Abstract
5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective ...clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes
WNT3
transcription, leading to activation of the WNT/β-catenin pathway in
Apc
Min/+
/Lgr5
EGFP
mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
Insulin, IGF axis, adiponectin, and inflammatory markers are associated with breast cancer. Given that physical activity improves prognosis of breast cancer survivors, we investigated the effects of ...exercise on these markers as potential mediators between physical activity and breast cancer.
PubMed, EMBASE, CENTRAL, CINAHL, and SportDiscus were searched up to December 3, 2015, to identify randomized controlled trials (RCT) that investigated the effect of exercise on insulin, IGF axis, and cytokines in breast cancer survivors. Weighted mean difference (WMD) was calculated using either fixed- or random-effects models on the basis of the heterogeneity of the studies.
A total of 18 studies involving 681 breast cancer survivors were included, and these numbers were reduced for individual biomarker analyses. We found that exercise significantly reduced fasting insulin levels WMD, -3.46 μU/mL; 95% confidence interval (CI), -5.97 to -0.95;
= 0.007. Furthermore, potentially meaningful but statistically nonsignificant changes were observed in insulin resistance (WMD, -0.73; 95% CI, -0.54 to 0.13;
= 0.23), adiponectin (WMD, 1.17 μg/mL; 95% CI, -0.87 to 3.20;
= 0.26), and C-reactive protein (WMD, -1.10 mg/L; 95% CI, -2.39 to 0.20;
= 0.10). Subgroup analyses showed that fasting insulin levels were significantly more impacted in studies in which intervention participants experienced a weight reduction (WMD, -7.10 μU/mL; 95% CI, -10.31 to -3.90;
< 0.001).
Exercise reduces fasting insulin levels in breast cancer survivors. This may be due to exercise-induced reductions in body weight.
Practitioners and clinicians may better help breast cancer prognosis be improved through exercise, anticipating physiological effects on cancer.
.
The Combined Aerobic and Resistance Exercise (CARE) Trial compared different types and doses of exercise performed during breast cancer chemotherapy. Here, we report the longer‐term follow‐up of ...patient‐reported outcomes, health‐related fitness and exercise behavior at 6, 12 and 24 months postintervention. A multicenter trial in Canada randomized 301 breast cancer patients initiating chemotherapy to thrice weekly, supervised exercise consisting of a standard dose of 25–30 min of aerobic exercise (STAN; n = 96), a higher dose of 50–60 min of aerobic exercise (HIGH; n = 101) or a combined dose of 50–60 min of aerobic and resistance exercise (COMB; n = 104) performed for the duration of chemotherapy (median of 17 weeks). Primary outcomes were patient‐reported outcomes including quality of life, cancer‐related symptoms and psychosocial outcomes. Secondary outcomes were objective health‐related fitness (assessed at 12 months only) and self‐reported exercise behavior. A total of 269 (89.4%) participants completed patient‐reported outcomes at all three follow‐up time points and 263 (87.4%) completed the health‐related fitness assessment at 12‐month follow‐up. COMB was significantly superior to (i) STAN for sleep quality at 6‐month follow‐up (p = 0.027); (ii) HIGH for upper body muscular endurance at 12‐month follow‐up (p = 0.020); and (iii) HIGH for meeting the resistance exercise guideline at 6‐month follow‐up (p = 0.006). Moreover, self‐reported meeting of the combined exercise guideline during follow‐up was significantly associated with better patient‐reported outcomes and health‐related fitness. Performing combined exercise during and after breast cancer chemotherapy may result in better longer‐term patient‐reported outcomes and health‐related fitness compared to performing aerobic exercise alone.
What's new?
While exercise during chemotherapy for breast cancer is associated with various improvements in patient health, including improved quality of life, it remains unclear what type and dose of exercise is most beneficial over the long term. Here, the long‐term effects of different exercise regimens on patient health were compared among stage I‐IIIc breast cancer patients initiating adjuvant chemotherapy. Relative to aerobic exercise alone, combined aerobic and resistance exercise yielded the greatest benefits for patients, both during and after chemotherapy. In particular, combined aerobic and resistance exercise was associated with superior upper and lower body muscular endurance and improved sleep quality.
This study proposes an interior permanent magnet (IPM) brushless dc (BLDC) motor design strategy that utilizes BLDC control based on Hall sensor signals. The magnetic flux of IPM motors varies ...according to the rotor position and abnormal Hall sensor problems are related to magnetic flux. To find the cause of the abnormality in the Hall sensors, an analysis of the magnetic flux density at the Hall sensor position by finite element analysis is conducted. In addition, an IPM model with a notch structure is proposed to solve abnormal Hall sensor problems and its magnetic equivalent circuit (MEC) model is derived. Based on the MEC model, an optimal rotor design method is proposed and the final model is derived. However, the Hall sensor signal achieved from the optimal rotor is not perfect. To improve the accuracy of the BLDC motor control, a rotor position estimation method is proposed. Finally, experiments are performed to evaluate the performance of the proposed IPM-type BLDC motor and the Hall sensor compensation method.
This paper discusses a motor that was designed to satisfy the size constraints of system by using ferrite magnet and has the same performance as rare-earth magnet motor. In general, the size of the ...motor is increased in order to meet the same performance of motor using a ferrite magnet, because of its very low energy density compared to the rare-earth magnet. In order to compensate for these drawbacks, spoke structures capable of generating maximum magnetic flux at the same rotor size have been frequently studied. However, the spoke type motor structure has a drawback that demagnetization occurs in a magnet-specific portion. However, because it affects harmonics of the airgap flux density by demagnetization, it affects mechanical torque ripple and vibration. Therefore, in this paper, the changed air-gap flux density due to the demagnetization phenomenon and the changed mechanical vibration are analyzed by the finite-element method. In addition, we proposed an optimal rotor structure that can reduce the demagnetization phenomenon of magnets in spoke interior permanent magnet synchronous motor. Experiments were performed to evaluate the reliability of the optimized design.
Increased serum levels of immunoglobulin E (IgE) is a risk factor for various diseases, including allergy and anaphylaxis. However, the source and ontogeny of B cells producing IgE under steady state ...conditions are not well defined. Here, we show plasma cells that develop in the thymus and potently secrete IgE and other immunoglobulins, including IgM, IgA, and IgG. The development of these IgE-secreting plasma cells are induced by IL-4 produced by invariant Natural Killer T cells, independent of CD1d-mediated interaction. Single-cell transcriptomics suggest the developmental landscape of thymic B cells, and the thymus supports development of transitional, mature, and memory B cells in addition to plasma cells. Furthermore, thymic plasma cells produce polyclonal antibodies without somatic hypermutation, indicating they develop via the extra-follicular pathway. Physiologically, thymic-derived IgEs increase the number of mast cells in the gut and skin, which correlates with the severity of anaphylaxis. Collectively, we define the ontogeny of thymic plasma cells and show that steady state thymus-derived IgEs regulate mast cell homeostasis, opening up new avenues for studying the genetic causes of allergic disorders.
As the demand for soft and flexible devices steadily increases, the ionic applications demonstrated with gel materials have come under the spotlight. Here, stretchable and wearable ionic diodes ...(SIDs) made from polyelectrolyte hydrogels are introduced. Polyelectrolyte hydrogels are mechanically modified using methacrylated polysaccharides while preserving the ion‐permselectivity of poly(sulfopropyl acrylate) potassium salt (PSPA) and poly(acrylamidopropyltrimethylammonium chloride) (PDMAPAA‐Q), forming ionic copolymers. Then, SIDs composed of polyelectrolyte copolymer hydrogels are fabricated in VHB substrates as a stretchable and transparent insulating layer which is engraved by a laser. The SIDs show rectifying behaviors beyond the stretch of 3 with the aid of perfect adhesion between hydrogels and elastomeric substrates, and preserve their rectifications over hundreds of cycles. The operation of the SID is visualized by a wearable ionic circuit which rectifies ionic currents and lightens the LED under the forward bias during finger movements.
A stretchable ionic diode is demonstrated from polyelectrolyte hydrogels. Polyelectrolyte gels are mechanically modified with maintaining their own ion‐selective properties to generate a P–N junction. With the aid of perfect adhesion between the hydrogel materials and an elastomeric substrate, ionic diodes can rectify ionic currents under the applied stretch beyond 3.
FLASH radiotherapy is an emerging radiotherapy technique used to spare normal tissues. It employs ultra-high dose rate radiation beams over 40 Gy/s, which is significantly higher than those of ...conventional radiotherapy. In this study, a fiber-optic radiation sensor (FORS) was fabricated using a plastic scintillator, an optical filter, and a plastic optical fiber to measure the ultra-high dose rate electron beams over 40 Gy/s used in FLASH radiotherapy. The radiation-induced emissions, such as Cherenkov radiation and fluorescence generated in a transmitting optical fiber, were spectrally discriminated from the light outputs of the FORS. To evaluate the linearity and dose rate dependence of the FORS, the outputs of the fiber-optic radiation sensor were measured according to distances from an electron scattering device, and the results were compared with those of an ionization chamber and radiochromic films. Finally, the percentage depth doses were obtained using the FORS as a function of depth in a water phantom. This study found that ultra-high dose rate electron beams over 40 Gy/s could be measured in real time using a FORS.
This study describes the research to improve the performance of motor generator for integrated starter generator (ISG) mounted on ecofriendly vehicles. The ISG must be able to start the engine by ...high torque at the starting mode and generate electric power at the generating mode. In particular, the existing automotive generator is a field winding alternator of CLAW POLE structure, so wound field synchronous machine (WFSM) was used in early ISG. However, it is difficult to control the starting of WFSM with instantaneous high starting torque required at the start and high field current is applied to field windings to generate the magnetic flux. But high field current generates high heat shortening the life of the device. Therefore, consequent pole wound field synchronous machine (CPWFSM) as a novel structure is proposed in this article. It is possible to generate instantaneous high torque easily at starting because of permanent magnet (PM). In the generating mode, CPWFSM can generate power in a wide operation speed that is proposed by taking advantage of WFSM. CPWFSM consists of consequent pole and field winding in the rotor. So it generates high torque with high responsiveness at starting compared with WFSM and it has the advantage of generating output power using low field current at various speed areas because of PM. Simulation of CPWFSM and WFSM is performed by finite-element method (FEM) of ANSYS Electromagnetic Suite (EM 19.0) software, and the experimental results are compared by the dynamo experiment.
The meridional distributions of fluorescent dissolved organic matter (FDOM) and various hydrologic properties were investigated along 67°E in the western Indian Ocean. Our results showed that the ...highest fluorescence of the humic FDOM (FDOMH) was discovered in the Indian Deep Water (IDW), and relatively lower values were observed in the intruding water masses from the upper layer (e.g., Circumpolar Deep Water (CDW), Antarctic Intermediate Water (AAIW), and South Indian Central Water (SICW)). The deep FDOMH was robustly correlated with apparent oxygen utilisation (AOU), as suggested by previous studies. In particular, the slopes of the regression line AOU on FDOMH varied for different water masses and the two humic components. In this study, to identify the factor inducing the variations of the slope, we estimated the relative water mass fraction of different water masses using a three-end-member mixing model with a salinity-FDOMH diagram. The distribution of water mass fractions was in good agreement with water mass distribution from the conventional method from temperature and salinity distribution and previous studies. The FDOMH components were positively correlated with the aged water mass fraction (i.e., IDW; r = 0.93) and negatively correlated with fresher ones originating from the upper water (r = −0.93, −0.51, and − 0.95 for CDW, AAIW, and SICW, respectively). The fluorescence ratio between the two FDOMH components was also observed to be linked to the water mass fractions. The results indicate that the distribution of FDOMH is attributed to the mixing of various deep-water masses during the global ocean circulation.
•Humic FDOM is enriched in IDW, but relatively depleted in AAIW, SICW, and CDW.•The slope of the humic FDOM-AOU relationship varies with depth and water masses.•Water mass fraction of Indian deep water was defined using salinity and humic FDOM.•The major factor controlling the deep FDOM distribution is water-mass mixing.
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