RGS20 promotes non-small cell lung carcinoma proliferation via autophagy activation and inhibition of the PKA-Hippo signaling pathway.

BACKGROUND: Novel therapeutic targets are urgently needed for treating drug-resistant non-small cell lung cancer (NSCLC) and overcoming drug resistance to molecular-targeted therapies. Regulator of G protein signaling 20 (RGS20) is identified as an upregulated factor in many cancers, yet its specific role and the mechanism through which RGS20 functions in NSCLC remain unclear. Our study aimed to identify the role of RGS20 in NSCLC prognosis and delineate associated cellular and molecular pathways. METHODS: Immunohistochemistry and lung cancer tissue microarray were used to verify the expression of RGS20 between NSCLC patients. CCK8 and cell cloning were conducted to determine the proliferation ability of H1299 and Anip973 cells in vitro. Furthermore, Transcriptome sequencing was performed to show enrichment genes and pathways. Immunofluorescence was used to detect the translocation changes of YAP to nucleus. Western blotting demonstrated different expressions of autophagy and the Hippo-PKA signal pathway. In vitro and in vivo experiments verified whether overexpression of RGS20 affect the proliferation and autophagy of NSCLC through regulating the Hippo pathway. RESULTS: The higher RGS20 expression was found to be significantly correlated with a poorer five-year survival rate. Further, RGS20 accelerated cell proliferation by increasing autophagy. Transcriptomic sequencing suggested the involvement of the Hippo signaling pathway in the action of RGS20 in NSCLC. RGS20 activation reduced YAP phosphorylation and facilitated its nuclear translocation. Remarkably, inhibiting Hippo signaling with GA-017 promoted cell proliferation and activated autophagy in RGS20 knock-down cells. However, forskolin, a GPCR activator, increased YAP phosphorylation and reversed the promoting effect of RGS20 in RGS20-overexpressing cells. Lastly, in vivo experiments further confirmed role of RGS20 in aggravating tumorigenicity, as its overexpression increased NSCLC cell proliferation. CONCLUSION: Our findings indicate that RGS20 drives NSCLC cell proliferation by triggering autophagy via the inhibition of PKA-Hippo signaling. These insights support the role of RGS20 as a promising novel molecular marker and a target for future targeted therapies in lung cancer treatment.

Clinical study of 57 cases of endovascular treatment for total subclavian artery occlusion.

OBJECTIVE: To investigate the safety and efficacy of endovascular treatment for totally occlusive lesions of the subclavian artery (SCA). METHODS: A retrospective study was performed on 57 patients treated with angioplasty and stenting, including 42 males and 15 females, with an average age of 61.8 years (range: 49 to 81 years). Efficacy, safety, and complications were evaluated. RESULTS: Procedural success was achieved for 47/57 patients and symptoms were relieved. Rat-tail occlusion is the most common type, and all cases were successfully recanalized. Plain type occlusion is less common with a recanalization rate of 55.6%. Hilly and plain occlusions are the main types of stent implantation failure. Through univariate analysis and trend matching analysis, the type of SCA occlusion and surgical approach had statistical significance on the success rate of surgery. The mean follow-up time was 34.6 ± 16.2 months. The cumulative stent patency rates at 1, 3, and 5 years were 95.5%, 86.4%, and 77.3% in the calcified plaque group and 92.0%, 76.0%, and 68.0% in the non-calcified plaque group, respectively. The 3-year and 5-year patency rates in the calcified plaque group were higher than those in the non-calcified plaque group (p < .05). CONCLUSION: Different occlusion types and surgical approaches can affect the surgical success rate. The combined femoral and brachial approach can improve the rate of recanalization of SCA occlusions. The patency rates at 3 and 5 years in the calcified plaque group were higher than those in the non-calcified plaque group.

Unlocking Enhanced Capacitive Deionization of NaTi2(PO4)3/Carbon Materials by the Yolk-Shell Design.

The low salt adsorption capacities (SACs) of benchmark carbon materials (usually below 20 mg g-1) are one of the most challenging issues limiting further commercial development of capacitive deionization (CDI), an energetically favorable method for sustainable water desalination. Sodium superionic conductor (NASICON)-structured NaTi2(PO4)3 (NTP) materials, especially used in combination with carbon to prepare NTP/C materials, provide emerging options for higher CDI performance but face the problems of poor cycling stability and dissolution of active materials. In this study, we report the development of the yolk-shell nanoarchitecture of NASICON-structured NTP/C materials (denoted as ys-NTP@C) using a metal-organic framework@covalent organic polymer (MOF@COP) as a sacrificial template and space-confined nanoreactor. As expected, ys-NTP@C exhibits good CDI performance, including exemplary SACs with a maximum SAC of 124.72 mg g-1 at 1.8 V in the constant-voltage mode and 202.76 mg g-1 at 100 mA g-1 in the constant-current mode, and good cycling stability without obvious performance degradation or energy consumption increase over 100 cycles. Furthermore, X-ray diffraction used to study CDI cycling clearly exhibits the good structural stability of ys-NTP@C during repeated ion intercalation/deintercalation processes, and the finite element simulation shows why yolk-shell nanostructures exhibit better performance than other materials. This study provides a new synthetic paradigm for preparing yolk-shell structured materials from MOF@COP and highlights the potential use of yolk-shell nanoarchitectures for electrochemical desalination.

Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway.

Gastric cancer (GC) is the most common malignant tumor of digestive system. Bufalin extracted from Venenum Bufonis is one of the most effective anticancer monomers, which has been proved to play anticancer roles in a variety of cancers such as ovarian cancer, prostate cancer and neuroblastoma. However, there are few studies on bufalin in GC, and lack of clear targets. The effect of bufalin on the proliferation and migration of GC cells was detected by CCK-8, scratch wound healing assay, transwell assay and Western blotting. The potential direct interaction proteins of bufalin were screened by human proteome microarray containing 21,838 human proteins. The target protein was determined by bioinformatics, and the binding sites were predicted by molecular docking technique. Biological experiments in vitro and in vivo were conducted to verify the effect of bufalin directly interaction protein and the mechanism of bufalin targeting the protein to inhibit the development of GC. The results showed that bufalin inhibited the proliferation and migration of MKN-45 and HGC-27 GC cell lines in vitro. BFAR, a direct interaction protein of bufalin has several potential binding sites to bufalin. BFAR is highly expressed in GC and promotes the occurrence and metastasis of GC by activating PI3K/AKT/mTOR signal pathway in vitro and in vivo. Bufalin reversed the promoting effect of BFAR on the carcinogenesis and metastasis of GC by down-regulating the expression of BFAR. Our results show that bufalin targeting BFAR inhibits the occurrence and metastasis of GC through PI3K/AKT/mTOR signal pathway. These results provide a new basis for bufalin as a promising drug for the treatment of GC.

Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by up-regulating RASSF2.

Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disorder with high mortality and morbidity rates. To date, no drug has shown to significantly alleviate the risk of AAA. Previous studies have indicated that hyperhomocysteinemia (HHcy) significantly increases the incidence of AAA by disrupting endothelial cell homeostasis; however, the potential molecular mechanisms require clarification. Herein, we aimed to integrate transcriptomics analysis and molecular biology experiments to explore the potential molecular targets by which HHcy may increase the incidence of AAA. We integrated two AAA data profiles (GSE57691 and GSE7084) based on previously published microarray ribonucleic acid sequencing (RNAseq) data from the GEO database. Additionally, 500 µM homocysteine-treated human aorta endothelium cells microarray dataset (GSE175748) was downloaded and processed. Subsequently, single-cell RNA-seq profiles of the aortic aneurysms (GSE155468) were downloaded, scaled, and processed for further analysis. The microarray profiles analysis demonstrated that the Ras association domain family member 2 (RASSF2) and interleukin (IL)-1ß are potentially the target genes involved in the HHcy-mediated aggravation of AAA formation. Single-cell RNAseq analysis revealed that RASSF2 might impair endothelial cell function by increasing inflammatory cell infiltration to participate in AAA formation. Finally, we conducted reverse transcription quantitative polymerase chain reaction and immunofluorescence analysis to validate the up-regulated mRNA expression of RASSF2 (p = 0.008) and IL-1ß (p = 0.002) in AAA tissue compared to control tissue. Immunofluorescence staining revealed overexpression of RASSF2 protein in AAA tissue sections compared to control tissue (p = 0.037). Co-localization of RASSF2 and the aortic endothelium cell marker, CD31, was observed in tissue sections, indicating the potential involvement of RASSF2 in aortic endothelial cells. To summarise, our preliminary study revealed that HHcy may worsen AAA formation by up-regulating the expression of RASSF2 and IL-1ß in aortic endothelium cells.

Architecting O3/P2 layered oxides by gradient Mn doping for sodium-ion batteries.

O3 phase layered oxides are highly attractive cathode materials for sodium-ion batteries because of their high capacity and decent initial Coulombic efficiency. However, their rate capability and long cycling life are unsatisfactory due to the narrow Na+ transfer channel and irreversible phase transitions of O3 phase during sodiation/desodiation process. Constructing O3/P2 multiphase structures has been proven to be an effective strategy to overcome these challenges. In this study, we synthesized bi-phasic structured O3/P2 Na(Ni2/9Fe1/3Cu1/9Mn1/3)1-xMnxO2 (x = 0.01, 0.02, 0.03, 0.04, 0.05) materials through Mn doping during sodiation process. Benefiting from surface P2 phase layer with the enhanced Na+ transfer dynamics and high structural stability, the Na(Ni2/9Fe1/3Cu1/9Mn1/3)0.98Mn0.02O2 (NFCM-M2) cathode delivers a reversible capacity of 139.1 mA h g-1 at 0.1 C, and retains 71.4 % of its original capacity after 300 cycles at 1 C. Our work provides useful guidance for designing multiphase cathodes and offers new insights into the structure-performance correlation for sodium-ion cathode materials.

Liquid-phase photo-induced covalent modification (PICM) of single-layer graphene by short-chain fatty acids.

We report an efficient photo-induced covalent modification (PICM) of graphene by short-chain fatty acids (SCFAs) with an alkyl chain at the liquid-solid interface for spatially resolved chemical functionalization of graphene. Light irradiation on monolayer graphene under an aqueous solution of the SCFAs with an alkyl chain efficiently introduces sp3-hybridized defects, where the reaction rates of PICM are significantly higher than those in pure water. Raman and IR spectroscopy revealed that a high density of methyl, methoxy, and acetate groups is covalently attached to the graphene surface while it was partially oxidized by other oxygen-containing functional groups, such as OH and COOH. A greater downshift of the G-band in Raman spectra was observed upon the PICM with longer alkyl chains, suggesting that the charge doping effect can be controlled by the alkyl chain length of the SCFAs. The systematic research and exploration of covalent modification in SCFAs provide new insight and a potentially facile method for bandgap engineering of graphene.

A light-mediated covalently patterned graphene substrate for graphene-enhanced Raman scattering (GERS).

We report covalently patterned graphene with acetic acid as a new potential candidate for graphene-enhanced Raman scattering (GERS). Rhodamine 6G molecules in direct contact with the covalently modified region show an enormous enhancement (∼25 times) compared to the pristine region at 532 nm excitation. The GERS enhancement with respect to the layer thickness of the probed molecule, excitation wavelength, and covalently attached groups is discussed.

Collagen peptide promotes DSS-induced colitis by disturbing gut microbiota and regulation of macrophage polarization.

Ulcerative colitis (UC) is an inflammatory bowel disease caused by mucosal immune system disorder, which has increased steadily all over the world. Previous studies have shown that collagen peptide (CP) has various beneficial biological activities, it is not clear whether the effect of CP on UC is positive or negative. In this study, 2.5% dextran sulfate sodium (DSS) was used to establish acute colitis in mice. Our results suggested that CP supplementation (200, 400 mg/kg/day) promoted the progression of colitis, increased the expression of inflammatory factors and the infiltration of colonic lamina propria macrophages. Gut microbiota analysis showed the composition changed significantly and inflammation promoted bacteria was after CP treatment. Meanwhile, the effect of CP on macrophage polarization was further determined in Raw264.7 cell line. The results showed that CP treatment could increase the polarization of M1 macrophages and promote the expression of inflammatory factors. In conclusion, our results showed that CP treatment could disrupt the gut microbiota of host, promote macrophage activation and aggravate DSS-induced colitis. This may suggest that patients with intestinal inflammation should not take marine derived CP.

All-Optical and One-Color Rewritable Chemical Patterning on Pristine Graphene under Water.

We report a facile all-optical method for spatially resolved and reversible chemical modification of a graphene monolayer. A tightly focused laser on graphene under water introduces an sp3-type chemical defect by photo-oxidation. The sp3-type defects can be reversibly restored to sp2 carbon centers by the same laser with higher intensity. The photoreduction occurs due to laser-induced local heating on the graphene. These optical methods combined with a laser direct writing technique allow photowriting and erasing of a well-defined chemical pattern on a graphene canvas with a spatial resolution of about 300 nm. The pattern is visualized by Raman mapping with the same excitation laser, enabling an optical read-out of the chemical information on the graphene. Here, we successfully demonstrate all-optical Write/Read-out/Erase of chemical functionalization patterns on graphene by simply adjusting the one-color laser intensity. The all-optical method enables flexible and efficient tailoring of physicochemical properties in nanoscale for future applications.

MoO2 nanoparticles embedded in N-doped hydrangea-like carbon as a sulfur host for high-performance lithium-sulfur batteries.

Lithium-sulfur batteries are considered to be promising energy storage devices owing to their high energy density, relatively low price and abundant resources. However, the low utilization of insulated active materials and shuttle effect have severely hindered the further development of lithium-sulfur batteries. Herein, MoO2 nanoparticles embedded in N-doped hydrangea-like carbon have been synthesized by liquid-phase reaction followed by an annealing process and used as a sulfur host. The nitrogen-doped carbon matrix improves electrical conductivity and provides pathways for smooth electron and Li ion transfer to uniformly dispersed sulfur. Meanwhile, MoO2 nanoparticles can absorb polysulfide ions by forming strong chemical bonds, which can effectively alleviate the polysulfide shuttling effect. These results showed a good rate performance: 1361, 1071, 925, 815 and 782 mA h g-1 at the current densities of 0.1, 0.2, 0.5, 1 and 2 A g-1, and capacity retention of 85% after 300 cycles at 1 A g-1. The excellent performance was due to the synergistic effects of the polar MoO2 and nitrogen-doped carbon matrix, which can effectively restrain and reutilize active materials by absorbing polysulfides and catalyzing the transformation of polysulfides.

Mo2C-Embedded Carambola-like N,S-Rich Carbon Framework as the Interlayer Material for High-Rate Lithium-Sulfur Batteries in a Wide Temperature Range.

The insulating nature of sulfur/Li2S and heavy shuttle effect of lithium polysulfides (LiPSs) hinder the commercialization of lithium-sulfur (Li-S) batteries. To address such issues, we designed and synthesized a porous carambola-like N,S-doped carbon framework embedded with Mo2C particles (designed as N,S-Mo2C/C-ACF) as the interlayer material to block the polysulfide shuttle and it behaves as a catalytic mediator for LiPS conversion. The modified separator of polypropylene functionalized by N,S-Mo2C/C-ACF, showing ultrafast wetting ability to the electrolyte and high lithium ion (Li+) conductivity, proves to be highly effective for inhibiting the polysulfide shuttle and simultaneously promoting the reutilization of adsorbed LiPSs. When used in Li-S batteries by coupling with a Super P/sulfur cathode, over a wide temperature range of 5-55 °C, the as-fabricated batteries delivered excellent rate capability and long cycle stability. Especially, at a high rate of 5 C, the discharge capacities of 405, 630, and 670 mA h gs-1 were achieved when tested at 5, 30, and 55 °C, respectively. The remarkable wide temperature performance is appealing for extended practical application of Li-S batteries.

A rational design of the coupling mechanism of physical adsorption and chemical charge effect for high-performance lithium-sulfur batteries.

Lithium sulfur batteries are considered as potential energy storage systems for electrical devices owing to their high energy density, low cost, and environmental friendliness. However, the hasty capacity fading originating from the solution and migration of polysulfides is the major obstacle for their industrial application. The polysulfide adsorption and repulsion effect achieved by adding an extra coating layer on the side of the cathode and separator have been separately proved to be effective in mitigating the shuttle effect. Herein, a cooperative coated separator, which employs a hybrid carbon matrix as the coated material, including an appropriate ratio of N-doped activated conductive carbon and commercial acetylene black, and sulfonated polystyrene as the binder, is established to prevent the migration of polysulfides and serves as a secondary current collector to reutilize the active materials for high-performance lithium sulfur batteries. The research results showed that the coated separator with 50 wt% N-doped activated conductive carbon as the coating material and sulfonated polystyrene as the binder showed highlighted cycle performance, and 731 mA h g-1 was maintained after 150 cycles at 800 mA g-1(the capacity retention was 86.0%). The superior performance may be because the coated separator can efficiently restrain the polysulfides by physical and chemical effects and also reject the polysulfides by the anion electrostatic effect. In summary, this study provides a new cooperative way to address the shuttle effect and promotes the development of lithium sulfur batteries.

Structure and electrochemical performance modulation of a LiNi0.8Co0.1Mn0.1O2 cathode material by anion and cation co-doping for lithium ion batteries.

Ni-rich layered transition metal oxides show great energy density but suffer poor thermal stability and inferior cycling performance, which limit their practical application. In this work, a minor content of Co and B were co-doped into the crystal of a Ni-rich cathode (LiNi0.8Co0.1Mn0.1O2) using cobalt acetate and boric acid as dopants. The results analyzed by XRD, TEM, XPS and SEM reveal that the modified sample shows a reduced energy barrier for Li+ insertion/extraction and alleviated Li+/Ni2+ cation mixing. With the doping of B and Co, corresponding enhanced cycle stability was achieved with a high capacity retention of 86.1% at 1.0C after 300 cycles in the range of 2.7 and 4.3 V at 25 °C, which obviously outperformed the pristine cathode (52.9%). When cycled after 300 cycles at 5C, the material exhibits significantly enhanced cycle stability with a capacity retention of 81.9%. This strategy for the enhancement of the electrochemical performance may provide some guiding significance for the practical application of high nickel content cathodes.

Insight into Preparation of Fe-Doped Na3V2(PO4)3@C from Aspects of Particle Morphology Design, Crystal Structure Modulation, and Carbon Graphitization Regulation.

The peak-loading shift function of sodium-ion batteries in large-grid energy store station poses a giant challenge on the account of poor rate performance of cathodes. NASICON type Na3V2(PO4)3 with a stable three-dimensional framework and fast ion diffusion channels has been regarded as one of the potential candidates and extensively studied. Nevertheless, a multilevel integrated tactic to boost the performance of Na3V2(PO4)3 in terms of crystal structure modulation, coated carbon graphitization regulation, and particle morphology design is rarely reported and deserves much attention. In this study, organic ferric was used to prepare Fe-doped Na3V2(PO4)3@C cathode on the account of low cost, environmental friendliness, and catalytic function of Fe on carbon graphitization. The density functional theory calculation depicts that the most stable site for Fe atom is the V site and moderate replacement of Fe at V position would reduce the band gap energy from 2.19 by 0.43 eV and improve the electron transfer, which is crucial for the intrinsic poor conductivity of Na3V2(PO4)3. The experimental results show that Fe element can be introduced into the bulk structure successfully, modulating relevant structural parameters. In addition, the coated carbon layer graphitization degree is also regulated due to the catalysis function of Fe. And, the decomposition of organic ferric would infuse the formation of porous structure, which can promote electrolyte permeation and shorten the electron/ion diffusion. Finally, the optimized Na3V1.85Fe0.15(PO4)3@C could possess a high capacity of 103.69 mA h g-1 and retain 91.45% after 1200 cycles at 1.0C as well as 94.45 mA h g-1 at 20C. In addition, the excellent performance is comprehensively elucidated via ex situ X-ray diffraction and pseudocapacitance characterization. The multifunction contribution of Fe-doping may provide new clue for designing porous electrode materials and a new sight into Fe-doped carbon-coated material.

Design and Synthesis of Layered Na2Ti3O7 and Tunnel Na2Ti6O13 Hybrid Structures with Enhanced Electrochemical Behavior for Sodium-Ion Batteries.

A novel complementary approach for promising anode materials is proposed. Sodium titanates with layered Na2Ti3O7 and tunnel Na2Ti6O13 hybrid structure are presented, fabricated, and characterized. The hybrid sample exhibits excellent cycling stability and superior rate performance by the inhibition of layered phase transformation and synergetic effect. The structural evolution, reaction mechanism, and reaction dynamics of hybrid electrodes during the sodium insertion/desertion process are carefully investigated. In situ synchrotron X-ray powder diffraction (SXRD) characterization is performed and the result indicates that Na+ inserts into tunnel structure with occurring solid solution reaction and intercalates into Na2Ti3O7 structure with appearing a phase transition in a low voltage. The reaction dynamics reveals that sodium ion diffusion of tunnel Na2Ti6O13 is faster than that of layered Na2Ti3O7. The synergetic complementary properties are significantly conductive to enhance electrochemical behavior of hybrid structure. This study provides a promising candidate anode for advanced sodium ion batteries (SIBs).

Efficacy of Bushenjianpi prescription on autoimmune premature ovarian failure in mice.

OBJECTIVE: To assess the efficacy of Bushenjianpi prescription (BSJPP), a formula from Traditional Chinese Medicine, on a mouse model of autoimmune premature ovarian failure (POF) induced by mouse zona pellucida (ZP3) and to investigate the mechanisms underlying the action. METHODS: After randomization, POF was induced in the model mice by immunization with ZP3. One week later, mice received low (8.1 mg/kg), moderate (16.2 mg/kg) and high (32.4 mg/kg) doses of BSJPP by gastrogavage once daily for 90 days. Premarin (0.03 mg/kg) served as the positive group. Serum samples were collected 1 week after the last dose and stored at -20 for analysis. After cervical dislocation, the uterus and ovaries were collected aseptically for evaluation by histological assessment, scanning electron microscopy, immunohistochemical staining, and Western blot and reverse transcription-polymerase chain reaction analyses. RESULTS: Serum E2 levels in POF model mice were decreased, whereas follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were dramatically increased. Serum levels of E2, LH and FSH were reduced in POF model mice treated with BSJPP (moderate and high doses) and premarin. Anti-bone morphogenetic protein 15 (BMP-15) and connexin 43 (Cx43) were repressed in autoimmune POF model mice, whereas high expression was observed in control mice and those treated with BSJPP (moderate and high doses) and premarin. CONCLUSION: BSJPP is effective in treating ZP3-induced POF in mice and the increase in the expression of BMP-15 and Cx43 may be implicated in the mechanism underpinning the action.