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Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, Western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also used. Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in patients with enteritis.NEW & NOTEWORTHY We uncover the pivotal role of miR-192-5p in fortifying intestinal barriers amidst inflammation. Reduced miR-192-5p levels correlated with compromised gut integrity during inflammation. Notably, boosting miR-192-5p reversed gut damage by enhancing autophagy via suppressing Rictor, offering a potential therapeutic strategy for fortifying the intestinal barrier and alleviating inflammation in patients with enteritis.
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Autofagia , Enteritis , Mucosa Intestinal , MicroARNs , Proteína Asociada al mTOR Insensible a la Rapamicina , MicroARNs/metabolismo , MicroARNs/genética , Animales , Proteína Asociada al mTOR Insensible a la Rapamicina/metabolismo , Proteína Asociada al mTOR Insensible a la Rapamicina/genética , Ratones , Mucosa Intestinal/metabolismo , Humanos , Enteritis/metabolismo , Enteritis/genética , Enteritis/patología , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/patología , Colitis/genética , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , MasculinoRESUMEN
Objective: The Obturator Functioning Scale (OFS) is a scale without formal measures of validity in any language. This study aimed to translate and adapt the OFS from English to Chinese and check its reliability and validity in Chinese-speaking patients with obturator prostheses after cancer-related maxillectomy. Methods: The 15-item Chinese preversion of the OFS was completed by 133 patients in three tertiary stomatological hospitals. Of these, 41 completed it again one week after the first measurement. The patients also completed the Chinese version of the University of Washington quality of life scale (UW-QOL, Version 4). Results: Item 12 ("upper lip feels numb") was deleted to achieve a better statistical fit. The 14-item Chinese version of the OFS (OFS-Ch) demonstrated high internal consistency (Cronbach's alpha = 0.908). The test-retest reliability coefficients for most items exceeded 0.90, indicating substantial reproducibility. Confirmatory factor analysis found that the scale consisted of three correlated factors: 1) eating (four items), 2) speech (five items), and 3) other problems (five items). This explained 70.2 % of the total variance using exploratory factor analysis. The scale was significantly convergent and discriminant and could validly discriminate between patients with Brown I and IId maxillary defects. Conclusions: Our results showed that the OFS-Ch scale is a valid tool for evaluating oral dysfunction and satisfaction with appearance for patients with the obturator prosthesis and identifying those at risk of poor obturator function in clinical settings.
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Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.
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Mitocondrias , Folículo Ovárico , Zinc , Femenino , Zinc/deficiencia , Zinc/metabolismo , Folículo Ovárico/metabolismo , Folículo Ovárico/crecimiento & desarrollo , Folículo Ovárico/efectos de los fármacos , Mitocondrias/metabolismo , Animales , Autofagia , Oocitos/metabolismo , Oocitos/efectos de los fármacos , Oocitos/crecimiento & desarrollo , Hormona Antimülleriana/metabolismo , Estrés Oxidativo , Ratones , Apoptosis , HumanosRESUMEN
Dual-ion batteries (DIBs) present great application potential in low-temperature energy storage scenarios due to their unique dual-ion working mechanism. However, at low temperatures, the insufficient electrochemical oxidation stability of electrolytes and depressed interfacial compatibility impair the DIB performance. Here, we design a variant-localized high-concentration solvation structure for universal low-temperature electrolytes (ν-LHCE) without the phase separation via introducing an extremely weak-solvating solvent with low energy levels. The unique solvation structure gives the ν-LHCE enhanced electrochemical oxidation stability. Meanwhile, the extremely weak-solvating solvent can competitively participate in the Li+-solvated coordination, which improves the Li+ transfer kinetics and boosts the formation of robust interphases. Thus, the ν-LHCE electrolyte not only has a good high-voltage stability of >5.5â V and proper Li+ transference number of 0.51 but also shows high ionic conductivities of 1 mS/cm at low temperatures. Consequently, the ν-LHCE electrolyte enables different types of batteries to achieve excellent long-term cycling stability and good rate capability at both room and low temperatures. Especially, the capacity retentions of the DIB are 77.7 % and 51.6 %, at -40 °C and -60 °C, respectively, indicating great potential for low-temperature energy storage applications, such as polar exploration, emergency communication equipment, and energy storage station in cold regions.
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Sodium-based dual ion batteries (SDIBs) have garnered significant attention as novel energy storage devices offering the advantages of high-voltage and low-cost. Nonetheless, conventional electrolytes exhibit low resistance to oxidation and poor compatibility with electrode materials, resulting in rapid battery failure. In this study, for the first time, a chlorination design of electrolytes for SDIB, is proposed. Using ethyl methyl carbonate (EMC) as a representative, chlorine (Cl)-substituted EMC not only demonstrates increased oxidative stability ascribed to the electron-withdrawing characteristics of chlorine atom, electrolyte compatibility with both the cathode and anode is also greatly improved by forming Cl-containing interface layers. Consequently, a discharge capacity of 104.6 mAh g-1 within a voltage range of 3.0-5.0 V is achieved for Na||graphite SDIB that employs a high graphite cathode mass loading of 5.0 mg cm-2, along with almost no capacity decay after 900 cycles. Notably, the Na||graphite SDIB can be revived for an additional 900 cycles through the replacement of a fresh Na anode. As the mass loading of graphite cathode increased to 10 mg cm-2, Na||graphite SDIB is still capable of sustaining over 700 times with ≈100% capacity retention. These results mark the best outcome among reported SDIBs. This study corroborates the effectiveness of chlorination design in developing high-voltage electrolytes and attaining enduring cycle stability of Na-based energy storage devices.
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Organics are gaining significance as electrode materials due to their merits of multi-electron reaction sites, flexible rearrangeable structures and redox reversibility. However, organics encounter finite electronic conductivity and inferior durability especially in organic electrolytes. To circumvent above barriers, we propose a novel design strategy, constructing conductive network structures with extended π-π superposition effect by manipulating intermolecular interaction. Tetralithium 1,4,5,8-naphthalenetetracarboxylate (LNTC) interwoven by carbon nanotubes (CNTs) forms LNTC@CNTs composite firstly for Li-ion storage, where multiple conjugated carboxyls contribute sufficient Li-ion storage sites, the unique network feature enables electrolyte and charge mobility conveniently combining electron delocalization in π-conjugated system, and the enhanced π-π superposition effect between LNTC and CNTs endows laudable structural robustness. Accordingly, LNTC@CNTs maintain an excellent Li-ion storage capacity retention of 96.4 % after 400â cycles. Electrochemical experiments and theoretical simulations elucidate the fast reaction kinetics and reversible Li-ion storage stability owing to the electron delocalization and π-π superposition effect, while conjugated carboxyls are reversibly rearranged into enolates during charging/discharging. Consequently, a dual-ion battery combining this composite anode and expanded graphite cathode exhibits a peak specific capacity of 122â mAh g-1 and long cycling life with a capacity retention of 84.2 % after 900â cycles.
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The acquisition of stable and high-areal-capacity S cathodes over 10 mA h cm-2 is a critical and indispensable step to realize the high energy density configuration. However, increasing the areal capacity of S cathodes often deteriorates the specific capacity and stability due to the aggravated dissolution of S and diffusion of solvable polysulfides in the thick electrode. Herein, the design of a freestanding composite cathode that leverages 3D covalent binding sites and chemical adsorption environment to offer dissolution-limiting and diffusion-blocking functions of S species is reported. By employing this architecture, the coin cell exhibits excellent cycling stability and an exceptional specific capacity of 1444.3 mA h g-1 (13 mA h cm-2), and the pouch cell configuration manifests a noteworthy areal capacity exceeding 11 mA h cm-2. This performance is coupled with excellent flexibility, demonstrated through consecutive bending cycle tests, even at a sulfur loading of 9.00 mg cm-2. This study lays the foundation for the development of flexible Li-S batteries with increased loading capacities and exceptional performance.
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The surface of AISI 52100 steel was pre-treated by laser remelting with different powers, and the vanadizing layer were prepared on remelted steel by pack cementation. The microstructure and properties of vanadizing layer were investigated by XRD, microhardness tester, metallographic microscope, scanning electron microscope, energy dispersive spectrometer, friction and wear tester. The critical load Lc was determined by observing the micro-scratch morphology of scratches through micro-scratch experiments, and its wear performance was studied. The results show that the hardness of remelting zone increase with the increase of laser power. When the laser power is 500 W, the microhardness is 424.6 HV0.2. The vanadizing layer formed on the remelting surfaces is uniform and dense. The layers are mainly composed of VCx phase and α-Fe/α'-Fe phase, the VC phase has the preferred orientation of (200) and (111) planes. There is a good metallurgical bonding between the vanadizing layer and the steelï¼ and the thickness is 2.7 µm-12.15 µm, the microhardness is 2050.7 HV0.2-2350.9 HV0.2. When the laser remelting power is 300 W, the vanadizing layer is better in thickness, microhardness and average friction coefficient, the bonding force Lc between the vanadizing layer and the substrate is about 41.59 N, and the main failure mode is the spalling of the vanadizing layer. It can be concluded that laser remelting pre-treatment can greatly improve the hardness and wear resistance.
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Glutamate dehydrogenase 1 (GLUD1) is an important enzyme in glutamine metabolism. Previously, we found GLUD1 was down-regulated in tumor tissues of hepatocellular carcinoma (HCC) patients by proteomics study. To explore its role in the progression of HCC, the expressional level of GLUD1 was firstly examined and presented as that both the protein and mRNA levels were down-regulated in tumor tissues compared to the normal liver tissues. GLUD1 overexpression significantly inhibited HCC cells proliferation, migration, invasion and tumor growth both in vitro and in vivo, while GLUD1 knocking-down promoted HCC progression. Metabolomics study of GLUD1 overexpressing and control HCC cells showed that 129 differentially expressed metabolites were identified, which mainly included amino acids, bases, and phospholipids. Moreover, metabolites in mitochondrial oxidative phosphorylation system (OXPHOS) were differentially expressed in GLUD1 overexpressing cells. Mechanistic studies showed that GLUD1 overexpression enhanced mitochondrial respiration activity and reactive oxygen species (ROS) production. Excessive ROS lead to mitochondrial apoptosis that was characterized by increased expression levels of p53, Cytochrome C, Bax, Caspase 3 and decreased expression level of Bcl-2. Furthermore, we found that the p38/JNK MAPK pathway was activated in GLUD1 overexpressing cells. N-acetylcysteine (NAC) treatment eliminated cellular ROS and blocked p38/JNK MAPK pathway activation, as well as cell apoptosis induced by GLUD1 overexpression. Taken together, our findings suggest that GLUD1 inhibits HCC progression through regulating cellular metabolism and oxidative stress state, and provide that ROS generation and p38/JNK MAPK pathway activation as promising methods for HCC treatment.
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INTRODUCTION: This study aimed to investigate the imaging features, clinical characteristics and neonatal outcomes of pregnancy luteoma. MATERIAL AND METHODS: We retrospectively analyzed patients with pregnancy luteoma admitted to the First Affiliated Hospital of Sun Yat-sen University between January 2003 and December 2022. We recorded their imaging features, clinical characteristics and neonatal outcomes. Additionally, we reviewed relevant studies in the field. RESULTS: In total, 127 cases were identified, including eight from our hospital and 119 from the literature. Most patients (93/127, 73.23%) were of reproductive age, 20-40 years old, and 66% were parous. Maternal hirsutism or virilization (such as deepening voice, acne, facial hair growth and clitoromegaly) was observed in 29.92% (38/127), whereas 59.06% of patients (75/127) were asymptomatic. Abdominal pain was reported in 13 patients due to compression, torsion or combined ectopic pregnancy. The pregnancy luteomas, primarily discovered during the third trimester (79/106, 74.53%), varied in size ranging from 10 mm to 20 cm in diameter. Seventy-five cases were incidentally detected during cesarean section or postpartum tubal ligation, and 39 were identified through imaging or physical examination during pregnancy. Approximately 26.61% of patients had bilateral lesions. The majority of pregnancy luteomas were solid and well-defined (94/107, 87.85%), with 43.06% (31/72) displaying multiple solid and well-circumscribed nodules. Elevated serum androgen levels (reaching values between 1.24 and 1529 times greater than normal values for term gestation) were observed in patients with hirsutism or virilization, with a larger lesion diameter (P < 0.001) and a higher prevalence of bilateral lesions (P < 0.001). Among the female infants born to masculinized mothers, 68.18% (15/22) were virilized. Information of imaging features was complete in 22 cases. Ultrasonography revealed well-demarcated hypoechoic solid masses with rich blood supply in 12 of 19 cases (63.16%). Nine patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and six exhibited solid masses, including three with multi-nodular solid masses. CONCLUSIONS: Pregnancy luteomas mainly manifest as well-defined, hypoechoic and hypervascular solid masses. MRI and CT are superior to ultrasonography in displaying the imaging features of multiple nodules. Maternal masculinization and solid masses with multiple nodules on imaging may help diagnose this rare disease.
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Luteoma , Neoplasias Ováricas , Recién Nacido , Femenino , Humanos , Embarazo , Adulto Joven , Adulto , Luteoma/diagnóstico por imagen , Neoplasias Ováricas/patología , Hirsutismo/diagnóstico , Cesárea , Estudios Retrospectivos , Virilismo/etiología , Virilismo/diagnósticoRESUMEN
During abscisic acid (ABA) signaling, reversible phosphorylation controls the activity and accumulation of class III SNF1-RELATED PROTEIN KINASE 2s (SnRK2s). While protein phosphatases that negatively regulate SnRK2s have been identified, those that positively regulate ABA signaling through SnRK2s are less understood. In this study, Arabidopsis thaliana mutants of Clade E Growth-Regulating 1 and 2 (EGR1/2), which belong to the protein phosphatase 2C family, exhibited reduced ABA sensitivity in terms of seed germination, cotyledon greening, and ABI5 accumulation. Conversely, overexpression increased these ABA-induced responses. Transcriptomic data revealed that most ABA-regulated genes in egr1 egr2 plants were expressed at reduced levels compared with those in Col-0 after ABA treatment. Abscisic acid up-regulated EGR1/2, which interact directly with SnRK2.2 through its C-terminal domain I. Genetic analysis demonstrated that EGR1/2 function through SnRK2.2 during ABA response. Furthermore, SnRK2.2 de-phosphorylation by EGR1/2 was identified at serine 31 within the ATP-binding pocket. A phospho-mimic mutation confirmed that phosphorylation at serine 31 inhibited SnRK2.2 activity and reduced ABA responsiveness in plants. Our findings highlight the positive role of EGR1/2 in regulating ABA signaling, they reveal a new mechanism for modulating SnRK2.2 activity, and provide novel insight into how plants fine-tune their responses to ABA.
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Proteínas de Arabidopsis , Arabidopsis , Fosforilación , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Serina/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
SARS-CoV-2 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what causes these conformational changes or how they influence the spike's functions. Here, we show that Lys417 in the RBD plays dual roles in the spike's structure: it stabilizes the closed conformation of the trimeric spike by mediating inter-spike-subunit interactions; it also directly interacts with ACE2 receptor. Hence, a K417V mutation has opposing effects on the spike's function: it opens up the spike for better ACE2 binding while weakening the RBD's direct binding to ACE2. The net outcomes of this mutation are to allow the spike to bind ACE2 with higher probability and mediate viral entry more efficiently, but become more exposed to neutralizing antibodies. Given that residue 417 has been a viral mutational hotspot, SARS-CoV-2 may have been evolving to strike a balance between infection potency and immune evasion, contributing to its pandemic spread.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Unión ProteicaRESUMEN
Exsolution of metal nanoparticles (NPs) on the surface of perovskite oxides is a promising approach for developing advanced catalytic materials through a "bottom-up" design strategy. Under a nonreducing ambient atmosphere utilizing pulsed electric current (PEC) treatment to promote the exsolution of perovskite oxides effectively overcomes the limitations inherent in conventional high-temperature vapor phase reduction (HTVPR) in situ exsolution methods. This paper presents the successful synthesis of (La0.7Sr0.3)0.8Ti0.93Ni0.07O3 (LSTN) perovskite oxide and (La0.7Sr0.3)0.8Ti0.93Co0.07O3 (LSTC) perovskite oxide using the sol-gel method, followed by PEC treatment at 600 V, 3 Hz, and 90 s. Utilizing various characterization techniques to confirm that PEC treatment can promote the exsolution of Co and Ni NPs under a nonreducing ambient atmosphere, the results indicated that the exsolved perovskite oxides exhibited significantly improved electrochemical properties. Furthermore, compared to the LSTN-PEC, LSTC-PEC demonstrates a lower onset potential of 1.504 V, a Tafel slope of 87.16 mV dec-1, lower impedance, higher capacitance, superior catalytic activity, and long-term stability.
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Nitric oxide (NO) is a key signaling molecule affecting the response of plants to salt stress; however, the underlying molecular mechanism is poorly understood. In this study, we conducted a phenotype analysis and found that the small GTPase RABG3E (RAB7) promotes salt tolerance in Arabidopsis thaliana. NO promotes the S-nitrosylation of RAB7 at Cys-171, which in turn helps maintain the ion balance in salt-stressed plants. Furthermore, the S-nitrosylation of RAB7 at Cys-171 enhances the enzyme's GTPase activity, thereby promoting vesicle trafficking and increasing its interaction with phosphatidylinositol phosphates-especially phosphatidylinositol-4-phosphate (PI4P). Exogenously applied PI4P increases vesicle trafficking and promotes salt tolerance depending on the S-nitrosylation of RAB7 at Cys-171. These findings illustrate a unique mechanism in salt tolerance, by which NO regulates vesicle trafficking and ion homeostasis through the S-nitrosylation of RAB7 and its interaction with PI4P.
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Proteínas de Arabidopsis , Arabidopsis , Tolerancia a la Sal , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Transducción de Señal , Óxido NítricoRESUMEN
Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease associated with CD4+ Th1 and Th17 cell immune responses. Tumour necrosis factor-associated factor 5 (TRAF5) deficiency has been shown to aggravate DSS-induced colitis. However, the potential role of TRAF5 in regulating CD4+ T cell immune responses in the pathogenesis of IBD remains unclear. TRAF5-/- CD4+ CD45RBhigh T cells and WT CD4+ CD45RBhigh T cells were transferred to Rag2-/- mice via intravenous (i.v.) tail injection, respectively, to establish a chronic colitis model. Adeno-associated virus (AAV)-mediated gene knockout technique was used to knock out runt-associated transcription factor 1 (Runx1) expression in vivo. Specific cytokines of Th1 and Th17 cells were detected by quantitative RT-PCR, immunohistochemistry, ELISA, and flow cytometry. In T-cell transfer colitis mice, the Rag2-/- mice reconstituted with TRAF5-/- CD4+ CD45RBhigh T cells showed more severe intestinal inflammation than the WT control group, which was characterised by increased expression of INF-γ, TNF-α, IL-17a. Furthermore, we found that the INF-γ+ CD4+ , IL17a+ CD4+ , and INF-γ+ IL17a+ CD4+ T cells in the intestinal mucosa of Rag2-/- mice reconstituted with TRAF5-/- CD4+ CD45RBhigh T cells were significantly higher than those of the WT control group by flow cytometry. Mechanistically, knockout Runx1 inhibited the differentiation of TRAF5-/- CD4+ T cells into Th1 and Th17 cells in the intestinal mucosa of T-cell transfer colitis mice. TRAF5 regulates Th1 and Th17 cell differentiation and immune response through Runx1 to participate in the pathogenesis of colitis. Thus targeting TRAF5 in CD4+ T cells may be a novel treatment for IBD.
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Colitis , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Células Th17 , Factor 5 Asociado a Receptor de TNF/metabolismo , Mucosa Intestinal , Inmunidad , Células TH1 , Ratones Endogámicos C57BL , Linfocitos T CD4-Positivos , Ratones Noqueados , Modelos Animales de Enfermedad , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismoRESUMEN
Prussian blue analogs (PBAs) are promising catalysts for green hydrogen production. However, the rational design of high-performing PBAs is challenging, which requires an in-depth understanding of the catalytic mechanism. Here FeMn@CoNi core-shell PBAs are employed as precursors, together with Se powders, in low-temperature pyrolysis in an argon atmosphere. This synthesis method enables the partial dissociation of inner FeMn PBAs that results in hollow interiors, Ni nanoparticles (NPs) exsolution to the surface, and Se incorporation onto the PBA shell. The resulting material presents ultralow oxygen evolution reaction (OER) overpotential (184 mV at 10 mA cm-2 ) and low Tafel slope (43.4 mV dec-1 ), outperforming leading-edge PBA-based electrocatalysts. The mechanism responsible for such a high OER activity is revealed, assisted by density functional theory (DFT) calculations and the surface examination before and after the OER process. The exsolved Ni NPs are found to help turn the PBAs into Se-doped core-shell metal oxyhydroxides during the OER, in which the heterojunction with Ni and the Se incorporation are combined to improve the OER kinetics. This work shows that efficient OER catalysts could be developed by using a novel synthesis method backed up by a sound understanding and control of the catalytic pathway.
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BACKGROUND: As one of the most commonly used folk medicines in "Dai" ethno-medicine system, Alstonia scholaris (l.) R. Br. has also been used for treat "water related diseases", such as chronic kidney disease. However, few study was reported for it on the intervention of chronic glomerulonephritis (CGN). PURPOSE: To investigate the effect and potential mechanism of indole alkaloids from A. scholaris leaves in ICR mice with adriamycin nephropathy, as well as providing experimental evidence for the further application. METHODS: ICR Mice were selected for injections of adriamycin (ADR) to induce the CGN model and administered total alkaloids (TA) and four main alkaloids continuously for 42 and 28 days, respectively. The pharmacological effects were indicated by serum, urine, and renal pathological observations. The targets and pathways of indole alkaloids on CGN intervention were predicted using the network pharmacology approach, and the immortalized mice glomerular podocyte (MPC5) cells model stimulated by ADR was subsequently selected to further verify this by western blotting and RT-qPCR methods. RESULTS: TA and four major compounds dramatically reduced the levels of urinary protein, serum urea nitrogen (BUN), and creatinine (CRE) in ADR - induced CGN mice, while increasing serum albumin (ALB) and total protein (TP) levels as well as ameliorating kidney damage. Moreover, four alkaloids effected on 33 major target proteins and 153 pathways in the CGN, among which, PI3K-Akt as the main pathway, an important pathway for kidney protection by network pharmacology prediction, and then the four target proteins - HRAS, CDK2, HSP90AA1, and KDR were screened. As a result, Val-and Epi can exert a protective effect on ADR-stimulated MPC5 cells injury at a concentration of 50 µM. Furthermore, the proteins and RNA expression of HRAS, HSP90AA1, and KDR were down-regulated, and CDK2 was up-regulated after the intervention of Val-and Epi, which were supported by Western blotting and RT-qPCR. Additionally, Val-and Epi inhibited ROS production in the MPC5 cells model. CONCLUSION: This study is the first to confirm the potential therapeutic effect of alkaloids from A. scholaris on CGN. TA with major bioactive components (vallesamine and 19epi-scholaricine) could exert protective effects against the ADR-induced CGN by regulating four key proteins: HRAS, CDK2, HSP90AA1, and KDR of the PI3K-Akt pathway.
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Alcaloides , Alstonia , Glomerulonefritis , Ratones , Animales , Ratones Endogámicos ICR , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Alcaloides Indólicos/farmacología , Alcaloides/farmacología , Alcaloides/uso terapéutico , Glomerulonefritis/inducido químicamente , Glomerulonefritis/tratamiento farmacológicoRESUMEN
Molecular Sierpinski triangles (STs), a family of elegant and well-known fractals, can be prepared on surfaces with atomic precision. Up to date, several kinds of intermolecular interactions such as hydrogen bond, halogen bond, coordination, and even covalent bond have been employed to construct molecular STs on metal surfaces. Herein a series of defect-free molecular STs have been fabricated via electrostatic attraction between potassium cations and electronically polarized chlorine atoms in 4,4â³-dichloro-1,1':3',1â³-terphenyl (DCTP) molecules on Cu(111) and Ag(111). The electrostatic interaction is confirmed both experimentally by scanning tunneling microscopy and theoretically by density functional theory calculations. These findings illustrate that electrostatic interaction can serve as an efficient driving force to construct molecular fractals, which enriches our toolbox for the bottom-up fabrication of complex functional supramolecular nanostructures.
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BACKGROUND AND PURPOSE: Emerging researches have regarded serum chloride as a capable predictor of mortality in liver cirrhosis. We aim to investigate the clinical role of admission chloride in cirrhotic patients with esophagogastric varices receiving transjugular intrahepatic portosystemic shunt (TIPS), which is unclear. METHODS: We retrospectively analyzed data of cirrhotic patients with esophagogastric varices undergoing TIPS in Zhongnan Hospital of Wuhan University. Mortality outcome was obtained by following up for 1-year after TIPS. Univariate and multivariate Cox regression were used to identify independent predictors of 1-year mortality post-TIPS. The receiver operating characteristic (ROC) curves were adopted to assess the predictive ability of the predictors. In addition, log-rank test and Kaplan-Meier (KM) analyses were employed to evaluate the prognostic value of predictors in the survival probability. RESULTS: A total of 182 patients were included ultimately. Age, fever symptom, platelet-to lymphocyte-ratio (PLR), lymphocyte-to-monocyte ratio (LMR), total bilirubin, serum sodium, chloride, and Child-Pugh score were related to 1-year follow-up mortality. In multivariate Cox regression analysis, serum chloride (HR = 0.823, 95%CI = 0.757-0.894, p < 0.001) and Child-Pugh score (HR = 1.401, 95%CI = 1.151-1.704, p = 0.001) were identified as independent predictors of 1-year mortality. Patients with serum chloride <107.35 mmol/L showed worse survival probability than those with serum chloride ≥107.35 mmol/L no matter with or without ascites (p < 0.05). CONCLUSION: Admission hypochloremia and increasing Child-Pugh score are independent predictors of 1-year mortality in cirrhotic patients with esophagogastric varices receiving TIPS.
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Várices Esofágicas y Gástricas , Derivación Portosistémica Intrahepática Transyugular , Várices , Humanos , Cloruros , Estudios Retrospectivos , Pronóstico , Cirrosis Hepática/complicaciones , Resultado del TratamientoRESUMEN
Current collectors are indispensable parts that provide electron transport and mechanical support of electrode materials in a battery. Nowadays, thin metal foils made of Cu and Al are used as current collectors of lithium batteries, but they do not contribute to the storage capacity. Therefore, decreasing the weight of current collectors can directly enhance the energy density of a battery. However, limited by the requirements of mechanical strength, it is difficult to reduce the weight of metal foils any further. Herein, a new type of current collectors made of 3D metallic glass-fiber fabrics (MGFs), which shows advantages of super-lightweight (2.9-3.2 mg cmâ»2 ), outstanding electrochemical stability for cathodes and anodes of lithium-ion and lithium-metal batteries (LMBs), fire resistance, high strength, and flexibility suitable for roll-to-roll electrode fabrication is reported. The gravimetric energy densities of lithium batteries exhibit improvements of 9-18% by only replacing the metal foils with the MGFs. In addition, MGFs are suitable for the fabrication of flexible batteries. A high-energy-density flexible lithium battery with an outstanding figure of merit of flexible battery (fbFOM ) and flexing stability is demonstrated.