Summary Nasopharyngeal carcinoma (NPC) is a common disease among southern Chinese. The major etiological factors proposed for NPC pathogenesis include genetic susceptibility, environment factors and ...EBV infection. In the high risk population, genetic susceptibility to NPC has been mapped to the HLA loci and adjacent genes in MHC region on chromosome 6p21. Consumption of preserved food including salted fish has been implicated in its etiology in earlier studies. Its contribution to pathogenesis of NPC remains to be determined. A decreasing trend of NPC incidence was observed in Hong Kong, Taiwan and Singapore in recent years which may be accounted by a change of dietary habits. A comprehensive epidemiological study will help to elucidate the relative importance of various risk factors in the pathogenesis of NPC. Despite the close association of EBV infection with NPC, the etiological role of EBV in NPC pathogenesis remains enigmatic. EBV infection in primary nasopharyngeal epithelial cells is uncommon and difficult to achieve. EBV does not transform primary nasopharyngeal epithelial cells into proliferative clones, which contrasts greatly with the well-documented ability of EBV to transform and immortalize primary B cells. Genetic alterations identified in premalignant nasopharyngeal epithelium may play crucial roles to support stable EBV infection. Subsequently, latent and lytic EBV gene products may drive clonal expansion and transformation of premalignant nasopharyngeal epithelial cells into cancer cells. Stromal inflammation in nasopharyngeal mucosa is believed to play an important role in modulating the growth and possibly drive the malignant transformation of EBV-infected nasopharyngeal epithelial cells. Furthermore, there are increasing evidences supporting a role of EBV infection to evade host immune surveillance. EBV-infected cells may have selective growth advantages in vivo by acquiring a stress–resistance phenotype. Understanding the etiological factors and pathogenesis of NPC will contribute effectively to the prevention and treatment of this disease.
Multiple structural phases of tellurium (Te) have opened up various opportunities for the development of two-dimensional (2D) electronics and optoelectronics. However, the phase-engineered synthesis ...of 2D Te at the atomic level remains a substantial challenge. Herein, we design an atomic cluster density and interface-guided multiple control strategy for phase- and thickness-controlled synthesis of α-Te nanosheets and β-Te nanoribbons (from monolayer to tens of μm) on WS
substrates. As the thickness decreases, the α-Te nanosheets exhibit a transition from metallic to n-type semiconducting properties. On the other hand, the β-Te nanoribbons remain p-type semiconductors with an ON-state current density (I
) up to ~ 1527 μA μm
and a mobility as high as ~ 690.7 cm
V
s
at room temperature. Both Te phases exhibit good air stability after several months. Furthermore, short-channel (down to 46 nm) β-Te nanoribbon transistors exhibit remarkable electrical properties (I
= ~ 1270 μA μm
and ON-state resistance down to 0.63 kΩ μm) at V
= 1 V.
Numerous studies have examined the associations between air pollution and stroke. However, little is known about the associations between air pollution and transient ischemic attack (TIA). In this ...study, we aimed to conduct a time-series study to systematically examine the associations between hospital admissions for TIA and air pollutants. Admissions for TIA (ICD-10: G45) from 1 January 2014 to 31 December 2016 were identified based on the primary diagnosis from 134 hospitals in Beijing, China. Hourly measurements of air pollutants were obtained from the National Air Pollution Monitoring System. Generalized additive models with quasi-Poisson regression were used to determine the associations for each pollutant. Additionally, stratified analysis was implemented to examine whether age, gender, temperature, and season were the potential effect modifiers. Restricted cubic spline was applied to investigate the exposure-response curve. In total, 109,975 hospital admissions for TIA were included. The positive associations were detected between PM
2.5
, PM
10
, SO
2
, NO
2
, and CO and hospital admissions for TIA. The effects of PM
2.5
and PM
10
in men are stronger than in women. Additionally, the effects of PM
2.5
, PM
10
, SO
2
, and O
3
are more pronounced on warm days than cool days. From exposure-response curves, we observe a nearly linear relationship for PM
2.5
, PM
10
, CO, and NO
2
. Further studies are needed to verify the association. This research contributes evidence on the association between air pollution and admissions for TIA in the low- and middle-income countries and may promote related public health policy development.
Studies have shown that psychosocial stress is involved in Alzheimer's disease (AD) pathogenesis; it induces M1 microglia polarization and production of pro-inflammatory cytokines, leading to ...neurotoxic outcomes and decreased β-amyloid (Aβ) clearance. Icariin has been proven to be an effective anti-inflammatory agent and to activate peroxisome proliferator-activated receptors gamma (PPARγ) which induces the M2 phenotype in the microglia. However, whether restraint/isolation stress reduces the clearance ability of microglia by priming and polarizing microglia to the M1 phenotype, and the effects of icariin in attenuating the inflammatory response and relieving the pathological changes of AD are still unclear.
APP/PS1 mice (male, aged 3 months) were randomly divided into a control group, a restraint/isolation stress group, and a restraint/isolation stress + icariin group. The restraint/isolation stress group was subjected to a paradigm to build a depressive animal model. Sucrose preference, open field, elevated plus maze, and Y maze test were used to assess the stress paradigm. The Morris water maze test was performed to evaluate spatial reference learning and memory. Enzyme-linked immunosorbent assay and immunohistochemistry were used to identify the microglia phenotype and Aβ accumulation. Western blotting was used to detect the expression of PPARγ in the hippocampus and prefrontal cortex (PFC).
Restraint/isolation stress induced significant depressive-like behaviors in APP/PS1 mice at 4 months of age and memory impairment at 10 months of age, while 6 months of icariin administration relieved the memory damage. Restraint/isolation stressed mice had elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, increased Aβ plaque accumulation and more M1 phenotype microglia in the hippocampus and PFC at 10 months of age, while 6 months of icariin administration relieved these changes. Moreover, restraint/isolation stressed mice had down-regulated PPARγ expression in the hippocampus and PFC at 10 months of age, while 6 months of icariin administration reversed the alteration, especially in the hippocampus.
Restraint/isolation stress induced depressive-like behaviors and spatial memory damage, over-expression of M1 microglia markers and more severe Aβ accumulation by suppressing PPARγ in APP/PS1 mice. Icariin can be considered a new treatment option as it induces the switch of the microglia phenotype by activating PPARγ.
Nano-piezoelectric materials have drawn tremendous research interest. However, characterization of their piezoelectric properties, especially measuring the piezoelectric strain coefficients, remains ...a challenge. Normally, researchers use an AFM-based method to directly measure nano-materials’ piezoelectric strain coefficients. But, the extremely small piezoelectric deformation, the influence from the parasitic electrostatic force, and the environmental noise make the measurement results questionable. In this paper, a resonant piezo-force microscopy method was used to accurately measure the piezoelectric deformation from 1D piezoelectric nanofibers. During the experiment, the AFM tip was brought into contact with the piezoelectric sample and set to work at close to its first resonant frequency. A lock-in amplifier was used to pick up the sample’s deformation signal at the testing frequency. By using this technique, the piezoelectric strain constant d33 of the Lead Zirconate Titanate (PZT) nanofiber with a diameter of 76 nm was measured. The result showed that d33 of this PZT nanofiber was around 387 pm/V. Meanwhile, by tracking the piezoelectric deformation phase image, domain structures inside PZT nanofibers were identified.
Under the background of a circular economy, this paper examines multi-tiered closed-loop supply chain network competition under carbon emission permits and discusses how stringent carbon regulations ...influence the network performance. We derive the governing equilibrium conditions for carbon-capped mathematical gaming models of each player and provide the equivalent variational inequality formulations, which are then solved by modified projection and contraction algorithms. The numerical examples empower us to investigate the effects of diverse carbon emission regulations (cap-and-trade regulation, mandatory cap policy, and cap-sharing scheme) on enterprises’ decisions. The results reveal that the cap-sharing scheme is effective in coordinating the relationship between system profit and carbon emission abatement, while cap-and-trade regulation loses efficiency compared with the cap-sharing scheme. The government should allocate caps scientifically and encourage enterprises to adopt green production technologies, especially allowing large enterprises to share carbon quotas. This study can also contribute to the enterprises’ decision-making and revenue management under different carbon emissions reduction regulations.
With the increasing popularity of ecological civilization and sustainable development, enterprises should consider environmental protection measures in their operations in addition to pursue their ...economic interests. This paper establsihes a closed-loop supply chain network model composed of multiple suppliers, manufacturers, retailers, recyclers, and demand markets—regarding their dual goals of the profit maximization and the minimization of carbon emissions. The conditions necessary for establishing overall equilibrium and an equilibrium model of the entire closed-loop supply chain network are determined by applying variational inequality and dual theory. A modified projection contraction algorithm is used to design a model-solving program. Finally, using numerical examples, the paper conducts a comparative static analysis on important parameters such as the weight coefficients of environmental protection objectives and consumers' awareness of low-carbon environmental protection and attains some beneficial enlightenment on management. The results indicate that when the environmental protection objectives of a certain type of enterprise increases, both the economic benefits and environmental protection performance will improve; when the environmental protection objectives of all enterprises increases simultaneously, environmental protection performance improves significantly, but the changes in economic benefits of different enterprises are inconsistent and profit coordination is more complex. Although consumers’ awareness of low-carbon preference could improve environmental performance, it reduces the overall profits of network members and the entire closed-loop supply chain network as a whole. The above conclusions can be used as a reference for the government in designing low-carbon environmental protection policy and in closed-loop supply chain research.
Abstract EBV-associated human malignancies may originate from B cells and epithelial cells. EBV readily infects B cells in vitro and transforms them into proliferative lymphoblastoid cell lines. In ...contrast, infection of human epithelial cells in vitro with EBV has been difficult to achieve. The lack of experimental human epithelial cell systems for EBV infection has hampered the understanding of biology of EBV infection in epithelial cells. The recent success to infect human epithelial cells with EBV in vitro has allowed systematic investigations into routes of EBV entry, regulation of latent and lytic EBV infection, and persistence of EBV infection in infected epithelial cells. Understanding the biology of EBV infection in human epithelial cells will provide important insights to the role of EBV infection in the pathogenesis of EBV-associated epithelial malignancies including nasopharyngeal carcinoma and gastric carcinoma.
Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on ...multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented.
In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models.
Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R.
Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC.
Sleep disturbance is a recognized risk factor for Alzheimer’s disease (AD), but the underlying micro-pathological evidence remains limited. To bridge this gap, we established an amyloid-β oligomers ...(AβO)-induced rat model of AD and subjected it to intermittent sleep deprivation (SD). Diffusion tensor imaging (DTI) and transmission electron microscopy were employed to assess white matter (WM) integrity and ultrastructural changes in myelin sheaths. Our findings demonstrated that SD exacerbated AβO-induced cognitive decline. Furthermore, we found SD aggravated AβO-induced asymmetrical impairments in WM, presenting with reductions in tract integrity observed in commissural fibers and association fasciculi, particularly the right anterior commissure, right corpus callosum, and left cingulum. Ultrastructural changes in myelin sheaths within the hippocampus and corpus callosum further confirmed a lateralized effect. Moreover, SD worsened AβO-induced lateralized disruption of the brain structural network, with impairments in critical nodes of the left hemisphere strongly correlated with cognitive dysfunction. This work represents the first identification of a lateralized impact of SD on the mesoscopic network and cognitive deficits in an AD rat model. These findings could deepen our understanding of the complex interplay between sleep disturbance and AD pathology, providing valuable insights into the early progression of the disease, as well as the development of neuroimaging biomarkers for screening early AD patients with self-reported sleep disturbances. Enhanced understanding of these mechanisms may pave the way for targeted interventions to alleviate cognitive decline and improve the quality of life for individuals at risk of or affected by AD.
Graphical Abstract
a
AβO injection and sleep deprivation were conducted on adult rats.
b
Sleep deprivation and AβO-induced neurotoxicity aggravated cognitive disability with a synergistic effect.
c
Sleep deprivation and AβO-induced neurotoxicity reduced the integrity of specific association fasciculi and commissural fibers with ultrastructural demyelination.
d
On the basis of white matter integrity destruction, the structural connection was disrupted. The exacerbated topological properties with lateralized effects were correlated with cognitive decline.
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