling strategies (Enet, LASSO and MCP) to develop alternative splicing genetic prediction models for identifying novel susceptibility loci and splicing introns for pancreatic cancer risk by assessing 8275 pancreatic cancer cases and 6723 controls of European ancestry. Data from 305 subjects of whom the majority are of European descent in the Genotype-Tissue Expression Project (GTEx) were used and both cis-acting and promoter-enhancer interaction regions were considered to build these models. We identified nine splicing events of seven genes (ABO, UQCRC1, STARD3, ETAA1, CELA3B, LGR4 and SFT2D1) that showed an association of genetically predicted expression with pancreatic cancer risk at a false discovery rate ≤0.05. Of these genes, UQCRC1 and LGR4 have not yet been reported to be associated with pancreatic cancer risk. Fine-mapping analyses supported likely causal associations corresponding to six splicing events of three genes (P4HTM, ABO and PGAP3). Our study identified novel genes and splicing events associated with pancreatic cancer risk, which can improve our understanding of the etiology of this deadly malignancy.
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Neoplasias Pancreáticas , Transcriptoma , Humanos , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Empalme del ARN , Neoplasias Pancreáticas/genética , Empalme Alternativo/genética , Polimorfismo de Nucleótido Simple/genética , Antígenos de Superficie , Elastasa Pancreática/genéticaRESUMEN
The carrier concentration in n-type layered Bi2 Te3 -based thermoelectric (TE) material is significantly impacted by the donor-like effect, which would be further intensified by the nonbasal slip during grain refinement of crushing, milling, and deformation, inducing a big challenge to improve its TE performance and mechanical property simultaneously. In this work, high-energy refinement and hot-pressing are used to stabilize the carrier concentration due to the facilitated recovery of cation and anion vacancies. Based on this, combined with SbI3 doping and hot deformation, the optimized carrier concentration and high texture degree are simultaneously realized. As a result, a peak figure of merit (zT) of 1.14 at 323 K for Bi2 Te2.7 Se0.3 + 0.05 wt.% SbI3 sample with the high bending strength of 100 Mpa is obtained. Furthermore, a 31-couple thermoelectric cooling device consisted of n-type Bi2 Te2.7 Se0.3 + 0.05 wt.% SbI3 and commercial p-type Bi0.5 Sb1.5 Te3 legs is fabricated, which generates the large maximum temperature difference (ΔTmax ) of 85 K at a hot-side temperature of 343 K. Thus, the discovery of recovery effect in high energy refinement and hot-pressing has significant implications for improving TE performance and mechanical strength of n-type Bi2 Te3 , thereby promoting its applications in harsh conditions.
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Coded aperture compressive temporal imaging (CACTI) is the mapping of multiple frames using different encoding patterns into a single measurement and then using an algorithm to reconstruct the required high-dimensional signals, thus enabling high-speed photography on low-speed cameras. An encoding pattern and a reconstruction algorithm both play a critical role for CACTI. To improve the quality of the reconstruction, in terms of encoding, we took advantage of the reflective properties of the digital micromirror device and used a complementary dual-mask pattern to obtain more projection information. In terms of decoding, we developed what we believe, to the best of our knowledge, is a new model combining the weighted Landweber regularization with the relaxation strategy and a deep denoiser. The experimental results show the superiority of our proposed encoding-decoding combination, which achieves better performance in terms of the peak SNR, structural similarity index measure, and visual effects.
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Distributed fiber optic sensors (DFOS) can detect structural cracks and structural deformation with high accuracy and wide measurement range. This study monitors the segmental prestressed bent cap, assembled with a large key dry joint, based on optical fiber technology, and it allows the comparison of its damaging process with that of a monolithic cast in place counterpart. The obtained results, comprising cross-section strain distributions, longitudinal strain profiles, neutral axis location, crack pattern, and the damage process, show that the DFOS technology can be successfully used to analyze the complex working stress state of the segmental beam with shear key joints, both in the elastic range and at the ultimate load, and to successfully identify the changing characteristics of the stress state of the segmental capping beam model when elastic beam theory no longer applies. The DFOS data confirm that the shear key joint, as the weak point of the segmental cap beam, results in the high stress concentration area, and the damage rate is higher than that of the cast-in-place beam. The accurate monitoring by the DFOS allows for the realization that the damage occurs at the premature formation of a concentrated compression zone on the upper part of the shear key.
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Sodium-ion batteries (SIBs) are developed to address the serious concern about the limited resources of lithium. To achieve high energy density, anode materials with a large specific capacity and a low operation voltage are highly desirable. Herein, microsized particles of gray Sn (α-Sn) are explored as an anode material of SIBs for the first time. The distinct structure of α-Sn endows it the reduced volume change, the improved interaction with polymer binders and the in situ formation of amorphous Sn, as supported by in situ XRD, TEM and DFT calculations. Therefore, α-Sn exhibits an excellent electrochemical performance, much better than ß-Sn widely used before. Even microsized particles of α-Sn without any treatments deliver a capacity of â¼451 mAh g-1 after 3500 cycles at 2 A g-1 or â¼464 mAh g-1 at 4 A g-1 in a rate test. The results indicate the promising potential of α-Sn in SIBs.
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Leaf senescence is an important factor affecting the functional transition from nutrient assimilation to nutrient remobilization in crops. The senescence of wheat leaves is of great significance for its yield and quality. In the leaf senescence process, transcriptional regulation is a committed step in integrating various senescence-related signals. Although the plant-specific transcriptional regulation factor valine-glutamine (VQ) gene family is known to participate in different physiological processes, its role in leaf senescence is poorly understood. We isolated TaVQ25-A and studied its function in leaf senescence regulation. TaVQ25-A was mainly expressed in the roots and leaves of wheat. The TaVQ25-A-GFP fusion protein was localized in the nuclei and cytoplasm of wheat protoplasts. A delayed senescence phenotype was observed after dark and abscisic acid (ABA) treatment in TaVQ25-A-silenced wheat plants. Conversely, overexpression of TaVQ25-A accelerated leaf senescence and led to hypersensitivity in ABA-induced leaf senescence in Arabidopsis. A WRKY type transcription factor, TaWRKY133, which is tightly related to the ABA pathway and affects the expression of some ABA-related genes, was found to interact with TaVQ25-A both in vitro and in vivo. Results of this study indicate that TaVQ25-A is a positive regulator of ABA-related leaf senescence and can be used as a candidate gene for wheat molecular breeding.
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Arabidopsis , Triticum , Triticum/genética , Ácido Abscísico , Senescencia de la Planta , Nutrientes , Glutamina , Arabidopsis/genéticaRESUMEN
The applications of alloy-type anode materials for Na-ion batteries are always obstructed by enormous volume variation upon cycles. Here, K+ ions are introduced as an electrolyte additive to improve the electrochemical performance via electrostatic shielding, using Sn microparticles (µ-Sn) as a model. Theoretical calculations and experimental results indicate that K+ ions are not incorporated in the electrode, but accumulate on some sites. This accumulation slows down the local sodiation at the "hot spots", promotes the uniform sodiation and enhances the electrode stability. Therefore, the electrode maintains a high specific capacity of 565â mAh g-1 after 3000 cycles at 2â A g-1 , much better than the case without K+ . The electrode also remains an areal capacity of ≈3.5â mAh cm-2 after 100 cycles. This method does not involve time-consuming preparation, sophisticated instruments and expensive reagents, exhibiting the promising potential for other anode materials.
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A large proportion of heritability for prostate cancer risk remains unknown. Transcriptome-wide association study combined with validation comparing overall levels will help to identify candidate genes potentially playing a role in prostate cancer development. Using data from the Genotype-Tissue Expression Project, we built genetic models to predict normal prostate tissue gene expression using the statistical framework PrediXcan, a modified version of the unified test for molecular signatures and Joint-Tissue Imputation. We applied these prediction models to the genetic data of 79 194 prostate cancer cases and 61 112 controls to investigate the associations of genetically determined gene expression with prostate cancer risk. Focusing on associated genes, we compared their expression in prostate tumor vs normal prostate tissue, compared methylation of CpG sites located at these loci in prostate tumor vs normal tissue, and assessed the correlations between the differentiated genes' expression and the methylation of corresponding CpG sites, by analyzing The Cancer Genome Atlas (TCGA) data. We identified 573 genes showing an association with prostate cancer risk at a false discovery rate (FDR) ≤ 0.05, including 451 novel genes and 122 previously reported genes. Of the 573 genes, 152 showed differential expression in prostate tumor vs normal tissue samples. At loci of 57 genes, 151 CpG sites showed differential methylation in prostate tumor vs normal tissue samples. Of these, 20 CpG sites were correlated with expression of 11 corresponding genes. In this TWAS, we identified novel candidate susceptibility genes for prostate cancer risk, providing new insights into prostate cancer genetics and biology.
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Biomarcadores de Tumor/genética , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/patología , Transcriptoma , Estudios de Casos y Controles , Metilación de ADN , Estudios de Seguimiento , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Pronóstico , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/genética , Sitios de Carácter Cuantitativo , Estados Unidos/epidemiologíaRESUMEN
The current study aims to examine prosodic sensitivity in Chinese children with dyslexia and its relation to Chinese reading in children with and without dyslexia. A total of 172 Chinese children from third grade to sixth grade in Taiwanese primary schools were recruited. Thirty (14 male) children were identified as having dyslexia, and the remaining children (N = 142; 67 male) were typically developing children matched with those with dyslexia as carefully as possible with respect to school, grade, and gender. Our results indicated that group differences were found for all three types of prosodic sensitivity. Moderation analyses showed that group had no significant interaction with prosodic sensitivity in predicting Chinese reading, so the participants in the two groups were combined in the following analyses. The results of the stepwise regression analyses showed that only lexical tone awareness could significantly predict Chinese character reading after controlling for phonological awareness, while only intonation awareness could significantly predict reading comprehension after controlling for Chinese character reading. The results provide preliminary evidence on the issue of prosodic sensitivity in Chinese children with dyslexia and its role in Chinese reading, which might provide a novel approach to the teaching of Chinese languages.
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Dislexia , Pueblo Asiatico , Niño , China , Dislexia/complicaciones , Humanos , Lenguaje , Masculino , Fonética , LecturaRESUMEN
AIM: Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer related death in women. Trastuzumab originator (Herceptin) is a monoclonal antibody used as a standard treatment for breast and metastatic gastric cancer when the cancer cells over-express human epidermal growth factor receptor type 2 (HER2). As the patent of Trastuzumab has now expired, biosimilars are moving into the market. It is still controversial to chose which trastuzumab biosimilar has the best treatment of HER2-positive breast cancer patients. We conducted this network meta-analysis to explore the best trastuzumab biosimilar in the treatment of HER2-positive breast cancer patients. METHODS: PubMed, Cochrane library databases, China National Knowledge infrastructure (CNKI) and WanFang database up to November 2021 were systematically searched. The following search terms were used: 'trastuzumab originator', and 'trastuzumab biosimilar'. No language restriction was imposed. The reference lists of all retrieved articles were also reviewed to identify additional articles missed by using these search terms. RESULTS: We got 10 studies to conduct network meta-analysis to evaluate efficacy and serious adverse reactions among various trastuzumab biosimilars and trastuzumab originator. The overall response rate (ORR) and pathological complete response (pCR) of SB3 were worse than trastuzumab originator significantly, while the ORR and pCR of other trastuzumab biosimilars had not yet reached statistical differences compared with each other. The cumulative ranking curve (SUCRA) probability indicated that the ORR from best to worst was CT-P6, Herceptin, HLX02, PF-05280014, R-TPR-016, BCD-022, MYL-1401O, SB3, and the pCR from best to worst was PF-05280014, CT-P6, Herceptin, ABP-980, SB3. The serious adverse events (SAEs) of CT-P6 were more than Herceptin and MYL-1401O significantly, while the SAEs of other trastuzumab biosimilars had not statistical differences. The SUCRA probability indicated that the SAEs from best to worst was MYL-1401O, Herceptin, PF-05280014, SB3, HLX02, BCD-22, CT-P6. CONCLUSION: There was no statistical difference in both ORR and pCR of various trastuzumab biosimilars and Herceptin except SB3. The ORR and pCR of SB3 were worse than Herceptin. Both CT-P6 and PF-05280014 are better in the overall curative effect, but CT-P6 had the highest serious adverse reactions when compared with others. The PF-05280014 might be a better trastuzumab biosimilar in the treatment of HER2-positive breast cancer patients.
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Biosimilares Farmacéuticos , Neoplasias de la Mama , Humanos , Femenino , Biosimilares Farmacéuticos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Metaanálisis en Red , ChinaRESUMEN
Coupled resonators represent a generic model for many physical systems. In this context, a microcantilever is a multimode resonator clamped at one end, and it finds extensive application in high-precision metrology and is expected to be of great potential use in emerging quantum technologies. Here, we explore the microcantilever as a flexible platform for realizing multimode nonlinear interactions. Multimode nonlinear coupling is achieved by (1:2) internal resonance (IR) and parametric excitation with efficient coherent energy transfer. Specifically, we demonstrate abundant tunable parametric behaviors via frequency and voltage sweeps; these behaviors include mode veering, degenerate four-wave mixing (D4WM) with satellite resonances, partial amplitude suppression, acoustic frequency comb (AFC) generation, mechanically induced transparency (MIT), and normal-mode splitting. The experiments depict a new scheme for manipulating multimode microresonators with IR and parametric excitation.