Journal of nature and science最新文献

Experiments on the maintenance of postural stability on flat stationary support surfaces (quiet standing) that show only limited modes of the potential configurations of balance stability have dominated investigations of balance in quiet upright standing. Recent studies have revealed coordination properties of the whole body in maintaining dynamic postural stability with the application of moving platform paradigms. This paper examines properties of candidate collective variables for postural control within the dynamic systems framework. Evidence is discussed in this paper for: (i) self-organization properties of dynamic postural balance; (ii) enhanced variability and entropy prior to a phase transition between center of mass and center of pressure coupling; (iii) co-existence of intermittent postural control strategies that oscillate between periodic to chaotic transitions to maintain upright postural balance. These collective findings indicate postural attractor dynamic states progressively emerge to the changing task constraints of a moving platform revealing insights into the deterministic and stochastic properties of the multiple time scales of human postural behavior.

Macrophages, the mature form of the monocytes, play a significant role in tissue homeostasis and immunity. In response to environmental cues, they can undergo classical or alternative activation, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by cigarette smoking. Although the contribution of cigarette smoke to various cellular processes has been extensively studied, its roles in macrophage polarization have been conflicting. This review discusses the molecular and functional differences of cigarette smoke-exposed macrophages that exist between pro-inflammatory and anti-inflammatory states. We also highlight the most recent advances in therapeutic potential of targeting signaling molecules associated with smoking to modulate macrophage plasticity and polarized activation.

Purpose: The studies investigate the anticancer activity of 5-fluorouracil (5-FU)-hyaluronidase (Hase) enzyme-loaded chitosan nanoparticles (5-FUChnps) using three-dimensional (3D) spheroid HCT-116 culture. Hase-loaded nanoparticles (Chnps) have recently been used to improve the efficacy of chemotherapeutic drugs for cancer treatment. It has been found that administration of Hase improves tumor vessel densities and increase perfusion within tumor.

Methods: Particle size and zeta potential of the nanoparticles were determined using a particle size analyzer while Fourier transform infrared (FTIR) was used to investigate the interactions among the various components making up the chitosan nanoparticles. Cytotoxic effects of 5-FU and 5FUchnps against dimensional (2D) and 3D spheroid cultures were assessed using trypan blue assay.

Results: Low molecular weight chitosan (Chi_L) nanoparticle size was determined to between 215 to 670 nm while medium molecular weight chitosan (Chi_M) nanoparticle size ranged from 151 to 778 nm. All 5FUChnps exhibited a zeta potential value ranging from +4 to +37 mV. Among the 16 formulations prepared, formulation #7 (5-FUChnps₇) was selected for the in-vitro cytotoxic studies based on its high 5-FU entrapment efficiency (59%). 5FUchnps treated 3D HCT-116 culture exhibited significant growth inhibition compared with 5-FU treated groups. Further, spheroids with significant growth inhibition exhibited high spheroid volume and non-spherical shapes.

Conclusion: 5-FUChnps were significantly cytotoxic to the 3D HCT-116 cultures than that of the free 5-FU. Chnps proved to have the ability to deliver and improve the anticancer activity of 5-FU in 3D HCT-116 culture studies.

Objectives: The objective of this study is to describe swallow:breath interaction (SwBr) and phase of respiration incident to swallow (POR) during non-nutritive suck in infants with bronchopulmonary dysplasia and determine if speech-language intervention can modify the characteristics of non-nutritive suck in these infants.

Methods: Logistic regression models were used to describe SwBr and POR in 16 low-risk preterm (LRP) infants and 43 infants with bronchopulmonary dysplasia. Infants with bronchopulmonary dysplasia were randomized to receive individualized intervention from a speech-language pathologist (BPDwithTX) or standard care (BPDnoTX).

Results: No significant differences were noted between low-risk infants and either group of BPD infants for the distribution of SwBr types. Infants with bronchopulmonary dysplasia showed minor differences in the progression of POR. Speech-Language intervention did not change the progression of SwBr or POR in infants with bronchopulmonary dysplasia.

Conclusion: Infants with bronchopulmonary dysplasia can improve the progression of SwBr through practice as effectively as low-risk preterm infants can. The minor differences in POR in infants with bronchopulmonary dysplasia are consistent with dysmature development as seen with other feeding studies of infants with this disease. Speech-Language intervention did not modify the developmental progression of swallow:breath interaction or phase of respiration incident to swallow.

Over the past 30 years, the incidence in of hepatocellular carcinoma (HCC) in the United States has tripled, largely due to untreated chronic Hepatitis C virus, alcoholic hepatitis, and non-alcoholic steatohepatitis (NASH). Additionally, the incidence of HCC among South Texas Hispanics is higher than elsewhere in the United States. The median age of HCC is 62 years in United States and 67 years in South Texas, with over 30% being 70 years of age or older. However, there is limited data on how to treat older adults with advanced HCC. In this review, we will discuss treatment options for older adults with advanced HCC, further emphasizing the need for prospective studies in this population.

Necroptosis is a subtype of regulated necrosis that occurs when caspases are inhibited or fail to activate. Stimulus of cell death receptors results in a signaling cascade that triggers caspase independent, immunogenic cell death. The core pathway relies on receptor interacting protein kinase (RIPK) 1 and 3, which interact through their receptor homotypic interacting motif (RHIM) domains, and form amyloid-like structures termed the necrosome. RIPK3 recruits and phosphorylates mixed lineage kinase domain-like pseudokinase (MLKL), the terminal mediator in the necroptotic pathway. MLKL polymerizes to form a second amyloid-like structure that causes cell membrane disruption resulting in cell death. Although the core necroptosis pathway has been elucidated, the details of MLKL membrane translocation and membrane disruption remain an open area of research.

The aim of this study was to determine the association of measures of skeletal muscle determined from ¹⁸F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine ¹⁸F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma.

DCE-MRI has been extensively used for diagnosis, prognosis and therapy monitoring of various diseases including cancer. However, it has been reported that the perfusion parameters measured by DCE-MRI largely vary across different research sites, preventing data comparison in multi-institutional clinical trials. Recently, novel perfusion phantoms have been developed to correct scanner-driven errors, enabling quality assurance of quantitative DCE-MRI measurement. However, the sources for the variability in quantitating perfusion parameters are not only MRI scanners but also software packages and imaging protocols set by the operators. In this manuscript, the various sources influencing the variability in quantitative DCE-MRI measurement are reviewed, and the proper solutions to minimize those are discussed.

Doxorubicin, a highly effective therapeutic agent against several types of cancer, is associated with serious side-effects, particularly cardiotoxicity. In addition, drug resistance leads to unsuccessful outcomes in many patients. There are no current biomarkers to indicate doxorubicin treatment response in patients. To understand the mechanisms of toxicity of doxorubicin, a whole-genome sensitivity screen was performed in the yeast S. cerevisiae. A deletion mutant of the yeast DNAJ (YDJ1), a J-domain heat-shock protein 40 (HSP40) was among the most sensitive strains. HSP40 is a co-chaperone to HSP70 and together refold denatured proteins into native conformation. The HSP40 YDJ1 is comprised of several highly-conserved domains and motifs that are essential in the heat-shock response. The cysteine-rich region has been implicated in protein-protein interaction with client proteins, farnesylation of YDJ1 facilitates attachment of YDJ1 to the ER and perinuclear membranes, and the histidine-proline-aspartic acid (HPD) tripeptide motif present in the J-domain, is responsible for the regulation of the ATPase activity of HSP70s. We have investigated the role of these motifs in the protection cytotoxic stress. We find that mutations in the HPD motif and cysteine-rich region of YDJ1 sensitize cells to doxorubicin and cisplatin, while a mutation in farnesylation results in a slightly protective effect. The sensitivity of the HPD and cysteine mutants is specific to oxidative stress and not to DNA double-strand breaks.

Neonatal intermittent hypoxia (IH) followed by re-oxygenation in normoxia or supplemental oxygen (IHR) increases the risk for severe retinopathy of prematurity (ROP). The exact timing for the onset of retinal damage which may guide strategic interventions during retinal development, is unknown. We tested the hypothesis that chronic exposure of the immature retina to neonatal IH induces early manifestations of retinal damage that can be utilized as key time points for strategic pharmacologic intervention. Newborn rats were exposed to IH within 2 hours of birth (P0) until P14, or allowed to recover in room air (RA) from P14 to P21 (IHR). Retinal integrity and angiogenesis biomarkers were progressively assessed before (P0), during IH, and post IH (recovery in RA), or IHR, and compared to normoxic age-matched controls. Retinal damage occurred as early as day 3 of neonatal IH, consistent with vascular abnormalities and disturbances in the astrocytic template. These abnormalities worsened during IHR. Pharmacologic and non-pharmacologic interventions to identify, prevent, or minimize neonatal IH should be implemented shortly after birth in high risk preterm newborns. This strategy may lead to a reduction in the outcome of severe ROP requiring later invasive treatments.