Severe burns induce a chronic hypermetabolic state that persists well past wound closure, indicating that additional internal mechanisms must be involved. Adipose tissue is suggested to be a central ...regulator in perpetuating hypermetabolism, although this has not been directly tested. Here, we show that thermogenic adipose tissues are activated in parallel to increases in hypermetabolism independent of cold stress. Using an adipose tissue transplantation model, we discover that burn-derived subcutaneous white adipose tissue alone is sufficient to invoke a hypermetabolic response in a healthy recipient mouse. Concomitantly, transplantation of healthy adipose tissue alleviates metabolic dysfunction in a burn recipient. We further show that the nicotinic acetylcholine receptor signaling pathway may mediate an immune-adipose crosstalk to regulate adipose tissue remodeling post-injury. Targeting this pathway could lead to innovative therapeutic interventions to counteract hypermetabolic pathologies.
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•Thermogenic adipocyte activation occurs in parallel to the post-burn hypermetabolic response•Subcutaneous white adipose tissue is sufficient to both induce and rescue hypermetabolism•Nicotinic acetylcholine receptor signaling regulates post-burn white adipose tissue metabolism•Inhibiting this pathway alleviates symptoms of hypermetabolism
Knuth et al. identify subcutaneous white adipose tissue as a central regulator of the hypermetabolic response to a severe burn, which may be mediated by sympathetic activation of the nicotinic acetylcholine receptor signaling pathway. Treatment with either sympathetic or nicotinic acetylcholine receptor antagonists mitigates post-burn hypermetabolism.
Previous investigations of the core gene regulatory circuitry that controls the pluripotency of embryonic stem (ES) cells have largely focused on the roles of transcription, chromatin and non-coding ...RNA regulators. Alternative splicing represents a widely acting mode of gene regulation, yet its role in regulating ES-cell pluripotency and differentiation is poorly understood. Here we identify the muscleblind-like RNA binding proteins, MBNL1 and MBNL2, as conserved and direct negative regulators of a large program of cassette exon alternative splicing events that are differentially regulated between ES cells and other cell types. Knockdown of MBNL proteins in differentiated cells causes switching to an ES-cell-like alternative splicing pattern for approximately half of these events, whereas overexpression of MBNL proteins in ES cells promotes differentiated-cell-like alternative splicing patterns. Among the MBNL-regulated events is an ES-cell-specific alternative splicing switch in the forkhead family transcription factor FOXP1 that controls pluripotency. Consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells during somatic cell reprogramming.
A new cost effective ferritic stainless steel for interconnect in solid oxide fuel cell (SOFC), named 460FC, has been developed and fabricated by the conventional continuous casting and rolling ...process. The oxidation characteristics and high temperature properties of 460FC were investigated at 800 °C and compared with those of Crofer22 which is a well-known representative alloy for the same application. Although the 460FC does not contain rare earth metals and does not limit the content of Si to extremely low level, it shows good electrical conductivity and low Cr evaporation rate. The performance of 460FC in the real cell was also evaluated with 25 cm2 active area single cell test up to 500 h and the degradation rate was almost similar or superior to Crofer22.
•A low cost ferritic stainless steel for interconnect in solid oxide fuel cell (SOFC) was developed.•The new alloy neither contains rare earth metals nor limits the Si content to extremely low level.•The oxidation characteristics and ASR of the new alloy was very similar to those of Crofer22.•The real cell test showed almost similar or superior performance of the new alloy to Crofer22.
Palladium (Pd) has been drawing increasing attention as a hydrogen (H2) detecting material due to its highly selective sensitivity to H2. However, at H2 concentrations above 2%, Pd undergoes an ...inevitable phase transition, causing undesirable electrical and mechanical alterations. In particular, nonlinear gas response (ΔR/R 0) that accompanies phase transition has been a great bottleneck for detecting H2 in high concentrations, which is especially important as there is a risk of explosion over 4% H2. Here, we propose a phase-transition-inhibited Pd nanowire H2 sensor that can detect up to 4% H2 with high linearity and high sensitivity. Based on the calculation of the change in free energy, we designed Pd nanowires that are highly adhered to the substrate to withstand the stress that leads to phase transition. We theoretically optimized the Pd nanowire dimensions using a finite element method simulation and then experimentally fabricated the proposed sensor by exploiting a developed nanofabrication method. The proposed sensor exhibits a high sensing linearity (98.9%) with high and stable sensitivity (ΔR/R 0/H2 = 875%·bar–1) over a full range of H2 concentrations (0.1–4%). Using the fabricated Pd sensors, we have successfully demonstrated a wireless sensor module that can detect H2 with high linearity, notifying real-time H2 leakage through remote communication. Overall, our work suggests a nanostructuring strategy for detecting H2 with a phase-transition-inhibited pure Pd H2 sensor with rigorous scientific exploration.
Retrospective study.
We identified radiological risk factors for neurological deficits in mid and low lumbar spinal fractures.
Although numerous studies have focused on radiological risk factors for ...neurological deficits in spinal cord injury or thoracolumbar junction area fractures, few have examined mid and low lumbar fractures at the cauda equina level.
We retrospectively reviewed 71 consecutive patients who suffered acute traumatic mid and low lumbar fractures (L2-L5) corresponding to the cauda equina level, as confirmed on magnetic resonance imaging. We defined a neurological deficit as present if the patient had any sensory or motor deficit in the lower extremity or autonomic system at the initial assessment. Various computed tomography parameters of canal stenosis, vertebral body compression, sagittal alignment, interpedicular distance, and presence of vertical laminar fractures were analyzed as independent risk factors to predict neurological deficits using multivariate logistic regression analyses.
At the initial assessment, 31 patients had neurological deficits. Fracture level, AO fracture type, canal encroachment ratio, vertebral compression ratio, interpedicular distance ratio, and presence of a vertical laminar fracture were significantly associated with the presence of neurological deficits (all P < 0.05). Multivariate logistic regression identified fracture level, canal encroachment ratio (adjusted odds ratio aOR 1.072, 95% confidence interval CI 1.018-1.129), and vertebral compression ratio (aOR 0.884, 95% CI 0.788-0.992) as independent predictors of a neurological deficit. Receiver operating characteristic curve analyses revealed that only the canal encroachment ratio had good discriminatory ability (area under the curve 0.874, 95% CI 0.791-0.957), and the optimal cutoff was 47% (canal diameter 6.6 mm) with 90.3% sensitivity and 80% specificity.
The canal encroachment ratio was most strongly associated with neurological deficits in traumatic mid and low lumbar fractures, with an optimal cutoff of 47%.
4.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of renal cysts, leading to the loss of functional nephrons. Recommendations for individuals with ADPKD ...to maintain a healthy diet and lifestyle are largely similar to those for the general population. However, recent evidence from preclinical models suggests that more tightly specified dietary regimens, including caloric restriction, intermittent fasting, and ketogenic diets, hold promise to slow disease progression, and the results of ongoing human clinical trials are eagerly awaited. These dietary interventions directly influence nutrient signaling and substrate availability in the cystic kidney, while also conferring systemic metabolic benefits. The present review focuses on the importance of local and systemic metabolism in ADPKD and summarizes current evidence for dietary interventions to slow disease progression and improve quality of life.
Statement of Significance: We offer the first comprehensive review of the current evidence for dietary interventions to slow ADPKD progression from preclinical animal models and early-stage clinical trials, and elucidate potential common mechanisms underlying their effect.
Mucus-secreting goblet cells are the dominant cell type in pulmonary diseases, e.g., asthma and cystic fibrosis (CF), leading to pathologic mucus metaplasia and airway obstruction. Cytokines ...including IL-13 are the major players in the transdifferentiation of club cells into goblet cells. Unexpectedly, we have uncovered a previously undescribed pathway promoting mucous metaplasia that involves VEGFa and its receptor KDR. Single-cell RNA sequencing analysis coupled with genetic mouse modeling demonstrates that loss of epithelial VEGFa, KDR, or MEK/ERK kinase promotes excessive club-to-goblet transdifferentiation during development and regeneration. Sox9 is required for goblet cell differentiation following Kdr inhibition in both mouse and human club cells. Significantly, airway mucous metaplasia in asthmatic and CF patients is also associated with reduced KDR signaling and increased SOX9 expression. Together, these findings reveal an unexpected role for VEGFa/KDR signaling in the defense against mucous metaplasia, offering a potential therapeutic target for this common airway pathology.
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•VEGFa/KDR suppresses mucous differentiation of club cells during regeneration•VEGFa/KDR signaling executes its epithelial function through MEK/ERK kinases•Sox9 mediates mucous metaplasia of the airway epithelium upon VEGFa/KDR inhibition•VEGFa/KDR/MEK blockage is linked to mucous metaplasia in asthma and cystic fibrosis
Jiang et al. demonstrate that the VEGFa/KDR pathway protects the airway epithelium against mucous metaplasia during regeneration. Suppressed VEGF signaling leads to increased levels of SOX9, which promotes goblet cell differentiation. These findings introduce critical players in airway mucous metaplasia that is commonly seen in asthma and CF.
An Au/Ni/
β
-Ga
2
O
3
Schottky barrier diode was fabricated on an 8.6-
μ
m-thick lightly doped drift region grown on heavily doped Ga
2
O
3
substrate, and its electrical and low-frequency noise ...characteristics were investigated. The diode showed excellent rectifying behavior with the reverse current being saturated with the applied bias and a magnitude of ∼ 10
−13
A. The diode exhibited a barrier height of 1.04 eV and a reasonably high reverse breakdown voltage of 540 V without employing any edge termination methods. The Schottky barrier parameters, such as barrier height, ideality factor, and series resistance, were obtained using a range of methods and found to be in close agreement with each other. The interface state density of the Au/Ni/
β
-Ga
2
O
3
Schottky diode obtained from the capacitance–voltage (
C
–
V
) method was lower than that determined from the forward current–voltage (
I
–
V
) characteristics, attributed to the inhomogeneous distribution of interface states at the interface. An analysis of the forward log
I
–log
V
plot of the Au/Ni/
β
-Ga
2
O
3
Schottky diode revealed ohmic-type conduction, and space-charge-limited current dominated the carrier transport mechanisms in lower and higher voltage ranges, respectively. For bias below 0.3 V, the low-frequency noise of the Au/Ni/
β
-Ga
2
O
3
Schottky diode was a linear combination of two noise components associated with uniformly distributed bulk traps of
β
-Ga
2
O
3
and the charge fluctuation in the generation-recombination center. On the other hand, for bias above 0.4 eV, the noise spectral density showed a 1/
f
2
dependence, indicating the domination of generation-recombination noise.
The high explosiveness of hydrogen gas in the air necessitates prompt detection in settings where hydrogen is used. For this reason, hydrogen sensors are required to offer rapid detection and possess ...superior sensing characteristics in terms of measurement range, linearity, selectivity, lifetime, and environment insensitivity according to the publicized protocol. However, previous approaches have only partially achieved the standardized requirements and have been limited in their capability to develop reliable materials for spatially accessible systems. Here, an electrical hydrogen sensor with an ultrafast response (∼0.6 s) satisfying all demands for hydrogen detection is demonstrated. Tailoring structural engineering based on the reaction kinetics of hydrogen and palladium, an optimized heating architecture that thermally activates fully suspended palladium (Pd) nanowires at a uniform temperature is designed. The developed Pd nanostructure, at a designated temperature distribution, rapidly reacts with hydrogen, enabling a hysteresis-free response from 0.1% to 10% and durable characteristics in mechanical shock and repetitive operation (>10,000 cycles). Moreover, the device selectively detects hydrogen without performance degradation in humid or carbon-based interfering gas circumstances. Finally, to verify spatial accessibility, the wireless hydrogen detection system has been demonstrated, detecting and reporting hydrogen leakage in real-time within just 1 s.
Abstract
Senescent cells accumulate in various tissues over time and contribute to tissue dysfunction and aging-associated phenotypes. Accumulating evidence suggests that cellular senescence can be ...inhibited through pharmacological intervention, as well as through treatment with soluble factors derived from embryonic stem cells (ESCs). In an attempt to investigate the anti-senescence factors secreted by ESCs, we analyzed mouse ESC-derived extracellular microRNAs in conditioned medium via microRNA array analysis. We selected mmu-miR-291a-3p as a putative anti-senescence factor via bioinformatics analysis. We validated its inhibitory effects on replicative, Adriamycin-induced, and ionizing radiation–induced senescence in human dermal fibroblasts. Treatment of senescent cells with mmu-miR-291a-3p decreased senescence-associated β-galactosidase activity, enhanced proliferative potential, and reduced mRNA and protein expression of TGF-β receptor 2, p53, and p21. mmu-miR-291a-3p in conditioned medium was enclosed in ESC-derived exosomes and exosomes purified from ESC conditioned medium inhibited cellular senescence. The inhibitory effects of mmu-miR-291a-3p were mediated through the TGF-β receptor 2 signaling pathway. Hsa-miR-371a-3p and hsa-miR-520e, the human homologs of mmu-miR-291a-3p, showed similar anti-senescence activity. Furthermore, mmu-miR-291a-3p accelerated the excisional skin wound healing process in aged mice. Our results indicate that the ESC-derived mmu-miR-291a-3p is a novel candidate agent that can be utilized for cell-free therapeutic intervention against aging and aging-related diseases.
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