RESUMEN

BACKGROUND: Growing evidence suggests that elective induction of labor at 39 weeks' gestation may lead to more favorable perinatal outcomes than expectant management, however, how to weigh the pros and cons of elective labor induction at 39 weeks, the expectation of spontaneous delivery at 40 or 41 weeks, or delayed labor induction at 40 or 41 weeks on neonatal and maternal outcomes remains a practical challenge in clinical decision-making. OBJECTIVE: We compared the neonatal and maternal outcomes between elective induction of labor at 39 weeks' gestation and expectant management in a real-world setting. We also divided the expectantly managed group and compared outcomes of the spontaneous delivery at 40 or 41 weeks' gestation group and the induced group at 40 or 41 weeks' gestation with those of the elective induction at 39 weeks' gestation group. STUDY DESIGN: This retrospective cohort study included 21,282 participants who delivered between January 1, 2019, and June 30, 2022. Participants were initially categorized into 3 groups at 39 weeks' gestation, namely elective induction of labor, spontaneous delivery, and expectant management, for the primary analysis in which elective induction was compared with expectant management. Subsequently, the expectant management group at 39 weeks' gestation was divided into 3 groups at 40 weeks, and participants who underwent expectant management at 40 weeks were then divided into 2 groups at 41 weeks' gestation, namely elective induction and spontaneous delivery. In total, 6 groups were compared in the secondary analysis with the elective induction at 39 weeks' gestation group serving as the reference group. RESULTS: At 39 weeks' gestational age, participants who underwent elective induction of labor had a significantly lower risk for the primary composite outcomes than participants who were managed expectantly (adjusted odds ratio, 0.72; 95% confidence interval, 0.55-0.95), and there was no significant difference in the risk for cesarean delivery between the 2 groups. After further dividing the expectantly managed group and comparing them with participants who underwent elective induction of labor at 39 weeks' gestation, those who underwent spontaneous delivery at 40 weeks' gestation had significantly lower risks for cesarean delivery (0.61; 0.52-0.71) and chorioamnionitis (0.78; 0.61-1.00) but a higher risk for fetal distress (1.39; 1.22-1.57); those with spontaneous delivery at 41 weeks' gestation had a significantly higher risk for fetal distress (1.44; 1.16-1.79), postpartum hemorrhage (1.83; 1.26-2.66), and prolonged or arrested labor (1.61; 1.02-2.54). Moreover, when compared with participants who underwent elective induction of labor at 39 weeks' gestation, participants who were induced later in gestation had significantly higher risks for adverse neonatal and maternal outcomes, especially at 40 weeks' gestation. CONCLUSION: Our findings indicate that elective induction of labor at 39 weeks' gestation was significantly associated with lower risks for adverse short-term neonatal and maternal outcomes when compared with expectant management. Moreover, our study highlights the nuanced trade-offs in risks and benefits between elective induction at 39 weeks' gestation and waiting for spontaneous labor or delayed induction at 40 or 41 weeks' gestation, thus providing valuable insights for clinical decision-making in practice.

RESUMEN

As a kind of aminoglycoside antibiotics, kanamycin (KAN) is widely applied to animal husbandry and aquaculture. However, the abuse of KAN causes the large-scale discharge of it into rivers, lakes and groundwater, which threatens environmental safety and human health. Therefore, it is imperative to develop a method that is applicable to detect KAN in an efficient and accurate way. The colorimetric method based on enzymes provides a feasible solution for the detection of organic pollutants. However, the extensive application of natural enzymes is constrained by high cost and low stability. Herein, a polyoxometalate-based nanozyme, namely [H7SiW9V3O40(DPA)3]·4H2O (SiW9V3/DPA) (DPA = dipyridylamine), is synthesized. As a low-cost nanozyme with high stability compared to natural enzymes, SiW9V3/DPA performs well in laccase-mimicking activity. It can be used to induce chromogenic reaction between 2,4-dichlorophenol (2,4-DP) and 4-aminoantipyrine (4-AP), which generates red products. With the addition of KAN, the color fades. That is to say, KAN can be detected with colorimetric assay in the concentration range 0.1 to 100 µM with high selectivity and low limit of detection (LOD) of 6.28 µM. Moreover, SiW9V3/DPA is applied to KAN detection in lake and river water and milk with satisfactory results. To sum up, polyoxometalate-based nanozyme is expected to provide a promising solution to the detection of organic pollutants in the aquatic environment.

Asunto(s)

Colorimetría , Kanamicina , Lacasa , Ampirona/química , Materiales Biomiméticos/química , Colorimetría/métodos , Kanamicina/análisis , Lacasa/química , Lacasa/metabolismo , Límite de Detección , Compuestos de Tungsteno/química , Contaminantes Químicos del Agua/análisis

RESUMEN

OBJECTIVE: To explore the relationship between changes in glycated hemoglobin (HbA1c) during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy (HIP). RESEARCH DESIGN AND METHODS: A total of 1,057 pregnant women who underwent serum HbA1c and delivered at Women's Hospital, Zhejiang University School of Medicine from May 2022 to March 2023, were included in this study. They were divided into four groups. Associations were evaluated using multivariate logistic regression analysis. RESULTS: In our study, an upward trend in HbA1c levels in the second trimester (HbA1c_S) and third trimester (HbA1c_T) among women without HIP was demonstrated. Multivariate logistics regression analysis showed significant associations: Pregnant women with HbA1c_S<5.5 %, HbA1c_T≥6.1 %, or with HbA1c_S≥5.5 %, HbA1c_T<6.1 % had a significant correlation with hypertensive disorders of pregnancy (HDP) (aOR:2.72, 95 %CI=1.24-5.97；aOR:2.59, 95 %CI=1.15-5.84). Furthermore, for each 1 % increase in the difference value of HbA1c between the second and third trimesters, the risk of HDP increased about 1.96 times, and the risk of delivering a large-for-gestational-age baby increased about 1.30 times. CONCLUSION: Among pregnant women without HIP, elevated HbA1c levels in the second or third trimester are associated with increased risks of adverse pregnancy outcomes.

Asunto(s)

Hemoglobina Glucada , Resultado del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Humanos , Femenino , Embarazo , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Adulto , Segundo Trimestre del Embarazo/sangre , Tercer Trimestre del Embarazo/sangre , Hiperglucemia/sangre , Hiperglucemia/epidemiología , Complicaciones del Embarazo/sangre , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/epidemiología , China/epidemiología

RESUMEN

While epidermal growth factor (EGF) shows promise in addressing the clinical manifestations of intestinal ulcerative diseases by activating the EGF receptor (EGFR)-mediated cell signaling, its clinical application is hampered by poor protein hydrolytic stability, low thermostability, and difficulty in modification. The development of a novel EGFR agonist for ulcerative colitis remains an urgent need, necessitating innovative solutions to overcome the limitations of current therapies via recombinant EGF protein. Herein, we introduce a novel DNA agonist for EGFR, Dimer-YL, which employs a bivalent aptamer to induce stable receptor dimerization, thereby activating the EGFR signaling and related cell behaviors. Dimer-YL has been demonstrated to recapitulate the EGF-promoted cellular behaviors, including proliferation and migration, as well as repair the damage of intercellular tight junctions. Furthermore, our findings demonstrate the potent therapeutic function of Dimer-YL in alleviating DSS-induced ulcerative colitis in vivo. Together, the present work has revealed Dimer-YL as an innovative DNA molecule for effective EGFR activation, offering promise for the development of EGFR-agonistic agents for therapeutic purposes.

Asunto(s)

Aptámeros de Nucleótidos , Colitis Ulcerosa , Receptores ErbB , Transducción de Señal , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Receptores ErbB/metabolismo , Aptámeros de Nucleótidos/farmacología , Aptámeros de Nucleótidos/química , Animales , Transducción de Señal/efectos de los fármacos , Ratones , Humanos , Proliferación Celular/efectos de los fármacos , ADN/metabolismo , Ratones Endogámicos C57BL , Sulfato de Dextran , Movimiento Celular/efectos de los fármacos

RESUMEN

Breast cancer is commonly treated through surgical resection, but a common complication of the procedure is lymphedema of the upper limbs, which can significantly impact patients' daily life. This study aims to investigate the knowledge, attitude, and practice (KAP) of breast cancer patients with regard to lymphedema complications. This cross-sectional study was conducted by a self-administered questionnaire between August and October 2022 toward breast cancer patients in our Hospital of Traditional Chinese Medicine. A total of 529 breast cancer patients were enrolled, including 186 (35.16%) aged < 50 years old. Participants had moderate knowledge, attitudes, and practices with scores of 18.24 ± 3.145 (possible range: 0-30), 62.24 ± 10.260 (possible range: 17-85), and 63.27 ± 20.967 (possible range: 21-105), respectively. Multivariate logistic regression showed that high school/technical secondary school (OR = 1.880, 95% CI = 1.107-3.194, P = 0.019) and being retired (OR = 0.482, 95% CI = 0.245-0.947, P = 0.034) were independently associated with good knowledge. Knowledge (OR = 1.321, 95% CI = 1.222-1.428, P < 0.001) was independently associated with a good attitude. Furthermore, knowledge (OR = 1.262, 95% CI = 1.151-1.384, P < 0.001) and attitude (OR = 1.122, 95% CI = 1.085-1.160, P < 0.001) were independently associated with good practice. Breast cancer patients have moderate knowledge, attitudes, and practices regarding lymphedema complications. Effective education and self-management programs are needed to improve patients' KAP toward lymphedema.

Asunto(s)

Neoplasias de la Mama , Linfedema , Humanos , Persona de Mediana Edad , Femenino , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Linfedema/etiología

RESUMEN

To investigate the effects of different anesthetic methods on postoperative immune function in patients undergoing gastrointestinal tumor resection. Ninety patients undergoing laparoscopic gastrointestinal tumor resection were divided into 3 groups. Patients in the GA group were anesthetized by total intravenous anesthesia. The GE group was anesthetized by general anesthesia combined with epidural anesthesia. The GN group was anesthetized by general anesthesia combined with bilateral Transversus Abdominis Plane block (TAP) and rectus sheath nerve blocks. General anesthesia is total intravenous anesthesia in all three groups. Blood samples were taken to test the changes of peripheral lymphocyte subtype analysis, and levels of plasma cortisol, epinephrine, norepinephrine. Also, the dosage of anesthetic drugs, recovery time, and visual analog scale (VAS) scores were recorded. Postoperative immune indexes, including CD4 count, CD8 count, B, and NK cells, in the GE group were significantly higher than those in NA and GA groups (P < 0.01). Perioperative stress indices, including epinephrine levels, norepinephrine level and aldosterone level, in the GE group were significantly lower than in the GA group and GN group (P < 0.01). The intraoperative/total sufentanil dosage and remifentanil dosage in the GE group were significantly lower than those in the GA and GN groups (P < 0.01). The VAS scores in the GE group were significantly better than those in GA and GN groups (P < 0.01). General anesthesia combined with epidural anesthesia attenuates the increase in inflammatory mediators. Its possible mechanisms include reducing perioperative stress response and reducing perioperative opioid use.

Asunto(s)

Neoplasias Gastrointestinales , Bloqueo Nervioso , Humanos , Dolor Postoperatorio , Músculos Abdominales/inervación , Bloqueo Nervioso/métodos , Anestesia General/métodos , Neoplasias Gastrointestinales/cirugía , Epinefrina , Norepinefrina , Inmunidad

RESUMEN

BACKGROUND: B cells play a pivotal role in regulating the immune response. The induction of B cell-mediated immunosuppressive function requires B cell activating signals. However, the mechanisms by which activated B cells mediate T-cell suppression are not fully understood. METHODS: We investigated the potential contribution of metabolic activity of activated B cells to T-cell suppression by performing in vitro experiments and by analyzing clinical samples using mass cytometry and single-cell RNA sequencing. RESULTS: Here we show that following activation, B cells acquire an immunoregulatory phenotype and promote T-cell suppression by metabolic competition. Activated B cells induced hypoxia in T cells in a cell-cell contact dependent manner by consuming more oxygen via an increase in their oxidative phosphorylation (OXPHOS). Moreover, activated B cells deprived T cells of glucose and produced lactic acid through their high glycolytic activity. Activated B cells thus inhibited the mammalian target of rapamycin pathway in T cells, resulting in suppression of T-cell cytokine production and proliferation. Finally, we confirmed the presence of tumor-associated B cells with high glycolytic and OXPHOS activities in patients with melanoma, associated with poor response to immune checkpoint blockade therapy. CONCLUSIONS: We have revealed for the first time the immunomodulatory effects of the metabolic activity of activated B cells and their possible role in suppressing antitumor T-cell responses. These findings add novel insights into immunometabolism and have important implications for cancer immunotherapy.

Asunto(s)

Linfocitos B , Linfocitos T , Inmunosupresores/farmacología , Sirolimus , Inmunoterapia

RESUMEN

3-Nitrotyrosine (3-NT), an oxidative stress biomarker, is closely associated with various diseases. Thus, rapid and sensitive detection of 3-NT is of great significance for preventing and treating diseases. Herein, we reported a new 3D zinc-based metal-organic framework (Zn-MOF) [Zn(L)(HBTC)] (L = (E)-4,4'-(ethene-1,2-diyl)bis[(N-pyridin-3-yl)benzamide], H3BTC = 1,3,5-benzenetricarboxylic acid), which was structurally characterized by single crystal X-ray diffraction, IR, PXRD and TG. The Zn-MOF can be used as a highly efficient fluorescence sensing material to provide a direct and low-cost method for the rapid detection of 3-NT and shows high sensitivity with a KSV value of 6.596 × 104 M-1, a rapid luminescence response within 24 s, excellent selectivity, high anti-interference ability and good recyclability. It is the first example of a MOF being used to directly detect 3-NT as a luminescence sensor to our knowledge. The sensing mechanism of the Zn-MOF towards 3-NT is discussed in detail, which provides a basis for the rational design of MOF sensing materials and their application in biomarker detection.

Asunto(s)

Estructuras Metalorgánicas , Biomarcadores , Estructuras Metalorgánicas/química , Tirosina/análogos & derivados , Zinc/química

RESUMEN

Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-ß activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-ß signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-ß axis as a potentially useful therapeutic target in GBM.

Asunto(s)

Glioblastoma/inmunología , Integrinas/inmunología , Células Asesinas Naturales/inmunología , Proteínas de Neoplasias/inmunología , Células Madre Neoplásicas/inmunología , Factor de Crecimiento Transformador beta/inmunología , Animales , Femenino , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/terapia , Xenoinjertos , Humanos , Integrinas/genética , Células Asesinas Naturales/patología , Masculino , Ratones , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Células Madre Neoplásicas/patología , Receptor Tipo II de Factor de Crecimiento Transformador beta/genética , Receptor Tipo II de Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/genética

RESUMEN

Two new Keggin-type polyoxometalate (POM)-based metal-organic complexes (MOCs) H3[Cu2(4-dpye)2(PMo12O40)] (1) and H[Cu2(4-Hdpye)2(PMo12O40)(H2O)4]·2H2O (2) were constructed with a new N,N'-bis (4-pyrimidinecarboxamido)-1,2-ethane (4-H2dpye) ligand by the hydrothermal/solvothermal method. Complex 1 was a 2D layered structure constructed from 1D metal-organic chains [Cu(4-dpye)]n and Keggin-type [PMo12O40]3- polyoxoanions. Complex 2 displays a 3D supramolecular framework formed by discrete [PMo12O40]3- polyoxoanions and binuclear metal-organic loops [Cu2(4-Hdpye)2]. The electrocatalytic behaviors of carbon paste electrodes modified by complexes 1 and 2 (1-CPE and 2-CPE) were investigated. The 1-CPE and 2-CPE were used as electrochemical sensors to detect trace Cr(vi), and the low limits of detection (LOD) are 1.27 × 10-7 M for 1 and 1.71 × 10-7 M for 2, which are lower than the maximum allowable concentration of Cr(vi) in drinking water specified by the World Health Organization (WHO). In addition, the performances of complexes 1 and 2 modified carbon cloth electrodes (1-CC and 2-CC) as supercapacitor materials have also been studied. The influence of the structure on electrocatalytic and capacitor performances is discussed.

RESUMEN

Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the disease becomes steroid refractory. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for the treatment of GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage of the plasticity of these cells in response to different microenvironments. In this study, we aimed to optimize cord blood tissue derived MSCs (CBti MSCs) by priming them using a regimen of inflammatory cytokines. This approach led to their metabolic reprogramming with enhancement of their glycolytic capacity. Metabolically reprogrammed CBti MSCs displayed a boosted immunosuppressive potential, with superior immunomodulatory and homing properties, even after cryopreservation and thawing. Mechanistically, primed CBti MSCs significantly interfered with glycolytic switching and mTOR signaling in T cells, suppressing T cell proliferation and ensuing polarizing toward T regulatory cells. Based on these data, we generated a Good Manufacturing Process (GMP) Laboratory protocol for the production and cryopreservation of primed CBti MSCs for clinical use. Following thawing, these cryopreserved GMP-compliant primed CBti MSCs significantly improved outcomes in a xenogenic mouse model of GVHD. Our data support the concept that metabolic profiling of MSCs can be used as a surrogate for their suppressive potential in conjunction with conventional functional methods to support their therapeutic use in GVHD or other autoimmune disorders.

Asunto(s)

Técnicas de Reprogramación Celular/métodos , Reprogramación Celular/fisiología , Sangre Fetal/citología , Enfermedad Injerto contra Huésped/prevención & control , Células Madre Mesenquimatosas/metabolismo , Animales , Reprogramación Celular/efectos de los fármacos , Reprogramación Celular/inmunología , Citocinas/farmacología , Femenino , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/inmunología , Ratones , Ratones Endogámicos NOD , Control de Calidad

RESUMEN

Immune checkpoint therapy has resulted in remarkable improvements in the outcome for certain cancers. To broaden the clinical impact of checkpoint targeting, we devised a strategy that couples targeting of the cytokine-inducible Src homology 2-containing (CIS) protein, a key negative regulator of interleukin 15 (IL-15) signaling, with fourth-generation "armored" chimeric antigen receptor (CAR) engineering of cord blood-derived natural killer (NK) cells. This combined strategy boosted NK cell effector function through enhancing the Akt/mTORC1 axis and c-MYC signaling, resulting in increased aerobic glycolysis. When tested in a lymphoma mouse model, this combined approach improved NK cell antitumor activity more than either alteration alone, eradicating lymphoma xenografts without signs of any measurable toxicity. We conclude that targeting a cytokine checkpoint further enhances the antitumor activity of IL-15-secreting armored CAR-NK cells by promoting their metabolic fitness and antitumor activity. This combined approach represents a promising milestone in the development of the next generation of NK cells for cancer immunotherapy.

Asunto(s)

Sangre Fetal/citología , Inmunoterapia Adoptiva , Interleucina-15/genética , Células Asesinas Naturales/efectos de los fármacos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas Supresoras de la Señalización de Citocinas/antagonistas & inhibidores , Aerobiosis , Animales , Antígenos CD19/inmunología , Linfoma de Burkitt/patología , Linfoma de Burkitt/terapia , Sistemas CRISPR-Cas , Línea Celular Tumoral , Técnicas de Inactivación de Genes , Glucólisis , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Interleucina-15/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/trasplante , Diana Mecanicista del Complejo 1 de la Rapamicina/fisiología , Ratones , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Proteínas Proto-Oncogénicas c-akt/fisiología , Receptores Quiméricos de Antígenos , Transducción de Señal/fisiología , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

Virus-specific T cells have proven highly effective for the treatment of severe and drug-refractory infections after hematopoietic stem cell transplant (HSCT). However, the efficacy of these cells is hindered by the use of glucocorticoids, often given to patients for the management of complications such as graft-versus-host disease. To address this limitation, we have developed a novel strategy for the rapid generation of good manufacturing practice (GMP)-grade glucocorticoid-resistant multivirus-specific T cells (VSTs) using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing technology. We have shown that deleting the nuclear receptor subfamily 3 group C member 1 (NR3C1; the gene encoding for the glucocorticoid receptor) renders VSTs resistant to the lymphocytotoxic effect of glucocorticoids. NR3C1-knockout (KO) VSTs kill their targets and proliferate successfully in the presence of high doses of dexamethasone both in vitro and in vivo. Moreover, we developed a protocol for the rapid generation of GMP-grade NR3C1 KO VSTs with high on-target activity and minimal off-target editing. These genetically engineered VSTs promise to be a novel approach for the treatment of patients with life-threatening viral infections post-HSCT on glucocorticoid therapy.

Asunto(s)

Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Edición Génica , Humanos , Receptores de Glucocorticoides/genética , Linfocitos T

RESUMEN

OBJECTIVE: To evaluate the effect of CYP2D6 *10 polymorphism (C 100C>T, rs1065852) on clinical outcomes of female Asian breast cancer patients with tamoxifen adjuvant treatment. METHODS: Meta-analysis of retrospective cohort studies published in July 2017 was performed. Fifteen studies with 1,794 Asian breast cancer patients were included, using strict eligibility requirements. Associations of disease-free survival (DFS), overall survival (OS) and recurrence rate after tamoxifen intake, with CYP2D6 *10 polymorphism were investigated through random effects models. RESULTS: CYP2D6 *10 polymorphism was found to have effect on DFS and recurrence rate in various comparison models, but not on overall survival in the female Asian breast cancer patients. CONCLUSION: In conclusion, our meta-analysis suggests that significant association of *10/*10 (TT) genotype with poorer DFS and recurrence exists in female Asian breast cancer patients with tamoxifen 20 mg/day adjuvant treatment. In the future, large and well-designed studies are required to illustrate the interactions of CYP2D6 genetic variants, including *10 polymorphism and tamoxifen response on female breast cancer patients.

RESUMEN

RapidSCAN is a new portable active crop canopy sensor with three wavebands in red, red-edge, and near infrared spectral regions. The objective of this study was to determine the potential and practical approaches of using this sensor for non-destructive diagnosis of rice nitrogen (N) status. Sixteen plot experiments and ten on-farm experiments were conducted from 2014 to 2016 in Jiansanjiang Experiment Station of the China Agricultural University and Qixing Farm in Northeast China. Two mechanistic and three semi-empirical approaches using the sensor's default vegetation indices, normalized difference vegetation index and normalized difference red edge, were evaluated in comparison with the top performing vegetation indices selected from 51 tested indices. The results indicated that the most practical and stable method of using the RapidSCAN sensor for rice N status diagnosis is to calculate N sufficiency index with the default vegetation indices and then to estimate N nutrition index non-destructively (R2 = 0.50-0.59). This semi-empirical approach achieved a diagnosis accuracy rate of 59-76%. The findings of this study will facilitate the application of the RapidSCAN active sensor for rice N status diagnosis across growth stages, cultivars and site-years, and thus contributing to precision N management for sustainable intensification of agriculture.

Asunto(s)

Productos Agrícolas/química , Nitrógeno/análisis , Oryza/química , Espectrofotometría Infrarroja/métodos , Agricultura/instrumentación , Agricultura/métodos , Biomasa , Calibración , Distribución Aleatoria , Espectrofotometría Infrarroja/instrumentación

RESUMEN

BACKGROUND AIMS: Despite ethnic diversity and ready availability of cryopreserved, human leukocyte antigen-typed cord blood (CB), delayed engraftment remains a significant hurdle to successful CB transplantation. Suboptimal homing of CB hematopoietic stem and progenitor cells (HSPCs) to the hematopoietic microenvironment (HM) is thought to be responsible and due to low levels of HSPC fucosylation. Fucosylation (decoration with sialyl-LewisX) may improve HSPC homing to HM by increasing the strength of HSPC/E-selectin interactions, where E-selectin is constitutively expressed by HM microvasculature. Enforced fucosylation of CB HSPCs using fucosyltransferases, increases the rate and magnitude of engraftment in xenogeneic transplant models. However, it is unclear whether endogenously fucosylated and non-fucosylated CB HSPC are qualitatively identical or whether endogenous fucosylation marks a qualitative difference between CB HSPC. If qualitatively identical, non-fucosylated CB HSPCs represent a good target for enforced fucosylation with improved engraftment conferred on an increased number of otherwise qualitatively identical HSPC. If qualitatively different, then conferring engraftment upon a majority, possibly lower "quality," non-fucosylated HSPCs by enforced fucosylation might inadvertently compromise engraftment. METHODS: Functional (xenogeneic engraftment, colony-forming unit and selectin-binding assays) and phenotypic analyses of fluorescence-activated cell sorting-isolated, endogenously fucosylated and non-fucosylated CB CD34+ cells were performed. RESULTS: Endogenous fucosylation of CB HSPCs exists as a continuum. Endogenously fucosylated HSPCs engrafted more efficiently in a xenogeneic transplantation model than non-fucosylated HSPCs. Outside of the differences in endogenous fucosylation, no other qualitative (functional and/or phenotypic) differences were identified. DISCUSSION: The majority of endogenously non-fucosylated CB HSPCs represent a good target for enforced fucosylation with the goal of improving engraftment following CB transplantation.

Asunto(s)

Antígenos CD34/metabolismo , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Sangre Fetal/citología , Fucosa/metabolismo , Supervivencia de Injerto , Animales , Células Cultivadas , Quimiotaxis/inmunología , Selectina E/metabolismo , Sangre Fetal/trasplante , Fucosiltransferasas/metabolismo , Glicosilación , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/metabolismo , Humanos , Ratones , Oligosacáridos/metabolismo , Receptores Mensajeros de Linfocitos/inmunología , Receptores Mensajeros de Linfocitos/metabolismo , Antígeno Sialil Lewis X , Inmunología del Trasplante

RESUMEN

BACKGROUND AIMS: Advantages associated with the use of cord blood (CB) transplantation include the availability of cryopreserved units, ethnic diversity and lower incidence of graft-versus-host disease compared with bone marrow or mobilized peripheral blood. However, poor engraftment remains a major obstacle. We and others have found that ex vivo fucosylation can enhance engraftment in murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI before transplantation is under clinical evaluation (NCT01471067). However, FTVII appears to be more relevant to hematopoietic cells and may alter acceptor substrate diversity. The present study compared the ability of FTVI and FTVII to improve the rapidity, magnitude, multi-lineage and multi-tissue engraftment of human CB hematopoietic stem and progenitor cells (HSPCs) in vivo. METHODS: CD34-selected CB HSPCs were treated with recombinant FTVI, FTVII or mock control and then injected into immunodeficient mice and monitored for multi-lineage and multi-tissue engraftment. RESULTS: Both FTVI and FTVII fucosylated CB CD34⁺ cells in vitro, and both led to enhanced rates and magnitudes of engraftment compared with untreated CB CD34⁺ cells in vivo. Engraftment after treatment with either FT was robust at multiple time points and in multiple tissues with similar multi-lineage potential. In contrast, only FTVII was able to fucosylate T and B lymphocytes. CONCLUSIONS: Although FTVI and FTVII were found to be similarly able to fucosylate and enhance the engraftment of CB CD34⁺ cells, differences in their ability to fucosylate lymphocytes may modulate graft-versus-tumor or graft-versus-host effects and may allow further optimization of CB transplantation.

Asunto(s)

Sangre Fetal/efectos de los fármacos , Fucosiltransferasas/administración & dosificación , Enfermedad Injerto contra Huésped/terapia , Animales , Modelos Animales de Enfermedad , Sangre Fetal/citología , Sangre Fetal/trasplante , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Ratones

RESUMEN

Taking rice variety Shennong 265 as test material, a hydroponic experiment was conducted to investigate the effects of Fe (0, 0.1, 0.25 and 0.5 mmol Fe2+ x L(-1)) and Cd (0, 0.1 and 1.0 umol Cd2+ x L(-1)) on the lipid peroxidation and antioxidative enzyme activities of rice plant. When the Fe was supplied alone, the shoot and root dry mass decreased significantly, but this phenomenon would not occur when the Cd was applied simultaneously. Applying Cd alone decreased the root malondialdehyde (MDA) and soluble protein contents, but applying Fe simultaneously alleviated the negative effects of Cd. Applying Fe decreased the Cd concentrations in shoots and roots, whereas applying Cd decreased the shoot and root Fe concentrations, indicating an obvious antagonistic interaction between Fe and Cd. The interaction of high concentration (1.0 micromol x L(-1)) Cd with Fe increased the root MDA and soluble protein contents, and decreased the root superoxide dismutase (SOD) and catalase (CAT) activities. These results indicated that applying definite amount of exogenous Fe could decrease the Cd accumulation in rice under low Cd stress, whereas high Cd stress would decrease the Fe absorption by rice and induce the lipid peroxidation in rice plant.

Asunto(s)

Cadmio/farmacología , Hierro/farmacología , Peroxidación de Lípido/efectos de los fármacos , Oryza/metabolismo , Superóxido Dismutasa/metabolismo , Catalasa/metabolismo , Oryza/efectos de los fármacos , Oryza/enzimología

RESUMEN

OBJECTIVE: To evaluate the shear bond strength (SBS) between alumina-toughened zirconia (ATZ) cores and veneering ceramics, investigate the effect of aging in artificial saliva on SBS and compare it with that of yttria-stabilized tetragonal zirconia polycrystals(Y-TZP). METHODS: Bars of ATZ and Y-TZP were layered with veneering ceramics in accordance to the recommendation of the manufacturer. Half of each group (n = 10) was aged at 134 °C (under 2 bar pressure) in an autoclave for 48 h. Subsequently, all specimens were subjected to shear force in a universal testing machine. The interface and fractured surface of the specimens were evaluated using scanning electron microscopy and X-ray energy dispersive spectroscopy. RESULTS: The initial mean SBS values in MPa±SD were 28.9±8.0 for ATZ and 26.2±7.6 for Y-TZP. After aging, the mean SBS values for ATZ and Y-TZP were 22.9±4.9 MPa and 22.8±6.9 MPa, respectively. Neither the differences between the SBS values of the ATZ and Y-TZP groups nor the influence of aging on all groups were statistically significant. CONCLUSIONS: The SBS between the ATZ core and the veneering ceramics was not affected by aging. The SBS of ATZ to veneering ceramics was not significantly different compared with that of Y-TZP.

Asunto(s)

Óxido de Aluminio/normas , Cerámica/normas , Coronas con Frente Estético/normas , Resistencia al Corte , Circonio/normas , Microscopía Electrónica de Rastreo , Falla de Prótesis , Saliva Artificial/farmacología , Análisis Espectral , Itrio/normas

RESUMEN

Autologous peripheral blood progenitor cell (PBPC) transplantation is the treatment of choice for selected myeloma patients. However, tumor cells contaminating the apheresis product are a potential source of relapse. Here we report a sequential purging strategy targeting mature and immature clonogenic myeloma cell populations in the autograft. Thawed PBPC products of myeloma patients were treated with rituximab to kill CD138(-)20(+) B cells (highly clonogenic immature cells), and bortezomib to target CD138(+) cells (normal and differentiated myeloma plasma cells), followed by coculture with allogeneic mesenchymal stem cells (MSC) from normal donors. After 7 days of coculture, nonadherent cells were removed and cultured in the absence of MSC for an additional 7 days. Then, efficacy of purging (removal of CD138(-)20(+) and CD138(+) cells) was assessed by flow cytometry and PCR. We used our ex vivo purging strategy to treat frozen aphereses from 16 patients. CD138(+) and CD138(-)20(+)(19(+)) cells present in the initial products were depleted more than 3 and 4 logs, respectively based on 10(6) flow-acquisition events, and to levels below the limit of detection by PCR. In contrast, total nucleated cell (TNC), CD34(+) cell, and colony-forming cell numbers were increased by approximately 12 to 20, 8-, and 23-fold, respectively. Overall, ex vivo treatment of apheresis products with rituximab, bortezomib, and coculture with normal donor MSC depleted mature and immature myeloma cells from clinical aphereses while expanding the normal hematopoietic progenitor cell compartment.

Asunto(s)

Anticuerpos Monoclonales de Origen Murino/farmacología , Purgación de la Médula Ósea/métodos , Ácidos Borónicos/farmacología , Células Madre Hematopoyéticas/efectos de los fármacos , Mieloma Múltiple/cirugía , Trasplante de Células Madre de Sangre Periférica/métodos , Pirazinas/farmacología , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antígenos CD34/biosíntesis , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Ácidos Borónicos/administración & dosificación , Bortezomib , Línea Celular Tumoral , Separación Celular/métodos , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Humanos , Magnetismo , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Pirazinas/administración & dosificación , Rituximab , Trasplante Autólogo