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Mesenchymal stem cells (MSCs) have been widely documented for their potential role in the treatment of various clinical disorders, including acute lung injury (ALI). ALI represents a clinical syndrome associated with histopathological diffuse alveolar damage. Recent evidence has demonstrated that exosomes derived from MSCs may serve as a reservoir of anti-apoptotic microRNAs (miRs) conferring protection from certain diseases. Hence, the current study was performed with the aim of investigating whether MSCs-exosomal miR-30b-3p could confer protection against ALI. A bioinformatic analysis and a dual luciferase assay were initially performed to verify that SAA3 was highly-expressed in ALI which was confirmed to be a target gene of miR-30b-3p. Next, the lipopolysaccharide (LPS)-treated type II alveolar epithelial cells (AECs) (MLE-12) were transfected with mimics or inhibitors of miR-30b-3p, or sh-SAA3. It was revealed that LPS induced AEC apoptosis, which could be inhibited by overexpressing miR-30b-3p by down-regulating the expression of SAA3. After co-culture of PKH26-labeled exosomes with MLE-12â¯cells, we found that the number of PKH26-labeled exosomes endocytosed by MLE-12â¯cells gradually increased. Furthermore, the LPS-treated MLE-12â¯cells co-cultured with MSC-exosomes overexpressing miR-30b-3p exhibited increased miR-30b-3p, decreased SAA3 level, as well as increased cell proliferation, accompanied by diminished cell apoptosis in LPS-treated MLE-12â¯cells. Finally, the protective effect of MSCs-exosomal miR-30b-3p on the AECs in vivo was investigated in an ALI mouse model with tail vein injection of MSC-exosomes with elevated miR-30b-3p, showing that overexpression of miR-30b-3p in MSC-exosomes conferred protective effects against ALI. Taken together, these findings highlighted the potential of MSC-exosomes overexpressing miR-30b-3p in preventing ALI. The exosomes derived from MSCs hold potential as future therapeutic strategies in the treatment of ALI.
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Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/prevenção & controle , Exossomos/fisiologia , Lipopolissacarídeos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Proteína Amiloide A Sérica/genética , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Regulação para Baixo/genética , Exossomos/genética , Exossomos/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Substâncias Protetoras/metabolismo , Proteína Amiloide A Sérica/metabolismoRESUMO
Purpose: To compare the efficacy and safety of two distinct doses of ulinastatin on late-onset acute renal failure (LARF) following orthotopic liver transplantation (OLT).Methods: The high-risk recipients that underwent OLT were divided into two groups according to ulinastatin dose: low-dose (LD) ulinastatin group, 0.8 million U/d; high-dose (HD) ulinastatin group, 1.6 million U/d. The primary outcome was the incidence of LARF, which was defined the newly onset acute kidney injury (AKI) stage III (KDIGO, 2012) within 7-28 post-transplant days. The second outcomes were early multiple organ retrieval assessments, length of hospital stay and safety events.Results: A total of 174 recipients were included (LD ulinastatin group, n = 55; HD ulinastatin group, n = 119). There was no significant difference in the incidence of LARF between LD (8/55, 14.50%) and HD (9/119, 7.56%) ulinastatin groups (HD vs. LD, HR, 0.49; 95%CI, 0.17-1.37; p = .1295). Multivariate Cox proportion risk regression model revealed HD ulinastatin (HR, 0.57; 95%CI, 0.38-0.98; p = .0464) was an independent protective factor for LARF. Early lactate level, oxygenation, AKI stage, graft function, and sequential organ failure assessment [SOFA] score were significantly improved in HD ulinastatin group versus LD ulinastatin group. No significant adverse events were observed in either group.Conclusions: Higher dose of ulinastatin (1.6 million U/d) might be preferable to prevent LARF after OLT, and it may contribute to the enhancement of early multiple organ recovery and thus attenuate the incidence of LARF.
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Injúria Renal Aguda/prevenção & controle , Glicoproteínas/administração & dosagem , Transplante de Fígado/efeitos adversos , Inibidores da Tripsina/administração & dosagem , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Adulto , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva , Tempo de Internação , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
KEY MESSAGE: Coincident regions on chromosome 4B for GW, on 5A for SD and TSS, and on 3A for SL and GNS were detected through an integration of a linkage analysis and a genome-wide association study (GWAS). In addition, six stable QTL clusters on chromosomes 2D, 3A, 4B, 5A and 6A were identified with high PVE% on a composite map. The panicle traits of wheat, such as grain number per spike and 1000-grain weight, are closely correlated with grain yield. Superior and effective alleles at loci related to panicles developments play a crucial role in the progress of molecular improvement in wheat yield breeding. Here, we revealed several notable allelic variations of seven panicle-related traits through an integration of genome-wide association mapping and a linkage analysis. The linkage analysis was performed using a recombinant inbred line (RIL) population (173 lines of F8:9) with a high-density genetic map constructed with 90K SNP arrays, Diversity Arrays Technology (DArT) and simple sequence repeat (SSR) markers in five environments. Thirty-five additive quantitative trait loci (QTL) were discovered, including eleven stable QTLs on chromosomes 1A, 2D, 4B, 5B, 6B, and 6D. The marker interval between EX_C101685 and RAC875_C27536 on chromosome 4B exhibited pleiotropic effects for GW, SL, GNS, FSN, SSN, and TSS, with the phenotypic variation explained (PVE) ranging from 5.40 to 37.70%. In addition, an association analysis was conducted using a diverse panel of 205 elite wheat lines with a composite map (24,355 SNPs) based on the Illumina Infinium assay in four environments. A total of 73 significant marker-trait associations (MTAs) were detected for panicle traits, which were distributed across all wheat chromosomes except for 4D, 5D, and 6D. Consensus regions between RAC875_C27536_611 and Tdurum_contig4974_355 on chromosome 4B for GW in multiple environments, between QTSS5A.7-43 and BS00021805_51 on 5A for SD and TSS, and between QSD3A.2-164 and RAC875_c17479_359 on 3A for SL and GNS in multiple environments were detected through linkage analysis and a genome-wide association study (GWAS). In addition, six stable QTL clusters on chromosomes 2D, 3A, 4B, 5A, and 6A were identified with high PVE% on a composite map. This study provides potentially valuable information on the dissection of yield-component traits and valuable genetic alleles for molecular-design breeding or functional gene exploration.
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Ligação Genética , Locos de Características Quantitativas , Sementes/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento , Triticum/genética , Mapeamento Cromossômico , Grão Comestível/genética , Estudos de Associação Genética , Desequilíbrio de Ligação , Repetições de Microssatélites , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To investigate the application and security of plasmapheresis combined with hemofiltration in the treatment of severe liver disease in middle and late pregnancy. METHODS: Clinical data of 29 patients of middle and late pregnancy with severe liver disease from March 2009 to November 2013 in the Third Affiliated Hospital of Sun Yat-sen University was analyzed retrospectively. According to the therapeutic schedule, patients were divided into control group (n=16, 18-29 years old, median age of 24 years old) and treatment group (n=13, 21-28 years old, median age of 25 years old). The informed consents of all patients were obtained and the ethical committee approval was received. The control group was given the treatment of resisting infection, protecting liver, reducing jaundice, supplying albumin and globulin, infusing blood coagulation and so on. The treatment group was given plasmapheresis and hemofiltration on the basis of the above-mentioned treatment. The differences of major clinical indicators such as MELD scores, APACHEII scores, total bilirubin (TB), albumin (ALB), prothrombin time activity (PTA) , fasting blood glucose (FPG), serum creatinine (Scr) of peripheral venous blood and arterial lactic acid (Lac) in patients of two groups were observed 6 hours before and 1, 3, 5 days after the treatment. The major clinical indicators in patients of two groups were compared by t test and the clinical efficient were compared by χ² test. RESULTS: There were no statistical differences of the clinical indicators between the two groups 6 hours before the treatment (all P>0.05). The MELD scores, APACHEII scores, TB, ALB, PTA, FPG, Scr, Lac were (25 ± 6) scores, (22 ± 5) scores, (197 ± 69) µmol/L, (30 ± 7) g/L, (55 ± 24)%, (5.7 ± 2.4) mmol/L, (111 ± 42) µmol/L, (2.3 ± 0.6) mmol/L in treatment group 1 day after treatment, and were (33 ± 8) scores, (30 ± 7) scores, (299 ± 113) µmol/L, (24 ± 6) g/L, (33 ± 11)%, (3.7 ± 1.7) mmol/L, (165 ± 82) µmol/L, (4.4 ± 1.5) mmol/L in control group, which improved significantly in the treated group compared to those in the control group. There was also significant improvement in those posttreatment d3, and 5 lab findings in the treatment group (P<0.05). The effective rate was higher in the treatment group (92%, 12/13) than the control group (56%, 9/16) (χ² =4.215, P<0.05). Kaplan-Meier analysis showed the combined treatment could significantly improve the 42 d survival rate in postpartum patients with liver function failure. One patient had transitional hypotension after plasma infusion and hemofiltration in the treatment group, but the blood pressure returned to normal 1 h after small dose of vasoconstrictor. CONCLUSION: The therapeutic effect of plasmapheresis combined with hemofiltration on the treatment of severe liver disease in middle and late pregnancy is safe and effective, and it could improve the clinical outcomes and survival rate.
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Hemofiltração , Hepatopatias , Plasmaferese , Adolescente , Adulto , Pressão Sanguínea , Feminino , Humanos , Estimativa de Kaplan-Meier , Gravidez , Complicações na Gravidez , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
Background: Tetanus is a rare surgical infectious disease with a high reported relevant mortality. It still remains a serious problem in public health, particularly in low-income and middle-income countries. The purpose of this study was to investigate the management and prognosis of adult generalized tetanus in our hospital. Methods: A total of 20 adult generalized tetanus patients were recruited in this retrospective observational study. Patients were retrieved from the hospital data base via discharge diagnosis. Patients were divided into two groups (Severe or Non-severe tetanus group) based on the severity of tetanus by using the Ablett classification. The differences between the two groups were compared. Results: The study included 11 males (55%) and 9 females (45%). All tetanus patients recovered. The median age was 53.5 years [IQR: 19-78]. There were 1 mild (Grade 1) case (5%),5 moderate (Grade 2) cases (25%), 2 severe (Grade 3) cases (10%), and 12 very severe (Grade 4) cases (60%). Nineteen patients (95%) did not have tetanus immunization before. The majority of patients were farmers (60%), and came from rural areas (60%). Thirteen (65%) patients had a history of puncture injury. The rate of wound debridement after admission was 60% overall. Thirteen (65%) patients required mechanical ventilation for a median of 21 [IQR:12-41] days. Autonomic instability occurred in 13 (65%) patients. Pulmonary infections occurred in 12 (60%) patients. Median duration of hospital stay was 29.5 [IQR:12-68] days. More patients in the Severe group needed ICU admission, wound debridement, mechanical ventilation and heavy sedation combined with muscle relaxants (p < 0.05). The hospital stay was significantly longer in patients in the Severe group (p < 0.05). Conclusion: After effective treatment, all adult patients with generalized tetanus in this study were cured and discharged. Severe tetanus requires early ICU treatment, wound debridement and effective treatment of autonomic instability.
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Tétano , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Prognóstico , Estudos Retrospectivos , Centros de Atenção Terciária , Tétano/terapia , Tétano/diagnóstico , Adulto Jovem , IdosoRESUMO
Numerous regression-based and machine learning techniques are available for the development of linear and nonlinear QSAR models that can accurately predict biological endpoints. Such tools can be quite powerful in the hands of an experienced modeler, but too frequently a disconnect remains between the modeler and project chemist because the resulting QSAR models are effectively black boxes. As a result, learning methods that yield models that can be visualized in the context of chemical structures are in high demand. In this work, we combine direct kernel-based PLS with Canvas 2D fingerprints to arrive at predictive QSAR models that can be projected onto the atoms of a chemical structure, allowing immediate identification of favorable and unfavorable characteristics. The method is validated using binding affinities for ligands from 10 different protein targets covering 7 distinct protein families. Models with significant predictive ability (test set Q(2) > 0.5) are obtained for 6 of 10 data sets, and fingerprints are shown to consistently outperform large collections of classical physicochemical and topological descriptors. In addition, we demonstrate how a simple bootstrapping technique may be employed to obtain uncertainties that provide meaningful estimates of prediction accuracy.
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Biologia Computacional/métodos , Relação Quantitativa Estrutura-Atividade , Gráficos por Computador , Determinação de Ponto Final , Análise dos Mínimos Quadrados , IncertezaRESUMO
Objective: Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis. Methods: Datasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN). Results: Analysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level. Conclusion: CYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.
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Armadilhas Extracelulares , Sepse , Choque Séptico , Humanos , Animais , Camundongos , Armadilhas Extracelulares/metabolismo , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/genética , Choque Séptico/genética , Biomarcadores , Perfilação da Expressão Gênica , NADPH Oxidase 2/genéticaRESUMO
Compound libraries comprise an integral component of drug discovery in the pharmaceutical and biotechnology industries. While in-house libraries often contain millions of molecules, this number pales in comparison to the accessible space of drug-like molecules. Therefore, care must be taken when adding new compounds to an existing library in order to ensure that unexplored regions in the chemical space are filled efficiently while not needlessly increasing the library size. In this work, we present an automated method to fill holes in an existing library using compounds from an external source and apply it to commercially available fragment libraries. The method, called Canvas HF, uses distances computed from 2D chemical fingerprints and selects compounds that fill vacuous regions while not suffering from the problem of selecting only compounds at the edge of the chemical space. We show that the method is robust with respect to different databases and the number of requested compounds to retrieve. We also present an extension of the method where chemical properties can be considered simultaneously with the selection process to bias the compounds toward a desired property space without imposing hard property cutoffs. We compare the results of Canvas HF to those obtained with a standard sphere exclusion method and with random compound selection and find that Canvas HF performs favorably. Overall, the method presented here offers an efficient and effective hole-filling strategy to augment compound libraries with compounds from external sources. The method does not have any fit parameters and therefore it should be applicable in most hole-filling applications.
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Descoberta de Drogas , Informática , Preparações Farmacêuticas/química , Bases de Dados de Produtos Farmacêuticos , Sinergismo FarmacológicoRESUMO
Purpose: Intracranial infection after neurosurgery is one of the most serious complications, especially extensively drug-resistant (XDR) Acinetobacter baumannii (A. baumannii) seriously affects the prognosis of patients. At present, there is little experience in the treatment of this infection and limited effective treatment options, like tigecycline or polymyxin B. Therefore, this report aims to describe the efficacy of tigecycline combined with polymyxin B by intrathecal (ITH) injection in the treatment of XDR intracranial infection with A. baumannii. Methods: We report a case of intracranial infection with XDR A. baumannii after ventricular drainage, treated by daily ITH and intravenous (IV) tigecycline, combined with polymyxin B ITH route. Moreover, tigecycline and polymyxin B treatments for XDR intracranial infection with A. baumannii that were reported in the literature were also reviewed and summarized. Results: The white blood cells (WBCs) of the patient's cerebrospinal fluid dropped to normal, and the symptoms of intracranial infection disappeared. The patient finally obtained good clinical results and transferred to the local hospital. Conclusion: The polymyxin B ITH route is an ideal treatment strategy for XDR A. baumannii. The IV plus ITH tigecycline may be an effective treatment option. However, more researches should be conducted to confirm our observation.
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Wheat (Triticum aestivum L.) flour mixing properties are essential quality parameters in the dough development process. Limited research on superior alleles for mixing properties has restricted their molecular improvement, and other factors related to the complex traits have been ignored. A molecular map of 9576 polymorphic markers in the RIL population (F8:9) (Shannong01-35/Gaocheng9411) was constructed to evaluate mixing property effects in three environments. The parents were selected with markedly distinct high-molecular-weight glutenin subunits (HMW-GS). This study not only evaluated mixing properties using conventional unconditional QTL mapping but also evaluated the relationships between protein-related traits using conditional QTL mapping. The analyses identified most additive QTLs for major mixing properties on chromosomes 1A, 1B, and 1D. Two major loci (1A.1-15 and 1D-1) associated with mixing properties have confirmed the important contributions of Glu-A1 and Glu-D1 to wheat quality at the QTL level, which were mainly affected by the gluten index. Another important locus, 1B.1-24 (associated with midline peak value and midline peak width, with high phenotypic variations explained), might represent a new variation distinct from Glu-B1. The favored alleles came from Gaocheng9411. Several mixing properties shared the same QTLs (1B.1-6 and 1A.1-15), indicating tight linkage or pleiotropism. Genotype-by-environment (G×E) interactions were also investigated in the present study. The QTL results in our study may improve our understanding of the genetic interrelationships between mixing properties and protein-related traits.
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Background: Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection (HAI) in patients with mechanical ventilation. VAP is largely preventable, and a comprehensive unit-based safety program (CUSP) has effectively reduced HAI. In this study, we aim to comprehensively investigate the effect of implementing the CUSP in patients requiring mechanical ventilation. Methods: In this uncontrolled before-and-after trial conducted in two intensive care unit (ICU) settings in China, patients requiring invasive mechanical ventilation were enrolled. Patients were divided into two groups based on the implementation of CUSP. The primary outcome was the incidence of VAP. The secondary outcomes were the time from intubation to VAP, days of antibiotic use for VAP treatments, rate of other infection, length of stay (LOS) in ICU, hospital LOS, and safety culture score. Joinpoint regression analysis was used to test the changes in trends of VAP rate for statistical significance. Propensity score matching (1:1 matching) was used to reduce the potential bias between CUSP and no CUSP groups. Univariate and multivariate logistic/linear regression analyses were performed to evaluate the association between the use of CUSP and clinical outcomes. This study was registered at the Chinese Clinical Trial Registry (chictr.org.cn), registration number: ChiCTR1900025391. Results: A total of 1,004 patients from the transplant ICU (TICU) and 1,001 patients from the surgical ICU (SICU) were enrolled in the study from January 2016 to March 2022. Before propensity score matching, the incidences of VAP decreased from 35.1/1,000 ventilator days in the no CUSP group to 12.3/1,000 ventilator days in the CUSP group in the TICU setting (adjusted odds ratio [OR], 0.30; 95% confidence interval [CI], 0.15-0.59). The results of the joinpoint regression analysis confirmed that the implementation of CUSP significantly decreased the incidences of VAP. After propensity score matching in TICU setting, the CUSP group reported a lower incidence of VAP (30.4 vs. 9.7, P = 0.003; adjusted OR = 0.26, 95% CI: 0.10-0.76), lower wound infection (3.4 vs. 0.9%, P = 0.048; adjusted OR = 0.73, 95% CI: 0.50-0.95), shorter ICU LOS [3.5(2.3-5.3) vs. 2.5(2.0-4.5) days; P = 0.003, adjusted estimate = -0.34, 95% CI: -0.92 to -0.14], and higher safety culture score (149.40 ± 11.74 vs. 153.37 ± 9.74; P = 0.002). Similar results were also observed in the SICU setting between the no CUSP and CUSP group. Conclusions: The implementation of CSUP for patients receiving mechanical ventilation could significantly reduce the incidences of VAP, and other infections, prolong the time until the VAP occurrence, reduces the days of antibiotic use for VAP, shorten the ICU and hospital LOS, and enhance the awareness of safety culture.
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Pneumonia Associada à Ventilação Mecânica , Humanos , Antibacterianos , China/epidemiologia , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Respiração Artificial , Ventiladores MecânicosRESUMO
OBJECTIVE: To investigate the relationship between hepatocellular carcinoma (HCC) recurrence and hepatitis B virus (HBV) recurrence. METHODS: The clinical data of 340 patients underwent liver transplantation due to HBV related end-stage liver disease and received long-term follow up in our hospital from Jan 2004 to Dec 2008 were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list and nucleoside analogues combined low-dose HBIG therapy during and after transplantation. Patients were regularly followed up at the outpatient, monitoring the HBV recurrence and survival. Multivariate Cox regression analysis was used to evaluate the risk factors for hepatitis recurrence. RESULTS: 33 patients suffered from HBV recurrence post transplantation. The 1-, 3- and 5- year recurrence rates were 7.0%, 10% and 13% respectively. The median HBV recurrence time was 5 months (1-21 months). COX regression analysis revealed that risk factors for HBV recurrence were HCC (HR = 2.98; 95% CI 1.08-8.25; P < 0.05) and pre-transplantation HBV-DNA load over 5 log10 copies/ml (HR = 3.99; 95% CI 1.85-8.62; P < 0.01). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which were 27.9% and 8.7% (HR = 4.58;95% CI 1.88-11.12; P < 0.01) respectively. 12 patients suffered from both HCC and HBV recurrence. Spearman correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times (r = 0.583, P < 0.05). CONCLUSIONS: Post transplantation HCC recurrence is a risk factor for HBV recurrence.
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Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Hepatite B/complicações , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/etiologia , Adulto , Feminino , Vírus da Hepatite B , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
In recent years, generative machine learning approaches have attracted significant attention as an enabling approach for designing novel molecular materials with minimal design bias and thereby realizing more directed design for a specific materials property space. Further, data-driven approaches have emerged as a new tool to accelerate the development of novel organic electronic materials for organic light-emitting diode (OLED) applications. We demonstrate and validate a goal-directed generative machine learning framework based on a recurrent neural network (RNN) deep reinforcement learning approach for the design of hole transporting OLED materials. These large-scale molecular simulations also demonstrate a rapid, cost-effective method to identify new materials in OLEDs while also enabling expansion into many other verticals such as catalyst design, aerospace, life science, and petrochemicals.
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Data-driven methods are receiving increasing attention to accelerate materials design and discovery for organic light-emitting diodes (OLEDs). Machine learning (ML) has enabled high-throughput screening of materials properties to suggest new candidates for organic electronics. However, building reliable predictive ML models requires creating and managing a high volume of data that adequately address the complexity of materials' chemical space. In this regard, active learning (AL) has emerged as a powerful strategy to efficiently navigate the search space by prioritizing the decision-making process for unexplored data. This approach allows a more systematic mechanism to identify promising candidates by minimizing the number of computations required to explore an extensive materials library with diverse variables and parameters. In this paper, we applied a workflow of AL that accounts for multiple optoelectronic parameters to identify materials candidates for hole-transport layers (HTL) in OLEDs. Results of this work pave the way for efficient screening of materials for organic electronics with superior efficiencies before laborious simulations, synthesis, and device fabrication.
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OBJECTIVES: Acute lung injury (ALI) remains a common cause of morbidity and mortality worldwide, and to date, there is no effective treatment for ALI. Previous studies have revealed that topical administration of mesenchymal stem cells (MSCs) can attenuate the pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance the survival and function of cells. The present study aimed to assess whether HS-pretreated MSCs could enhance immunomodulation and recovery from ALI. MATERIALS AND METHODS: HS pretreatment was performed at 42 °C for 1 h, and changes in biological characteristics and secretion functions were detected. In an in vivo mouse model of ALI, we intranasally administered pretreated umbilical cord-derived MSCs (UC-MSCs), confirmed their therapeutic effects, and detected the phenotypes of the macrophages in bronchoalveolar lavage fluid (BALF). To elucidate the underlying mechanisms, we cocultured pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in the macrophages were assessed. RESULTS: The data showed that UC-MSCs did not exhibit significant changes in viability or biological characteristics after HS pretreatment. The administration of HS-pretreated UC-MSCs to the ALI model improved the pathological changes and lung damage-related indexes, reduced the proinflammatory cytokine levels, and modulated the M1/M2 macrophage balance. Mechanistically, both the in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs, which negatively modulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in alveolar macrophages. These effects were partially reversed by knocking down HSP70 expression. CONCLUSION: HS pretreatment can enhance the beneficial effects of UC-MSCs in inhibiting NLRP3 inflammasome activation in macrophages during ALI. The mechanism may be related to the upregulated expression of HSP70.
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Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Lesão Pulmonar Aguda/terapia , Animais , Resposta ao Choque Térmico , Inflamassomos , Pulmão , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genéticaRESUMO
OBJECTIVE: To observe the effect of artificial liver support system (ALSS) after liver transplantation on the survival rate of severe hepatitis patients. METHODS: Patients with severe hepatitis with model for end stage liver disease (MELD) score above 35 were divided into two groups according to whether pre-transplantation ALSS was instituted (n=23) or not (n=41). Evaluation was performed on the day when the patient entered into the waiting list and 1 day pre-transplantation. Survival rates and survival curves were estimated with Kaplan-Meier method. Log-Rank test for trends was used when comparing curves. RESULTS: There was no significant difference between two groups when comparing the parameters including prothrombin time, fibrinogen, total bilirubin, blood ammonia, creatinine, MELD score on the day of entering into the waiting list (all P>0.05). After the therapy of ALSS, the parameters of ALSS group were significantly improved comparing to those of the control group (all P<0.01). MELD score of ALSS group on the day pre-transplant was decreased significantly comparing to that on the day entering into the waiting list (37.6+/-2.0 vs. 41.4+/-2.2, P<0.01), with the difference in MELD score (DeltaMELD) of -3.8. MELD score of control group on the day entering into the waiting list and 1 day pre-transplant was 40.6+/-1.7 and 41.0+/-1.6 respectively, with DeltaMELD of +0.4 ( P>0.05). The blood loss and operation time in ALSS group was significantly less than the control group [(4 070.0+/-688.1) ml vs. (4 905.9+/-1 142.1) ml, (9.4+/-1.1) hours vs. (10.5+/-1.0) hours, P<0.05 and P<0.01). Thirty days and 1 year survival rate of ALSS group was 91% and 82%, and that of control group was 76% and 59% respectively (P=0.044). CONCLUSION: ALSS can improve the survival rate of patients with severe hepatitis undergoing liver transplantation through ameliorating physiological status, lessening blood loss during operation and operation time.
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Transplante de Fígado/mortalidade , Fígado Artificial , Adulto , Estado Terminal , Feminino , Seguimentos , Hepatite/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , PrognósticoRESUMO
The crystal structures, photoluminescence properties, and transport properties of a series of new "114" oxides CaBa1-xSrxZn2Al2O7 (x = 0-1) were investigated in detail. Careful Rietveld refinements performed on solid solution samples revealed that the structural symmetry of CaBa1-xSrxZn2Al2O7 evolves from hexagonal P63mc (x < 0.2) to trigonal P31c (0.2 ≤ x ≤ 0.6) and then to orthorhombic Pna21 (x > 0.6) with an increase of the Sr2+-content, which is cooperative with the rotation of T1O4 tetrahedra around the c-axis. Eu3+ was used as a local structural probe to gain an insight into the structure, which further corroborated the correctness of the observed structural symmetry descending sequence in CaBa1-xSrxZn2Al2O7. More importantly, the reduction of structural symmetry is also associated with a tendency from layered ordering to complete charge ordering transition for Zn2+/Al3+ cations, which was revealed to have a significant influence on the transport properties. These findings are expected to offer a route to manipulate the physical properties of "114" oxides containing magnetic cations.
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This work was supported by National 13th Five-Year Science and Technology Plan Major Projects of China (2017ZX10203205-006-001); National Key R&D Plan (2017YFA0104304); National Natural Science Foundation of China (81770648 81972286); Guangdong Natural Science Foundation (2015A030312013, 2018A0303130305); Science and Technology Program of Guangdong Province (2017B020209004, 20169013, 2017B030314027). This has now been corrected in both the PDF and HTML versions of the Article.
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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the severe lung damage and respiratory failure without effective therapy. However, there was a lack of understanding of the mechanism by which exosomes regulate autophagy during ALI/ARDS. Here, we found lipopolysaccharide (LPS) significantly increased inflammatory factors, administration of exosomes released by human umbilical cord mesenchymal stem cells (hucMSCs) successfully improved lung morphometry. Further studies showed that miR-377-3p in the exosomes played a pivotal role in regulating autophagy, leading to protect LPS induced ALI. Compared to exosomes released by human fetal lung fibroblast cells (HFL-1), hucMSCs-exosomes overexpressing miR-377-3p more effectively suppressed the bronchoalveolar lavage (BALF) and inflammatory factors and induced autophagy, causing recoveration of ALI. Administration of miR-377-3p expressing hucMSCs-exosomes or its target regulatory-associated protein of mTOR (RPTOR) knockdown significantly reduced ALI. In summary, miR-377-3p released by hucMSCs-exosomes ameliorated Lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy in vivo and in vitro.