Cigarette Smoking Accelerated Brain Aging and Induced Pre-Alzheimer-Like Neuropathology in Rats

Cigarette smoking has been proposed as a major risk factor for aging-related pathological changes and Alzheimer's disease (AD). To date, little is known for how smoking can predispose our brains to dementia or cognitive impairment. This study aimed to investigate the cigarette smoke-induced pathological changes in brains. Male Sprague-Dawley (SD) rats were exposed to either sham air or 4% cigarette smoke 1 hour per day for 8 weeks in a ventilated smoking chamber to mimic the situation of chronic passive smoking. We found that the levels of oxidative stress were significantly increased in the hippocampus of the smoking group. Smoking also affected the synapse through reducing the expression of pre-synaptic proteins including synaptophysin and synapsin-1, while there were no changes in the expression of postsynaptic protein PSD95. Decreased levels of acetylated-tubulin and increased levels of phosphorylated-tau at 231, 205 and 404 epitopes were also observed in the hippocampus of the smoking rats. These results suggested that axonal transport machinery might be impaired, and the stability of cytoskeleton might be affected by smoking. Moreover, smoking affected amyloid precursor protein (APP) processing by increasing the production of sAPPβ and accumulation of β–amyloid peptide in the CA3 and dentate gyrus region. In summary, our data suggested that chronic cigarette smoking could induce synaptic changes and other neuropathological alterations. These changes might serve as evidence of early phases of neurodegeneration and may explain why smoking can predispose brains to AD and dementia

Gating a Single Cell:A Label-Free and Real-Time Measurement Method for Cellular Progression

There is an ever-growing need for more advanced methods to study the response of cancer cells to new therapies. To determine cancer cells’ response from a cell-mortality perspective to various cancer therapies, we report a label-free and real time method to monitor the in situ response of individual HeLa cells using a single cell gated transistor (SCGT). As a cell undergoes apoptotic cell death, it experiences changes in morphology and ion concentrations. This change is well in line with the threshold voltage of the SCGT, which has been verified by correlating the data with the cell morphologies by scanning electron microscopy and the ion-concentration analysis by inductively-coupled plasma mass spectrometry (ICPMS). This SCGT could replace patch clamps to study single cell activity via direct measurement in real time. Importantly, this SCGT can be used to study the electrical response of a single cell to stimuli that leaves the membrane intact

Fingertip‐skin‐inspired highly sensitive and multifunctional sensor with hierarchically structured conductive graphite/polydimethylsiloxane foams

Fingertip skin exhibits high sensitivity in a broad pressure range, and can detect diverse stimuli, including textures, temperature, humidity, etc. Despite adopting diverse microstructures and functional materials, achieving skin sensor devices possessing high pressure sensitivity over a wide linear range and with multifunctional sensing capabilities is still challenging. Herein, inspired by the microstructures of fingertip skin, a highly sensitive skin sensor is demonstrated with a linear response over a broad pressure range and multifunctional sensing capabilities. The porous sensing layer is designed with hierarchical microstructures on the surface. By optimizing the porosity and the graphite concentration, a fabricated skin sensor device exhibits a superior sensitivity of 245 kPa−1 over a broad linear pressure range from 5 Pa to 120 kPa. For practical application demonstrations, the sensor devices are utilized to monitor subtle wrist pulse and diverse human motions including finger bending, wrist bending, and feet movement. Furthermore, this novel sensor device demonstrates potential applications in recognizing textures and detecting environmental temperatures, thereby marking an important progress for constructing advanced electronic skin

Comparative Effectiveness of Interventions for Global Cognition in Patients With Mild Cognitive Impairment: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Background: There is a lack of study comprehensively comparing the effects of all existing types of interventions on global cognition among patients with mild cognitive impairment (MCI).Aims: To conduct a network meta-analysis to evaluate the effectiveness of different types of interventions in improving global cognition among MCI patients.Methods: Randomized controlled trials (RCTs) assessing the effects of pharmacological or non-pharmacological interventions on the Mini-Mental State Examination (MMSE) in MCI patients were included. Two authors independently screened the studies and extracted the data. Random-effects network meta-analysis was used to synthesize the data. Results were summarized as mean difference (MD) and corresponding 95% CIs of MMSE in forest plots.Results: Fifty RCTs with 5,944 MCI patients met the inclusion criteria and 49 were included in the network meta-analysis. Compared with the control group, cognition-based intervention (MD = 0.80, 95% CI 0.04–1.57), physical exercise (MD = 1.92, 95% CI 1.19–2.64), combined physical exercise and cognition-based intervention (MD = 1.86, 95% CI 0.60–3.12), and antioxidants (MD = 0.94, 95% CI 0.04–1.83) had positive effects on MMSE in participants with MCI. There was no significant difference between all other interventions included and the control group.Conclusions: This study suggested that cognition-based intervention, physical exercise, combined physical exercise and cognition-based intervention, and antioxidants could be among the most effective interventions on global cognition in older adults with MCI. The availability, acceptability, and cost-effectiveness of interventions should also be taken into consideration when selecting interventions.Registration: PROSPERO CRD42020171985

Bioinspired, self-powered, and highly sensitive electronic skin for sensing static and dynamic pressures

Flexible piezoresistive pressure sensors obtain global research interest owing to their potential applications in healthcare, human–robot interaction, and artificial nerves. However, an additional power supply is usually required to drive the sensors, which results in increased complexity of the pressure sensing system. Despite the great efforts in pursuing self-powered pressure sensors, most of the self-powered devices can merely detect the dynamic pressure and the reliable static pressure detection is still challenging. With the help of redox-induced electricity, a bioinspired graphite/polydimethylsiloxane piezoresistive composite film acting both as the cathode and pressure sensing layer, a neoteric electronic skin sensor is presented here to detect not only the dynamic forces but also the static forces without an external power supply. Additionally, the sensor exhibits a fascinating pressure sensitivity of ∼103 kPa–1 over a broad sensing range from 0.02 to 30 kPa. Benefiting from the advanced performance of the device, various potential applications including arterial pulse monitoring, human motion detecting, and Morse code generation are successfully demonstrated. This new strategy could pave a way for the development of next-generation self-powered wearable devices

Embryonic Lethality in Mice Lacking the Nuclear Factor of Activated T Cells 5 Protein Due to Impaired Cardiac Development and Function

Nuclear factor of activated T cells 5 protein (NFAT5) is thought to be important for cellular adaptation to osmotic stress by regulating the transcription of genes responsible for the synthesis or transport of organic osmolytes. It is also thought to play a role in immune function, myogenesis and cancer invasion. To better understand the function of NFAT5, we developed NFAT5 gene knockout mice. Homozygous NFAT5 null (NFAT5−/−) mouse embryos failed to develop normally and died after 14.5 days of embryonic development (E14.5). The embryos showed peripheral edema, and abnormal heart development as indicated by thinner ventricular wall and reduced cell density at the compact and trabecular areas of myocardium. This is associated with reduced level of proliferating cell nuclear antigen and increased caspase-3 in these tissues. Cardiomyocytes from E14.5 NFAT5−/− embryos showed a significant reduction of beating rate and abnormal Ca2+ signaling profile as a consequence of reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and ryanodine receptor (RyR) expressions. Expression of NFAT5 target genes, such as HSP 70 and SMIT were reduced in NFAT5−/− cardiomyocytes. Our findings demonstrated an essential role of NFAT5 in cardiac development and Ca2+ signaling. Cardiac failure is most likely responsible for the peripheral edema and death of NFAT5−/− embryos at E14.5 days

Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass

Objective: To investigate the role of the cumulus cells and the cumulus matrix in affecting the penetrability, morphology, acrosome reaction, and motility of human spermatozoa penetrating the cumulus oophorus. Design: Controlled experimental laboratory study. Setting: University gynecology unit. Patient(s): Women undergoing assisted reproduction treatment and men visiting the subfertility clinics. Intervention(s): Human spermatozoa were allowed to penetrate through the cumulus oophorus and cell-depleted cumulus matrix in a capillary, and were treated with cumulus cell extract or hyaluronic acid. Main Outcome Measure(s): The morphology, acrosomal status, and motility of human spermatozoa were determined. Result(s): Fewer spermatozoa could penetrate the fresh cell-depleted matrix compared with intact cumulus oophorus. Spermatozoa that penetrated through the cumulus oophorus had higher percentages of normal morphology and acrosome reaction and had specific motility pattern. These effects were lost or reduced in the cell-depleted matrix that had been stored overnight. Hyaluronic acid, a main component of the cumulus matrix at concentration found in the cumulus oophorus, modulated sperm motility but did not affect spontaneous acrosome reaction. Cumulus cell extract did not affect sperm motility, but induced acrosome reaction. Conclusion(s): Both the cumulus matrix and the cumulus cells contribute to the effect of cumulus oophorus on spermatozoa penetrating through it. © 2009 American Society for Reproductive Medicine.postprin