Background/Aims: Hypoxic microenvironment, a common feature of hepatocellular carcinoma (HCC), can induce HIF-1α expression and promote the epithelial-mesenchymal transition (EMT) and invasion of ...cancer cells. However, the underlying molecular mechanisms have not fully elucidated. Methods: HCC cells were cultured under controlled hypoxia conditions or normoxic conditions. Transwell assays were used to examine the migration and invasion capacity. HIF-1α siRNA, cyclopamine (a SMO antagonist) and GLI1 siRNA were used to inhibit HIF-1α transcription or Hh signaling activation. Results: In present study, we first observed a strongly positive correlation between HIF-1α and GLI1 expression in HCC tissues. Then, we showed that hypoxia significantly promoted EMT process and invasion of HCC cells, associated with activating the non-canonical Hh pathway without affecting SHH and PTCH1 expression. HIF-1α knockdown mitigated hypoxia-induced SMO and GLI1 expression, EMT invasion of HCC cells. Moreover, the SMO inhibitor or GLI1 siRNA also reversed the hypoxia-driven EMT and invasion of HCC cells under hypoxia condition. Here, we show that non-canonical Hh signaling is required as an important role to switch on hypoxia-induced EMT and invasion in HCC cells. In addition, we found that hypoxia increased ROS production and that ROS inhibitors (NAC) blocked GLI1-dependent EMT process and invasion under hypoxic conditions. To determine a major route of ROS production, we tested whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is involved in hypoxia-induced ROS production. NOX4 expression was found to be increased at both mRNA and protein levels in hypoxic HCC cells. Furthermore, siRNA-mediated knockdown of NOX4 expression abolished hypoxia induced ROS generation and GLI1-dependent activation and invasion of HCC cells. Conclusion: Our findings indicate that hypoxia triggers ROS-mediated GLI1-dependent EMT progress and invasion of HCC cells through induction of NOX4 expression. Thus, hypoxia-driven ROS mediated non-canonical Hh signaling may play an important role in the initiation of EMT and provides a potential marker for cancer prevention and treatment.
Metal halide perovskites are promising for applications in light‐emitting diodes (LEDs), but still suffer from defects‐mediated nonradiative losses, which represent a major efficiency‐limiting factor ...in perovskite‐based LEDs (PeLEDs). Reported here is a strategy to synthesize molecular passivators with different anchoring groups for defects passivation. The passivated perovskite thin films exhibit improved optoelectronic properties as well as reduced grain size and surface roughness, thus enable highly efficient PeLEDs with an external quantum efficiency of 15.6 % using an imidazolium terminated passivator. Further demonstrated is that the in situ formation of low‐dimensional perovskite phase on the surface of three‐dimensional perovskite nanograins is responsible for surface defects passivation, which leads to significantly enhanced device performance. Our results provide new fundamental insights into the role of organic molecular passivators in boosting the performance of PeLEDs.
Organic molecular passivators with different terminal groups are synthesized, which can effectively passivate the surface defects of MAPbI3‐based films by forming mixed‐phase perovskite nanograins. Moreover, highly efficient PeLEDs with EQE of 15.6 % are achieved by utilizing an imidazolium terminated passivator. This work opens up a new opportunity of molecular engineering for the development of high‐performance PeLEDs.
Background Emerging evidence from observational studies and clinical trials suggests a connection between the gut microbiota and variations in bone mineral density (BMD). Nonetheless, the specific ...association between gut microbiota and BMD alterations at different skeletal sites has not been comprehensively explored. To address this, we employed Genome-Wide Association Study (GWAS) summary statistics from a publicly accessible database, conducting a two-sample Mendelian Randomization analysis to elucidate the potential causal relationship between gut microbiota composition and BMD. Methods This study utilized two distinct thresholds for screening instrumental variables (IVs), followed by an extensive series of quality control procedures to identify IVs that were significantly related to exposure. Gut microbiota were classified into two sets based on hierarchical levels: phylum, class, order, family, and genus. Bone mineral density (BMD) data were systematically collected from four skeletal sites: femoral neck, lumbar spine, forearm, and heel. For Mendelian Randomization (MR) analysis, robust methods including Inverse-Variance Weighting (IVW) and the Wald Ratio Test were employed. Additional analytical tests such as the Outlier Test, Heterogeneity Test, ‘Leave-One-Out’ Test, and Pleiotropy Test were conducted to assess the impact of horizontal pleiotropy, heterogeneities, and the genetic variation stability of gut microbiota on BMD causal associations. The MR Steiger Directionality Test was applied to exclude studies with potential directional biases. Results In this two-sample Mendelian randomization analysis, we utilized five sets of exposure GWAS (Genome-Wide Association Studies) summary statistics and four sets of outcome GWAS summary statistics. The initial analysis, applying a threshold of p < 5 × 10 −6 , identified 48 significant causal relationships between genetic liability in the gut microbiome and bone mineral density (BMD). A subsequent analysis with a more stringent threshold of p < 5 × 10 −8 uncovered 14 additional causal relationships. Upon applying the Bonferroni correction, 9 results from the first analysis and 10 from the second remained statistically significant. Conclusion Our MR analysis revealed a causal relationship between gut microbiota and bone mineral density at all sites, which could lead to discoveries in future mechanistic and clinical studies of microbiota-associated osteoporosis.
Two-dimensional (2D) MXenes such as Ti3C2, Ti2C, Mo2C, and Mo1.33C have shown excellent electrochemical performances as supercapacitor electrodes, and the exploration of new and/or high-capacity ...MXene-based supercapacitor electrode materials is an active field. In this work, 2D multi-layered V4C3 MXene has been synthesized by selectively etching Al from V4AlC3 and it shows a high capacitance of 209 F g−1 at 2 mV s−1, good rate performance, and stable long cyclic performance with capacitance retention rate of 97.23% after 10000 cycles at 10 A g−1 in 1 M H2SO4. Importantly, the pseudocapacitance (∼100.1 F g−1) accounts for about 37% of the total capacity (∼268.5 F g−1) for V4C3 MXene electrode. Therefore, the high specific capacitance of V4C3 MXene is not only due to their wide interlayer spacing (∼0.466 nm), large specific surface areas (∼31.35 m2 g−1) and pore volumes (∼0.047 cm3 g−1), and good hydrophilicity but also attributed to the abundant valence states of vanadium (+2, +3, and +4). The high rate performance and excellent cycling stability of V4C3 MXene electrodes are mainly attributed to the high electronic conductivity (1137 S m−1 at 300 K). The present work provides another promising MXene-based supercapacitor electrode material.
Here we report on the synthesis of two-dimensional multi-layered V4C3 MXene and its electrochemical performances as supercapacitor electrode. Large interlayer spacing and specific surface area as well as excellent hydrophilicity are obtained in as-prepared V4C3 MXene. As a supercapacitor electrode, it shows high capacitance (∼209 F g−1 at 2 mV s−1), good rate performance, and stable long cyclic performance (capacitance retention rate is 97.23% after 10000 cycles at 10 A g−1) in 1 M H2SO4 electrolyte. Display omitted
•Two-dimensional multi-layered V4C3 MXene is synthesized by etching Al from V4AlC3.•V4C3 possesses large interlayer spacing and specific surface as well as good hydrophilicity and electrical conductivity.•As supercapacitors electrode materials, V4C3 shows excellent electrochemical performance in 1 M H2SO4.•V4C3 MXene is a typical pseudocapacitive electrode material for supercapacitors.
Drainage development and climatic fluctuations shape the phylogeographic patterns of freshwater fish species. In this study, we used the mitochondrial control region to determine the population ...structure and demographical history of the leopard mandarin fish (
Siniperca scherzeri
) in the Pearl River drainage and to test whether the historical development of the river and climatic changes that occurred in southern China have influenced the phylogeographic patterns of this species. Phylogenetic analyses, the use of haplotype networks, and population structure analyses revealed two geographically distinct genetic lineages, A and B. Lineage A was widespread in the Xijiang and Beijiang Rivers, whereas lineage B was only detected in the Dongjiang River. Dating analyses and biogeographic analyses indicated that the two lineages originated from a vicariance event 1.11 million years ago (Ma), which coincides with the historical development of the drainage during the early Quaternary period. Demographic analyses showed that the populations of lineage B experienced sharp demographic contraction of 0.01 Ma, which suggests that sea-level transgression after the Last Glacial Maximum may have played a critical role in the population demography of lineage B. By contrast, the populations of lineage A were less influenced by the sea-level transgression owing to larger distribution ranges. Overall, our study uncovered the phylogeographic patterns of
Siniperca scherzeri
in the Pearl River drainage and provides valuable information for the management and conservation of this species.
Abstract
Background
Neuropsychiatric systemic lupus erythematosus (NPSLE), with various morbidities and multiple manifestations in the central nervous system, remains a limited standard for ...diagnosis. Our study was to discover novel biomarkers for improving the diagnostic efficiency for NPSLE.
Methods
We performed a quantitative planar protein antibody microarray to screen 1000 proteins in cerebrospinal fluid from controls, systemic lupus erythematosus (SLE, non-NPSLE) patients, and NPSLE patients. Differentially expressed proteins (DEPs) as candidate biomarkers were developed into a custom multiplexed protein antibody array for further validation in an independent larger cohort. Subsequently, we used least absolute shrinkage and selection operator regression (LASSO) analysis and multivariable logistic regression analysis for optimizing feature selection and constructing a diagnostic model. A receiver operating characteristic curve (ROC) was generated to assess the effectiveness of the models.
Results
The expression of 29 proteins in CSF was significantly altered in the comparison of the three groups. We selected 17 proteins as candidate biomarkers in accordance with protein interaction analysis. In the larger cohort, we identified 5 DEPs as biomarkers for NPSLE, including TCN2, CST6, KLK5, L-selectin, and Trappin-2. The diagnostic model included 3 hub proteins (CST6, TCN2, KLK5) and was best at discriminating NPSLE from SLE patients. These CSF biomarkers were also highly associated with disease activity. In addition, there were 6 molecules with remarkable changes in NPSLE CSF and hippocampus, which indicated the consistency of the environment in the brain and the promising molecular targets in the pathogenesis of NPSLE.
Conclusions
The dual-chips screening strategy demonstrated KLK5, L-selectin, Trappin-2, TCN2, and CST6 as CSF biomarkers for diagnosing NPSLE.
Aiming at sealing failure problem of packer rubber during well testing and completion, a new type of “nanofluidic packer rubber” is developed. The nanofluidic packer rubber is composed of honeycomb ...matrix skeleton encapsulating nanofluidic system as stuffing. Taking ZSM-5 zeolite/water nanofluidic system as an example stuffing for the nanofluidic packer rubber, the application properties are studied by means of experiment. Ten loading/unloading cycles are carried out on the pretreated zeolite/water stuffing at different loading rates and system temperatures on a pressure-volume characteristic test bench. The impact law of loading rate and system temperature on repeatable practicability, pressure threshold, and deformation capacity of the stuffing are obtained and the influence mechanisms are discussed. Results show that the zeolite/water stuffing works stable and repeatable after the first three loading/unloading cycles. The loading rate has lifting effects on throughput capacity, pressure threshold and deformation capacity when system temperature is under 75°C. With the increase of system temperature, pressure threshold decrease, and throughput capacity and deformation capacity increase. All the application characteristics found in zeolite/water stuffing are favorable for improving the working performance of packer rubber. This work provides theoretical and data support for the application of the nanofluidic packer rubber.
Aiming at obtaining the application characteristics of more nanofluidic stuffing to enrich the database of nanofluidic packer rubber, three zeolite-based nanofluidic types of stuffing with water, ...glycerin, and a saturated aqueous solution of KCl (hereinafter referred to as saturated KCl solution) as the functional liquids were studied using experiments. The results showed that all the three zeolite-based nanofluidic stuffing types could be applied as stuffing for nanofluidic packer rubber. The setting pressure ranges for zeolite/water, zeolite/glycerin, and zeolite/saturated KCl solution stuffing were 21.71 to 30.62 MPa, 15.31 to 23.57 MPa, and 27.50 to 38.83 MPa, and the specific deformation quantities of the three stuffing types were 72.76, 102.07, and 77.54 mm3∙g−1, respectively. In zeolite/saturated KCl solution stuffing, the number of liquid molecules retained in the nanochannels was the minimum; thus, this stuffing type was the most stable during application. The order of the equivalent surface tensions of the three zeolite-based stuffing types in the confined nanochannels was consistent with the order of the gas–liquid surface tensions in the bulk phase. The equivalent surface tension, which reflected the interaction between liquid–solid phases, dominated the pressure threshold, the deformation capacity, and the stability of nanofluidic stuffing. This research study provided data support for the application of nanofluidic packer rubber.
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Perovskite solar cells (PSCs) have achieved remarkable progress in the past decade and become the most powerful challenger of traditional silicon photovoltaics. Among the many ...designs, bifacial PSCs have received widespread attention these days due to their ability to fully utilize environmental reflection and scattering light to enhance energy yield. They also can provide better aesthetic design for building-integrated photovoltaics (BIPVs). However, the potential of bifacial PSCs is not limited to these traditional applications. Importantly, such architecture also serves as a universal component for multi-junction cells and photon engineering, which are both critical for further efficiency improvement. In this review, the requirements of different functional layers under various applications are described in detail, starting from the structure of bifacial PSCs. The application developments are introduced, including albedo utilization, semitransparent PSCs (ST-PSCs), TSCs. The present issues (such as stability, large area, recombination of carriers at the back electrode and toxicity etc.) and the extra challenges of bifacial PSCs are highlighted. It is hoped that this review can provide new ideas for the future development and further improve the competitiveness of PSCs.
The long-term and large-scale utilization of fertilizers and pesticides in facility agriculture leads to groundwater pollution. However, the coexistence and interactions between organic fertilizers ...(i.e., organic matter), toxic metals, and pesticides in shallow groundwater have seldom been studied. Thus, the study sought to characterize said interactions via fluorescence, ultraviolet–visible spectroscopy (UV–Vis), and Fourier-transform infrared spectroscopy coupled with two-dimensional correlation spectroscopy and chemometric techniques. The results indicated that groundwater DOM was comprised of protein-, polysaccharide-, and lignin-like substances derived from organic fertilizers. Protein-like substances accounted for the binding of Co, Ni, and Fe, while polysaccharide- and lignin-like substances were mainly responsible for Cr and Mo complexation. Moreover, lignin- and polysaccharide-like substances played a key role in the binding of pesticides (i.e., dichlorodiphenyltrichloroethane DDT, endosulfan, γ-hexachlorocyclohexane γ-HCH, monocrotophos, chlorpyrifos, and chlorfenvinphos), rendering the conversion of γ-HCH to β-hexachlorocyclohexane (β-HCH) and the degradation of DDT to dichlorobenzene dichloroethylene (DDE) ineffective. However, the presence of protein-like substances in groundwater benefited the degradation and conversion of γ-HCH and α-endosulfan. Redundancy analyses showed that lignin- and polysaccharide-like matter had the most impacts on the coexistence of DOM with toxic metals and pesticides.
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•Interactions between DOM and toxic metals/pesticides in groundwater were analyzed.•Groundwater DOM comprised protein-, polysaccharide-, and lignin-like substances.•DOM functional groups bonded with toxic metals and pesticides.•Groundwater DOM was found to affect the degradation and conversion of pesticides.
Lignin- and polysaccharide-like matter had the most impacts on the coexistence of DOM with toxic metals and pesticides.
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