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With an eye on the role of structure size and topology, this study explores the mechanical behavior of nanoporous (NP) Nb made by liquid-metal dealloying. Results from X-ray nanotomography and macro-compression tests confirm that coarsening degrades the yield strength and that Young's modulus deviates from scaling laws developed for NP Au made by dealloying in aqueous media. We find that the scaled genus of NP Nb is lower than what has been reported for NP Au, and this low connectivity provides an obvious explanation for the low modulus. Furthermore, the structural dispersion implies that additional structural descriptors should be acknowledged.

Abstract Intravenous (systemic) bolus injection of fentanyl (FNT) reportedly induces an immediate vagal‐mediated apnea; however, the precise origin of vagal afferents responsible for this apnea remains unknown. We tested whether intralaryngeal (local) application of FNT would also trigger an apnea and whether the apneic response to both local and systemic administration of FNT was laryngeal afferent‐mediated. Cardiorespiratory responses to FNT were recorded in anesthetized male adult rats with and without bilateral sectioning of the superior laryngeal nerve (SLNx) or peri‐SLN capsaicin treatment (SLNcap) to block local C‐fiber signal conduction. Opioid mu‐receptor (MOR)‐immunoreactivity was detected in laryngeal C‐ and myelinated neurons. We found that local and systemic administration of FNT elicited an immediate apnea. SLNx, rather than SLNcap, abolished the apneic response to local FNT application though MORs were abundantly expressed in both laryngeal C‐ and myelinated neurons. Importantly, SLNx failed to affect the apneic response to systemic FNT administration. These results lead to the conclusion that laryngeal afferents' MORs are responsible for the apneic response to local, but not systemic, administration of FNT.

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0–0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs.

Bio-based polyurethanes are novel material with potential advantages for sustainable development, and their development play significant roles in promoting sustainability. Curcumin, a natural monomer, possesses high biological activity and features a symmetrical chemical structure with various functional groups such as phenolic hydroxyl, carbonyl and benzene ring. The presence of hydroxyl groups in the structure of curcumin provides essential conditions for its involvement in polyurethane synthesis. This review article provides an overview of the applications of curcumin as a chain extender, crosslinking agent and end-capper in polyurethanes, as well as its effects on the chemical structure, mechanical properties, and chemical stability of polyurethanes. Furthermore, the functional applications of curcumin-based polyurethanes in various fields such as medicine, food packaging, and coatings are discussed. Finally, considering the current research status and inherent properties of curcumin, the future prospects of curcumin-based polyurethanes are contemplated.

Introduction: Research has revealed that the tumor microenvironment (TME) is associated with the progression of malignancy. The combination of meaningful prognostic biomarkers related to the TME is expected to be a reliable direction for improving the diagnosis and treatment of non-small cell lung cancer (NSCLC).Method and Result: Therefore, to better understand the connection between the TME and survival outcomes of NSCLC, we used the “DESeq2” R package to mine the differentially expressed genes (DEGs) of two groups of NSCLC samples according to the optimal cutoff value of the immune score through the ESTIMATE algorithm. A total of 978 up-DEGs and 828 down-DEGs were eventually identified. A fifteen-gene prognostic signature was established via LASSO and Cox regression analysis and further divided the patients into two risk sets. The survival outcome of high-risk patients was significantly worse than that of low-risk patients in both the TCGA and two external validation sets (p-value < 0.05). The gene signature showed high predictive accuracy in TCGA (1-year area under the time-dependent ROC curve (AUC) = 0.722, 2-year AUC = 0.708, 3-year AUC = 0.686). The nomogram comprised of the risk score and related clinicopathological information was constructed, and calibration plots and ROC curves were applied, KEGG and GSEA analyses showed that the epithelial-mesenchymal transition (EMT) pathway, E2F target pathway and immune-associated pathway were mainly involved in the high-risk group. Further somatic mutation and immune analyses were conducted to compare the differences between the two groups. Drug sensitivity provides a potential treatment basis for clinical treatment. Finally, EREG and ADH1C were selected as the key prognostic genes of the two overlapping results from PPI and multiple Cox analyses. They were verified by comparing the mRNA expression in cell lines and protein expression in the HPA database, and clinical validation further confirmed the effectiveness of key genes.Conclusion: In conclusion, we obtained an immune-related fifteen-gene prognostic signature and potential mechanism and sensitive drugs underling the prognosis model, which may provide accurate prognosis prediction and available strategies for NSCLC.

Bulk nanoporous platinum (np-Pt) samples with a remarkably fine ligament size down to 2 nm and good mechanical robustness were fabricated for the first time by electrochemically dealloying Pt15Cu85 master alloy in 1 mol L−1 H2SO4 at 60 ℃. The as-prepared np-Pt shows an electrochemically active specific surface area as high as 25 m2/g due to the ultrafine nanostructure. The active surface area remains almost invariable even after 15% macroscopic compressive strain. Furthermore, np-Pt shows considerably high thermal stability due to the low surface diffusivity of Pt. Np-Pt is a promising surface- or interface-controlled functional material, particularly when excellent electrochemical and mechanical performance are necessary due to its high surface-to-volume ratio and mechanical robustness. This work demonstrated the potential application of np-Pt as an electrochemical actuation material. In-situ dilatometry experiments revealed that the surface adsorption–desorption of OH species on np-Pt causes significant strain variations. The proposed np-Pt electrochemical actuator shows an operating voltage down to 1.0 V, a large reversible strain amplitude of 0.37%, and a strain energy density of 1.64 MJ/m³.

Abstract To accurately identify the functions of tumour‐cell‐derived extracellular vesicles (T‐EVs), EVs directly isolated from tumour tissues are much preferred over those derived from in vitro cultured tumour cell lines. However, the functional analysis of T‐EVs has still been severely limited by the difficulty in selective isolation of T‐EVs from tissue‐derived heterogeneous EVs, which also contain non‐tumour cell‐derived EVs. We here establish an untouched isolation strategy that specifically collects natural T‐EVs from tumour tissues by removing non‐tumour‐cell‐derived EVs. Different from traditional immunomagnetic separation, our isolation materials are directly bound to undesired non‐tumour‐cell‐derived EVs, preserving the natural properties of T‐EVs. Using this strategy, we reveal the distinct performances of tissue‐derived T‐EVs in organotropism to lymph nodes, immunosuppression and angiogenesis. The present work, which takes an extraordinary step forward in the isolation of EV subpopulation from tumour tissues, would dramatically accelerate the investigation of EV heterogeneity.

Oral cancer is one of the most common cancers worldwide, of which more than half of patients are diagnosed at a locally advanced stage with poor prognosis due to recurrence, metastasis and resistant to treatment. Thus, it is imperative to further explore the potential mechanism of development and drug resistance of oral cancer. Exosomes are small endosome-derived lipid nanoparticles that are released by cells. Since the cargoes of exosomes were inherited from their donor cells, the cargo profiles of exosomes can well recapitulate that of their donor cells. This is the theoretical basis of exosome-based liquid biopsy, providing a tool for early diagnosis of oral cancer. As an important intracellular bioactive cargo delivery vector, exosomes play a critical role in the development of oral cancer by transferring their cargoes to receipt cells. More importantly, recent studies have revealed that exosomes could induce therapy-resistance in oral cancer through multiple ways, including exosome-mediated drug efflux. In this review, we summarize and compare the role of exosomes in the diagnosis, development and therapy-resistant of oral cancer. We also highlight the clinical application of exosomes, and discuss the advantages and challenges of exosomes serving as predictive biomarker, therapy target and therapy vector in oral cancer.

Voa protein is a subunit of V-ATPase proton pump which is essential to acidify intracellular organelles including synaptic vesicles. Voa1 is one of the four isoforms of Voa family with strong expression in neurons. Our present study was aimed to examine the role of Voa1 protein in mammalian brain neurons. To circumvent embryonic lethality, we generated conditional Voa1 knockout mice in which Voa1 was selectively deleted from forebrain pyramidal neurons. We performed experiments in the Voa1 knockout mice of ages 5–6 months to assess the persistent effects of Voa1 deletion. We found that the Voa1 knockout mice exhibited poor performance in the Morris water maze test compared to control mice. In addition, synaptic field potentials of the hippocampal CA1 region were greatly diminished in the Voa1 knockout mice when examined in brain slices in vitro. Furthermore, brain histological experiments showed severe degeneration of dorsal hippocampal CA1 neurons while CA3 neurons were largely preserved. The CA1 neurodegeneration was associated with general brain atrophy as overall hemispheric areas were reduced in the Voa1 cKO mice. Despite the CA1 degeneration and dysfunction, electroencephalographic recordings from the hippocampal CA3 area revealed aberrant spikes and non-convulsive discharges in the Voa1 knockout mice but not in control mice. These hippocampal spikes were suppressed by single intra-peritoneal injection of diazepam which is a benzodiazepine GABAA receptor enhancer. Together these results suggest that Voa1 related activities are essential for the survival of the targeted neurons in the dorsal hippocampal CA1 as well as other forebrain areas. We postulate that the Voa1 knockout mice may serve as a valuable model for further investigation of V-ATPase dysfunction related neuronal degeneration and functional abnormalities in forebrain areas particularly the hippocampus.

A number of Mobile-Assisted-Language-Learning (MALL) apps have been developed to enlarge students' vocabulary. However, few studies have discussed the potential to learn words deeply and productively. Therefore, this study evaluated the effectiveness of a mind mapping MALL app as an aid to assist northern Taiwan EFL participants in learning vocabulary. The research questions aimed to examine changes in vocabulary learning outcomes, and the perspectives the participants held regarding the app. Data were collected through tests (pretest, posttest and delayed posttest), visualized vocabulary knowledge mind mappings, and surveys. The posttest results showed the use of the mind mapping MALL app enhanced EFL vocabulary learning (t = 3.68, p<0.05; Cohen's d = 0.81, r = 0.38). In addition, based on the questionnaire responses, experimental participants agreed that not only did the MALL app provide them with a feasible way to move from receptive ways of learning to productive ways of learning, but it also bolstered word consciousness and word retention. Analytical ANCOVA results also verified that learners benefited more from the mind mapping app with respect to learning performance in their delayed posttest (t = 3.45, p<.05; Cohen's d = 0.77, r = 0.36). The findings may be construed as an effective method towards learning foreign words and further exploring the potential of vocabulary learning and MALL.

BackgroundFew reference equations exist for healthy adults of various races for pulmonary diffusing capacity for nitric oxide (DLNO). The purpose of this study was to collect pilot data to demonstrate that race-specific reference equations are needed for DLNO.MethodsAfrican Americans (blacks) were chosen as the comparative racial group. In 2016, a total of 59 healthy black subjects (27 males and 32 females) were recruited to perform a full battery of pulmonary function tests. In the development of DLNO reference equations, a white reference sample (randomly drawn from a population) matched to the black sample for sex, age, and height was used. Multiple linear regression equations for DLNO, alveolar volume (VA), and pulmonary diffusing capacity for carbon monoxide (DLCO) using a 5-6 s breath-hold were developed.ResultsOur models demonstrated that sex, age2, race, and height explained 71% of the variance in DLNO and DLCO, with race accounting for approximately 5-10% of the total variance. After normalizing for sex, age2, and height, blacks had a 12.4 and 3.9 mL/min/mmHg lower DLNO and DLCO, respectively, compared to whites. The lower diffusing capacity values in blacks are due, in part, to their 0.6 L lower VA (controlling for sex and height).ConclusionThe results of this pilot data reveal small but important and statistically significant racial differences in DLNO and DLCO in adults. Future reference equations should account for racial differences. If these differences are not accounted for, then the risk of falsely diagnosing lung disease increase in blacks when using reference equations for whites.

Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.

Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is down- regulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration. [ABSTRACT FROM AUTHOR]

Background: Senescence-accelerated mouse prone 8 (SAMP8) and age- matched SAMR1 mice are used to study the pathogenesis and therapeutics of Alzheimer's disease (AD); however, the molecular mechanisms are not completely understood. Objective: This study aimed to examine the effects of the 5-month administration of formononetin in SAMP8 mice and used RNA-seq to explore the molecular targets. Methods: SAMP8 mice were orally administered formononetin (0, 8, and 16 mg/kg) from 4 months of age, and age-matched SAMR1 mice were used as controls. Behavioral tests were performed in 9-month-old mice, followed by histopathologic analysis. Total RNA from the hippocampus was isolated and subjected to RNA-seq, RT-qPCR, and bioinformatics analysis. Results: The 9-month-old SAMP8 mice exhibited cognition deficits, evidenced by novel object recognition, open-field test, elevated plus maze, and passive avoidance. Nissl bodies in the cortex and hippocampus were decreased. Formononetin treatments ameliorated behavioral deficits and improved morphological changes, which were evidenced by Nissl and H&E staining. RNA-seq revealed distinct gene expression patterns between SAMP8 and SAMR1 mice. Differentially expressed genes in SAMP8 mice were attenuated or normalized by formononetin. Ingenuity pathway analysis (IPA) of canonical pathway and upstream regulators revealed increases in proinflammatory factors and immune dysfunction and decreases in NRF2 and SIRT-1 signaling pathways, leading to neuroinflammation. Formononetin treatment attenuated or reversed these molecular changes. The transcriptome of SAMP8 mice was correlated with transcriptomic profiles of other AD mouse models in the GEO database. Conclusion: Neuroinflammation and decreased antioxidant and SIRT-1 signaling contributed to cognitive deficits in aged SAMP8 mice, which are potential therapeutic targets of formononetin in combination with other therapies. [ABSTRACT FROM AUTHOR]

Four species of the cosmopolitan genus Asaphes Walker, 1834 (Hymenoptera: Chalcidoidea: Asaphesinae, family incerta sedis) are recorded from Xinjiang Uyghur Autonomous Region, China, bringing the number of known species in China to eight. In addition to Asaphes suspensus (Nees ab Esenbeck), 1834 and A. vulgaris Walker, 1834, A. fuyunis Li & Zhang, sp. nov. is newly described based on females and A. californicus Girault, 1917, previously known only from North and South America, is newly recorded from China. These four species are differentiated using an integrative taxonomic approach that includes COI barcode data and morphometrics, and are illustrated using macrophotography. Additionally, the 13 described world species of Asaphes are tabulated and females of the eight recognized Chinese species are keyed. [ABSTRACT FROM AUTHOR]

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for onetube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPACas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the mechanism of RNA-binding protein hnRNP A1 in mouse hippocampal neurons (HT22) on glycolysis. Methods: RIP and CLIP-qPCR were performed by HT22 in vitro to observe the mechanism of hnRNP A1 regulating the expression of key proteins in glycolysis. The RNA binding domain of hnRNP A1 protein in HT22 was inhibited by VPC-80051, and the effect of hnRNP A1 on glycolysis of HT22 was observed. Lentivirus overexpression of hnRNP A1 was used to observe the effect of overexpression of hnRNP A1 on glycolysis of Aβ25-35-injured HT22. The expression of hnRNP A1 in brain tissues of wild-type mice and triple-transgenic (APP/PS1/Tau) AD mice at different ages was studied by Western blot assay. Results: The results of RIP experiment showed that hnRNP A1 and HK1 mRNA were significantly bound. The results of CLIP-qPCR showed that hnRNP A1 directly bound to the 2605-2821 region of HK1 mRNA. hnRNP A1 inhibitor can down-regulate the expression of HK1 mRNA and HK1 protein in HT22 cells. Overexpression of hnRNP A1 can significantly reduce the toxic effect of Aβ25-35 on neurons via the hnRNP A1/HK1/pyruvate pathway. In addition, inhibition of hnRNP A1 binding to amyloid precursor protein (APP) RNA was found to increase A25-35 expression, while Aβ25-35 also down-regulated hnRNP A1 expression by enhancing phosphorylation of p38 MAPK in HT22. They interact to form bidirectional regulation, further down-regulating the expression of hnRNP A1, and ultimately aggravating glycolytic dysfunction. Protein immunoblotting showed that hnRNP A1 decreased with age in mouse brain tissue, and the decrease was greater in AD mice, suggesting that the decrease of hnRNP A1 may be a predisposed factor in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]