Highly Selective Artificial K+ Transporters Reverse Liver Fibrosis In Vivo.

Liver fibrosis is a life-threatening disease that currently lacks clinically effective therapeutic agents. Given the close correlation between dysregulated intracellular K+ homeostasis and the progression of liver fibrosis, developing artificial K+ transporters mimicking the essential function of their natural counterparts in regulating intracellular K+ levels might offer an appealing yet unexplored treatment strategy. Here, we present an unconventional class of artificial K+ transporters involving the "motional" collaboration between two K+ transporter molecules. In particular, 6C6 exhibits an impressive EC50 value of 0.28 µM (i.e., 0.28 mol % relative to lipid) toward K+ and an exceptionally high K+/Na+ selectivity of 15.5, representing one of the most selective artificial K+ transporters reported to date. Most importantly, our study demonstrates, for the first time, the potential therapeutic effect of K+-selective artificial ion transporters in reversing liver fibrosis both in vitro and in vivo.

Fluorescence super-resolution microscopy via fluctuation-based multi-route synergy.

Fluorescence fluctuation-based super-resolution microscopy (FF-SRM) is an economical and widely applicable technique that significantly enhances the spatial resolution of fluorescence imaging by capitalizing on fluorescence intermittency. However, each variant of FF-SRM imaging has inherent limitations. This study proposes a super-resolution reconstruction strategy (synSRM) by synergizing multiple variants of the FF-SRM approach to address the limitations and achieve high-quality and high-resolution imaging. The simulation and experimental results demonstrate that, compared to images reconstructed using single FF-SRM algorithms, by selecting suitable synSRM routes according to various imaging conditions, further improvements of the spatial resolution and image reconstruction quality can be obtained for super-resolution fluorescence imaging.

Recent advances on COF-based single-atom and dual-atom sites for oxygen catalysis.

Covalent organic frameworks (COFs) have emerged as promising platforms for the construction of single-atom and dual-atom catalysts (SACs and DACs), owing to their well-defined structures, tunable pore sizes, and abundant active sites. In recent years, the development of COF-based SACs and DACs as highly efficient catalysts has witnessed a remarkable surge. The synergistic interplay between the metal active sites and the COF has established the design and fabrication of COF-based SACs and DACs as a prominent research area in electrocatalysis. These catalytic materials exhibit promising prospects for applications in energy storage and conversion devices. This review summarizes recent advances in the design, synthesis, and applications of COF-based SACs and DACs for oxygen catalysis. The catalytic mechanisms of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are comprehensively explored, providing a comparative analysis to elucidate the correlation between the structure and performance, as well as their functional attributes in battery devices. This review highlights a promising approach for future research, emphasizing the necessity of rational design, breakthroughs, and in-situ characterization to further advance the development of high-performance COF-based SACs and DACs for sustainable energy applications.

Pore structure of the mixed sedimentary reservoir of Permian Fengcheng Formation in the Hashan area, Junggar Basin.

The Permian Fengcheng Formation (P1f.) in the Hashan area, situated on the southwestern margin of the Junggar Basin, has witnessed a remarkable breakthrough in shale oil exploration in recent years with nearly 789 million tons of shale oil resources. As a unique set of mixed sedimentary shales, the Fengcheng Formation in the Hashan area is characterized by mixed sedimentation of terrigenous siliciclastic sediments, authigenic minerals, and tuffaceous materials. However, the understanding of pore characteristics in the mixed sedimentary reservoir still remains limited, prohibiting accurate estimation of the oil content and insights into oil mobility. Scanning electron microscopy (SEM), X-ray diffraction (XRD), mercury injection capillary pressure (MICP), nuclear magnetic resonance (NMR), X-Ray Computer Tomography (X-CT), and geochemical analysis were performed to investigate the pore size distribution and main controlling factors of the mixed sedimentary reservoir. Results showed that the main pore types in the mixed sedimentary reservoir are intergranular pores and dissolution pores. The pores of the P1f. mixed shales in the Hashan area were classified into II-micropores (< 25 nm), I-micropores (25-100 nm), mesopores (100-1000 nm) and macropores (> 1000 nm). In general, the mixed sedimentary rocks of P1f. formation feature few macropores but a large number of micropores and mesopores. The CS exhibits the most favourable physical properties among all lithofacies. It is concluded that the abundance and maturity of organic matter, mineral composition, sedimentary structure, and diagenesis of reservoir together impact the pore structure in the mixed sedimentary reservoirs. The maturity of organic matter and the content of tuffaceous minerals are the most significant in influencing the pore structure of P1f. shales. Overall, the pore structure of complex lithologic reservoir formed by mixed deposition and its influence on physical properties are studied, and the characteristics of the microscopic pore-throat system of the dominant lithofacies in the Hashan area are clarified, which is of great significance as a guide for the exploration and development of mixed sedimentary reservoirs in continental shale oil in China.

Halogenated retinoid derivatives as dual RARα and RXRα modulators for treating acute promyelocytic leukemia cells.

Acute promyelocytic leukemia (APL), a distinctive subtype of acute myeloid leukemia (AML), is characterized by the t(15; 17) translocation forming the PML-RARα fusion protein. Recent studies have revealed a crucial role of retinoid X receptor α (RXRα) in PML-RARα's tumorigenesis. This necessitates the development of dual RARα and RXRα targeting compounds for treating APL. Here, we developed a pair of brominated retinoid isomers, 5a and 5b, exhibiting RARα agonistic selectivity among the RAR subtypes and RXRα partial agonistic activities. In the treatment of APL cells, low doses (RARα activation range) of 5a and 5b degrade PML-RARα and strongly induce differentiation, while higher doses (RXRα activation range) induce G2/M arrest and apoptosis in both all-trans retinoic acid (ATRA)-sensitive and resistant cells. We replaced the bromine in 5a with chlorine or iodine to obtain compounds 7 or 8a. Interestingly, the chlorinated compound 7 tends to activate RXRα and induce G2/M arrest and apoptosis, while the iodinated compound 8a tends to activate RARα and induce differentiation. Together, our work underscores several advantages and characteristics of halogens in the rational design of RARα and RXRα ligands, offering three promising drug candidates for treating both ATRA-sensitive and resistant APL.

Origin of Grain-Coating Chlorite and Implications for Reservoir Quality in the Triassic Deep-Buried Volcaniclastic Sandstones, Central Junggar Basin, Northwestern China.

The occurrence and genesis of grain-coating chlorite were investigated in order to evaluate the impact of grain-coating chlorite on preserving porosity in the deep-buried Triassic Karamay volcaniclastic sandstones based on thin sections, scanning electron microscopy, and an electron probe. Grain-coating chlorite was formed during the eogenesis, originating from the precursor of smectite through the solid-state transformation (SST) mechanism. The hydration and dissolution of unstable, intermediately basic volcanic rock fragments provided essential Fe2+ and Mg2+ ions for the formation of grain-coating chlorite. Due to relatively high stability and low susceptibility to dissolution, acidic volcanic rock fragments could not promote chlorite formation but resulted in authigenic quartz and clays as pore-filling cements. This process would destroy reservoir properties. Under high hydraulic conditions, medium- to coarse-grained sandstone experienced saltation transport, creating significant velocity differentials and pressure differentials on grain surfaces. Subsequently, clay grains adhere to the surfaces, forming grain-coating chlorite during diagenesis with good continuity. In contrast, pebbly sandstone undergoes rolling transport, resulting in smaller velocity differentials on grain surfaces. This makes relatively ineffective clay adsorption and leads to discontinuous grain-coating chlorite in subsequent stages. Under weak hydraulic conditions, grains and clay particles in fine-grained sandstone undergo suspended transport, lacking mutual movement and velocity differentials. Clay particles cannot effectively cover particles but instead fill the pores between them. Therefore, continuous grain-coating chlorite is more commonly developed in the medium- to coarse-grained sandstones and is crucial for inhibiting quartz cementation with a coverage rate exceeding 80%. Inadequate coatings fail to inhibit quartz cementation effectively, while excessive coatings may block pore throats. Optimal protection of primary porosity could occur only when grain-coating chlorite is moderately developed.

Catalyst-Free Activation and Fixation of Nitrogen by Laser-Induced Conversion.

Ultrafast N2 fixation reactions are quite challenging. Currently used methods for N2 fixation are limited, and strong dinitrogen bonds usually need to be activated via extreme temperature or pressure or by the use of an energy-consuming process with sophisticated catalysts. Herein, we report a novel laser-based chemical method for N2 fixation under ambient conditions without catalysts, this method is called laser bubbling in liquids (LBL), and it directly activates N2 in water (H2O) and efficiently converts N2 into valuable NH3 (max: 4.2 mmol h-1) and NO3- (0.17 mmol h-1). Remarkably, the highest yields of NH3 and NO3- are 4 orders of magnitude greater than the best values for electrocatalysis reported to date. Notably, we further validate the experimental mechanism by using optical emission spectroscopy to detect the production of intermediate plasma and by employing isotope tracing. We also establish that an extremely high-temperature environment far from thermodynamic equilibrium inside a laser-induced bubble and the kinetic process of rapid quenching of bubbles is crucial for N2 activation and fixation to generate NH3 and NOx via LBL. Based on these results, it is shown that LBL is a simple, safe, efficient, green, and sustainable technology that enables the rapid conversion of the renewable feedstocks H2O and N2 to NH3 and NO3-, facilitating new prospects for chemical N2 fixation.

High Sensitivity and Wide Linear Range Flexible Piezoresistive Pressure Sensor with Microspheres as Spacers for Pronunciation Recognition.

Flexible piezoresistive pressure sensors have received great popularity in flexible electronics due to their simple structure and promising applications in health monitoring and artificial intelligence. However, the contradiction between sensitivity and detection range limits the application of the sensors in the medium-pressure regime. Here, a flexible piezoresistive pressure sensor is fabricated by combining a hierarchical spinous microstructure sensitive layer and a periodic microsphere array spacer. The sensor achieves high sensitivity (39.1 kPa-1) and outstanding linearity (0.99, R2 coefficient) in a medium-pressure regime, as well as a wide range of detection (100 Pa-160.0 kPa), high detection precision (<0.63‰ full scale), and excellent durability (>5000 cycles). The mechanism of the microsphere array spacer in improving sensitivity and detection range was revealed through finite element analysis. Furthermore, the sensors have been utilized to detect muscle and joint movements, spatial pressure distributions, and throat movements during pronouncing words. By means of a full-connect artificial neural network for machine learning, the sensor's output of different pronounced words can be precisely distinguished and classified with an overall accuracy of 96.0%. Overall, the high-performance flexible pressure sensor based on a microsphere array spacer has great potential in health monitoring, human-machine interface, and artificial intelligence of medium-pressure regime.

Stretchable, Transparent, and Ultra-Broadband Terahertz Shielding Thin Films Based on Wrinkled MXene Architectures.

With the increasing demand for terahertz (THz) technology in security inspection, medical imaging, and flexible electronics, there is a significant need for stretchable and transparent THz electromagnetic interference (EMI) shielding materials. Existing EMI shielding materials, like opaque metals and carbon-based films, face challenges in achieving both high transparency and high shielding efficiency (SE). Here, a wrinkled structure strategy was proposed to construct ultra-thin, stretchable, and transparent terahertz shielding MXene films, which possesses both isotropous wrinkles (height about 50 nm) and periodic wrinkles (height about 500 nm). Compared to flat film, the wrinkled MXene film (8 nm) demonstrates a remarkable 36.5% increase in SE within the THz band. The wrinkled MXene film exhibits an EMI SE of 21.1 dB at the thickness of 100 nm, and an average EMI SE/t of 700 dB µm-1 over the 0.1-10 THz. Theoretical calculations suggest that the wrinkled structure enhances the film's conductivity and surface plasmon resonances, resulting in an improved THz wave absorption. Additionally, the wrinkled structure enhances the MXene films' stretchability and stability. After bending and stretching (at 30% strain) cycles, the average THz transmittance of the wrinkled film is only 0.5% and 2.4%, respectively. The outstanding performances of the wrinkled MXene film make it a promising THz electromagnetic shielding materials for future smart windows and wearable electronics.

Phase separation of Nur77 mediates XS561-induced apoptosis by promoting the formation of Nur77/Bcl-2 condensates.

The orphan nuclear receptor Nur77 is a critical regulator of the survival and death of tumor cells. The pro-death effect of Nur77 can be regulated by its interaction with Bcl-2, resulting in conversion of Bcl-2 from a survival to killer. As Bcl-2 is overexpressed in various cancers preventing them from apoptosis and promoting their resistance to chemotherapy, targeting the apoptotic pathway of Nur77/Bcl-2 may lead to new cancer therapeutics. Here, we report our identification of XS561 as a novel Nur77 ligand that induces apoptosis of tumor cells by activating the Nur77/Bcl-2 pathway. In vitro and animal studies revealed an apoptotic effect of XS561 in a range of tumor cell lines including MDA-MB-231 triple-negative breast cancer (TNBC) and MCF-7/LCC2 tamoxifen-resistant breast cancer (TAMR) in a Nur77-dependent manner. Mechanistic studies showed XS561 potently induced the translocation of Nur77 from the nucleus to mitochondria, resulting in mitochondria-related apoptosis. Interestingly, XS561-induced accumulation of Nur77 at mitochondria was associated with XS561 induction of Nur77 phase separation and the formation of Nur77/Bcl-2 condensates. Together, our studies identify XS561 as a new activator of the Nur77/Bcl-2 apoptotic pathway and reveal a role of phase separation in mediating the apoptotic effect of Nur77 at mitochondria.

Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer.

BACKGROUND: Colorectal cancer is a common malignant tumor in China, and its incidence in the elderly is increasing annually. Inflammatory bowel disease is a group of chronic non-specific intestinal inflammatory diseases, including ulcerative colitis and Crohn's disease. AIM: To assess the effect of screening colonoscopy frequency on colorectal cancer mortality. METHODS: We included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December 2022. Surgical indicators, oncological indicators, and survival rates were compared between the groups. The results of 104 patients who met the above criteria were extracted from the database (laparoscopic colectomy group = 63, open colectomy group = 41), and there were no statistically significant differences in the baseline data or follow-up time between the two groups. RESULTS: Intraoperative blood loss, time to first ambulation, and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy group. The differences in overall mortality, tumor-related mortality, and recurrence rates between the two groups were not statistically significant, and survival analysis showed that the differences in the cumulative overall survival, tumor-related survival, and cumulative recurrence-free rates between the two groups were not statistically significant. CONCLUSION: In elderly patients with colorectal cancer, laparoscopic colectomy has better short-term outcomes than open colectomy, and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

Endocytic activation and exosomal secretion of matriptase stimulate the second wave of EGF signaling to promote skin and breast cancer invasion.

The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.

Laser direct overall water splitting for H2 and H2O2 production.

Hydrogen (H2) and hydrogen peroxide (H2O2) play crucial roles as energy carriers and raw materials for industrial production. However, the current techniques for H2 and H2O2 production rely on complex catalysts and involve multiple intermediate steps. In this study, we present a straightforward, environmentally friendly, and highly efficient laser-induced conversion method for overall water splitting to simultaneously generate H2 and H2O2 at ambient conditions without any catalysts. The laser direct overall water splitting approach achieves an impressive light-to-hydrogen energy conversion efficiency of 2.1%, with H2 production rates of 2.2 mmol/h and H2O2 production rates of 65 µM/h in a limited reaction area (1 mm2) within a short real reaction time (0.36 ms/h). Furthermore, we elucidate the underlying physics and chemistry behind the laser-induced water splitting to produce H2 and H2O2. The laser-induced cavitation bubbles create an optimal microenvironment for water-splitting reactions because of the transient high temperatures (104 K) surpassing the chemical barrier required. Additionally, their rapid cooling rate (1010 K/s) hinders reverse reactions and facilitates H2O2 retention. Finally, upon bubble collapse, H2 is released while H2O2 remains dissolved in the water. Moreover, a preliminary amplification experiment demonstrates the potential industrial applications of this laser chemistry. These findings highlight that laser-based production of H2 and H2O2 from water holds promise as a straightforward, environmentally friendly, and efficient approach on an industrial scale beyond conventional chemical catalysis.

Engineering Symmetry-Breaking Centers and d-Orbital Modulation in Triatomic Catalysts for Zinc-Air Batteries.

Unraveling the configuration-activity relationship and synergistic enhancement mechanism (such as real active center, electron spin-state, and d-orbital energy level) for triatomic catalysts, as well as their intrinsically bifunctional oxygen electrocatalysis, is a great challenge. Here we present a triatomic catalyst (TAC) with a trinuclear active structure that displays extraordinary oxygen electrocatalysis for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), greatly outperforming the counterpart of single-atom and diatomic catalysts. The aqueous Zn-air battery (ZAB) equipped with a TAC-based cathode exhibits extraordinary rechargeable stability and ultrarobust cycling performance (1970 h/3940 cycles at 2 mA cm-2, 125 h/250 cycles at 10 mA cm-2 with negligible voltage decay), and the quasi-solid-state ZAB displays outstanding rechargeability and low-temperature adaptability (300 h/1800 cycles at 2 mA cm-2 at -60 °C), outperforming other state-of-the-art ZABs. The experimental and theoretical analyses reveal the symmetry-breaking CoN4 configuration under incorporation of neighboring metal atoms (Fe and Cu), which leads to d-orbital modulation, a low-shift d band center, weakened binding strength to the oxygen intermediates, and decreased energy barrier for bifunctional oxygen electrocatalysis. This rational tricoordination design as well as an in-depth mechanism analysis indicate that hetero-TACs can be promisingly applied in various electrocatalysis applications.

Efficient and Rapid Hydrogen Extraction from Ammonia-Water via Laser Under Ambient Conditions without Catalyst.

As a good carrier of hydrogen, ammonia-water has been employed to extract hydrogen in many ways. Here, we demonstrate a simple, green, ultrafast, and highly efficient method for hydrogen extraction from ammonia-water by laser bubbling in liquids (LBL) at room temperature and ambient pressure without catalyst. A maximum apparent yield of 33.7 mmol/h and a real yield of 93.6 mol/h were realized in a small operating space, which were far higher than the yields of most hydrogen evolution reactions from ammonia-water under ambient conditions. We also established that laser-induced cavitation bubbles generated a transient high temperature, which enabled a very suitable environment for hydrogen extraction from ammonia-water. The laser used here can serve as a demonstration of potentially solar-pumped catalyst-free hydrogen extraction and other chemical synthesis. We anticipate that the LBL technique will open unprecedented opportunities to produce chemicals.

Flexible, Transparent and Conductive Metal Mesh Films with Ultra-High FoM for Stretchable Heating and Electromagnetic Interference Shielding.

Despite the growing demand for transparent conductive films in smart and wearable electronics for electromagnetic interference (EMI) shielding, achieving a flexible EMI shielding film, while maintaining a high transmittance remains a significant challenge. Herein, a flexible, transparent, and conductive copper (Cu) metal mesh film for EMI shielding is fabricated by self-forming crackle template method and electroplating technique. The Cu mesh film shows an ultra-low sheet resistance (0.18 Ω â–¡-1), high transmittance (85.8%@550 nm), and ultra-high figure of merit (> 13,000). It also has satisfactory stretchability and mechanical stability, with a resistance increases of only 1.3% after 1,000 bending cycles. As a stretchable heater (ε > 30%), the saturation temperature of the film can reach over 110 °C within 60 s at 1.00 V applied voltage. Moreover, the metal mesh film exhibits outstanding average EMI shielding effectiveness of 40.4 dB in the X-band at the thickness of 2.5 µm. As a demonstration, it is used as a transparent window for shielding the wireless communication electromagnetic waves. Therefore, the flexible and transparent conductive Cu mesh film proposed in this work provides a promising candidate for the next-generation EMI shielding applications.

Non-Covalently Stapled H+ /Cl- Ion Channels Activatable by Visible Light for Targeted Anticancer Therapy.

The development of stimuli-responsive artificial H+ /Cl- ion channels, capable of specifically disturbing the intracellular ion homeostasis of cancer cells, presents an intriguing opportunity for achieving high selectivity in cancer therapy. Herein, we describe a novel family of non-covalently stapled self-assembled artificial channels activatable by biocompatible visible light at 442 nm, which enables the co-transport of H+ /Cl- across the membrane with H+ /Cl- transport selectivity of 6.0. Upon photoirradiation of the caged C4F-L for 10 min, 90 % of ion transport efficiency can be restored, giving rise to a 10.5-fold enhancement in cytotoxicity against human colorectal cancer cells (IC50 =8.5 µM). The mechanism underlying cancer cell death mediated by the H+ /Cl- channels involves the activation of the caspase 9 apoptosis pathway as well as the scarcely reported disruption of the autophagic processes. In the absence of photoirradiation, C4F-L exhibits minimal toxicity towards normal intestine cells, even at a concentration of 200 µM.

Exosomes from adipose-derived mesenchymal stem cells improve liver fibrosis by regulating the miR-20a-5p/TGFBR2 axis to affect the p38 MAPK/NF-κB pathway.

OBJECTIVE: Human adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) are active constituents for treating liver fibrosis. This paper attempted to preliminarily explain the functional mechanism of ADSC-Exos in liver fibrosis through the p38 MAPK/NF-κB pathway. METHODS: The cell models of hepatic fibrosis were established by inducing LX-2 cells with TGF-ß1. Mouse models of liver fibrosis were established by treating mice with CCl4. The in vivo and in vitro models of liver fibrosis were treated with ADSC-Exos. ADSCs were identified by flow cytometry/Alizarin red/oil red O/alcian blue staining. ADSC-Exos were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. LX-2 cell proliferation/viability were evaluated by MTT/BrdU assays. Exosomes were tracked in vivo and body weight changes in mice were monitored. Hepatic pathological changes were observed by HE/Masson staining. α-SMA/collagen I levels in liver tissues were assessed by immunohistochemistry. HA/PIIINP concentrations were measured using the magnetic particle chemiluminescence method. Liver function was assessed using an automatic analyzer. miR-20a-5p level was measured by RT-qPCR. The mRNA levels of fibrosis markers were determined by RT-qPCR, and their protein levels and levels of MAPK/NF-κB pathway-related proteins, as well as TGFBR2 protein level were measured by Western blot. The P65 nuclear expression in mouse liver tissues was quantified by immunofluorescence. RESULTS: ADSC-Exos suppressed TGF-ß1-induced LX-2 cell proliferation and fibrosis and reduced mRNA and protein levels of fibrosis markers in vitro. ADSC-Exos ameliorated liver fibrosis by inhibiting the p38 MAPK/NF-κB pathway activation. ADSC-Exos inhibited activation of the p38 MAPK/NF-κB pathway via regulating the miR-20a-5p/TGFBR2 axis. The in vivo experiment asserted that ADSC-Exos were mainly distributed in the liver, and ADSC-Exos relieved liver fibrosis in mice, which was evidenced by alleviating decreased body weight, reducing collagen and enhancing liver function, and repressed the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis. CONCLUSION: ADSC-Exos attenuated liver fibrosis by suppressing the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis.

Nuclear receptor RXRα binds the precursor of miR-103 to inhibit its maturation.

BACKGROUND: The maturation of microRNAs (miRNAs) successively undergoes Drosha, Dicer, and Argonaute -mediated processing, however, the intricate regulations of the individual miRNA maturation are largely unknown. Retinoid x receptor alpha (RXRα) belongs to nuclear receptors that regulate gene transcription by binding to DNA elements, however, whether RXRα binds to miRNAs to exert physiological functions is not known. RESULTS: In this work, we found that RXRα directly binds to the precursor of miR-103 (pre-miR-103a-2) via its DNA-binding domain with a preferred binding sequence of AGGUCA. The binding of RXRα inhibits the processing of miR-103 maturation from pre-miR-103a-2. Mechanistically, RXRα prevents the nuclear export of pre-miR-103a-2 for further processing by inhibiting the association of exportin-5 with pre-miR-103a-2. Pathophysiologically, the negative effect of RXRα on miR-103 maturation correlates to the positive effects of RXRα on the expression of Dicer, a target of miR-103, and on the inhibition of breast cancer. CONCLUSIONS: Our findings unravel an unexpected role of transcription factor RXRα in specific miRNA maturation at post-transcriptional level through pre-miRNA binding, and present a mechanistic insight regarding RXRα role in breast cancer progression.

Flexible, Transparent, and Wafer-Scale Artificial Synapse Array Based on TiOx /Ti3 C2 Tx Film for Neuromorphic Computing.

A high-density neuromorphic computing memristor array based on 2D materials paves the way for next-generation information-processing components and in-memory computing systems. However, the traditional 2D-materials-based memristor devices suffer from poor flexibility and opacity, which hinders the application of memristors in flexible electronics. Here, a flexible artificial synapse array based on TiOx /Ti3 C2 Tx film is fabricated by a convenient and energy-efficient solution-processing technique, which realizes high transmittance (≈90%) and oxidation resistance (>30 days). The TiOx /Ti3 C2 Tx memristor shows low device-to-device variability, long memory retention and endurance, a high ON/OFF ratio, and fundamental synaptic behavior. Furthermore, satisfactory flexibility (R = 1.0 mm) and mechanical endurance (104 bending cycles) of the TiOx /Ti3 C2 Tx memristor are achieved, which is superior to other film memristors prepared by chemical vapor deposition. In addition, high-precision (>96.44%) MNIST handwritten digits recognition classification simulation indicates that the TiOx /Ti3 C2 Tx artificial synapse array holds promise for future neuromorphic computing applications, and provides excellent high-density neuron circuits for new flexible intelligent electronic equipment.