Strain-invariant stretchable radio-frequency electronics.

Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics1-7. However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains8-15. Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain.

Characteristics of Human Nasal Turbinate Stem Cells under Hypoxic Conditions.

This study investigated the influence of hypoxic culture conditions on human nasal inferior turbinate-derived stem cells (hNTSCs), a subtype of mesenchymal stem cells (MSCs). It aimed to discern how hypoxia affected hNTSC characteristics, proliferation, and differentiation potential compared to hNTSCs cultured under normal oxygen levels. After obtaining hNTSCs from five patients, the samples were divided into hypoxic and normoxic groups. The investigation utilized fluorescence-activated cell sorting (FACS) for surface marker analysis, cell counting kit-8 assays for proliferation assessment, and multiplex immunoassays for cytokine secretion study. Differentiation potential-osteogenic, chondrogenic, and adipogenic-was evaluated via histological examination and gene expression analysis. Results indicated that hNTSCs under hypoxic conditions preserved their characteristic MSC phenotype, as confirmed by FACS analysis demonstrating the absence of hematopoietic markers and presence of MSC markers. Proliferation of hNTSCs remained unaffected by hypoxia. Cytokine expression showed similarity between hypoxic and normoxic groups throughout cultivation. Nevertheless, hypoxic conditions reduced the osteogenic and promoted adipogenic differentiation potential, while chondrogenic differentiation was relatively unchanged. These insights contribute to understanding hNTSC behavior in hypoxic environments, advancing the development of protocols for stem cell therapies and tissue engineering.

Comparative effectiveness of hypoglossal nerve stimulation and alternative treatments for obstructive sleep apnea: a systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) is the primary therapeutic modality for obstructive sleep apnea (OSA) management. However, despite efforts to encourage patients to comply with CPAP usage, long-term adherence remains low. Consequently, surgical intervention for OSA is considered a secondary option for patients who exhibit non-compliance with CPAP. Therefore, we conducted systematic review and meta-analysis assessed the relative effectiveness of hypoglossal nerve stimulation (HNS) treatment and alternative surgical interventions for managing OSA. Five databases were searched. Studies were included if they measured polysomnography parameters and assessed sleep apnea-related quality of life (Epworth Sleepiness Scale [ESS]) both before and after HNS, and compared these outcomes with control, CPAP, or airway surgery (uvulopalatopharyngoplasty, expansion sphincter pharyngoplasty, or tongue base surgery) groups. A total of 10 studies (2209 patients) met the inclusion criteria. Compared to other airway surgeries, the rates of post-treatment apnea-hypopnea index (AHI) < 10 and < 15 events/h were significantly lower in the HNS group (odds ratio [OR] 5.33, 95% confidence interval [CI] 1.21-23.42; and 2.73, 95% CI 1.30-5.71, respectively). Additionally, postoperative AHI was significantly lower in the HNS group than in all other airway surgery groups (AHI: mean difference [MD] -8.00, 95% CI -12.03 to-3.97 events/h). However, there were no significant differences in the rate of post-treatment AHI < 5 events/h (OR 1.93, 95% CI 0.74-5.06) or postoperative ESS score (MD 0.40, 95% CI-1.52 to 2.32) between the two groups. HNS is an effective option for selected patients with moderate-to-severe OSA and CPAP intolerance.

Are statins effective in preventing chronic rhinosinusitis? A systematic review and meta-analysis.

OBJECTIVES: To evaluate the association between statin use and chronic rhinosinusitis (CRS). DESIGN AND SETTING: Systematic review and meta-analysis. The methodological quality of studies was assessed using the Newcastle-Ottawa scale. PARTICIPANTS: Patients with CRS. MAIN OUTCOME MEASURES: Pooled odds ratios (ORs) with 95% confidence interval (CIs) in analyses of studies that compared the prevalence of CRS, nasal polyp, difference of Lund-Kennedy endoscopic score, Lund-Mackay CT score and Sino-nasal Outcome Test-22. RESULTS: The analysis included eight studies and 445 465 patients. Patients who used statins were at lower risk for CRS than those who did not (OR = 0.7457, 95% CI = 0.6629-0.8388, p < 0.0001, I2 = 0.0%). Patients with hyperlipidaemia were at higher risk for CRS than those with normal serum levels of lipid (OR = 1.3590, 95% CI = 1.2831-1.4394, p < 0.0001, I2 = 33.3%). However, there were no significant differences in the risk for nasal polyps between CRS patients using statins or not (OR = 1.0931, 95% CI = 0.7860-1.5202, p = 0.5968, I2 = 0.0%). Additionally, statin use was not related to Lund-Kennedy endoscopic scores, Lund-Mackay CT scores or sino-nasal outcome test-22 scores in CRS patients. CONCLUSION: The risk for CRS is lower in patients who use statins and those without hyperlipidaemia.

Heat-Killed Enterococcus faecalis EF-2001 Induces Human Dermal Papilla Cell Proliferation and Hair Regrowth in C57BL/6 Mice.

Minoxidil is the most widely used treatment for hair growth, but has been associated with several side effects. In this study, we investigated the effects of heat-killed Enterococcus faecalis EF-2001 on hair loss prevention and regrowth using human dermal papilla cells and male C57BL/6 mice. To examine the effects of EF-2001, we used minoxidil as the positive control. In the in vitro experiments, EF-2001 treatment (75-500 µg/mL) led to the proliferation of human dermal papilla cells in a concentration-dependent manner. In the in vivo experiment, the topical application of 200 µL EF-2001 on the dorsal surface of C57BL/6 male mice led to hair growth. Changes in hair regrowth were examined by visual comparison and hematoxylin and eosin staining of skin sections. We also determined the expression levels of marker genes (Wnt) and growth factors (fibroblast growth factor, insulin growth factor 1, and vascular endothelial growth factor) in the skin tissues of the back of each mouse using a quantitative polymerase chain reaction. EF-2001 accelerated the progression of hair regrowth in mice and promoted hair-follicle conversion from telogen to anagen, likely by increasing the expression levels of growth factors and marker genes.

Heat-Killed Enterococcus faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway.

Increasing consumption of food with high caloric density and a sedentary lifestyle have influenced the increasing obesity prevalence worldwide. The recent pandemic has contributed to this problem. Obesity refers to a state in which lipid accumulates excessively in adipocytes and adipose tissues. Dried heat-killed Enterococcus faecalis (EF-2001) prevents allergic mechanisms, inflammation, and tumor progression. In the present study, we investigated the effects of EF-2001 on high fat diet (HFD)-induced obese rats. The degree of obesity in experimental rats was reduced after 6 weeks of oral administration of 3 mg/kg or 30 mg/kg dosages of EF-2001, indicating regulating effects in rats with HFD-induced obesity. We found that EF-2001 decreased the amounts of total cholesterol, triglyceride, and non-high density lipoprotein (HDL) in HFD-induced obese rats. The effects of EF-2001 on 3T3-L1 adipocytes stained with Oil red O stain are shown in reductions of lipid accumulation, respectively. In addition, we examined the relationships between EF-2001 treatment and mechanisms for the insulin signaling of adipogenesis in 3T3-L1 cells. EF-2001 induced down-regulation in phosphorylation of Erk, JNK, and Akt through the inhibition of insulin receptor phosphorylation. EF-2001 inhibits the expressions of C/EBP-α and PPAR-γ, a lipid metabolism-related transcription factor through confocal microscope observation and Western blot on 3T3-L1 adipocytes and HFD-induced obese rats. Based on our results, intake of EF-2001 significantly prevented HFD-induced obesity in rats through inhibition of C/EBP-α and PPAR-γ in the insulin signaling pathway on lipid accumulation.

Effectiveness of using a bioabsorbable implant (Latera) to treat nasal valve collapse in patients with nasal obstruction: systemic review and meta-analysis.

BACKGROUND: Nasal obstruction is a common cause of breathing problems with lateral wall insufficiency (LWI) a key anatomic contributor. Recently, a bioabsorbable nasal implant was introduced to correct LWI and treat nasal obstruction. The goal of this study was to perform a systematic review with meta-analysis to determine the efficacy of the bioabsorbable nasal implant for treating nasal obstruction caused by LWI. METHODS: Five databases (PubMed, SCOPUS, EMBASE, Web of Science, and the Cochrane Database) were independently reviewed by 2 researchers, starting at the earliest time point recorded in the database to September 2019. Studies that scored endoscopic lateral wall movement and nasal obstruction related to quality of life (QOL) postoperatively before and after bioabsorbable nasal implants and those that compared the outcomes of nasal implants (treatment group) with outcomes of sham surgery (control group) were included in the analysis. RESULTS: Five studies (396 patients) met the inclusion criteria. Bioabsorbable nasal implants significantly reduced endoscopic lateral wall motion compared to pretreatment values and also improved QOL at 12 months postoperatively. Most adverse effects following the nasal implant, such as skin or mucosal reaction, infection, or implant retrieval, were reported with a 5% incidence rate. All adverse outcomes were resolved without significant sequelae. Compared with sham surgery, bioabsorbable nasal implants significantly improved disease-specific QOL. CONCLUSION: Bioabsorbable nasal implants may reduce nasal wall movement and subjective symptom scores compared to preoperative status. More randomized clinical trials must be conducted to further verify the effectiveness of bioabsorbable nasal implants.

Co-amplification of EBNA-1 and PyLT through dhfr-mediated gene amplification for improving foreign protein production in transient gene expression in CHO cells.

Despite the relatively low transfection efficiency and low specific foreign protein productivity (qp) of Chinese hamster ovary (CHO) cell-based transient gene expression (TGE) systems, TGE-based recombinant protein production technology predominantly employs CHO cells for pre-clinical research and development purposes. To improve TGE in CHO cells, Epstein-Barr virus nuclear antigen-1 (EBNA-1)/polyoma virus large T antigen (PyLT)-co-amplified recombinant CHO (rCHO) cells stably expressing EBNA-1 and PyLT were established using dihydrofolate reductase/methotrexate-mediated gene amplification. The level of transiently expressed Fc-fusion protein was significantly higher in the EBNA-1/PyLT-co-amplified pools compared to control cultures. Increased Fc-fusion protein production by EBNA-1/PyLT-co-amplification resulted from a higher qp attributable to EBNA-1 but not PyLT expression. The qp for TGE-based production with EBNA-1/PyLT-co-amplified rCHO cells (EP-amp-20) was approximately 22.9-fold that of the control culture with CHO-DG44 cells. Rather than improved transfection efficiency, this cell line demonstrated increased levels of mRNA expression and replicated DNA, contributing to an increased qp. Furthermore, there was no significant difference in N-glycan profiles in Fc-fusion proteins produced in the TGE system. Taken together, these results showed that the use of rCHO cells with co-amplified expression of the viral elements EBNA-1 and PyLT improves TGE-based therapeutic protein production dramatically. Therefore, EBNA-1/PyLT-co-amplified rCHO cells will likely be useful as host cells in CHO cell-based TGE systems.

Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.

Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.

Allele-specific regulation of mutant Huntingtin by Wig1, a downstream target of p53.

p53 has been implicated in the pathophysiology of Huntington's disease (HD). Nonetheless, the molecular mechanism of how p53 may play a unique role in the pathology remains elusive. To address this question at the molecular and cellular biology levels, we initially screened differentially expressed molecules specifically dependent on p53 in a HD animal model. Among the candidate molecules, wild-type p53-induced gene 1 (Wig1) is markedly upregulated in the cerebral cortex of HD patients. Wig1 preferentially upregulates the level of mutant Huntingtin (Htt) compared with wild-type Htt. This allele-specific characteristic of Wig1 is likely to be explained by higher affinity binding to mutant Htt transcripts than normal counterpart for the stabilization. Knockdown of Wig1 level significantly ameliorates mutant Htt-elicited cytotoxicity and aggregate formation. Together, we propose that Wig1, a key p53 downstream molecule in HD condition, play an important role in stabilizing mutant Htt mRNA and thereby accelerating HD pathology in the mHtt-p53-Wig1 positive feedback manner.

Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory-inhibitory synapse formation in the mature cortex.

Neuregulin-1 (NRG1) and its receptor ErbB4 influence several processes of neurodevelopment, but the mechanisms regulating this signalling in the mature brain are not well known. DISC1 is a multifunctional scaffold protein that mediates many cellular processes. Here we present a functional relationship between DISC1 and NRG1-ErbB4 signalling in mature cortical interneurons. By cell type-specific gene modulation in vitro and in vivo including in a mutant DISC1 mouse model, we demonstrate that DISC1 inhibits NRG1-induced ErbB4 activation and signalling. This effect is likely mediated by competitive inhibition of binding of ErbB4 to PSD95. Finally, we show that interneuronal DISC1 affects NRG1-ErbB4-mediated phenotypes in the fast spiking interneuron-pyramidal neuron circuit. Post-mortem brain analyses and some genetic studies have reported interneuronal deficits and involvement of the DISC1, NRG1 and ErbB4 genes in schizophrenia, respectively. Our results suggest a mechanism by which cross-talk between DISC1 and NRG1-ErbB4 signalling may contribute to these deficits.

Dab2IP GTPase activating protein regulates dendrite development and synapse number in cerebellum.

DOC-2/DAB-2 interacting protein (Dab2IP) is a GTPase activating protein that binds to Disabled-1, a cytosolic adapter protein involved in Reelin signaling and brain development. Dab2IP regulates PI3K-AKT signaling and is associated with metastatic prostate cancer, abdominal aortic aneurysms and coronary heart disease. To date, the physiological function of Dab2IP in the nervous system, where it is highly expressed, is relatively unknown. In this study, we generated a mouse model with a targeted disruption of Dab2IP using a retrovirus gene trap strategy. Unlike reeler mice, Dab2IP knock-down mice did not exhibit severe ataxia or cerebellar hypoplasia. However, Dab2IP deficiency produced a number of cerebellar abnormalities such as a delay in the development of Purkinje cell (PC) dendrites, a decrease in the parallel fiber synaptic marker VGluT1, and an increase in the climbing fiber synaptic marker VGluT2. These findings demonstrate for the first time that Dab2IP plays an important role in dendrite development and regulates the number of synapses in the cerebellum.

Dab2ip regulates neuronal migration and neurite outgrowth in the developing neocortex.

Dab2ip (DOC-2/DAB2 interacting protein) is a member of the Ras GTPase-activating protein (GAP) family that has been previously shown to function as a tumor suppressor in several systems. Dab2ip is also highly expressed in the brain where it interacts with Dab1, a key mediator of the Reelin pathway that controls several aspects of brain development and function. We found that Dab2ip is highly expressed in the developing cerebral cortex, but that mutations in the Reelin signaling pathway do not affect its expression. To determine whether Dab2ip plays a role in brain development, we knocked down or over expressed it in neuronal progenitor cells of the embryonic mouse neocortex using in utero electroporation. Dab2ip down-regulation severely disrupts neuronal migration, affecting preferentially late-born principal cortical neurons. Dab2ip overexpression also leads to migration defects. Structure-function experiments in vivo further show that both PH and GRD domains of Dab2ip are important for neuronal migration. A detailed analysis of transfected neurons reveals that Dab2ip down- or up-regulation disrupts the transition from a multipolar to a bipolar neuronal morphology in the intermediate zone. Knock down of Dab2ip in neurons ex-vivo indicates that this protein is necessary for proper neurite development and for the expression of several major neuronal microtubule associated proteins (MAPs), which are important for neurite growth and stabilization. Thus, our study identifies, for the first time, a critical role for Dab2ip in mammalian cortical development and begins to reveal molecular mechanisms that underlie this function.

The accuracy of intramedullary tibial guide of sagittal alignment of PCL-substituting total knee arthroplasty.

Experimental and clinical studies on the accuracy of the intramedullary alignment method have produced different results, and few have addressed accuracy in the sagittal plane. Reported deviations are not only attributable to the alignment method but also to radiological errors. The purpose of this study was to evaluate the accuracy of the intramedullary alignment method in the sagittal plane using computed tomography (CT) and 3-dimensional imaging software. Thirty-one TKAs were performed using an intramedullary alignment method involving the insertion of a long 8-mm diameter rod into the medullary canal to the distal metaphysis of the tibia. All alignment instruments were set to achieve an ideal varus/valgus angle of 0° in the coronal plane and a tibial slope of 0° in the sagittal plane. The accuracy of the intramedullary alignment system was assessed by measuring the coronal tibial component angle and sagittal tibial slope angles, i.e., angles between the tibial anatomical axis and the tangent to the medial and lateral tibial plateau or the cut-surface. The mean coronal tibial component angle was 88.5° ± 1.2° and the mean tibial component slope in the sagittal plane was 1.6° ± 1.2° without anterior slope. Our intramedullary tibial alignment method, which involves passing an 8-mm diameter long rod through the tibial shaft isthmus, showed good accuracy (less than 3 degrees of variation and no anterior slope) in the sagittal plane in neutral or varus knees.