This study aimed at evaluating the predictive ability of the Physical Resilience Instrument for Older Adults (PRIFOR) for the recovery of frailty, activity of daily living (ADL), and quality of life ...in older adults suffering from acute health stressors. The longitudinal study was adopted and patients aged 65 and older with Clinical Frailty Scale (CFS) scores between 4 and 6 were included. The PRIFOR was used to assess physical resilience at baseline. Katz ADL, CFS and EuroQoL 5-dimension Questionnaire (EQ 5D) scores were all assessed at baseline and one month after discharge. The mean age of the 192 participants was 76.29 ± 6.53 years, and 50.5% were female. After adjusting for the baseline condition, the PRIFOR was only significantly associated with the CFS (β=−0.183, p<0.001) at one month after discharge. Our study results provide evidence of the predictive capacity of the PRIFOR for recovery from frailty.
Naive T cells respond to antigen stimulation by exiting from quiescence and initiating clonal expansion and functional differentiation, but the control mechanism is elusive. Here we describe that ...Raptor-mTORC1-dependent metabolic reprogramming is a central determinant of this transitional process. Loss of Raptor abrogated T cell priming and T helper 2 (Th2) cell differentiation, although Raptor function is less important for continuous proliferation of actively cycling cells. mTORC1 coordinated multiple metabolic programs in T cells including glycolysis, lipid synthesis, and oxidative phosphorylation to mediate antigen-triggered exit from quiescence. mTORC1 further linked glucose metabolism to the initiation of Th2 cell differentiation by orchestrating cytokine receptor expression and cytokine responsiveness. Activation of Raptor-mTORC1 integrated T cell receptor and CD28 costimulatory signals in antigen-stimulated T cells. Our studies identify a Raptor-mTORC1-dependent pathway linking signal-dependent metabolic reprogramming to quiescence exit, and this in turn coordinates lymphocyte activation and fate decisions in adaptive immunity.
Display omitted
•mTORC1-dependent metabolic reprogramming drives exit of T cells from quiescence•mTORC1 coordinates T cell glycolysis, lipogenesis, and oxidative phosphorylation•Raptor links glucose metabolism to cytokine responsiveness and Th2 cell generation•Raptor integrates TCR and CD28 costimulation signals
The small heat shock protein, α-crystallin, exists in two isoforms, αA and αB, and displays strong ability against stress-induced apoptosis. Regarding their functional mechanisms, we and others have ...demonstrated that they are able to regulate members in both caspase and Bcl-2 families. In addition, we have also shown that αA and αB may display differential anti-apoptotic mechanisms under certain stress conditions. While αA-crystallin regulates activation of the AKT signaling pathway, αB negatively regulates the MAPK pathway to suppress apoptosis induced by UV and oxidative stress. Although previous studies revealed that αA and αB could regulate members in both caspase and Bcl-2 families, the molecular mechanism, especially the in vivo regulation still waits to be elucidated. In the present communication, we present both in vitro and in vivo evidence to further demonstrate the regulation of caspase-3 and Bax by αA and αB. First, Surface Plasmon Resonance (SPR) and yeast two-hybrid selection analysis demonstrate that αA and αB directly bind to caspase-3 and Bax with differential affinities. Second, immunohistochemistry reveals that αA and αB regulate caspase-3 and Bax at different developmental stages of mouse embryo. Third, coimmunoprecipitation shows that αA and αB form in vivo interacting complexes with caspase-3 and Bax. Together, our results further confirm that αA and αB regulate caspase-3 and Bax in vitro and in vivo to regulate lens differentiation.
We consider a two-dimensional (2-D) model of an autophoretic particle. Beyond a certain emission/absorption rate (characterized by a dimensionless Péclet number, $Pe$) the particle is known to ...undergo a bifurcation from a non-motile to a motile state, with different trajectories, going from a straight to a chaotic motion by increasing $Pe$. From the full model, we derive a reduced closed model which involves only two time-dependent complex amplitudes $C_1(t)$ and $C_2(t)$ corresponding to the first two Fourier modes of the solute concentration field. It consists of two coupled nonlinear ordinary differential equations for $C_1$ and $C_2$ and presents several advantages: (i) the straight and circular motions can be handled fully analytically; (ii) complex motions such as chaos can be analysed numerically very efficiently in comparison with the numerically expensive full model involving partial differential equations; (iii) the reduced model has a universal form dictated only by symmetries (meaning that the form of the equations does not depend on a given phoretic model); (iv) the model can be extended to higher Fourier modes. The derivation method is exemplified for a 2-D model, for simplicity, but can easily be extended to three dimensions, not only for the presently selected phoretic model, but also for any model in which chemical activity triggers locomotion. A typical example can be found, for example, in the field of cell motility involving acto-myosin kinetics. This strategy offers an interesting way to cope with swimmers on the basis of ordinary differential equations, allowing for analytical tractability and efficient numerical treatment.
Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, ...genetic origin, and clinical management remain controversial.
Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes.
The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0–11.2).
The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.
•The adenocarcinoma component and squamous cell carcinoma component of adenosquamous carcinoma share a common clonal origin.•High incidence of trunk EGFR and TP53 mutation were noted in adenosqumous cell carcinoma, while the overall genomic profile of adenosqumous cell carcinoma is more similar to adenocarcinoma than squmous cell carcinoma.•EGFR-TKIs should be the standard first-line therapy for advanced stage adenosquamous carcinoma with EGFR mutation.
Background
Several previous researches had found artery stiffness associated skeletal muscle mass, but not considering muscle strength and physical performance, which also were compositions of ...sarcopenia. This study aims to reveal the relationship of artery stiffness and sarcopenia using the Asian Working Group for Sarcopenia criteria.
Methods
Study was performed on 1002 Chinese community dwelling participants aged ≥65 years from November 2016 to March 2017. Body composition, muscle strength, physical performance, and brachial-ankle pulse wave velocity (baPWV) considering as artery stiffness index were measured.
Results
In multiple regression analysis, baPWV was associated with handgrip (β=−0.13, P=0.04) and Relative skeletal muscle mass index (ASM/Ht
2
) (β=−0.02, P<0.01), but not with 4-meter velocity (P=0.21). Multiple logistic regression analysis showed that 1-SD (3.50m/s) increased in baPWV was still associated with a 11% (CI, 4%–20%; P<0.01) higher odds of being sarcopenia. In the gender subgroup analysis, the relationship of baPWV and sarcopenia remain significant in men (OR, 1.23; 95% CI, 1.07–1.42, P<0.01), but not in women (P=0.07).
Conclusions
High brachial-ankle pulse wave velocity is associated with sarcopenia in Chinese community-dwelling elderly, with gender differences.
Previous results from our trial showed that adding oxaliplatin to radiotherapy (RT) increased survival in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we ...present the data of long-term efficacy and late toxic effects.
Between January 2001 and January 2003, 115 Patients with nonkeratinizing/undifferentiated locoregionally advanced NPC were randomly to receive either RT alone (n = 56) or plus concurrent oxaliplatin 70 mg/m2 weekly for six cycles (n = 59).
After a median follow-up of 114 months (range 18–139 months), the 5-year overall survival (OS) and metastasis-free survival (MFS) rates in the concurrent chemoradiotherapy (CCRT) group were significantly higher than those observed in the RT-alone group (OS, 73.2% versus 60.2%, P = 0.028; MFS, 74.7% versus 63.0%, P = 0.027). However, CCRT did not improve locoregional failure-free survival significantly. Subgroup analyses showed that the superiorities of CCRT mainly existed in the T3-4N0-1 stage subgroup (OS: HR = 0.394, P = 0.034). The grade 3/4 late toxic effects were similar in the two groups.
The long-term follow-up data confirms the role of CCRT as a treatment of locoregionally advanced NPC. Oxaliplatin can be considered as an alternative optional therapeutic regimen for these patients due to its high efficiency and low toxic effect.
There is an overabundance of microswimmers in nature, including bacteria, algae, mammalian cells and so on. They use flagellum, cilia or global shape changes (amoeboid motion) to move forward. In the ...presence of confining channels, these swimmers exhibit often non-trivial behaviours, such as accumulation at the wall, navigation and so on, and their swimming speed may be strongly influenced by the geometric confinement. Several numerical studies have reported that the presence of walls either enhances or reduces the swimming speed depending on the nature of the swimmer, and also on the confinement. The purpose of this paper is to provide an analytical explanation of several previously obtained numerical results. We treat the case of amoeboid swimmers and the case of squirmers having either a tangential (the classical situation) or normal velocity prescribed at the swimmer surface (pumper). For amoeboid motion we consider a quasi-circular swimmer which allows us to tackle the problem analytically and to extract the equations of the motion of the swimmer, with several explicit analytical or semi-analytical solutions. It is found that the deformation of the amoeboid swimmer as well as a high enough order effect due to confinement are necessary in order to account for previous numerical results. The analytical theory accounts for several features obtained numerically also for non-deformable swimmers.
The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the ...Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.
The development of high-performance and low-cost oxygen reduction and evolution catalysts that can be easily integrated into existing devices is crucial for the wide deployment of energy storage ...systems that utilize O2-H2O chemistries, such as regenerative fuel cells and metal-air batteries. Herein, we report an NHB-activated N-doped hierarchical carbon （NHC） catalyst synthesized via a scalable route, and demonstrate its device integration. The NHC catalyst exhibited good performance for both the oxygen reduction reaction （ORR） and the oxygen evolution reaction （OER）, as demonstrated by means of electrochemical studies and evaluation when integrated into the oxygen electrode of a regenerative fuel cell. The activities observed for both the ORR and the OER were comparable to those achieved by state-of-the-art Pt and Ir catalysts in alkaline environments. We have further identified the critical role of carbon defects as active sites for electrochemical activity through density functional theory calculations and high-resolution TEM visualization. This work highlights the potential of NHC to replace commercial precious metals in regenerative fuel cells and possibly metal-air batteries for cost-effective storage of intermittent renewable energy.
PDF
