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Introduction Hypoxia-inducible factor (HIF)1α has been shown to be activated and induces a glycolytic shift under hypoxic condition, however, little attention was paid to the role of HIF1α-actuated fructolysis in hypoxia-induced heart injury. Objectives In this study, we aim to explore the molecular mechanisms of miR-155-mediated fructose metabolism in hypoxic cardiac fibroblasts (CFs). Methods Immunostaining, western blot and quantitative real-time reverse transcription PCR (qRT-PCR) were performed to detect the expression of glucose transporter 5 (GLUT5), ketohexokinase (KHK)-A and KHK-C in miR-155−/− and miR-155wt CFs under normoxia or hypoxia. A microarray analysis of circRNAs was performed to identify circHIF1α. Then CoIP, RIP and mass spectrometry analysis were performed and identified SKIV2L2 (MTR4) and transformer 2 alpha (TRA2A), a member of the transformer 2 homolog family. pAd-SKIV2L2 was administrated after coronary artery ligation to investigate whether SKIV2L2 can provide a protective effect on the infarcted heart. Results When both miR-155−/− and miR-155wt CFs were exposed to hypoxia for 24 h, these two cells exhibited an increased glycolysis and decreased glycogen synthesis, and the expression of KHK-A and KHK-C, the central fructose-metabolizing enzyme, was upregulated. Mechanistically, miR-155 deletion in CFs enhanced SKIV2L2 expression and its interaction with TRA2A, which suppresses the alternative splicing of HIF1α pre-mRNA to form circHIF1α, and then decreased circHIF1α contributed to the activation of fructose metabolism through increasing the production of the KHK-C isoform. Finally, exogenous delivery of SKIV2L2 reduced myocardial damage in the infarcted heart. Conclusion In this study, we demonstrated that miR-155 deletion facilitates the activation of fructose metabolism in hypoxic CFs through regulating alternative splicing of HIF1α pre-mRNA and thus circHIF1ɑ formation.

Luminescent hydrogen-bonded organic frameworks (HOFs) have attracted increasing attention due to their corresponding luminescence that enables readily visualization of structural dynamics. HOFs wit...

RNA–binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development by regulating premRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remain unclear. In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that a higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted BC cell proliferation, while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanistically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and suppressing the transcription of miR-625-5p, which directly targets RBM24 and suppresses RBM24 expression. RBM24-regulated BC cell proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop. These results indicate that the RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop participates in BC progression. Disruption of this pathway may be a potential therapeutic strategy for BC treatment., Bladder cancer: Tracking down the molecular mechanisms A protein called RBM24 promotes progression of bladder cancer (BC) by forming a positive feedback loop with a specific transcription factor, driving cancer cell proliferation. Survival rates for BC are low, and the current imperfect understanding of the underlying mechanisms makes it difficult to treat. Ping-Ying Guo at Hebei Medical University in Shijiazhuang, China, and co-workers investigated the role of RBM24, known to be involved in other cancers, and found increased levels in BC tissues. Higher levels were associated with a poor prognosis. Further investigation revealed that RBM24 boosts levels of the transcription factor, which suppresses a molecule that in turn suppresses RBM24, forming a positive feedback loop promoting BC cell proliferation. Interrupting the feedback loop decreased tumor size in a mouse model. These results may help identify better treatments for BC.

With the rapid development of nanotechnology, the size of a device reaches sub-nanometer scale. The larger resistivity of interconnect leads to serious overheating of integrated circuits. Silicon-based electronic devices have also reached the physical limits of their development. The use of carbon nanotubes instead of traditional wires has become a new solution for connecting nano-structures. Nanocluster particles serving as brazing material play an important role in stabilizing the connection of carbon nanotubes, which places higher demands for nanoscale manipulation techniques. In this paper, the dynamic processes under different operating scenarios were simulated and analyzed, including probe propulsion nanoparticle operation, probe pickup nanoparticle operation and probe pickup nanocluster particle operation. Then, the SEM (Scanning Electron Microscope) was used for nanoparticle manipulation experiments. The smallest unit of carbon nanotube wire was obtained by three-dimensional (3D) construction of a carbon nanotube–silver nanocluster particle (CN-AgNP), which verified the feasibility of 3D manipulation of carbon nanotube wire construction. The experiments on the construction of carbon nanotube–nanocluster particle structures in three-dimensional operation were completed, and the smallest unit of carbon nanotube wire was constructed. This nano-fabrication technology will provide an efficient and mature technical means in the field of nano-interconnection.

White-light emitting (WLE) polymers have attracted continuous attention for their promising applications in solid-state lighting, flexible display and related fields. However, achieving dual-emission and pure white-light emission in a single-component polymer is still challenging. In this study, a brominated single-component polymer BrOD-TFB was designed and synthesized, which shows dual-emission and white light emission properties in solution and room-temperature phosphorescence (RTP) in thin films. The dual-emission properties can be tuned by concentration, solvent polarity, and excitation energy. Spectral analyses and theoretical calculations reveal that the origin of the high-energy emission band (HEB) is intramolecular charge transfer (ICT) along the polymer chain, whilst the low-energy emission band (LEB) originates from the excited-state related to the intra-chain and inter-chain C-Br⋯π interactions as demonstrated by the single-crystal structure of the model compound. Appropriate control of the formation and the destruction of the halogen-assisted interactions can initiate white-light emission in the single-component polymer. More interestingly, by dispersing BrOD-TFB (0.1 wt%) in a non-emissive, colorless and transparent polymer, the characteristics of this white-light emission can be fully demonstrated while exhibiting unexpected RTP properties, with photoluminescence quantum efficiency (ΦPL) of up to 23% and CIE coordinates of (0.32, 0.32).

Objective: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for vascular remodeling. Natural compounds with diterpene chinone or phenolic acid structure from Salvia miltiorrhiza, an eminent medicinal herb widely used to treat cardiovascular diseases in China, can effectively attenuate vascular remodeling induced by vascular injury. However, it remains unknown whether Salvia miltiorrhiza-derived miRNAs can protect VSMCs from injury by environmental stimuli. Here, we explored the role and underlying mechanisms of Salvia miltiorrhiza-derived Sal-miR-1 and 3 in the regulation of VSMC migration and monocyte adhesion to VSMCs induced by thrombin. Methods: A mouse model for intimal hyperplasia was established by the ligation of carotid artery and the injured carotid arteries were in situ-transfected with Sal-miR-1 and 3 using F-127 pluronic gel. The vascular protective effects of Sal-miR-1 and 3 were assessed via analysis of intimal hyperplasia with pathological morphology. VSMC migration and adhesion were analyzed by the wound healing, transwell membrane assays, and time-lapse imaging experiment. Using loss- and gain-of-function approaches, Sal-miR-1 and 3 regulation of OTUD7B/KLF4/NMHC IIA axis was investigated by using luciferase assay, co-immunoprecipitation, chromatin immunoprecipitation, western blotting, etc. Results: Salvia miltiorrhiza-derived Sal-miR-1 and 3 can enter the mouse body after intragastric administration, and significantly suppress intimal hyperplasia induced by carotid artery ligation. In cultured VSMCs, these two miRNAs inhibit thrombin-induced the migration of VSMCs and monocyte adhesion to VSMCs. Mechanistically, Sal-miR-1 and 3 abrogate OTUD7B upregulation by thrombin via binding to the different sites of the OTUD7B 3'UTR. Most importantly, OTUD7B downregulation by Sal-miR-1 and 3 attenuates KLF4 protein levels via decreasing its deubiquitylation, whereas decreased KLF4 relieves its repression of transcription of NMHC IIA gene and thus increases NMHC IIA expression levels. Further, increased NMHC IIA represses VSMC migration and monocyte adhesion to VSMCs via maintaining the contractile phenotype of VSMCs. Conclusions: Our studies not only found the novel bioactive components from Salvia miltiorrhiza but also clarified the molecular mechanism underlying Sal-miR-1 and 3 inhibition of VSMC migration and monocyte adhesion to VSMCs. These results add important knowledge to the pharmacological actions and bioactive components of Salvia miltiorrhiza. Sal-miR-1 and 3-regulated OTUD7B/KLF4/NMHC IIA axis may represent a therapeutic target for vascular remodeling.

Strong intermolecular interactions that are in favour of elevating the luminescence efficiencies of aggregation-induced emission luminogens (AIEgens) are usually detrimental to the generation of obvious mechanochromism (MC). Therefore, it remains a challenge to develop MC-active AIE compounds that show high fluorescence quantum yield and a significant emission wavelength change simultaneously. Herein, a purely organic AIEgen and its ionic species, namely, TCPy and TCPyP, have been constructed by simultaneously employing tetraphenylethene (TPE) and phenylacrylonitrile as essential chromophores. It is found that both luminogens are highly emissive in the solid state and afford content ΦF,s values of 0.90 and 0.52, respectively. Concurrently, TCPy has been determined to possess mechanochromism (MC) properties, but only gives a small emission variation of 14 nm under mechanical stimuli. By contrast, TCPyP exhibits remarkable and reversible MC with a large Δλem,max value of up to 90 nm, representing the state-of-the-art MC performance for ionic AIEgens. Single crystal analysis reveals that the prominent MC of TCPyP mainly originates from the presence of bulky hexafluorophosphate anions in the crystal structure, which can enlarge the intermolecular distance to slightly weaken the intermolecular interactions and thereby result in the transformation of H-aggregates to J-aggregates upon grinding treatment. Besides, TCPyP shows much higher mitochondrial specificity in comparison with TCPy and enables mitochondrial staining with high brightness and good biocompatibility in living cells. Moreover, an abnormal phenomenon of secondary aggregation emission enhancement is observed by using this ionic AIEgen as a bioprobe for in vivo imaging, which allows long-term tracking of the tumor in nude mice. All these results suggest that the ionic AIEgen TCPyP has potential for various practical applications, including sensing, anti-counterfeiting, cell imaging and cancer diagnosis.

The role of aromatic π bridges (called π-linkers), which are used to connect multiple D and A groups in asymmetric thermally activated delayed fluorescence (TADF) emitters, remains a critical issue for the development of high-efficiency organic light-emitting diodes (OLEDs). In this work, based on our previous asymmetric TADF emitter (SCP) with electron donors carbazole (D) and phenothiazine (D′), we introduced different numbers of phenyl rings as π-linkers on both sides of SCP, leading to four D–A–D′ TADF emitters (PCz, 2PCz, PSz, and 2PSz) with different levels of conjugation. Experimental and theoretical results reveal that the π-linker distance has a significant effect on excited state regulation and thereby the optoelectronic properties. In comparison, the TADF emitters (PCz, and PSz) with shorter π-linkers exhibit higher photoluminescence quantum yields, due to effective suppression of conformation changes between ground state and excited state, and consequently higher device performance with external quantum efficiencies (EQEs) ranging from 20% to 30% achieved. This work provides an insight into the relationship between molecular design and optoelectronic properties of asymmetric TADF emitters.

Background STAT5 plays an important role in the transformation of hematopoietic cells by BCR-ABL. However, the downstream target genes activated by STAT5 in chronic myeloid leukemia (CML) cells remain largely unclear. Here, we investigated the mechanistic functional relationship between STAT5A-regulated microRNA and CML cell apoptosis. Methods The expression of USP15, Caspase-6, STAT5A-regulated miR-202-5p and STAT5A was detected by qRT-PCR and Western blotting in CML cell lines and PBMCs of CML patients. Cell apoptosis was evaluated by flow cytometry. Both gain- and loss-of-function experiments were used to investigate the roles of USP15, miR-202-5p and STAT5A in CML. Luciferase reporter assay detected the effect of miR-202-5p on USP15 expression. Xenograft animal model was used to test the effect of anti-miR-202-5p and pimozide on K562 cell xenograft growth. Results USP15 expression was significantly downregulated in CML cell lines and PBMCs of CML patients. Depletion of USP15 increased, whereas overexpression of USP15 reduced the resistance of CML cells to Imatinib. Further, decreased deubiquitinating activity of USP15 by USP15 downregulation led to reduced caspase-6 level, thus attenuating CML cell apoptosis. Mechanistically, miR-202-5p was upregulated in K562G cells and negatively regulated USP15 expression by directly targeting USP15 3′-UTR. Correspondingly, upregulation of miR-202-5p enhanced the resistance of CML cells to Imatinib by inhibiting cell apoptosis. Importantly, STAT5A was upregulated in CML cells and directly activated miR-202-5p transcription by binding to the pre-miR-202 promoter. Pimozide induced CML cell apoptosis and significantly reduced K562 cell xenograft growth in vivo by blocking STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis. Conclusions we provide the first evidence that de-regulated STAT5A/miR-202-5p/USP15/Caspase-6 regulatory axis suppresses the apoptosis of CML cells, targeting this pathway might be a promising therapeutic approach for the treatment of CML.

Cross-modal hashing technology is a key technology for real-time retrieval of large-scale multimedia data in real-world applications. Although the existing cross-modal hashing methods have achieved impressive accomplishment, there are still some limitations: (1) some cross-modal hashing methods do not make full consider the rich semantic information and noise information in labels, resulting in a large semantic gap, and (2) some cross-modal hashing methods adopt the relaxation-based or discrete cyclic coordinate descent algorithm to solve the discrete constraint problem, resulting in a large quantization error or time consumption. Therefore, in order to solve these limitations, in this paper, we propose a novel method, named Discrete Semantics-Guided Asymmetric Hashing (DSAH). Specifically, our proposed DSAH leverages both label information and similarity matrix to enhance the semantic information of the learned hash codes, and the ℓ2,1 norm is used to increase the sparsity of matrix to solve the problem of the inevitable noise and subjective factors in labels. Meanwhile, an asymmetric hash learning scheme is proposed to efficiently perform hash learning. In addition, a discrete optimization algorithm is proposed to fast solve the hash code directly and discretely. During the optimization process, the hash code learning and the hash function learning interact, i.e., the learned hash codes can guide the learning process of the hash function and the hash function can also guide the hash code generation simultaneously. Extensive experiments performed on two benchmark datasets highlight the superiority of DSAH over several state-of-the-art methods.

Heteroaromatic-conjugated aromatic molecules have inspired numerous interests in rechargeable batteries like Li-ion batteries, but were limited by low conductivity and easy dissolution in electrolytes. Herein, we immobilize a nitrogen-rich aromatic molecule tricycloquinazoline (TQ) and CuO 4 unit into a two-dimensional (2D) conductive Metal-Organic Framework (MOF) to unlock their potential for Li + storage. TQ was identified redox activity with Li + for the first time. With a synergistic effect of TQ and CuO 4 unit, the 2D conductive MOF, named Cu-HHTQ (HHTQ = 2,3,7,8,12,13-hexahydroxytricycloquinazoline), can facilitate the Li + /e - transport and ensure a resilient electrode, resulting in a high capacity of 657.6 mAh g -1 at 600 mA g -1 with extraordinary high-rate capability and impressive cyclability. Our findings highlight an efficient strategy of constructing electrode materials for energy storage with combining multiple redox-active moieties into conductive MOFs.

Many vision–language models that output natural language, such as image-captioning models, usually use image features merely for grounding the captions and most of the good performance of the model can be attributed to the language model, which does all the heavy lifting, a phenomenon that has persisted even with the emergence of transformer-based architectures as the preferred base architecture of recent state-of-the-art vision–language models. In this paper, we make the images matter more by using fast Fourier transforms to further breakdown the input features and extract more of their intrinsic salient information, resulting in more detailed yet concise captions. This is achieved by performing a 1D Fourier transformation on the image features first in the hidden dimension and then in the sequence dimension. These extracted features alongside the region proposal image features result in a richer image representation that can then be queried to produce the associated captions, which showcase a deeper understanding of image–object–location relationships than similar models. Extensive experiments performed on the MSCOCO dataset demonstrate a CIDER-D, BLEU-1, and BLEU-4 score of 130, 80.5, and 39, respectively, on the MSCOCO benchmark dataset.

Excessive release of cytokines such as IL-1β and other inflammatory mediators synthesized and secreted by macrophages is the fundamental link of uncontrolled inflammatory response in sepsis. 17β-Estradiol (E2) plays anti-inflammatory and vascular protective effects by regulating leukocyte infiltration and the expression of chemokines or cytokines induced by injury. However, the role of E2 in the inflammatory response of macrophages in sepsis and its mechanism are still not fully understood. In the present study, we show that E2 alleviates vascular inflammation in sepsis mice induced by cecal ligation puncture (CLP). E2 significantly decreases RAW 264.7 cell inflammation response by downregulating the expression of NLRP3. Furthermore, we found that miR-29a-5p was significantly downregulated in LPS-treated macrophages. Treating RAW 264.7 cells with E2 markedly upregulated the miR-29a-5p expression level. More importantly, we demonstrated that miR-29a-5p repressed NLRP3 expression by directly targeting its 3 ′ -UTR. Loss- and gain-of-function experiments revealed that transfection of the miR-29a-5p mimic abrogates LPS-induced macrophage inflammation. Moreover, depletion of miR-29a-5p by its inhibitor largely promotes LPS-induced macrophage inflammation. In summary, miR-29a-5p upregulation induced by E2 alleviated RAW 264.7 cell inflammation response by aggravating miR-29a-5p repression of NLRP3 expression. E2 exerts significant anti-inflammatory efficacy in macrophages by regulating the miR-29a-5p/NLRP3 axis. Targeting miR-29a-5p may be a novel therapeutic strategy to suppress sepsis-induced vascular inflammation.

Escherichia coli O157: H7 (E. coli O157: H7) is a foodborne pathogenic bacterium which can cause fever, diarrhoea and vomiting in humans. Thus, a rapid, simple, and specific bioprobe for pathogen detection in contaminated foods has been attracted more and more attention. In this work, the strong fluorescent amino-functionalized graphene quantum dots (af-GQDs) were prepared by hydrothermal method. The microtopographic height, surface morphology and spectroscopic properties of af-GQDs are characterized by the high resolution transmission electron microscope (HRTEM), atomic force microscope (AFM), UV-vis, fluorescence, Raman spectroscopic techniques. All the results showed that the af-GQDs can be effectively applied in the preparation of biocompatible immunofluorescence probe and in the detection of E. coli O157: H7. The minimum detection limit is 100 cfu/mL. It is a simple, rapid, sensitive, low-cost and easy to be popularized method, which provides a feasible way to monitor E. coli O157: H7 in food safety.

Acyl-coenzyme A: cholesterol acyltransferases (ACATs) play the significant role in the formation of cholesterol esters. One form of this enzyme is ACAT2, which not only regulates the balance of cholesterol metabolism in cells but also participates in the “escape” mechanism of hepatocellular carcinoma (HCC) cells. The natural product pyripyropene A (PPPA) and its analogs are the only chemical ACAT2-specific inhibitors. To develop simpler analogs and endeavor to remove a portion of multichiral centers and enrich a variety of analogs, new PPPA analogs are creatively designed and synthesized based on previous work. Among these new analogs, 7a and 9f show better activity and selective inhibition of ACAT2 compared with PPPA. These results will provide a new future for potential therapeutic use in atherosclerosis and HCC.

A pair of chiral aggregation-induced emission (AIE) enantiomers and their racemate exhibit not only distinctively different circularly polarized luminescence behaviors, but also completely opposite mechanoluminescence (ML) activities. The data from single crystal analysis identifies that the bright ML of the AIE enantiomers is probably activated by their molecular chirality, which enables unique chiral crystal structures with a polar space group and compact molecular packing. These experimental findings provide a direction for harvesting prominent ML from AIE luminogens. Concurrently, high contrast mechanochromism with larger ΔλPL,max and ΔΦF,s values by up to 140 nm and 0.61 respectively have been achieved from this AIE system, which represents the state-of-the-art mechanochromic performance for ML emitters. Moreover, force-induced white-light emission and thermally activated delayed fluorescence have also been observed. The results of theoretical calculations suggest that the destruction of intermolecular interactions and conversion of molecular conformation account for the significant multiple-variations in emission properties triggered by a single mechanical stimulus.

Background Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. Methods The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. Results Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. Conclusions These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.

Chronic angiotensin II (Ang II) stimulation induces vascular smooth muscle cell (VSMC) senescence, and circRNAs and members of the ILF3 family are implicated in cellular senescence, but the mechanism underlying regulation of circRNAs and ILF3 by Ang II in VSMCs remains poorly understood. Here, a model of Ang II-induced VSMC senescence and the renal artery of hypertensive patients were used to investigate the roles and mechanisms of circACTA2 and ILF3 in VSMC senescence. We show that circACTA2 expression was elevated in Ang II-stimulated VSMCs and in the vascular walls of hypertensive patients. circACTA2 knockdown largely abrogated Ang II-induced VSMC senescence as shown by decreased p21 expression and increased CDK4 expression as well as by decreased SA β-gal-positive cells. Oligo pull-down and RIP assays revealed that both circACTA2 and CDK4 mRNA could bind with ILF3, and Ang II facilitated circACTA2 association with ILF3 and attenuated ILF3 interaction with CDK4 mRNA. Mechanistically, increased circACTA2 by Ang II reduced ILF3 association with CDK4 mRNA by competing with CDK4 mRNA to bind to ILF3, which decreases CDK4 mRNA stability and protein expression, thus leading to Ang II-induced VSMC senescence. Targeting the circACTA2-ILF3-CDK4 axis may provide a novel therapeutic strategy for VSMC senescence-associated cardiovascular diseases.

In this paper, we report a novel design of a microspherical lens assembly that can realize super-resolution optical imaging in air with super-wide field of view (FOV). The microspherical lens assembly is made from a barium titanate glass (BTG) microsphere that is glued to a microspherical crown lens through optical adhesive. Experimental results show that super-resolution optical imaging in air can be achieved under a regular optical microscope when the microspherical lens assembly is brought sufficiently close to the sample surface. Super-wide FOV is also achieved when a larger BTG microsphere is used and there seems no obvious limitation on the size of the BTG microsphere as long as the curvature of the microspherical crown lens is properly tuned. Simulation study suggests that the focus point of the microlens needs to close to the bottom surface of the BTG microsphere in order to achieve the super-resolution optical imaging. The novel microspherical lens assembly will make the microsphere based super-resolution imaging a step further close to practical applications.

The transcription factor E2F1 regulates the expression of the miR-20b-5p precursor and is involved in epithelial-to-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β1) induces EMT in prostate cancer (PCa) by binding to TGF-beta receptor 2 (TGFBR2) to activate TGF-β signaling. However, the relationship between TGFBR2, E2F1, and miR-20b-5p in the modulation of EMT in PCa cells remains unknown. In this study, we found that the level of miR-20b-5p expression was significantly lower in PC3 and DU145 cells than that in prostate epithelial (RWPE-1) cells, and TGF-β1 treatment further down-regulated miR-20b-5p expression in these two cell lines. Functional studies showed that miR-20b-5p suppressed TGF-β1-induced migration and invasion of PC3 and DU145 cells by up-regulating E-cadherin and down-regulating vimentin, leading to TGF-β1-induced inhibition of EMT. Using gain and loss of function experiments, it was shown that E2F1 mediated TGF-β1 regulation of miR-20b-5p expression. Further, a luciferase activity assay showed that TGFBR2 was a direct target of miR-20b-5p in PCa cells. These results suggest that miR-20b-5p, TGFBR2, and E2F1 form a regulatory loop to modulate EMT induced by TGF-β1. A novel regulatory mechanism underlying the miR-20b-5p/TGFBR2/E2F1 axis is involved in TGF-β1-induced EMT of PCa cells, and miR-20b-5p may be a potential therapeutic target for PCa.

Commercial carbazole has been widely used to synthesize organic functional materials that have led to recent breakthroughs in ultralong organic phosphorescence1, thermally activated delayed fluorescence2,3, organic luminescent radicals4 and organic semiconductor lasers5. However, the impact of low-concentration isomeric impurities present within commercial batches on the properties of the synthesized molecules requires further analysis. Here, we have synthesized highly pure carbazole and observed that its fluorescence is blueshifted by 54 nm with respect to commercial samples and its room-temperature ultralong phosphorescence almost disappears6. We discover that such differences are due to the presence of a carbazole isomeric impurity in commercial carbazole sources, with concentrations

Among numerous noble-metal-free electrocatalysts, molybdenum sulfides are recognized as promising candidates for hydrogen evolution reaction (HER). Owing to abundant under-coordinated sulfur atoms serving as catalytically active centers, intensive spectra studies have revealed that the HER property of amorphous molybdenum sulfide (a-MoSx) is superior to crystal molybdenum sulfide (c-MoS2). In this work, nitrogen-doped active carbon (NAC) is obtained through plasma treatment and amorphous MoSx/NAC hybrid catalyst films are electrodeposited on carbon fiber papers (CFP) which are employed as porous three-dimensional electrodes with low resistivity. The incorporation of NAC increases the electrochemically active surface area, enhances the electron transport, and facilitates the reaction kinetics. Moreover, the functionality durability benefits from synergistic effect between a-MoSx and NAC. Thus, the obtained hybrid catalyst delivers the excellent HER activity, requiring only 203 mV overpotential to achieve a geometrical current density of 100 mA cm−2 with a Tafel slope of ∼43.9 mV per decade.

Catalytic micro- and nanorobots exhibit self-propulsion in the presence of chemical fuels such as glucose, hydrogen peroxide. Generally, swimmers incorporate a catalyst as a part of their structure for the decomposition of a chemical fuel. Several applications such as active drug delivery, minimally invasive surgery, and water remediation, have been envisaged. In this letter, we investigated the influence of geometric variable of catalytic microrobot to their swimming behaviors in hydrogen peroxide (H2O2) solutions. V-shaped microrobots with various opening angles (45°, 90°, and 135°), and triangle-shaped microrobots that have similar dimensions with V-shaped microrobots, have been fabricated by focused-ion-beam etching on commercial platinum microwires. Swimming tests were performed in 15% and 30% H2O2 solutions. We have found that V-shaped microrobot with 45° opening angle showed a superior swimming speed of 4.3 μm/s in 15% H2O 2 solution, while 90° microrobot exhibits a speed of 1.52 μm/s. The 135° V-shaped microrobot and all triangle-shaped microrobots have not shown any obvious motions in 30% H2O2 solution. Our observation that the swimming performances of various shaped microrobots change in tandem proves the necessity of structural asymmetry in designing catalytic micro- and nanorobots.

Background/Aims: This study determined the role and mechanism of action of transcription factor EB (TFEB) in H2O2-induced neuronal apoptosis. Methods: SH-SY5Y cells were treated with Akt inhibitor/activator and different concentrations of H2O2. Cell apoptosis was detected by flow cytometric analysis. Akt and TFEB phosphorylation and PARP cleavage were determined by Western blotting. HEK293T cells were transfected with different truncated TFEB mutants and HA-Akt-WT; SH-SY5Y cells were transfected with Flag-vector, Flag-TFEB, Flag-TFEB-S467A or Flag-TFEB-S467D; and TFEB interaction with Akt was determined by co-immunoprecipitation and GST pull-down assays. Results: A low concentration of H2O2 induces TFEB phosphorylation at Ser467 and nuclear translocation, facilitating neuronal survival, whereas a high concentration of H2O2 promotes SH-SY5Y cell apoptosis via suppressing TFEB Ser467 phosphorylation and nuclear translocation. The TFEB-S467D mutant is more easily translocated into the nucleus than the non-phosphorylated TFEB-S467A mutant. Further, Akt physically binds to TFEB via its C-terminal tail interaction with the HLH domain of TFEB and phosphorylates TFEB at Ser467. Mutation of TFEB-Ser467 can prevent the phosphorylation of TFEB by Akt, preventing inhibition of oxidative stress-induced apoptosis. Conclusions: Oxidative stress induces neuronal apoptosis through suppressing TFEB phosphorylation at Ser467 by Akt, providing a novel therapeutic strategy for neurodegenerative diseases.

Thienyl containing triarylethylene derivatives, namely 2ThDpF and 3ThDpF, with photochromic properties have been designed and synthesized. These new photochromic molecules with simple chemical structures show fast-response and striking photochromic behaviors in the solution-state, in the solid-state and in polymer films. Based on 2ThDpF, a real-time and repeatable photoresponsive surface was fabricated. Upon UV-light irradiation for 1 minute, most of the 2ThDpF nano-aggregates on the SiO2 substrate changed from cone-shaped to hump-shaped and the contact angles of a water droplet drastically increased from 43° to 95° simultaneously. The surface morphology and wettability can easily be reverted by white-light irradiation for 5 minutes. The key issues to affect the real-time morphology and wettability changes are also discussed in-depth based on single-crystal analyses and TDDFT calculations. Therefore, these triarylethylene derivatives with simple molecular structures are attractive in the areas of photochromism and photoresponsive surfaces.

Excess inflammatory microglia activation deteriorates the pathological degree of spinal cord injury (SCI). We here employed microglia samples in vitro and murine model in vivo to trace the role of inhibition of Arhgef3 in inflammatory response post SCI. From the specimen analysis of lipopolysaccharide (LPS)-induced inflammatory microglia, we found that Arhgef3 expression was positively relative to microglia activation. In vitro, LPS caused the microglia inflammatory activation and induced upregulation of the Arhgef3 expression. Interestingly, presence of Arhgef3 could activate RhoA through promoting Rho GTPases, but silencing of Arhgef3 decreased RhoA activation and inhibited the microglia inflammation. Moreover, disruption of Arhgef3 inhibited the GTP-RhoA, resulted in a suppression of proinflammatory cytokines, and alleviated the LPS-elicited inflammatory genes expression. Moreover, artificially decreasing Arhgef3 expression remarkedly reduced ROS generation after LPS treatment. In vivo of a mouse mechanical contusion-induced SCI model, inhibition of Arhgef3 reduced the ratio of GTP-RhoA/Total-RhoA, and prevented SCI via mitigating the microglial inflammatory phenotype and decreased secondary neurological injury. Besides, inhibition of Arhgef3 prevented alleviated the degree of demyelination but did not affect neuronal regeneration. Meaningfully, absence of Arhgef3 improved mouse locomotor recovery post SCI. Taken together, Arhgef3 involves the microglial activation and inflammatory response following neural injury, and targeted disrupting of which may indicate a promising therapeutic direction in preventing SCI.

Inducible NO synthase (iNOS) expression and peroxynitrite formation are significantly increased in diabetic vascular tissues. Transcription factor KLF5 activates iNOS gene transcription and is involved in vascular inflammatory injury and remodeling. However, mutual regulation between KLF5, iNOS and peroxynitrite in diabetic vascular inflammation, as well as the underlying mechanisms, remain largely unknown. In this study, we found a marked increase in KLF5 and iNOS expression in vascular smooth muscle cells (VSMC) of diabetic patients. High glucose-induced expression of KLF5 and iNOS was also observed in cultured mouse VSMCs. Further investigation showed that high glucose induced KLF5 nitration by iNOS-mediated peroxynitrite generation, and nitrated KLF5 increased its interaction with NF-κB p50 and thus cooperatively activated the expression of inflammatory cytokines TNF-α and IL-1β. Furthermore, we showed that the VSMC-specific knockout of KLF5 dramatically reduced inflammatory cytokine expression in the vascular tissues of diabetic mice. Moreover, 17β-estradiol (E2) inhibited high glucose-mediated effects in VSMCs, and in the response to E2, estrogen receptor (ER) α competed with KLF5 for binding to NF-κB p50, which in turn leads to the suppression of inflammatory gene expression in VSMCs. Together, the present findings were the first to show that KLF5 expression and nitration by iNOS-mediated peroxynitrite are necessary for the induction of TNF-α and IL-1β expression in VSMCs of diabetic vascular tissues.

Interfacial engineering methods have been developed to solve defect issues of perovskite solar cells (PSCs). However, traditional surface passivation has limited effects on eliminating defect-forming residuals, while secondary grain growth (SGG) is restricted by limited choices of additives and intrinsic properties of perovskites. Here, a pincer strategy of taking advantages of surface passivation and SGG is proposed to modify both exterior and interior of CH3 NH3 PbI3 (MAPbI3 ) perovskite, by employing cyanoacetate-containing donor-acceptor compounds (CA-D-A) including 2-cyano-3-(3,4,5-trimethoxyphenyl)acrylic acid (CA), methanaminium 2-cyano-3-(3,4,5-trimethoxyphenyl)acrylate (CAMA), and aminomethaniminium (Z)-2-cyano-3-(3,4,5-trimethoxyphenyl)acrylate (CAFA). In comparison to untreated perovskite, CA-D-A treated perovskites present better crystallinity because of SGG, lower trap densities due to the synergistic effect of surface passivation and SGG, and tuned energy levels induced by CA-D-A. Accordingly, the CA-D-A treated MAPbI3 -based PSCs exhibit higher open-circuit voltage and fill factor than the control PSC without any treatment, leading to improved power conversion efficiency (PCE) and enhanced device stability, especially the CAMA treated PSCs with an average PCE promoted from 17.77 (control PSCs) to 18.71%, and importantly an excellent PCE of 19.71% through further optimization. This work provides an effective strategy for developing highly efficient and stable PSCs with the assistance of both surface passivation and SGG.

The widespread presence of humic acids (HAs) and chromium (Cr) in aquatic systems and drinking water sources is a serious threat to the environment and human being. However, no studies on the potential interaction and simultaneous removal of these two types of contaminants have been conducted. Here, a novel electro-Fenton process was reported for the effective and simultaneous removal of HAs and Cr(VI), where H2O2 was in situ produced from the electro-generated H2 and O2 on the Pd/Fe3O4 nanocatalyst surface and Fe(II) was provided from the support. We show that HAs exhibit as reductants and sorbents as well as electron shuttles for the removal of Cr(VI); HAs were efficiently mineralized, as revealed by a total organic carbon removal efficiency of beyond 90%, and Cr(VI) was completely reduced with 90% of total Cr removal. The Pd/Fe3O4 nanocatalysts, as electron transfer and hydrogen atom transfer carriers, were found to play fundamental roles for the removal of HAs and Cr(VI). The HAs degradation was driven by the sequentially involved O 2 - and OH radicals during electro-Fenton process. The reduction of Cr(VI) was primarily attributed to the contributions from Pd/Fe3O4 nanoparticles and atomic hydrogen on the catalyst surface. In a similar manner, a good recycle of Fe3+ to Fe2+ was accelerated, which favored the Fenton reaction to generate reactive oxidizing species. Importantly, the energy consumption of this electro-Fenton process for HAs degradation was almost 2 orders of magnitude lower than those of reported electrochemical oxidation. The Pd/Fe3O4 nanocatalysts showed excellent removal performances for HAs and Cr(VI) after eight times repeated treatment. This work reports a cost-effective methodology for simultaneous removal of HAs and Cr(VI) and provides a new insight into efficient elimination of complex contaminants by heterogeneous catalysis.

Selective hydrogenations of alkynes are a class of essential reactions in organic synthesis chemistry. Particularly, the selective hydrogenation of acetylene to ethylene is a key step in the production of polymers. Here we have successfully performed selective hydrogenation of acetylene to ethylene in N,N-dimethylformamide by iron-based nanoparticles, especially by Pd–Fe bimetallic NPs. NaBH4 as a hydrogen source can significantly increase the catalytic performances of nanocatalysts for acetylene hydrogenation. More importantly, the reaction is carried out at exceptionally mild temperature and under additive-free conditions with high ethylene selectivity (>90%) as well as excellent catalyst reactivity and stability. By this strategy, we could attain a catalytic activity higher by a factor of 2.2 orders of magnitude than that of the currently used industrial method. This approach may open a new way to perform selective acetylene and other alkynes hydrogenation under mild conditions, and offer another promi...

A method of picking up carbon nanotubes (CNTs) from nanotube bulk by van der Waals force inside a scanning electron microscopy is presented. An atomic force microscope cantilever was employed as end effector of nanorobotics manipulators for CNT picking up. A manipulation strategy was established by analysing the van der Waals force of three different types of contacting models. Three groups of experiments were designed and carried out to investigate the effects of different factors. Factors including pickup angle, pickup contact area between the CNT and the cantilever and pickup speed of the end effector were discussed. The results shown that a pickup angle at 90.1° and a pickup speed lower than 10 nm/step with a pickup contact length more than 1.5 µm would increase the probability of picking up CNT successfully.

Commercial carbazole has been widely used to synthesize organic functional materials that entwine with the recent breakthroughs in thermally activated delayed fluorescence, organic luminescent radicals and organic laser diodes. Recently, the strategy of stabilizing triplet excited states in carbazole derivatives ignited the booming development of organic room temperature afterglow (RTA). The unusual RTA of carbazole and its derivatives was elaborated by crystal quality and packing. However, impurity hypotheses in organic RTA have been under debate for nearly a century. Here we show that an isomer of carbazole, accompanying the commercial sources with less than 0.5%, is the key to activating RTA for many carbazole derivatives. As compared to commercial carbazole, the fluorescence of lab-synthesized carbazole is blue-shifted by 54 nm and the well-known RTA disappears. The same phenomenon is also observed for a series of carbazole derivatives. Interestingly, even 0.01% isomer doping could yield the reported RTA. Our results demonstrate that the isomer doping in carbazole derivatives is responsible for their RTA. The impurity effect has also been confirmed for dibenzothiophene based RTA. We anticipate that isomer doping effect is applicable to many organic semiconductors derived from commercial carbazole, which will drive the review of organic functional materials in optoelectronics.

RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates β-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-β-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-β-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/β-catenin feedback loop.

An isolated electron gun which could stably work at 500nA for more than 30 hours was proposed. The electron gun has a hybrid structure of multi-walled carbon nanotube (MWCNT) covered with Platinum tip. The gap between electrodes was adjusted by a nanomanipulation system to control the growth length and working distance inside a scanning electron microscope (SEM). About 374nm Platinum nanowire was in-situ growth in the tip of a single MWCNT with a precursor of cyclopentadienyl-trimethyl-platinum (IV) (CpPtMe3) to synthesized an electron gun. The working current stable at 500nA transferred from the tip of electron gun protected by the Platinum, with the working distance about 1 um, working voltage below 150V. It can work at a very low vacuum, it is about three orders of magnitude smaller than the vacuum required for a conventional gun. Moreover, the monitoring of SEM and the field emission characteristics shows that the electron gun has excellent stability during continue working which reached 50hours. The electron gun only consumed about 0.002um per working hour. The experimental result showed that the electron gun has broad application prospects in various field emission devices.

Because of the optical diffraction limit, standard optical microscopies are not suitable to directly observe the biological samples with the small size between 5 to 150 nm. It has been experimentally demonstrated that microspheres have the ability of super-resolution imaging. Here, we report a probe-combined microsphere which consists of a barium titanate microsphere with the diameter of $50 \sim 100 \mu m$ and a probe. The finite element method is performed by the COMSOL Multiphysics software to confirm that the probe has no influence on the microsphere imaging. When the probe-combined microsphere was installed on a three-dimensional precision translation stage, it can be moved to the desirable area to capture the tiny feature of rat liver slices and the appearance of cells. What’s more, the probe-combined microsphere can adsorb the cells on the back of the microsphere, and thus it can be used as a tool to pick up cells. Another probe can operate the cells and morphological changes of cells can be observed through the microsphere at the same time.

Small energy gap boosts dual-channel triplet harvesting via TADF and UOP, which suppresses long-lived triplet concentration quenching. An infrared laser (808 nm) is able to induce persistent emission under ambient conditions., Due to inefficient molecular design strategies, two-photon-excited ultralong organic room temperature phosphorescence (TPUOP) has not yet been reported in single-component materials. Herein, we present an innovative design method by dual-channel triplet harvesting to obtain the first bright TPUOP molecule with a lifetime of 0.84 s and a quantum efficiency of 16.6%. In compound o-Cz the donor and acceptor units are connected at the ortho position of benzophenone, showing intramolecular space charge transfer. Therefore, the two-photon absorption ability is improved due to the enhanced charge transfer character. Moreover, the small energy gap boosts dual-channel triplet harvesting via ultralong thermally activated delayed fluorescence and H-aggregation phosphorescence, which suppresses the long-lived triplet concentration quenching. Through two-photon absorption, a near-infrared laser (808 nm) is able to trigger the obvious ultralong emission under ambient conditions. This research work provides valuable guidance for designing near-infrared-excited ultralong organic room temperature phosphorescence materials.