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1.
J Clin Lab Anal ; 38(1-2): e25008, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38235610

RESUMEN

PURPOSE: Blood culture (BC) remains the gold standard for the diagnosis of bloodstream infections. Improving the quality of clinical BC samples, optimizing BC performance, and accelerating antimicrobial susceptibility test (AST) results are essential for the early detection of bloodstream infections and specific treatments. METHODS: We conducted a retrospective multicenter study using 450,845 BC specimens from clinical laboratories obtained from 19 teaching hospitals between 1 January 2021 and 31 December 2021. We evaluated key performance indicators (KPIs), turnaround times (TATs), and frequency distributions of processing in BC specimens. We also evaluated the AST results of clinically significant isolates for four different laboratory workflow styles. RESULTS: Across the 10 common bacterial isolates (n = 16,865) and yeast isolates (n = 1011), the overall median (interquartile range) TATs of AST results were 2.67 (2.05-3.31) and 3.73 (2.98-4.64) days, respectively. The specimen collections mainly occurred between 06:00 and 24:00, and specimen reception and loadings mainly between 08:00 and 24:00. Based on the laboratory workflows of the BCs, 16 of the 19 hospitals were divided into four groups. Time to results (TTRs) from specimen collection to the AST reports were 2.35 (1.95-3.06), 2.61 (1.98-3.32), 2.99 (2.60-3.87), and 3.25 (2.80-3.98) days for groups I, II, III, and IV, respectively. CONCLUSION: This study shows the related BC KPIs and workflows in different Chinese hospitals, suggesting that laboratory workflow optimization can play important roles in shortening time to AST reports and initiation of appropriate timely treatment.


Asunto(s)
Laboratorios , Sepsis , Humanos , Cultivo de Sangre , Laboratorios Clínicos , Factores de Tiempo , Hospitales de Enseñanza , Sepsis/diagnóstico
2.
Sensors (Basel) ; 23(15)2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37571787

RESUMEN

Soil salinization is a major obstacle to land productivity, crop yield and crop quality in arid areas and directly affects food security. Soil profile salt data are key for accurately determining irrigation volumes. To explore the potential for using Landsat 8 time-series data to monitor soil salinization, 172 Landsat 8 images from 2013 to 2019 were obtained from the Alar Reclamation Area of Xinjiang, northwest China. The multiyear extreme dataset was synthesized from the annual maximum or minimum values of 16 vegetation indices, which were combined with the soil conductivity of 540 samples from soil profiles at 0~0.375 m, 0~0.75 m and 0~1.00 m depths in 30 cotton fields with varying degrees of salinization as investigated by EM38-MK2. Three remote sensing monitoring models for soil conductivity at different depths were constructed using the Cubist method, and digital mapping was carried out. The results showed that the Cubist model of soil profile electrical conductivity from 0 to 0.375 m, 0 to 0.75 m and 0 to 1.00 m showed high prediction accuracy, and the determination coefficients of the prediction set were 0.80, 0.74 and 0.72, respectively. Therefore, it is feasible to use a multiyear extreme value for the vegetation index combined with a Cubist modeling method to monitor soil profile salinization at a regional scale.

3.
Nano Lett ; 20(12): 8469-8475, 2020 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-33174417

RESUMEN

Weyl semimetals have drawn considerable attention for their exotic topological properties in many research fields. When in combination with s-wave superconductors, the supercurrent can be carried by their topological surface channels, forming junctions mimicking the behavior of Majorana bound states. Here, we present a transmon-like superconducting quantum intereference device (SQUID) consisting of lateral junctions made of Weyl semimetal Td-MoTe2 and superconducting leads of niobium nitride (NbN). The SQUID is coupled to a readout cavity made of molybdenum rhenium (MoRe), whose response at high power reveals the existence of the constituting Josephson junctions (JJs). The loop geometry of the circuit allows the resonant frequency of the readout cavity to be tuned by the magnetic flux. We demonstrate a JJ made of MoTe2 and a flux-tunable transmon-like circuit based on Weyl semimetals. Our study provides a platform to utilize topological materials in SQUID-based quantum circuits for potential applications in quantum information processing.

4.
Curr Oncol Rep ; 19(2): 10, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28220448

RESUMEN

PURPOSE OF REVIEW: Though numerous treatment options are available to address cancer pain, inadequate management continues to be an ongoing problem worldwide. RECENT FINDINGS: A systematic review of the recent scientific literature was conducted with attention to new therapies along with reports of general consensus that were analyzed. Pain research continues to be difficult and though numerous guidelines have been developed, adequate powered studies are not common. Good practice would suggest a comprehensive approach to cancer pain management taking into account the many options available and treating each patient with a personalized therapeutic program. Though there is a very low number of randomized control trials, this probably reflects the difficulty in conducting these studies in heterogeneous cancer pain patient populations in sufficient numbers to yield credible study power.


Asunto(s)
Dolor en Cáncer/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Manejo del Dolor , Dolor en Cáncer/complicaciones , Dolor en Cáncer/patología , Humanos , Neoplasias/complicaciones , Neoplasias/patología , Medicina de Precisión
5.
Guang Pu Xue Yu Guang Pu Fen Xi ; 37(1): 156-61, 2017 Jan.
Artículo en Zh | MEDLINE | ID: mdl-30195285

RESUMEN

Plant canopy pigment concentration is a critical variable for agricultural remote sensing due to its close relationship to leaf nitrogen content. The aims of this study were to: (1) compare the prediction performances on chlorophyll, chlorophyll-a and b, and carotenoid concentration in jujube leaf at canopy scale between partial least squares regression (PLSR) and support vector machine (SVM), (2) develop quantitative models to estimate pigment concentration in jujube canopy using hyperspectral data and provide theoretical and technical support for rapidly, non-destructive, less expensive and eco-friendly measuring the concentration. Results from correlation analysis showed that jujube canopy pigment concentration correlated strongly with hyperspectral data. What's more, the hyperspectral data was better correlated by chlorophyll and chlorophyll-a than chlorophyll-b and carotenoid. Results of independent samples tested in predicting performance indicated that both of the PLSR and SVM models could effectively estimate pigment concentration, however, with different prediction precisions. Additionally, the precision of SVM outperformed PLSR for predicting chlorophyll and carotenoid. Whereas chlorophyll-a and chlorophyll-b were better predicted using PLSR than SVM. Compared among all the pigments' prediction precisions with corresponding optimal inversion models showed that prediction precisions on chlorophyll, chlorophyll-a and carotenoid were superior to chlorophyll-b. The determination coefficients and residual prediction deviation from predicting chlorophyll, chlorophyll-a and carotenoid were higher than 0.8 and 2.0, respectively, while the mean relative error values were lower than 13%. And the corresponding values from predicting chlorophyll-b were 0.60%, 20.79% and 1.79% respectively.


Asunto(s)
Ziziphus , Carotenoides , Clorofila , Clorofila A , Frutas , Análisis de los Mínimos Cuadrados , Modelos Teóricos , Pigmentación , Hojas de la Planta , Análisis Espectral , Máquina de Vectores de Soporte
6.
Mar Drugs ; 14(12)2016 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-27897975

RESUMEN

Nine polyketides, including two new benzophenone derivatives, peniphenone (1) and methyl peniphenone (2), along with seven known xanthones (3-9) were obtained from mangrove endophytic fungus Penicillium sp. ZJ-SY2 isolated from the leaves of Sonneratia apetala. Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Compounds 1, 3, 5, and 7 showed potent immunosuppressive activity with IC50 values ranging from 5.9 to 9.3 µg/mL.


Asunto(s)
Inmunosupresores/química , Inmunosupresores/farmacología , Penicillium/química , Policétidos/química , Policétidos/farmacología , Animales , Benzofenonas/química , Lythraceae/microbiología , Espectroscopía de Resonancia Magnética/métodos , Masculino , Ratones , Ratones Endogámicos BALB C , Hojas de la Planta/microbiología , Compuestos de Espiro/química , Árboles/microbiología , Xantonas/química
7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(5): 1365-9, 2015 May.
Artículo en Zh | MEDLINE | ID: mdl-26415461

RESUMEN

The precipitation of floating and sinking dust on leaves of plants is called as foliar dustfall. To monitor foliar dustfall, it will provide fundamental basis for environmental assessment and agricultural disaster evaluation of dust area. Therefore, the aim of this work to (1) study the effect of foliar dustfall content (FDC) on high spectral characteristics of pear leaves, (2) analyze the relationship between reflectances and FDC, and (3) establish high spectral remote sensing quantitative inversion model of FDC. The results showed that FDC increased reflectances of visible band (400~700 nrn) with maximum band of 666 nm. Absolute and relative rates of change were -10. 50% and -62. 89%, respectively. The FDC decreased reflectances of near infrared band (701 ~ 1 050 nm) with maximum band of 758 nm. Absolute and relative rates of change were 12. 04% and 41. 75%, respectively. After dustfall was removed, reflection peak of green light and absorption valley of red and blue light became prominent, and slope of 500~750 nm wake band increased when FDC was more than 20 g . m-2. While FDC just slightly affected shape and area of reflection peak of green light when FDC was less than 20 g . m-2. FDC were positive and negative correlated with reflectances of visible band and near infrared band, respectively. Maximum correlation coefficient (0. 61) showed at 663 nm. All of 7 inversion models, the model based on the first-order differential of logarithm of the reciprocal had better stability and predictive ability. The coefficient of determination(R2), root mean square error (RMSE) and relative percent deviation (RPD) of this model were 0. 78, 3. 37 and 2. 09, respectively. The results of this study can provide a certain reference basis for hyperspectral remote sensing of FDC.


Asunto(s)
Polvo , Hojas de la Planta , Pyrus , Tecnología de Sensores Remotos , Análisis Espectral , Agricultura , Luz , Modelos Teóricos
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(2): 510-4, 2014 Feb.
Artículo en Zh | MEDLINE | ID: mdl-24822430

RESUMEN

The objective of the present article is to ascertain the mechanism of hyperspectral remote sensing monitoring for soil salinization, which is of great importance for improving the accuracy of hyperspectral remote sensing monitoring. Paddy soils in Wensu, Hetian and Baicheng counties of the southern Xinjiang were selected. Hyperspectral data of soils were obtained. Soil salt content (S(t)) an electrical conductivity of 1:5 soil-to-water extracts (EC(1:5)) were determined. Relationships between S(t) and EC(1:5) were studied. Correlations between hyperspectral indices and S(t), and EC(1:5) were analyzed. The inversion accuracy of S(t) using hyperspectral technique was compared with that of EC(1:5). Results showed that: significant (p<0.01) relationships were found between S(t) and EC(1:5) for soils in Wensu and Hetian counties, and correlation coefficients were 0.86 and 0.45, respectively; there was no significant relationship between S(t) and EC(1:5) for soils in Baicheng county. Therefore, the correlations between S(t) and EC(1:5) varied with studied sites. S(t) and EC(1:5) were significantly related with spectral reflectance, first derivative reflectance and continuum-removed reflectance, respectively; but correlation coefficients between S(t) and spectral indices were higher than those between EC(1:5) and spectral indices, which was obvious in some sensitive bands for soil salinization such as 660, 35, 1229, 1414, 1721, 1738, 1772, 2309 nm, and so on. Prediction equations of St and EC(1:5) were established using multivariate linear regression, principal component regression and partial least-squares regression methods, respectively. Coefficients of determination, determination coefficients of prediction, and relative analytical errors of these equations were analyzed. Coefficients of determination and relative analytical errors of equations between S(t) and spectral indices were higher than those of equations between EC(1:5) and spectral indices. Therefore, the responses of high spectral information to St were more sensitive than those of high spectral information to EC(1:5). Accuracy of St predicted from high spectral data was higher than that of EC(1:5) estimated from high spectral data. The results of this study can provide a theoretical basis to improve hyperspectral remote sensing monitoring accuracy of soil salinization.

10.
Bone ; 183: 117094, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38582289

RESUMEN

The present study aimed to establish and evaluate a preclinical model of steroid-associated osteonecrosis (SAON) in mice. Sixteen 24-week-old male C57BL/6 mice were used to establish SAON by two intraperitoneal injections of lipopolysaccharide (LPS), followed by three subcutaneous injections of methylprednisolone (MPS). Each injection was conducted on working day, with an interval of 24 h. Six cycles of injections were conducted. Additional twelve mice (age- and gender-matched) were used as normal controls. At 2 and 6 weeks after completing induction, bilateral femora and bilateral tibiae were collected for histological examination, micro-CT scanning, and bulk RNA sequencing. All mice were alive until sacrificed at the indicated time points. The typical SAON lesion was identified by histological evaluation at week 2 and week 6 with increased lacunae and TUNEL+ osteocytes. Micro-CT showed significant bone degeneration at week 6 in SAON model. Histology and histomorphometry showed significantly lower Runx2+ area, mineralizing surface (MS/BS), mineral apposition rate (MAR), bone formation rate (BFR/BS), type H vessels, Ki67+ (proliferating) cells, and higher marrow fat fraction, osteoclast number and TNFα+ areas in SAON group. Bulk RNA-seq revealed changed canonical signaling pathways regulating cell cycle, angiogenesis, osteogenesis, and osteoclastogenesis in the SAON group. The present study successfully established SAON in mice with a combination treatment of LPS and MPS, which could be considered a reliable and reproducible animal model to study the pathophysiology and molecular mechanism of early-stage SAON and to develop potential therapeutic approaches for the prevention and treatment of SAON.


Asunto(s)
Lipopolisacáridos , Osteonecrosis , Masculino , Ratones , Animales , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Osteonecrosis/tratamiento farmacológico , Esteroides , Osteogénesis , Metilprednisolona/uso terapéutico
11.
Cell Death Dis ; 15(8): 613, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39179546

RESUMEN

Clear cell renal cell carcinoma (ccRCC) demonstrates enhanced glycolysis, critically contributing to tumor development. Programmed death-ligand 1 (PD-L1) aids tumor cells in evading T-cell-mediated immune surveillance. Yet, the specific mechanism by which glycolysis influences PD-L1 expression in ccRCC is not fully understood. Our research identified that the glycolysis-related gene (GRG) HK3 has a unique correlation with PD-L1 expression. HK3 has been identified as a key regulator of O-GlcNAcylation in ccRCC. O-GlcNAcylation exists on the serine 900 (Ser900) site of EP300 and can enhance its stability and oncogenic activity by preventing ubiquitination. Stably expressed EP300 works together with TFAP2A as a co-transcription factor to promote PD-L1 transcription and as an acetyltransferase to stabilize PD-L1 protein. Furthermore, ccRCC exhibits interactive dynamics with tumor-associated macrophages (TAMs). The uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), which serves as a critical substrate for the O-GlcNAcylation process, facilitates TAMs polarization. In ccRCC cells, HK3 expression is influenced by IL-10 secreted by M2 TAMs. Our study elucidates that HK3-mediated O-GlcNAcylation of EP300 is involved in tumor immune evasion. This finding suggests potential strategies to enhance the efficacy of immune checkpoint blockade therapy.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Células Renales , Proteína p300 Asociada a E1A , Hexoquinasa , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Proteína p300 Asociada a E1A/metabolismo , Antígeno B7-H1/metabolismo , Hexoquinasa/metabolismo , Hexoquinasa/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Animales , Evasión Inmune , Macrófagos Asociados a Tumores/metabolismo , Glucólisis , Ratones
12.
Plants (Basel) ; 13(16)2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39204725

RESUMEN

The objectives of this study were to explore the mechanism of stem mechanical strength in direct-seeded rice (DSR) as affected by paclobutrazol, especially its related endogenous hormone and cell wall component changes in culm tissue and response to the application of paclobutrazol. Field experiments were conducted in Changchun County, Jilin Province, China, by using two japonica rice varieties, Jiyujing and Jijing305, with soaking seeds in paclobutrazol at concentrations of (0 mg L-1, S0; 50 mg L-1; S1; 100 mg L-1; S2; 150 mg L-1, S3; 200 mg L-1, S4) in 2021 and 2022. The results suggest that the application of paclobutrazol increased the grain yield and reduced the lodging rate of DSR. Compared with the S0 treatments, soaking the seeds in paclobutrazol treatments rapidly shortened the length of the basal internode by decreasing the endogenous indole acetic acid (IAA) and gibberellin A3 (GA3) contents in culm tissue. The larger breaking strength (M) was attributed to a higher section modulus (SM) and bending stress (BS). The higher mechanical tissue thickness in culm tissue under paclobutrazol treatments, which was raised by higher endogenous zeatin and zeatin riboside (Z+ZR) content in culm tissue, increased the culm diameter, culm wall thickness, and section modulus (SM) of the internode. Compared with the S0 treatments, soaking the seeds in paclobutrazol treatments increased the cellulose content, lignin content, activities of lignin-related enzymes, and expression of key genes in lignin biosynthesis, as well as resulted in a higher bending stress (BS) to enhance the culm breaking strength (M).

13.
Oncogene ; 43(18): 1386-1396, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38467852

RESUMEN

Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Neovascularización Patológica , Ubiquitina , Animales , Femenino , Humanos , Masculino , Ratones , Angiogénesis , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Línea Celular Tumoral , ADN Metiltransferasa 3A/metabolismo , Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Indazoles/farmacología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Regiones Promotoras Genéticas , Pirimidinas/farmacología , Factor de Transcripción Sp1/metabolismo , Factor de Transcripción Sp1/genética , Sulfonamidas/farmacología , Ubiquitina/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética
14.
Biomater Res ; 28: 0079, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296854

RESUMEN

Ischemic stroke is a devastating disease and one of the leading causes of mortality worldwide. Overproduction of reactive oxygen species and inflammatory response contribute to secondary damage following ischemic insult. Nanozymes with robust anti-oxidative stress properties possess therapeutic possibility for ischemic insult. However, insufficiency of nanozyme accumulation in the neuronal mitochondria hindered their application. Herein, we constructed polydopamine-coated Prussian blue nanoparticles (PB@PDA NPs) to realize the targeting neuronal mitochondria for ischemic stroke, with the properties of antioxidant and anti-inflammation. After administration, much higher accumulation of PB@PDA NPs in the brain was observed compared to that in the PB NP group. Moreover, PB@PDA NPs effectively attenuated brain infarct than that of PB NPs in neonatal mice following hypoxia-ischemia (HI) insult. PB@PDA NPs mainly colocated with neuronal mitochondria in vivo and in vitro. Apart from attenuating oxidative stress, PB@PDA NPs also suppressed neuronal apoptosis and counteracted inflammation, which effectively promote a short- and long-term functional recovery in HI mice. Further, the therapeutic efficacy of PB@PDA NPs was also found in adult ischemic mice via tail vein injection. Collectively, these findings illustrate that PB@PDA NPs via system injection accumulate in neuronal mitochondria and are beneficial for ischemic stroke.

15.
Behav Brain Res ; 468: 115028, 2024 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-38723677

RESUMEN

Early life stress (ELS) increases the risk of depression later in life. Programmed cell death factor 4 (PDCD4), an apoptosis-related molecule, extensively participates in tumorigenesis and inflammatory diseases. However, its involvement in a person's susceptibility to ELS-related depression is unknown. To examine the effects and underlying mechanisms of PDCD4 on ELS vulnerability, we used a "two-hit" stress mouse model: an intraperitoneal injection of lipopolysaccharide (LPS) into neonatal mice was performed on postnatal days 7-9 (P7-P9) and inescapable foot shock (IFS) administration in adolescent was used as a later-life challenge. Our study shows that compared with mice that were only exposed to the LPS or IFS, the "two-hit" stress mice developed more severe depression/anxiety-like behaviors and social disability. We detected the levels of PDCD4 in the hippocampus of adolescent mice and found that they were significantly increased in "two-hit" stress mice. The results of immunohistochemical staining and Sholl analysis showed that the number of microglia in the hippocampus of "two-hit" stress mice significantly increased, with morphological changes, shortened branches, and decreased numbers. However, knocking down PDCD4 can prevent the number and morphological changes of microglia induced by ELS. In addition, we confirmed through the Golgi staining and immunohistochemical staining results that knocking down PDCD4 can ameliorate ELS-induced synaptic plasticity damage. Mechanically, the knockdown of PDCD4 exerts neuroprotective effects, possibly via the mediation of BDNF/AKT/CREB signaling. Combined, these results suggest that PDCD4 may play an important role in the ELS-induced susceptibility to depression and, thus, may become a therapeutic target for depressive disorders.


Asunto(s)
Proteínas Reguladoras de la Apoptosis , Depresión , Hipocampo , Ratones Endogámicos C57BL , Plasticidad Neuronal , Proteínas de Unión al ARN , Estrés Psicológico , Animales , Masculino , Ratones , Animales Recién Nacidos , Proteínas Reguladoras de la Apoptosis/metabolismo , Conducta Animal/fisiología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/metabolismo , Depresión/fisiopatología , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Hipocampo/metabolismo , Lipopolisacáridos/farmacología , Microglía/metabolismo , Plasticidad Neuronal/fisiología , Proteínas de Unión al ARN/metabolismo , Estrés Psicológico/metabolismo , Femenino
16.
J Immunother Cancer ; 12(4)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589248

RESUMEN

BACKGROUND: Despite the encouraging outcome of chimeric antigen receptor T cell (CAR-T) targeting B cell maturation antigen (BCMA) in managing relapsed or refractory multiple myeloma (RRMM) patients, the therapeutic side effects and dysfunctions of CAR-T cells have limited the efficacy and clinical application of this promising approach. METHODS: In this study, we incorporated a short hairpin RNA cassette targeting PD-1 into a BCMA-CAR with an OX-40 costimulatory domain. The transduced PD-1KD BCMA CAR-T cells were evaluated for surface CAR expression, T-cell proliferation, cytotoxicity, cytokine production, and subsets when they were exposed to a single or repetitive antigen stimulation. Safety and efficacy were initially observed in a phase I clinical trial for RRMM patients. RESULTS: Compared with parental BCMA CAR-T cells, PD-1KD BCMA CAR-T cell therapy showed reduced T-cell exhaustion and increased percentage of memory T cells in vitro. Better antitumor activity in vivo was also observed in PD-1KD BCMA CAR-T group. In the phase I clinical trial of the CAR-T cell therapy for seven RRMM patients, safety and efficacy were initially observed in all seven patients, including four patients (4/7, 57.1%) with at least one extramedullary site and four patients (4/7, 57.1%) with high-risk cytogenetics. The overall response rate was 85.7% (6/7). Four patients had a stringent complete response (sCR), one patient had a CR, one patient had a partial response, and one patient had stable disease. Safety profile was also observed in these patients, with an incidence of manageable mild to moderate cytokine release syndrome and without the occurrence of neurological toxicity. CONCLUSIONS: Our study demonstrates a design concept of CAR-T cells independent of antigen specificity and provides an alternative approach for improving the efficacy of CAR-T cell therapy.


Asunto(s)
Mieloma Múltiple , Receptores Quiméricos de Antígenos , Humanos , Antígeno de Maduración de Linfocitos B/genética , Antígeno de Maduración de Linfocitos B/metabolismo , Regulación hacia Abajo , Mieloma Múltiple/terapia , Fenotipo , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T , Ensayos Clínicos Fase I como Asunto
17.
IEEE Trans Pattern Anal Mach Intell ; 45(11): 13422-13437, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37384464

RESUMEN

Deep learning on large-scale data is currently dominant nowadays. The unprecedented scale of data has been arguably one of the most important driving forces behind its success. However, there still exist scenarios where collecting data or labels could be extremely expensive, e.g., medical imaging and robotics. To fill up this gap, this paper considers the problem of data-efficient learning from scratch using a small amount of representative data. First, we characterize this problem by active learning on homeomorphic tubes of spherical manifolds. This naturally generates feasible hypothesis class. With homologous topological properties, we identify an important connection - finding tube manifolds is equivalent to minimizing hyperspherical energy (MHE) in physical geometry. Inspired by this connection, we propose a MHE-based active learning (MHEAL) algorithm, and provide comprehensive theoretical guarantees for MHEAL, covering convergence and generalization analysis. Finally, we demonstrate the empirical performance of MHEAL in a wide range of applications for data-efficient learning, including deep clustering, distribution matching, version space sampling, and deep active learning.

18.
IEEE Trans Pattern Anal Mach Intell ; 45(2): 2458-2474, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35294343

RESUMEN

This paper addresses the deep face recognition problem under an open-set protocol, where ideal face features are expected to have smaller maximal intra-class distance than minimal inter-class distance under a suitably chosen metric space. To this end, hyperspherical face recognition, as a promising line of research, has attracted increasing attention and gradually become a major focus in face recognition research. As one of the earliest works in hyperspherical face recognition, SphereFace explicitly proposed to learn face embeddings with large inter-class angular margin. However, SphereFace still suffers from severe training instability which limits its application in practice. In order to address this problem, we introduce a unified framework to understand large angular margin in hyperspherical face recognition. Under this framework, we extend the study of SphereFace and propose an improved variant with substantially better training stability - SphereFace-R. Specifically, we propose two novel ways to implement the multiplicative margin, and study SphereFace-R under three different feature normalization schemes (no feature normalization, hard feature normalization and soft feature normalization). We also propose an implementation strategy - "characteristic gradient detachment" - to stabilize training. Extensive experiments on SphereFace-R show that it is consistently better than or competitive with state-of-the-art methods.

19.
J Phys Chem B ; 127(41): 8938-8949, 2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37816076

RESUMEN

Cardanol is a green biosurfactant with broad application prospects, which is expected to be used to enhance oil recovery (EOR). This paper designed two types of surfactants (extended and nonextended), including six kinds of nonionic and anion-nonionic surfactants. The position changes of PO and EO chains and the effects of different hydrophilic groups on the interface properties were studied with molecular dynamics simulations by constructing a model of crude oil (containing four components) and water molecules. The results of interfacial tension and solvent-accessible surface area showed that the interfacial properties of sulfate were better than those of sulfonates and nonionic surfactants. Meanwhile, the interface properties of nonextended surfactants were better than those of extended surfactants. The gyration radius (Rg) and tilt angle data demonstrated that when EO chains were located between hydrophobic groups and PO chains (nonextended surfactants), the adsorption capacity of surfactants at crude oil and water interfaces could be effectively improved. The radial distribution function of the hydrophilic group and hydrophobic group of surfactants with water molecules and four components of the crude oil molecule, respectively, explained that surfactants (8EO8POSO4) had better emulsification performance when the intermolecular interactions between crude oil and water two phases were relatively balanced. This study provides a theoretical reference for the design of oil-displacement surfactants and the mechanism analysis of emulsification properties.

20.
Photoacoustics ; 29: 100458, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36816882

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the formation of new vessels, synovial proliferation and destruction of articular cartilage. However, characteristic early diagnostic and therapeutic monitoring methods are still lacking. We report a study using a photoacoustic/ultrasound (PA/US) dual-mode imaging for RA disease. By establishing a collagen-induced (CIA) RA mouse model to classify disease states based on a subjective grading system, PA/US imaging allows real-time assessment of synovial erosion and vascular opacification within the knee joint in different disease states at high spatial resolution. The system also quantitatively monitors subcutaneous vascular physiology and morphology in the hind paw of mice, measuring the area and photoacoustic signal intensity of vascular proliferation and showing a positive correlation with disease grading. Compared to traditional subjective scoring of arthritis severity, the PA/US imaging is more sensitive i.e., vascular signals and synovial erosion can be observed early in the course of arthritis.

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