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Aqueous zinc ion batteries (AZIBs) have attracted much attention for their safety, low cost and high theoretical capacity. Nevertheless, Zn dendrites and the adverse reactions such as corrosion, hydrogen evolution and passivation on the anode affect the cycle life and stability of AZIBs. Herein, superabsorbent starch (SS) was employed on Zn foil to form an artificial interface protection layer, which inhibited the formation of dendrites by guiding the uniform deposition of Zn2+. SS with a large amount of oxygen-containing functional group is superabsorbent, which can attract the active water around the hydrated Zn2+, promoting the desolvation process of the hydrated Zn2+ and significantly inhibiting the occurrence of hydrogen evolution reaction. In addition, the inherent pore structure of the SS artificial interfacial layer can induce uniform nucleation of Zn2+ and inhibit the dendrites growth. Moreover, compared to bare Zn//MnO2 cell (44.1 %), the capacity retention of Zn@SS//MnO2 cell remained as high as 87.8 % after 1000 cycles at 1.5 A g-1. The simple method provided a new method for the rapid development of AZIBs.
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Clusteroluminescence (CL) materials without largely conjugated structures have gained significant attention due to their unique photophysical properties and potential in bioimaging. However, low luminescence efficiency and short emission wavelength limit their development. This work designs three luminogens with CL properties (CLgens) by introducing n-electron-involved through-space conjugation (TSC) into diarylmethane. Apart from single-photon excited long-wavelength (688 nm) and high-efficiency (29%) CL, two-photon clusteroluminescence (TPCL) is successfully achieved in such small luminogens with only two isolated heteroatomic units. TSC stabilized in the aggregate state has been proven to realize efficient spatial electron delocalization similar to conventionally conjugated compounds. Encouraged by the excellent TPCL properties, two-photon imaging of blood vessels in vivo and biocompatibility verification utilizing CLgens are also achieved. This work illustrates the essential role of TSC in promoting nonlinear optical properties of CLgens and may facilitate further design and development of the next generation of bioprobes with excellent biocompatibility.
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Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.
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Rapid and scientific quality evaluation is a hot topic in the research of food and medicinal plants. With the increasing popularity of derivative products from Eucommia ulmoides leaves, quality and safety have attracted public attention. The present study utilized multi-source data and traditional machine learning to conduct geographical traceability and content prediction research on Eucommia ulmoides leaves. Explored the impact of different preprocessing methods and low-level data fusion strategy on the performance of classification and regression models. The classification analysis results indicated that the partial least squares discriminant analysis (PLS-DA) established by low-level fusion of two infrared spectroscopy techniques based on first derivative (FD) preprocessing was most suitable for geographical traceability of Eucommia ulmoides leaves, with an accuracy rate of up to 100 %. Through regression analysis, it was found that the preprocessing methods and data blocks applicable to the four chemical components were inconsistent. The optimal partial least squares regression (PLSR) model based on aucubin (AU), geniposidic acid (GPA), and chlorogenic acid (CA) had a residual predictive deviation (RPD) value higher than 2.0, achieving satisfactory predictive performance. However, the PLSR model based on quercetin (QU) had poor performance (RPD = 1.541) and needed further improvement. Overall, the present study proposed a strategy that can effectively evaluate the quality of Eucommia ulmoides leaves, while also providing new ideas for the quality evaluation of food and medicinal plants.
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Eucommiaceae , Plantas Medicinales , Eucommiaceae/química , Plantas Medicinales/química , Quercetina/análisis , Geografía , Análisis de los Mínimos Cuadrados , Hojas de la Planta/químicaRESUMEN
Achieving a highly robust zinc (Zn) metal anode is extremely important for improving the performance of aqueous Zn-ion batteries (AZIBs) for advancing "carbon neutrality" society, which is hampered by the uncontrollable growth of Zn dendrite and severe side reactions including hydrogen evolution reaction, corrosion, and passivation, etc. Herein, an interlayer containing fluorinated zincophilic covalent organic framework with sulfonic acid groups (COF-S-F) is developed on Zn metal (Zn@COF-S-F) as the artificial solid electrolyte interface (SEI). Sulfonic acid group (- SO3H) in COF-S-F can effectively ameliorate the desolvation process of hydrated Zn ions, and the three-dimensional channel with fluoride group (-F) can provide interconnected channels for the favorable transport of Zn ions with ion-confinement effects, endowing Zn@COF-S-F with dendrite-free morphology and suppressed side reactions. Consequently, Zn@COF-S-F symmetric cell can stably cycle for 1,000 h with low average hysteresis voltage (50.5 mV) at the current density of 1.5 mA cm-2. Zn@COF-S-F|MnO2 cell delivers the discharge specific capacity of 206.8 mAh g-1 at the current density of 1.2 A g-1 after 800 cycles with high-capacity retention (87.9%). Enlightening, building artificial SEI on metallic Zn surface with targeted design has been proved as the effective strategy to foster the practical application of high-performance AZIBs.
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Recently, lanthanide (Ln) luminescent nanocrystals have attracted increasing attention in various fields such as biomedical imaging, lasers, and anticounterfeiting. However, due to the forbidden 4f-4f transition of lanthanide ions, the absorption cross-section and luminescence brightness of lanthanide nanocrystals are limited. To address the challenge, we constructed an optical oscillator-like system to repeatedly simulate lanthanide nanocrystals to enhance the absorption efficiency of lanthanide ions on excitation photons. In this optical system, the upconversion luminescence (UCL) of Tm3+ emission of ~450 nm excited by a 980 nm laser can be amplified by a factor beyond 104 . The corresponding downshifting luminescence of Tm3+ at 1460 nm was enhanced by three orders of magnitude. We also demonstrated that the significant luminescence enhancement in the designed optical oscillator-like system was general for various lanthanide nanocrystals including NaYF4 :Yb3+ /Ln3+ , NaErF4 @NaYF4 and NaYF4 :Yb3+ /Ln3+ @NaYF4 :Yb3+ @NaYF4 (Ln = Er, Tm, Ho) regardless of the wavelengths of excitation sources (808 and 980 nm). The mechanism study revealed that both elevated laser power in the optical system and multiple excitations on lanthanide nanocrystals were the main reason for the luminescence amplification. Our findings may benefit the future development of low-threshold upconversion and downshifting luminescence of lanthanide nanocrystals and expand their applications.
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Elementos de la Serie de los Lantanoides , Nanopartículas , Elementos de la Serie de los Lantanoides/química , Luminiscencia , Nanopartículas/química , Luz , IonesRESUMEN
BACKGROUND: Wandering spleen is rare clinically. It is characterized by displacement of the spleen in the abdominal and pelvic cavities and can have congenital or acquired causes. Wandering spleen involves serious complications, such as spleen torsion. The clinical symptoms range from asymptomatic abdominal mass to acute abdominal pain. Surgery is required after diagnosis. Cases of wandering spleen torsion with portal vein thrombosis (PVT) are rare. There is no report on how to eliminate PVT in such cases. CASE SUMMARY: Ultrasound and computed tomography revealed a diagnosis of wandering spleen torsion with PVT in a 31-year-old woman with a history of childbirth 16 mo previously who received emergency treatment for upper abdominal pain. She recovered well after splenectomy and portal vein thrombectomy combined with continuous anticoagulation, and the PVT disappeared. CONCLUSION: Rare and nonspecific conditions, such as wandering splenic torsion with PVT, must be diagnosed and treated early. Patients with complete splenic infarction require splenectomy. Anticoagulation therapy and individualized management for PVT is feasible.
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The mechanism of extracellular matrix metalloproteinase inducer (EMMPRIN) in the regulation of liver fibrosis has not been clarified. This study aims to investigate the role of EMMPRIN S-nitrosylation (SNO) in the regulation of hepatic stellate cell (HSC) migration and matrix metalloproteinase (MMP) activities in liver fibrosis. The results from the tissue microarrays and rat/mouse liver tissues suggest that EMMPRIN mRNA and protein levels in the fibrotic livers are lower than those in the corresponding normal control livers, but higher SNO level of EMMPRIN in fibrotic liver area was shown by immunohistochemistry, immunofluorescence staining, and biotin-switch assay conversely in vivo. Primary EMMPRIN comes from hepatocytes and liver sinus epithelial cells (LSECs) rather than quiescent HSCs. To mimic the uptake of extrinsic EMMPRIN, supernatants from mouse primary hepatocytes/293 cells transfected with EMMPRIN wild-type plasmids (WT) and EMMPRIN SNO site (cysteine 87) mutation plasmids (MUT) were collected and added to JS-1/LX2 cell medium. The MUT EMMPRIN diminishes SNO successfully, enhances the activities of MMP2 and MMP9, and subsequently increases HSC migration. In conclusion, SNO of EMMPRIN influences HSC migration and MMP activities in liver fibrosis. This finding may shed light on the possible regulatory mechanism of MMPs in ECM accumulation in liver fibrosis.
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Basigina , Cirrosis Hepática , Animales , Ratones , Ratas , Basigina/genética , Basigina/metabolismo , Células Epiteliales/metabolismo , Hepatocitos/metabolismo , Cirrosis Hepática/metabolismo , Células Estrelladas Hepáticas/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismoRESUMEN
CD97 (ADGRE5) is an adhesion G protein-coupled receptor (aGPCR) which plays crucial roles in immune system and cancer. However, the mechanism of CD97 activation and the determinant of G13 coupling selectivity remain unknown. Here, we present the cryo-electron microscopy structures of human CD97 in complex with G13, Gq, and Gs. Our structures reveal the stalk peptide recognition mode of CD97, adding missing information of the current tethered-peptide activation model of aGPCRs. For instance, a revised "FXφφφ" motif and a framework of conserved aromatic residues in the ligand-binding pocket. Importantly, structural comparisons of G13, Gq, and Gs engagements of CD97 reveal key determinants of G13 coupling selectivity, where a deep insertion of the α helix 5 and a closer contact with the transmembrane helix 6, 5, and 3 dictate coupling preferences. Taken together, our structural study of CD97 provides a framework for understanding CD97 signaling and the G13 coupling selectivity.
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Proteínas de Unión al GTP , Receptores Acoplados a Proteínas G , Humanos , Microscopía por Crioelectrón , Péptidos , Receptores Acoplados a Proteínas G/metabolismo , Transducción de SeñalRESUMEN
Early intervention of liver fibrosis can prevent its further irreversible progression. Both excess reactive oxygen species (ROS) and transforming growth factor beta(TGF-ß)/drosophila mothers against decapentaplegic protein (SMADS) pathway balance disorder promote the progression of hepatic stellate cell (HSC) activation, but existing therapeutic strategies failed to focus on those two problems. A new biomimetic mesoporous polydopamine nandrug (MPO) was constructed for liver fibrosis therapy with multiple targets and reliable biosafety. The MPO was formed by mesoporous polydopamine (mPDA) which has the effect of ROS elimination and encapsulated with anti-fibrotic drug -oxymatrine (OMT) which can intervene liver fibrosis targeting TGF-ß/SMADSpathway. Particularly, the nanodrug was completed by macrophage-derived exosome covering. The MPO was confirmed to possess a desired size distribution with negative zeta potential and exhibite strong ROS scavenger ability. Besides, in vitro studies, MPO showed efficient endocytosis and superior intracellular ROS scavenging without cytotoxicity; in vivo studies, MPO effectively cleared the excessive ROS in liver tissue and balanced the TGF-ß/SMADS pathways, which in turn inhibited HSC activation and showed superior anti-liver fibrosis therapeutic efficiency with good biological safety. Taken together, this work showed highlights the great potential of the MPO for ameliorating liver fibrosis via ROS elimination and TGF-ß/SMADS balancing.
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Nanopartículas , Factor de Crecimiento Transformador beta , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Fibrosis , Nanopartículas/uso terapéutico , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Moderate caffeine intake decreases the risk of metabolic disorders and all-cause mortality, and the mechanism may be related to its ergogenic actions. Thyroid hormones are vital in metabolic homeostasis; however, their association with caffeine intake has rarely been explored. OBJECTIVE: To investigate the association between caffeine intake and thyroid function. METHODS: We collected data on demographic background, medical conditions, dietary intake, and thyroid function from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Subgroups were classified using two-step cluster analysis, with sex, age, body mass index (BMI), hyperglycemia, hypertension, and cardio-cerebral vascular disease (CVD) being used for clustering. Restrictive cubic spline analysis was employed to investigate potential nonlinear correlations, and multivariable linear regression was used to evaluate the association between caffeine consumption and thyroid function. RESULTS: A total of 2,582 participants were included, and three subgroups with different metabolic features were clustered. In the most metabolically unhealthy group, with the oldest age, highest BMI, and more cases of hypertension, hyperglycemia, and CVD, there was a nonlinear relationship between caffeine intake and serum thyroid stimulating hormone (TSH) level. After adjusting for age, sex, race, drinking, smoking, medical conditions, and micronutrient and macronutrient intake, caffeine intake of less than 9.97 mg/d was positively associated with serum TSH (p = 0.035, standardized ß = 0.155); however, moderate caffeine consumption (9.97-264.97 mg/d) indicated a negative association (p = 0.001, standardized ß = - 0.152). CONCLUSIONS: Caffeine consumption had a nonlinear relationship with serum TSH in people with metabolic disorders, and moderate caffeine intake (9.97 ~ 264.97 mg/d) was positively associated with serum TSH.
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Cafeína , Hipertensión , Glándula Tiroides , Tirotropina , Humanos , Cafeína/efectos adversos , Encuestas Nutricionales , Tirotropina/sangre , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/fisiologíaRESUMEN
Y-box binding protein 1 (YBX1) has been reported to be involved in the transcriptional regulation of various pathophysiological processes, such as inflammation, oxidative stress, and epithelial-mesenchymal transformation. However, its precise role and mechanism in regulating hepatic fibrosis remain unclear. In this study, we aimed to investigate the effects of YBX1 on liver fibrosis and its potential mechanism. The expression of YBX1 in human liver microarray, mice tissues and primary mouse hepatic stellate cells (HSCs) was validated to be upregulated in several hepatic fibrosis models (CCl4 injection, TAA injection, and BDL). Hepatic-specific Ybx1 overexpression exacerbated the liver fibrosis phenotypes in vivo and in vitro. Moreover, the knockdown of YBX1 significantly improved TGF-ß-induced fibrosis in the LX2 cell (a hepatic stellate cell line). Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) of hepatic-specific Ybx1 overexpression (Ybx1-OE) mice with CCl4 injection showed increasing chromatin accessibility than CCl4 only group. Functional enrichments of open regions in the Ybx1-OE group indicated that extracellular matrix (ECM) accumulation, lipid purine metabolism, and oxytocin-related pathways were more accessible in the Ybx1-OE group. Accessible regions of the Ybx1-OE group in the promoter also suggested significant activation of genes related to liver fibrogenesis, such as response to oxidative stress and ROS, lipid localization, angiogenesis and vascular development, and inflammatory regulation. Moreover, we screened and validated the expression of candidate genes (Fyn, Axl, Acsl1, Plin2, Angptl3, Pdgfb, Ccl24, and Arg2), which might be potential targets of Ybx1 in the pathogenesis of liver fibrosis.
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Cromatina , Transducción de Señal , Humanos , Ratones , Animales , Cromatina/metabolismo , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Lípidos , Células Estrelladas Hepáticas/metabolismoRESUMEN
Object: We explored developing an internal validation model to predict the moderate to severe endoscopic activity of ulcerative colitis (UC) patients based on non-invasive or minimally-invasive parameters. Methods: Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and Mayo endoscopic subscore were performed for UC patients who met the criteria from January 2017 to August 2021 through the electronic database of our center. Logistic regression and a least absolute shrinkage and selection operator (Lasso) regression model were performed to screen the risk factors of moderate to severe UC activity. The nomogram was established subsequently. Discrimination of the model was evaluated using the concordance index (c-index), and the calibration plot and 1,000 Bootstrap were used to evaluate the model's performance and conduct internal validation. Results: Sixty-five UC patients were included in this study. According to UCEIS criteria,45 patients were moderate to severe endoscopic activity. 26 potential predictors of UC were analyzed by logistic and Lasso regression showed that vitamin D (Vit D), albumin (ALB), prealbumin (PAB), and fibrinogen (Fbg) were the best predictors of moderate to severe endoscopic activity of UC. We used these 4 variables to develop a dynamic nomogram prediction model. The c-index was 0.860, which means good discrimination. The calibration plot and Bootstrap analysis showed that the prediction model accurately distinguished the moderate to severe endoscopic activity in UC patients. The prediction model was verified using a cohort of UC patients with moderate to severe activity defined by the Mayo endoscopic subscore, and it was found that the model still had good discrimination and calibration (c-index = 0.891). Conclusion: The model containing Vit D, ALB, PAB, and Fbg was a good tool for evaluating UC activity. The model is simple, accessible, and user-friendly, which has broad application prospects in clinical practice.
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Lysophosphatidylserine (LysoPS) is a lipid mediator that induces multiple cellular responses through binding to GPR174. Here, we present the cryo-electron microscopy (cryo-EM) structure of LysoPS-bound human GPR174 in complex with Gs protein. The structure reveals a ligand recognition mode, including the negatively charged head group of LysoPS forms extensive polar interactions with surrounding key residues of the ligand binding pocket, and the L-serine moiety buries deeply into a positive charged cavity in the pocket. In addition, the structure unveils a partially open pocket on transmembrane domain helix (TM) 4 and 5 for a lateral entry of ligand. Finally, the structure reveals a Gs engaging mode featured by a deep insertion of a helix 5 (αH5) and extensive polar interactions between receptor and αH5. Taken together, the information revealed by our structural study provides a framework for understanding LysoPS signaling and a rational basis for designing LysoPS receptor-targeting drugs.
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Receptores Acoplados a Proteínas G , Transducción de Señal , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Ligandos , Microscopía por CrioelectrónRESUMEN
BACKGROUND: Gastrointestinal adverse drug reactions (GADRs) of direct-acting antiviral agents (DAAs) in patients with chronic hepatitis C are underestimated. AIM: This study aimed to comprehensively evaluate the gastrointestinal safety of DAAs in patients with chronic hepatitis C. METHOD: The US FDA Adverse Event Reporting System database was searched for GADR cases reported from 01 to 2012 to 30 September 2021. Twelve DAA types used for hepatitis C virus were included. The top 30 GADRs were assessed based on the use of DAAs, number of cases, and clinical features. A case-non-case disproportionality approach was used to confirm pharmacovigilance signals, whereby reporting odds ratios (ROR) with 95% CI were calculated. RESULTS: Nausea (70.01/1000), diarrhoea (39.10/1000), and vomiting (31.68/1000) accounted for the highest number of cases. The pooled median time-to-onset of the top 30 GADRs was 13 days (Q1-Q3: 2-38) and the proportion of drug discontinuation was 19.17%. The highest number of DAA-related cases involved ledipasvir/sofosbuvir (21.86%), sofosbuvir/velpatasvir (21.77%), and sofosbuvir (13.41%). When DAAs were considered as a class drug, after adjusting for age, sex, concomitant diseases and drugs that potentially induced GADRs, significant RORs for specific GADRs were noted, including abdominal discomfort (1.62, 95% CI 1.32-1.99), constipation (1.54, 95% CI 1.26-1.89), dyspepsia (1.25, 95% CI 1.01-1.55), abdominal distension (1.36, 95% CI 1.05-1.75), faeces discoloured (1.77, 95% CI 1.15-2.73), and gastric ulcer (2.37, 95% CI 1.28-4.41). CONCLUSION: Clinicians should have a deeper understanding of GADRs to improve the gastrointestinal tolerance of patients with chronic hepatitis C.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hepatitis C Crónica , Hepatitis C , Humanos , Sofosbuvir/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Antivirales/uso terapéutico , Farmacovigilancia , Hepatitis C/tratamiento farmacológicoRESUMEN
Adhesion G-protein-coupled receptors (aGPCRs) play key roles in a diversity of physiologies. A hallmark of aGPCR activation is the removal of the inhibitory GAIN domain and the dipping of the cleaved stalk peptide into the ligand-binding pocket of receptors; however, the detailed mechanism remains obscure. Here, we present cryoelectron microscopy (cryo-EM) structures of ADGRL3 in complex with Gq, Gs, Gi, and G12. The structures reveal unique ligand-engaging mode, distinctive activation conformation, and key mechanisms of aGPCR activation. The structures also reveal the uncharted structural information of GPCR/G12 coupling. A comparison of Gq, Gs, Gi, and G12 engagements with ADGRL3 reveals the key determinant of G-protein coupling on the far end of αH5 of Gα. A detailed analysis of the engagements allows us to design mutations that specifically enhance one pathway over others. Taken together, our study lays the groundwork for understanding aGPCR activation and G-protein-coupling selectivity.
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Proteínas de Unión al GTP , Receptores Acoplados a Proteínas G , Ligandos , Microscopía por Crioelectrón , Receptores Acoplados a Proteínas G/metabolismo , Proteínas de Unión al GTP/metabolismoRESUMEN
Adhesion G protein-coupled receptors (aGPCRs) are keys of many physiological events and attractive targets for various diseases. aGPCRs are also known to be capable of self-activation via an autoproteolysis process that removes the inhibitory GAIN domain on the extracellular side of receptor and releases a stalk peptide to bind and activate the transmembrane side of receptor. However, the detailed mechanism of aGPCR activation remains elusive. Here, we report the cryo-electron microscopy structures of GPR110 (ADGRF1), a member of aGPCR, in complex with Gq, Gs, Gi, G12 and G13. The structures reveal distinctive ligand engaging model and activation conformations of GPR110. The structures also unveil the rarely explored GPCR/G12 and GPCR/G13 engagements. A comparison of Gq, Gs, Gi, G12 and G13 engagements with GPR110 reveals details of G-protein engagement, including a dividing point at the far end of the alpha helix 5 (αH5) of Gα subunit that separates Gq/Gs engagements from Gi/G12/G13 engagements. This is also where Gq/Gs bind the receptor through both hydrophobic and polar interaction, while Gi/G12/G13 engage receptor mainly through hydrophobic interaction. We further provide physiological evidence of GPR110 activation via stalk peptide. Taken together, our study fills the missing information of GPCR/G-protein engagement and provides a framework for understanding aGPCR activation and GPR110 signaling.