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Hematopoietic stem cells are a group of heterogeneity cells with the potential to differentiate into various types of mature blood cells. Their basic biological properties include quiescence, self-renewal, multilineage differentiation, and homing ability, with the homing of exogenous hematopoietic stem cells after transplantation becoming a new focus, while the first three properties share some similarity in mechanism due to connectivity. In various complex mechanisms, the role of E3 ubiquitin ligases in hematopoietic homeostasis and malignant transformation is receiving increasing attention. As a unique part, E3 ubiquitin ligases play an important role in physiological regulation mechanism of posttranslational modification. In this review, we focus on the recent progress of the crucial role of E3 ubiquitin ligases that target specific proteins for ubiquitination to regulate biological properties of hematopoietic stem cells. Additionally, this paper deals with E3 ubiquitin ligases that affect the biological properties through aging and summarizes the relevant applications of targeting E3 ligases in hematopoietic malignancies. We present some ideas on the clinical application of E3 ubiquitin ligase to regulate hematopoietic stem cells and also believe that it is meaningful to study the upstream signal of these E3 ubiquitin ligases because hematopoietic stem cell dysfunction is caused by deficiency of some E3 ligases.

The cornea is the outmost ocular tissue and plays an important role in protecting the eye from environmental insults. Corneal epithelial wounding provokes pain and fear and contributes to the most ocular trauma emergency assessments worldwide. ZEB1 is an essential transcription factor in development; but its roles in adult tissues are not clear. We identify Zeb1 is an intrinsic factor that facilitates corneal epithelial wound healing. In this study, we demonstrate that monoallelic deletion of Zeb1 significantly expedites corneal cell death and inhibits corneal epithelial EMT-related cell migration upon an epithelial debridement. We provide evidence that Zeb1-regulation of corneal epithelial wound healing is through the repression of genes required for Tnfa-induced epithelial cell death and the induction of genes beneficial for epithelial cell migration. We suggest utilizing TNF-α antagonists would reduce TNF/TNFR1-induced cell death in the corneal epithelium and inflammation in the corneal stroma to help corneal wound healing.

Osteoimmunology focuses on the intermodulation between bone and the immune system. Lipopolysaccharide (LPS)-induced bone loss models are commonly used to investigate the interface between inflammation and osteoporosis. Circulating exosomes can regulate physiological and pathological processes through exosomal microRNAs and proteins. In this study, we observed reduced osteoblast number and bone formation in LPS-induced bone loss mice (LPS mice). Levels of circulating exosomes were increased by ~ twofold in LPS mice, and the expression of exosomal miRNAs was significantly changed. miRNAs (miRNA-125b-5p, miRNA-132-3p, and miRNA-214-3p) that were reported to inhibit osteoblast activity were significantly increased in the serum exosomes and bone tissues of LPS mice. Additionally, LPS-induced increases in exosomes significantly inhibited the osteogenic differentiation of MC3T3-E1 cells.

The commonly-used superstrate configuration (depositing front subcell first and then depositing back subcell) in all-perovskite tandem solar cells is disadvantageous for long-term stability due to oxidizable narrow-bandgap perovskite assembled last and easily exposable to air. Here we reverse the processing order and demonstrate all-perovskite tandems in a substrate configuration (depositing back subcell first and then depositing front subcell) to bury oxidizable narrow-bandgap perovskite deep in the device stack. By using guanidinium tetrafluoroborate additive in wide-bandgap perovskite subcell, we achieve an efficiency of 25.3% for the substrate-configured all-perovskite tandem cells. The unencapsulated devices exhibit no performance degradation after storage in dry air for 1000 hours. The substrate configuration also widens the choice of flexible substrates: we achieve 24.1% and 20.3% efficient flexible all-perovskite tandem solar cells on copper-coated polyethylene naphthalene and copper metal foil, respectively. Substrate configuration offers a promising route to unleash the commercial potential of all-perovskite tandem solar cells.

Objective This study aimed to establish a new scoring system that includes histological quantitative features derived from coronary computed tomographic angiography (CCTA) to predict the efficiency of chronic total occlusion percutaneous coronary intervention (CTO-PCI). Methods This study analyzed clinical, morphological, and histological characteristics of 207 CTO lesions in 201 patients (mean age 60.0 [52.0–65.0] years, 85% male), which were recruited from two centers. The primary endpoint was a guidewire successfully crossing the lesions within 30 m. The new predictive model was generated by factors that were determined by multivariate analysis. The CCTA plaque (CTAP) score that included a quantitative plaque characteristic was developed by assigning an appropriate integer score to each independent predictor, then summing all points. In addition, the CTAP score was compared with other predictive scores based on CCTA. Results The endpoint was achieved in 63% of the lesions. The independent predictors included previous CTO-PCI failure, the proximal blunt stump, proximal side branch, distal side branch, occluded segment bending > 45°, and high-density plaque volume (fibrous volume + calcified volume) ≥ 19.9 mm3. As the score increased from 0 to 5, the success rate of the guidewire crossing within 30 m decreased from 96 to 0%. Comparing the CTAP score with other predictive scores, the CTAP score showed the highest discriminant power (c-statistic = 0.81 versus 0.73–0.77, p value 0.02–0.07). The CTAP score showed similar results for procedural success. Conclusion The CTAP score efficiently predicted the guidewire crossing efficiency and procedural success. Key Points • An increase in high-density plaque volume (fibrous + dense calcium) was more probable to reduce the efficiency of crossing and lead to procedural failure. • The new prediction scoring system with the addition of the quantitative characteristics of plaques had an improved predictive ability compared with the traditional prediction scoring system.

3D-fluid attenuation inversion recovery (FLAIR) collected 4 h after intravenous gadolinium injection can delineate the perilymphatic space (PLS) from the endolymphatic space (ELS) to capture endolymphatic hydrops, the pathological counterpart of Ménière's disease. We aimed to optimize visualization of such inner ear internal anatomy using 3D-FLAIR without injection.3D-FLAIR signal from different fluid compartments such as PLS and ELS was first simulated. Then, twenty-two healthy subjects were scanned at 3.0-T MRI with non-injected 3D-FLAIR using variable T2 preparations (T2Preps) (OFF, 200, 400, and 600 ms) and variable inversion times (TIs) (from 224 to 5000 ms) and different resolutions (1.0 × 1.0 × 1.5, 0.6 × 0.6 × 0.8, and 0.6 × 0.6 × 0.6 mmThe PLS and ELS were differentiated when T2Prep was used but not without. The relative contrast was larger with T2Prep at 400 ms than at 200 or 600 ms (0.72 ± 0.22 vs. 0.44 ± 0.11, p = 0.019; and 0.72 ± 0.22 vs. 0.46 ± 0.28, p = 0.034, respectively). The saccule and utricle were best delineated in 87. % cases with T2Prep = 400 and TI = 2100 ms at the highest resolution. Visualization of the saccule and utricle in the optimized non-injected 3D-FLAIR was similar to conventional injected 3D-FLAIR in a patient.Combining a specific T2Prep and TI in non-injected 3D-FLAIR could separate PLS and ELS and even the saccule and utricle, paving the way toward future application to diagnose Ménière's disease.• MRI can capture the internal anatomy of inner ear without injection of contrast media. • Specific parameters consisting of a T2 preparation of 400 ms and an inversion time of 2100 ms must be used to visualize the saccule and utricle on non-injected 3D-FLAIR.

A common phenomenon called social buffering (SB), communication within conspecific animals is a benefit for a stressed individual to better recover from aversive events, is crucial to all mammals. Although the dopamine reward system has been implicated in SB, it is not clear which neuronal populations are relevant and how they contribute. Here, we adopted a learned helplessness (LH) animal model of depression and found that LH subjects housed with a conspecific partner show better performance in the shuttle box test, showing that SB improves the stress-coping abilities to deal with stress. Bidirectional manipulation of ventral tegmental area (VTA) dopamine neurons by chemogenetic tools can mimic or block the SB effect in LH mice. To screen for SB-induced structure plasticity of VTA dopamine neurons, we employed viral genetic tools for mapping input and output architecture and found LH- and SB-triggered circuit-level changes in neuronal ensembles. Zona incerta (ZI), an overlapping brain region, was significantly changed in both anterograde and retrograde tracing during LH and SB. These results reveal a neural loop with structural plasticity between VTA dopamine neurons and ZI underlies the SB effects in LH and lays a foundation for studying how VTA dopamine neurons regulate SB-related neural circuits.

Development and progression of many kidney diseases are substantially influenced by aberrant protein acetylation modifications of gene expression crucial for kidney functions. Histone deacetylase (HDAC) expression alterations are detected from renal samples of patients and animal models of various kidney diseases, and the administrations of HDAC inhibitors display impressive renal protective effects in vitro and in vivo. However, when the expression alterations of multiple HDACs occur, not all the HDACs causally affect the disease onset or progression. Identification of a single HDAC as a disease-causing factor will allow subtype-targeted intervention with less side effect. HDAC3 is a unique HDAC with distinct structural and subcellular distribution features and co-repressor dependency. HDAC3 is required for kidney development and its aberrations actively participate in many pathological processes, such as cancer, cardiovascular diseases, diabetes, and neurodegenerative disorders, and contribute significantly to the pathogenesis of kidney diseases. This review will discuss the recent studies that investigate the critical roles of HDAC3 aberrations in kidney development, renal aging, renal cell carcinoma, renal fibrosis, chronic kidney disease, polycystic kidney disease, glomerular podocyte injury, and diabetic nephropathy. These studies reveal the distinct characters of HDAC3 aberrations that act on different molecules/signaling pathways under various renal pathological conditions, which might shed lights into the epigenetic mechanisms of renal diseases and the potentially therapeutic strategies.

The perturbed mK(3,1) equation is restudied to further explore the dynamics of solitary wave solutions by combining the geometric singular perturbation theorem and bifurcation analysis in this paper. Besides the solitary waves presented in literature [1–3], we show that this equation possesses a family of solitary waves which decay to some constants determined by their wave speeds and a parameter. It is shown that a portion of the solitary wave solutions to the mK(3,1) equation will persist under small perturbations and the wave speed selection principle is presented as well. In addition to the solitary waves, each of which has only one crest or trough and approximates to a solitary wave of the unperturbed equation as the perturbation parameter tends to zero, we theoretically prove the existence of a new type of solitary waves with coexisting crest and trough. The numerical simulations are carried out, and the results are in complete agreement with our theoretical analysis.

Advanced deep learning technology has made great progress in generic object detection of autonomous driving, yet it is still challenging to detect small road hazards in a long distance owing to lack of large-scale small-object datasets and dedicated methods. This work addresses the challenge from two aspects. Firstly, a self-collected long-distance road object dataset (TJ-LDRO) is introduced, which consists of 109,337 images and is the largest dataset so far for the small road object detection research. Secondly, a vanishing-point-guided context-aware network (VCANet) is proposed, which utilizes the vanishing point prediction block and the context-aware center detection block to obtain semantic information. The multi-scale feature fusion pipeline and the upsampling block in VCANet are introduced to enhance the region of interest (ROI) feature. The experimental results with TJ-LDRO dataset show that the proposed method achieves better performance than the representative generic object detection methods. This work fills a critical capability gap in small road hazards detection for high-speed autonomous vehicles.

This paper aims to develop, in a case of multiple water sources, an optimal operational strategy that can be used in arid/semiarid regions by water decision-makers to schedule the use of each source over time, to control the artificial recharge to aquifers, to improve the energy efficiency related to the water supply system, to determine the optimal amount of water each source should supply over a period, and to minimise the water costs. In this regard, a novel, cost effective, and advanced optimal controller to operate a water supply system in arid/semiarid regions has been developed. This model is designed as a multi-constraint non-linear programming model that meets the demand for an ever-growing population, and considers in its formulation multiple surface water sources, aquifers, desalination plants, recycled water plants, the seasonal availability of surface water and groundwater, the monthly rainfall variability, and the seasonal energy price. To verify the effectiveness of the developed model, a real case study was conducted. The results obtained showed a 3% reduction in the water supply cost and sustainable improvement in groundwater management, demonstrating the model’s capacity to manage aquifer recharge efficiently, to optimally schedule the use of water sources. Adopting this strategy improves water security and the energy security in an urban region as it decreases the use of energy-intensive water sources during seasons with high electricity demand.

Background Individual and environmental health outcomes are frequently linked to changes in the diversity of associated microbial communities. Thus, deriving health indicators based on microbiome diversity measures is essential. While microbiome data generated using high-throughput 16S rRNA marker gene surveys are appealing for this purpose, 16S surveys also generate a plethora of spurious microbial taxa. Results When this artificial inflation in the observed number of taxa is ignored, we find that changes in the abundance of detected taxa confound current methods for inferring differences in richness. Experimental evidence, theory-guided exploratory data analyses, and existing literature support the conclusion that most sub-genus discoveries are spurious artifacts of clustering 16S sequencing reads. We proceed to model a 16S survey’s systematic patterns of sub-genus taxa generation as a function of genus abundance to derive a robust control for false taxa accumulation. These controls unlock classical regression approaches for highly flexible differential richness inference at various levels of the surveyed microbial assemblage: from sample groups to specific taxa collections. The proposed methodology for differential richness inference is available through an R package, Prokounter. Conclusions False species discoveries bias richness estimation and confound differential richness inference. In the case of 16S microbiome surveys, supporting evidence indicate that most sub-genus taxa are spurious. Based on this finding, a flexible method is proposed and is shown to overcome the confounding problem noted with current approaches for differential richness inference. Package availability: https://github.com/mskb01/prokounter

Through a simple solvothermal method, the bimetallic sulfide nanomaterial (Ni–Mo–S) was successfully grown on the surface of CeO2 to restrain the severe photogenerated electron–hole recombination of CeO2. The presence of a close contact interface between the 0D metal sulfide particles and the 2D CeO2 sheet is conducive to charge transfer. Meanwhile, the introduction of Ni–Mo–S nanoparticles on 2D CeO2 can accelerate surface electron mobility, which could obviously inhibit the combination of electrons and holes. Also, there are many unsaturation sites of metal sulfide introduced on the surface and low hydrogen evolution overpotential, which can serve as active sites for hydrogen evolution. In addition, the 2D structure of CeO2 can provide a support framework for the 0D Ni–Mo–S particles, thereby greatly reducing the recombination of useful electrons and holes. All of these advantages of photocatalysts discussed above make for the enhancement of photocatalyst catalytic performance, which equal to about 66 times compared with pure CeO2. Besides, a series of research tests were carried out from different angles to support the relevant results and proposed possible reaction mechanisms.

In this paper, eight solid-state diffusion couples in fcc ternary Cu-Ni-Al alloys at 1073, 1173 and 1273 K were prepared, and the corresponding composition profiles were measured with an electron probe microanalyzer (EPMA) technique. Based on the measured composition profiles and HitDIC software, a set of reliable atomic mobility descriptions in the fcc Cu-Ni-Al system were directly established, from which the composition- and temperature-dependent interdiffusion coefficient matrices were evaluated. Then, the three-dimensional (3D) main interdiffusivity surfaces for fcc Cu-Ni-Al systems were constructed. The diffusion rate of Al is faster than that of Ni. Both the main interdiffusivities of Al and Ni increase with the increase of Al concentration but decrease with Ni concentration. The reliability of the evaluated interdiffusivities was first validated by reproducing the measured composition profiles and interdiffusion fluxes. After that, the interdiffusivities and corresponding uncertainties at intersection points of diffusion couples were evaluated by using the Matano–Kirkaldy method combined with distribution functions. Especially all the interdiffusion coefficients estimated from the present mobility parameters are within the bounds of the uncertainties, which further quantitatively verified the reliability of the present mobility descriptions. The accuracy of the as-determined mobility is further highlighted via combining with the reported thermodynamic descriptions, which enables an accurate prediction of the volume of Ni3Al precipitates in the Cu-Ni-Al alloy during artificial aging. The present work indicates that with the accurate thermodynamic as well as boundary mobility descriptions, reliable ternary mobility descriptions can be achieved by combining the diffusion couple experiments with the HitDIC modeling.

Biomass and pig manure have distinct compositions and the co-pyrolysis of them has gained much attention. However, the influence of volatiles interaction on the properties of the char was still unclear. In this study, lignin was selected as the model component of biomass with pig manure for co-pyrolysis at 600 °C. The results indicate that volatiles from co-pyrolysis promoted re-condensation reaction, resulting in the higher char yield (48.0% in co-pyrolysis versus 31.0% in pyrolysis of single manure) and the formation of more aromatics in bio-oil. The co-pyrolysis also facilitated the dehydrogenation and dehydration reactions, which accounted for the elimination of oxygen and nitrogen contents and thus a higher carbon content (64.7% in the co-pyrolysis versus the averaged value of 46.4% from the pyrolysis of single feedstock), higher crystallinity and thermal stability of the char. The in-situ diffuse reflection infrared Fourier transform spectroscopy (DRIFTS) characterization results demonstrated that the functionalities abundances of char with temperature was influenced by volatiles interaction via accelerating the carbonization reaction. In addition, the high heating value (HHV) of char was obviously improved by cross-interaction of volatiles during co-pyrolysis (24.4 MJ/Kg in co-pyrolysis versus averaged value of 15.1 MJ/Kg from single pyrolysis), implying that the co-pyrolysis enhanced the energy density of the resulting char.

Chemical dealloying is an emerging strategy that can be applied to synthesize porous materials. The structure morphologies of the active materials were precisely regulated by designing the various NaOH corrosion solutions. Three-dimensional micro–nanorods-like structure Ni75Cu25O bimetallic oxide with ultra-high electrochemical properties have been obtained, which used Al65Cu15Ni20 precursors through a dealumination strategy. Meanwhile, three-dimensional micro–nanorods-like structure Ni75Cu25O demonstrates an unusual extraordinary specific capacitance (16.96 F cm−2 at 10 mV s−1) and excellent cycling stability (100.8% retention after 5000 cycles at 10 mV s−1). Here, the transition bimetallic oxides by using the dealloying strategy can be applied to develop novel guidances and ideas for the generation of energy storage devices.

Hard carbon is considered to be one of the most promising anodes for sodium-ion batteries (SIBs), but high cost and poor cycle stability limit the large-scale application for SIBs. Here, a new kind of low-cost sycamore fruit seed hard carbon was prepared by facile pyrolysis at different temperatures as anode for SIBs. With the large interlayer spacing, the reversible specific capacity of sycamore fruit seed carbonized at 1100 °C can reach 323 mAh g−1 at the current density of 0.1 C. When cycled at 0.4 C, the reversible specific capacity is 246.9 mAh g−1, following the capacity retention is 87.85% after 300 cycles. Moreover, we find although the different interlayer spacings (d002 ≥ 0.37 nm) of graphite crystallites of the obtained hard carbon beneficial for the Na+ storage, the smaller d002 limits the diffusion of Na+ inevitably, which affects their cycle stability. This research furnishes a competitive choice about anode materials for the industrialized SIBs.

Although some co-risk factors and hemodynamic alterations are involved in hypertension progression, their direct biomechanical effects are unclear. Here, we constructed a high-hydrostatic-pressure cell-culture system to imitate constant hypertension and identified novel molecular classifications of human aortic smooth muscle cells (HASMCs) by single-cell transcriptome analysis. Under 100-mmHg (analogous to healthy human blood pressure) or 200-mmHg (analogous to hypertension) hydrostatic pressure for 48 h, HASMCs showed six distinct vascular SMC (VSMC) clusters according to differential gene expression and gene ontology enrichment analysis. Especially, two novel HASMC subsets were identified, named the inflammatory subset, with CXCL2, CXCL3 and CCL2 as markers, and the endothelial-function inhibitory subset, with AKR1C2, AKR1C3, SERPINF1 as markers. The inflammatory subset promoted CXCL2&3 and CCL2 chemokine expression and secretion, triggering monocyte migration; the endothelial-function inhibitory subset secreted SERPINF1 and accelerated prostaglandin F2α generation to inhibit angiogenesis. The expression of the two VSMC subsets was greatly increased in arterial media from patients with hypertension and experimental animal models of hypertension. Collectively, we identified high hydrostatic pressure directly driving VSMCs into two new subsets, promoting or exacerbating endothelial dysfunction, thereby contributing to the pathogenesis of cardiovascular diseases.

A Ni-based metal-organic framework (Ni-MOF) modified electrode was fabricated for electrochemical detection of dopamine. The Ni-MOF was synthesized by ionothermal synthesis method using an ionic liquid as a template. The morphology and composition of the Ni-MOF were characterized by scanning electron microscope, X-ray diffraction, thermogravimetric analysis, and attenuated total reflection Fourier transform infrared spectroscopy. Electrochemical responses of the Ni-MOF modified electrode toward dopamine were performed using differential pulse voltammetry. The electrochemical sensing performance of the Ni-MOF modified electrode toward dopamine was improved by the introduction of ionic liquid with a wide linear range (0.2–100 μmol L−1), and a low detection limit (60 nmol L−1). Further studies indicated that the modified electrode exhibited great selectivity to dopamine in complex mixtures, and the Ni-MOF modified electrode also has excellent stability and reproducibility. Moreover, the analysis of real samples confirmed that the modified electrode has a certain reliability.

Transition metal phosphides (TMPs) are a hopeful noble-metal-free catalysts for water splitting. In this study, we used a three-dimensional nanostructure on nickel substrate to easily synthesize a nickel–cobalt phosphide electrocatalyst (NixCoyP, x = 1, 1.5, 2; y = 1, 1.5, 2) through hydrothermal reaction and in situ phosphorylation. The NiCo1.5 P exhibited relatively excellent oxygen evolution activity performance, and it only needed the overpotentials of 123 mV for HER in 1 M KOH to perform the current densities of 10 mA cm−2. It is worth mentioning that the Ni2CoP exhibited better bifunctional electrocatalyst characteristics. As to water splitting, the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) require 197 and 253 mV overpotentials separately to provide a current density of 10 mA cm−2. Its relatively excellent electrochemical performance can be ascribed to the high-density sea urchin-like three-dimensional structure, which provides greater specific surface area and more active site. Besides, Ni2CoP also shows long-term durability lasting 80,000 s, and on this basis, there is no distinct deactivation. This work emphasizes that Ni2P and CoP play a vital role relative to the good activity of HER. Moreover, the unique morphology with self-supported structure provides a larger specific surface area, making it possible the exposure of higher amount of active sites for HER. These self-supported electrocatalysts that do not require a binder could also make the electrode more active and stable. This work, therefore, presents a strategy that is controllable and feasible strategy for the synthesis of bimetallic phosphides with unique morphology and high HER and OER activity.

Automated techniques and tools for the construction and analysis of systems are inevitable to manage the complexity of the current systems. Such techniques and tools are the subject of interest of the International Conference on Tools and Algorithms for the Construction and Analysis of Systems—TACAS. This special issue of Software Tools for Technology Transfer presents extended versions of five selected papers from the 25th edition of TACAS that took place in 2019. All of the papers included into this special issue aim at various aspects of automated design and formal verification and hence contribute to development of more reliable computer systems.

The study on the temperature-dependent kinetic behavior of intermetallic compounds (IMCs) in Mg–Al–Zn (AZ) series alloy system is important since its close interrelation with the microstructure evolution under various alloying conditions as well as the T-dependent performance. However, there is a very lack of experimental study on the diffusion kinetics of the ternary IMCs in the AZ series alloy systems. The current work combines the diffusion couple technique and numerical inverse method to investigate the T-dependent kinetic coefficients, i.e., the parabolic growth constant (PGC) and interdiffusion coefficients, for ϕ-Mg5Al2Zn2 ternary IMC in the Mg–Al–Zn alloy system. The Arrhenius formula of both PGC and main interdiffusivities is obtained, i.e., $${}_{{}}^{\phi } k_{p} = 5.48 \times 10^{ - 5} \exp \left( {\frac{120010}{{RT}}} \right)$$ m2/s, $${}_{{}}^{\phi } \tilde{D}_{{{\text{MgMg}}}}^{Al} = 3.48 \times 10^{ - 10} \exp \left( {\frac{50420}{{RT}}} \right)$$ m2/s and $${}_{{}}^{\phi } \tilde{D}_{{{\text{ZnZn}}}}^{Al} = 2.87 \times 10^{ - 7} \exp \left( {\frac{91440}{{RT}}} \right)$$ m2/s, based on which a numerical reproduction of the experimentally determined IMC growth is performed for verification. By comparing the current experimental and calculation results, the rate-controlling factor of the temperature-dependent diffusion growth of ϕ ternary IMC in the Mg–Al–Zn system is further discussed.

Obesity is a risk factor for many chronic diseases, and is associated with increased incidence rate of type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. Adipocyte differentiation play critical role during development of obesity. Latexin (LXN), a mammalian carboxypeptidase inhibitor, plays important role in the proliferation and differentiation of stem cells, and highlights as a differentiation-associated gene that was significantly downregulated in prostate stem cells and whose expression increases through differentiation. However, it is unclear whether LXN is involved in adipocyte differentiation. The aim of this study was to evaluate the role of LXN on adipocyte differentiation, as well as its effects on high fat-induced obesity and metabolic disorders. In this study, we determine the expression of LXN in adipose tissue of lean and fat mice by Western blot, qPCR and immunohistochemistry. We found that LXN in fat tissues was continuous increased during the development of diet-induced obesity. We fed wild-type (WT) and LXN−/−mice with high-fat diet (HFD) to study the effects of LXN on obesity and related metabolic functions. We found that mice deficient in LXN showed resistance against high-fat diet (HFD)-induced obesity, glucose tolerance, insulin tolerance and hepatic steatosis. In vitro studies indicated that LXN was highly induced during adipocyte differentiation, and positively regulated adipocyte differentiation and adipogenesis in 3T3-L1 cells and primary preadipocytes. Functional analysis revealed that the expression of LXN was positively regulated by mTOR/RXR/PPARɤ signaling pathway during the differentiation of adipocytes, while LXN deletion decreased the protein level of PPARɤ in adipocyte through enhancing FABP4 mediated ubiquitination, which led to impaired adipocyte differentiation and lipogenesis. Collectively, our data provide evidence that LXN is a key positive regulator of adipocyte differentiation, and therapeutics targeting LXN could be effective in preventing obesity and its associated disorders in clinical settings.

Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior., Using a three-chamber vicarious social defeat stress model in mice, Qi et al. show that chronic emotional stress (CES) induced anxiety-like behavior and transient social interaction changes. Bidirectional modulation of NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior.

We study a quasi-one-dimensional classical Poisson–Nernst–Planck model for ionic flow through a membrane channel with two positively charged ion species (cations) and one negatively charged, and with zero permanent charges. We treat the model problem as a boundary value problem of a singularly perturbed differential system. Under the framework of the geometric singular perturbation theory, together with specific structures of this concrete model, the existence of solutions to the boundary value problem is established and, for a special case that the two cations have the same valences, we are able to derive approximations of the individual fluxes and the I–V (current–voltage) relation explicitly, from which, our two main focuses in this work, boundary layer effects on ionic flows and competitions between two cations, are analyzed in great details. Critical potentials are identified and their roles in characterizing these effects are studied. Nonlinear interplays among physical parameters, such as boundary concentrations and potentials, diffusion coefficients and ion valences, are characterized, which could potentially provide efficient ways to control and affect some biological functions. Numerical simulations are performed, and numerical results are consistent with our analytical ones.

The present article deals with entropy analysis and mass transfer process on asymmetric peristaltic propulsion of nanofluid under convection and magnetic effects. The second law of thermodynamics is used to formulate the mathematical modeling. The Williamson fluid model is contemplated to examine nanofluid behavior in asymmetric conditions. The effects of viscous dissipation are also included with thermophoretic and Brownian motion body forces. An appropriate transformation is used to formulate the mathematical modeling, which leads to the resulting nonlinear coupled partial differential equations in the wave frame. To determine the solutions of the formulated differential equations, homotopy perturbation method is used. The significant outcomes are discussed for entropy, temperature, concentration, and, velocity profile in favor of all the leading parameters. The irreversible process is also discussed and calculated with the help of the Bejan number. The present analysis helps to examine the hemodynamics process and is also beneficial in polymer processing.

The thermally developed particle–fluid motion of a coupled stress fluid through a nonuniform finite wavy channel is studied. A sinusoidal peristaltic wave is traveling in the channel with a constant velocity, long wavelength and low Reynolds number. A coupled stress fluid model is applied to study the flow behavior in the channel. The mathematical model is formulated using dimensionless variables, and exact, analytical solutions are derived. The analytical expressions for the heat transfer, the velocity profile, the stream functions, the concentration profile, and the volumetric flow rate are obtained for the fluid and the particulate phase. Numerical integration is performed to determine the characteristics of the pumping rate. Results are discussed for all the variables examined in terms of the flow parameters.

Reaction atmosphere is one of the principle reaction parameters affecting the pyrolysis of biomass. At elevated temperatures, in addition to gases, organics are also regarded as part of the reaction atmosphere. In this study, the impacts of the co-feeding of formic acid or acetic acid on the pyrolysis behaviour of cellulose were investigated at 400 and 600 °C, respectively. The results showed that the co-feeding of the acids significantly affected properties of both the resulting bio-oil and biochar. Co-feeding of acetic acid remarkably promoted formation of heavier organics with π-conjugated structures, while the presence of formic acid suppressed their evolution, especially at the lower pyrolysis temperature of 400 °C. The co-feeding of the carboxylic acids increased the yields of biochar. Furthermore, the co-feeding of formic acid or acetic acid also affected the elemental composition, the defective structure, the crystallinity and the thermal stabilities of the resulting biochar at varied pyrolysis temperature in the distinct ways. The carboxylic acids or their derivatives interfered with the formation of the volatiles or reacted directly with the organic components on surface of biochar, which substantially modified the physiochemical properties of the biochar.

The three-dimensional (3D) nanofluid flow among the rotating circular plates filled with nanoparticles and gyrotactic microorganisms is studied. A generalized form of the magnetic Reynolds number is used for the mathematical modeling of the ferro-nanofluid flow. The torque effects on the lower and upper plates are calculated. A differential transform scheme with the Pade approximation is used to solve the coupled highly nonlinear ordinary differential equations. The results show that the squeeze Reynolds number significantly suppresses the temperature, microorganism, and nanoparticle concentration distribution, and agree well with those obtained by the numerical method.

A comprehensive understanding of solidification behavior of Mg–Al–Zn–Bi alloys is necessary for designing novel casting Bi-modified AZ alloys. In this paper, 21 Mg–Al–Zn–Bi alloys were prepared to investigate the phase constituents, morphologies, grain sizes and area fractions of precipitates in as-cast microstructures, as well as their phase transition temperatures and solidification paths by using X-ray diffraction, scanning electron microscopy, optical microscopy and differential scanning calorimetric techniques. It was found that the Bi addition leads to the formation of α-Mg3Bi2 phase, which became coarse flake as Bi content increased. Besides, the Bi addition can modify the morphology of eutectic γ-Al12Mg17 phase and refine the grain size of primary phase. Moreover, the measured area fractions of precipitates increased steadily as Bi content increased, which were comparable with the model-predicated values. After that, the calculated liquidus projections in the Mg-rich corner of Mg–Al–Zn–Bi quaternary system were employed for demonstrating the effects of Bi addition on the solidification sequences. Additionally, the phase transition temperatures predicted via Scheil solidification simulations agreed well with measured values. The present work indicated that the combination of experimental investigations and thermodynamic calculations can serve as an efficient method to obtain accurate and comprehensive solidification behavior of Bi-modified Mg–Al–Zn alloys.

Two-dimensional Ruddlesden–Popper phase (2DRP) perovskites are known to exhibit improved photostability and environmental stability compared with their three-dimensional (3D) counterparts. However, fundamental questions remain over the interaction between the bulky alkylammoniums and the 2DRP perovskite framework. Here, we unambiguously demonstrate that a sulfur–sulfur interaction is present for a new bulky alkylammonium, 2-(methylthio)ethylamine hydrochloride (MTEACl). In addition to a weaker van der Waals interaction, the interaction between sulfur atoms in two MTEA molecules enables a (MTEA)2(MA)4Pb5I16 (n = 5) perovskite framework with enhanced charge transport and stabilization. The result is 2DRP perovskite solar cells with significantly improved efficiency and stability. Cells with a power conversion efficiency as high as 18.06% (17.8% certified) are achieved, along with moisture tolerance for up to 1,512 h (under 70% humidity conditions), thermal stability for 375 h (at 85 °C) and stability under continuous light stress (85% of the initial efficiency retained over 1,000 h of operation at the maximum power point). Two-dimensional perovskite solar cells have been engineered to be robust against moisture, high temperatures and light stress.

Learning from large-scale and high-dimensional data still remains a computationally challenging problem, though it has received increasing interest recently. To address this issue, randomized reduction methods have been developed by either reducing the dimensionality or reducing the number of training instances to obtain a small sketch of the original data. In this paper, we focus on recovering a high-dimensional classification/regression model from random sketched data. We propose to exploit the intrinsic sparsity of optimal solutions and develop novel methods by increasing the regularization parameter before the sparse regularizer. In particular, (i) for high-dimensional classification problems, we leverage randomized reduction methods to reduce the dimensionality of data and solve a dual formulation on the random sketched data with an introduced sparse regularizer on the dual solution; (ii) for high-dimensional sparse least-squares regression problems, we employ randomized reduction methods to reduce the scale of data and solve a formulation on the random sketched data with an increased regularization parameter before the sparse regularizer. For both classes of problems, by exploiting the intrinsic sparsity of the optimal dual solution or the optimal primal solution we provide formal theoretical guarantee on the recovery error of learned models in comparison with the optimal models that are learned from the original data. Compared with previous studies on randomized reduction for machine learning, the present work enjoy several advantages: (i) the proposed formulations enjoys intuitive geometric explanations; (ii) the theoretical guarantee does not rely on any stringent assumptions about the original data (e.g., low-rankness of the data matrix or the data are linearly separable); (iii) the theory covers both smooth and non-smooth loss functions for classification; (iv) the analysis is applicable to a broad class of randomized reduction methods as long as the reduction matrices admit the Johnson–Lindenstrauss type of lemma. We also present empirical studies to support the proposed methods and the presented theory.