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A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor-angiotensin-converting enzyme 2 (ACE2)-in humans3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD-ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.
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Betacoronavirus/química , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Receptores Virales/química , Receptores Virales/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Zoonosis/virología , Enzima Convertidora de Angiotensina 2 , Animales , Betacoronavirus/efectos de los fármacos , Betacoronavirus/metabolismo , Sitios de Unión , COVID-19 , China/epidemiología , Quirópteros/virología , Coronavirus/química , Coronavirus/aislamiento & purificación , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Cristalización , Cristalografía por Rayos X , Reservorios de Enfermedades/virología , Euterios/virología , Humanos , Modelos Moleculares , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Neumonía Viral/virología , Unión Proteica , Dominios Proteicos , Estabilidad Proteica , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/química , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/genética , Zoonosis/epidemiología , Zoonosis/transmisiónRESUMEN
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
Electrochemical upcycling of end-of-life polyethylene terephthalate (PET) using renewable electricity offers a route to generate valuable chemicals while processing plastic wastes. However, it remains a huge challenge to design an electrocatalyst with reliable structure-property relationships for PET valorization. Herein, spinel Co3O4 with rich oxygen vacancies for improved activity toward formic acid (FA) production from PET hydrolysate is reported. Experimental investigations combined with theoretical calculations reveal that incorporation of VO into Co3O4 not only promotes the generation of reactive hydroxyl species (OH*) species at adjacent tetrahedral Co2+ (Co2+ Td), but also induces an electronic structure transition from octahedral Co3+ (Co3+ Oh) to octahedral Co2+ (Co2+ Oh), which typically functions as highly-active catalytic sites for ethylene glycol (EG) chemisorption. Moreover, the enlarged Co-O covalency induced by VO facilitates the electron transfer from EG* to OH* via Co2+ Oh-O-Co2+ Td interaction and the following CâC bond cleavage via direct oxidation with a glyoxal intermediate pathway. As a result, the VO-Co3O4 catalyst exhibits a high half-cell activity for EG oxidation, with a Faradaic efficiency (91%) and productivity (1.02 mmol cm-2 h-1) of FA. Lastly, it is demonstrated that hundred gram-scale formate crystals can be produced from the real-world PET bottles via two-electrode electroreforming, with a yield of 82%.
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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
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
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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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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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
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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Multifunctional thermal management materials with highly efficient electromagnetic wave (EMW) absorption performance are urgently required to tackle the heat dissipation and electromagnetic interference issues of high integrated electronics. However, the high thermal conductivity (λ) and outstanding EMW absorption performance are often incompatible with each other in a single material. Herein, a through-thickness arrayed NiCo2 O4 /graphene oxide/carbon fibers (NiCO@CFs) elastomer with integrated functionalities of high thermal conductivity, highly efficient EMW absorption, and excellent compressibility is reported. The NiCO@CFs elastomer realizes a high out-of-plane thermal conductivity of 15.55 W m-1 K-1 , due to the through-thickness vertically aligned CFs framework. Moreover, the unique horizontal segregated magnetic network effectively reduces the electrical contact between the CFs, which significantly enhances impedance matching of NiCO@CFs elastomer. As a result, the vertically arrayed NiCO@CFs elastomer synchronously exhibits ultrabroad effective absorption bandwidth of 8.25 GHz (9.75-18 GHz) at a thickness of 2.4 mm, good impedance matching, and a minimum reflection loss (RLmin ) of -55.15 dB. Given these outstanding findings, the multifunctional arrayed NiCO@CFs elastomer opens an avenue for applications in EMW absorption and thermal management. This strategy of constructing thermal/electrical/mechanical pathways provides a promising way for the high-performance multifunctional materials in electronic devices.
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The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.
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Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Inmunogenicidad Vacunal , Nanopartículas/uso terapéutico , Enzima Convertidora de Angiotensina 2/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Modelos Animales de Enfermedad , Diseño de Fármacos , Femenino , Células HEK293 , Humanos , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Dominios Proteicos/inmunologíaRESUMEN
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
A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) is causing the global coronavirus disease 2019 (COVID-19) pandemic. Understanding how SARS-CoV-2 enters human cells is a high priority for deciphering its mystery and curbing its spread. A virus surface spike protein mediates SARS-CoV-2 entry into cells. To fulfill its function, SARS-CoV-2 spike binds to its receptor human ACE2 (hACE2) through its receptor-binding domain (RBD) and is proteolytically activated by human proteases. Here we investigated receptor binding and protease activation of SARS-CoV-2 spike using biochemical and pseudovirus entry assays. Our findings have identified key cell entry mechanisms of SARS-CoV-2. First, SARS-CoV-2 RBD has higher hACE2 binding affinity than SARS-CoV RBD, supporting efficient cell entry. Second, paradoxically, the hACE2 binding affinity of the entire SARS-CoV-2 spike is comparable to or lower than that of SARS-CoV spike, suggesting that SARS-CoV-2 RBD, albeit more potent, is less exposed than SARS-CoV RBD. Third, unlike SARS-CoV, cell entry of SARS-CoV-2 is preactivated by proprotein convertase furin, reducing its dependence on target cell proteases for entry. The high hACE2 binding affinity of the RBD, furin preactivation of the spike, and hidden RBD in the spike potentially allow SARS-CoV-2 to maintain efficient cell entry while evading immune surveillance. These features may contribute to the wide spread of the virus. Successful intervention strategies must target both the potency of SARS-CoV-2 and its evasiveness.
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Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Internalización del Virus , Enzima Convertidora de Angiotensina 2 , Línea Celular , Humanos , Evasión Inmune , Peptidil-Dipeptidasa A/química , Peptidil-Dipeptidasa A/metabolismo , Dominios Proteicos , Receptores de Coronavirus , Receptores Virales/química , Receptores Virales/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/química , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Activación ViralRESUMEN
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
Background: The prognosis of middle-aged patients with colorectal cancer (CRC) treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for middle-aged patients with CRC. Patients and Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was performed to handle the selection bias based on age, gender, body mass index, tumour location, AJCC stage and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and disease-free survival (DFS). Results: After PSM, 154 patients were included in each group. Compared with the OR group in the total cohort, there were better survival outcomes in the LR group for 5-year OS and 5-year DFS (both P < 0.001). These differences were observed for Stage II and III diseases and for all CRC, irrespective of location. The multivariate analysis showed that tumour ≥5 cm (hazard ratio [HR] = 1.750, 95% confidence interval [CI]: 1.026-2.986, P = 0.040), Stage III (HR = 14.092, 95% CI: 1.894-104.848, P = 0.010) and LR (HR = 0.300, 95% CI: 0.160-0.560, P < 0.001) were independently associated with OS. Pre-operative carcinoembryonic antigen ≥5 ng/ml (HR = 3.954, 95% CI: 1.363-11.473, P = 0.011), Stage III (HR = 6.206, 95% CI: 1.470-26.200, P = 0.013) and LR (HR = 0.341, 95% CI: 0.178-0.653, P = 0.001) were independently associated with DFS. Conclusions: In middle-aged patients with CRC, LR achieves better survival than OR. Complications are similar, except for less blood loss and shorter post-surgical hospital stay with LR.
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Prussian blue analogs (PBAs) are considered as efficient catalysts for energy-related applications due to their porous nanoscale architectures containing finely disseminated active sites. Their catalytic capability can be greatly boosted by the rational design and construction of complex PBA hybrid nanostructures. However, present-day structure engineering inevitably involves additional etchant or procedure. Herein, a facile, yet controllable one-pot self-assembly strategy is introduced to prepare hierarchical core-shell polymetallic PBAs (featuring bimetallic FeMn PBAs cores and CoNi PBAs shells) with hollow nano-cages/solid nano-cube architectures. The detailed characterization of material morphology/composition, assisted with theoretical simulations, reveals the underlying formation mechanism where the key factor is the control of the nucleation rate via the use of chelating agent (citrates) and reaction kinetics. The resulting FeMn@CoNi-H compound is found to accelerate the oxygen evolution reaction activity with a low overpotential (236 mV at a current density 10 mA cm-2 ) as well as a low Tafel slope (58.4 mV dec-1 ). Such an impressive performance is endowed by the rational compositional and structural design with optimized electronic structures as well as an increase in exposed active sites. This work provides a robust, cost-effective pathway that enables chemical and morphological control in creating high-performance catalysts for water electrolysis.
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The ever-increasing development of flexible and wearable electronics has imposed unprecedented demand on flexible batteries of high energy density and excellent mechanical stability. Rechargeable lithium (Li) metal battery shows great advantages in terms of its high theoretical energy density. However, the use of Li metal anode for flexible batteries faces huge challenges in terms of its undesirable dendrite growth, poor mechanical flexibility, and slow fabrication speed. Here, a highly scalable Li-wicking strategy is reported that allows ultrafast fabrication of mechanically flexible and electrochemically stable Li metal anodes. Through the rational design of the interface and structure of the wicking host, the mean speed of Li-wicking reaches 10 m2 min-1 , which is 1000 to 100 000 fold faster than the reported electrochemical deposition or thermal infusion methods and meets the industrial fabrication speed. Importantly, the Li-wicking process results in a unique 3D Li metal structure, which not only offers remarkable flexibility but also suppresses the dendrite formation. Paring the Li metal anode with lithium-iron phosphate or sulfur cathode yields flexible full cells that possess a high charging rate (8.0 mA cm-2 ), high energy density (300-380 Wh kg-1 ), long cycling stability (over 550 cycles), and excellent mechanical robustness (500 bending cycles).
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Electrónica , Litio , Acción Capilar , ElectrodosRESUMEN
Coronaviruses recognize a variety of receptors using different domains of their envelope-anchored spike protein. How these diverse receptor recognition patterns affect viral entry is unknown. Mouse hepatitis coronavirus (MHV) is the only known coronavirus that uses the N-terminal domain (NTD) of its spike to recognize a protein receptor, CEACAM1a. Here we determined the cryo-EM structure of MHV spike complexed with mouse CEACAM1a. The trimeric spike contains three receptor-binding S1 heads sitting on top of a trimeric membrane-fusion S2 stalk. Three receptor molecules bind to the sides of the spike trimer, where three NTDs are located. Receptor binding induces structural changes in the spike, weakening the interactions between S1 and S2. Using protease sensitivity and negative-stain EM analyses, we further showed that after protease treatment of the spike, receptor binding facilitated the dissociation of S1 from S2, allowing S2 to transition from pre-fusion to post-fusion conformation. Together these results reveal a new role of receptor binding in MHV entry: in addition to its well-characterized role in viral attachment to host cells, receptor binding also induces the conformational change of the spike and hence the fusion of viral and host membranes. Our study provides new mechanistic insight into coronavirus entry and highlights the diverse entry mechanisms used by different viruses.
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Antígeno Carcinoembrionario/química , Virus de la Hepatitis Murina/química , Virus de la Hepatitis Murina/fisiología , Receptores Virales/química , Glicoproteína de la Espiga del Coronavirus/química , Internalización del Virus , Animales , Antígeno Carcinoembrionario/metabolismo , Antígeno Carcinoembrionario/ultraestructura , Línea Celular Tumoral , Microscopía por Crioelectrón , Células HEK293 , Humanos , Fusión de Membrana , Ratones , Modelos Moleculares , Unión Proteica , Conformación Proteica , Conformación Proteica en Hélice alfa , Dominios Proteicos , Multimerización de Proteína , Proteolisis , Receptores Virales/metabolismo , Receptores Virales/ultraestructura , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/ultraestructura , Acoplamiento ViralRESUMEN
OBJECTIVES: We aimed to evaluate changes in the contrast-enhanced ultrasound (CEUS) parameters in patients with idiopathic retroperitoneal fibrosis (RPF) before and after treatment, and to analyse the value of CEUS to assess RPF activity. METHODS: We performed a prospective study that included patients with idiopathic RPF who were treated for RPF at our hospital from April 2016 to April 2019. All patients underwent CEUS examination and some of them underwent positron emission tomography/computed tomography (PET/CT) examination simultaneously. CEUS parameters included tube wall and peripheral thickness, arterial wall intensity, and lumen intensity. The changes in CEUS parameters before and after treatment were evaluated, and their correlations with the standardised uptake value (SUVmax), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed. RESULTS: Thirty-one active idiopathic RPF patients were enrolled, of whom 11 underwent PET/CT examination before treatment. Tube wall and peripheral thickness (r=0.743, p<0.01) and arterial wall intensity (r=0.702, p<0.05) both correlated significantly with SUVmax. Lumen intensity did not correlate significantly with SUVmax (r=0.544, p=0.084). The correlation coefficients between lesion thickness and ESR levels were 0.508 (p=0.037), between lesion thickness and CRP levels were 0.575 (p=0.016). Arterial wall intensity and lumen intensity were not significantly correlated with ESR or CPR levels. Tube wall and peripheral thickness, arterial wall intensity, decreased significantly after treatment (p=0.001), while the lumen intensity was not significantly changed after treatment. CONCLUSIONS: Our findings suggest that CEUS, a radiation-free and repeatable detection method, is effective for assessing idiopathic RPF disease activity.
Asunto(s)
Fibrosis Retroperitoneal , Sedimentación Sanguínea , Medios de Contraste , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Fibrosis Retroperitoneal/diagnóstico por imagen , Ultrasonografía/métodosRESUMEN
The exsolution of nanoparticles (NPs) on material surfaces exhibits good performance with great potential in the field of catalysis. In this study, a method with twice lasers treatment (TLT) is proposed for the first time to rapidly promote the exsolution of Co NPs to the surface of (La0.7Sr0.3)0.93Ti0.93Co0.07O3(LSTC) by laser rapid heating to enhance the electrochemical performance of the LSTC. The entire process from precursor powder-stable perovskite crystal structure-Co NPs exsolution on the LSTC surface takes only ≈36 s by TLT. The Co NPs exsolution was confirmed by x-ray diffractometer, scanning electron microscopy and high-resolution transmission electron microscopy. After TLT, a large number of Co NPs reached 75 particlesµm-2appeared on the surface of LSTC with the onset potential of 1.38 V, the overpotential of 214 mV, and the Tafel slope of 81.14 mV dec-1, showing good catalytic activity and long-term stability. The novel process of using TLT to rapidly induce exsolution of NPs enables the rapid preparation of nanoparticle-decorated perovskite materials with better electrochemical properties, thus enriching exsolution technology and opening a new avenue for surface science research.