Flash heating process for efficient meat preservation.

Maintaining food safety and quality is critical for public health and food security. Conventional food preservation methods, such as pasteurization and dehydration, often change the overall organoleptic quality of the food products. Herein, we demonstrate a method that affects only a thin surface layer of the food, using beef as a model. In this method, Joule heating is generated by applying high electric power to a carbon substrate in <1 s, which causes a transient increase of the substrate temperature to > ~2000 K. The beef surface in direct contact with the heating substrate is subjected to ultra-high temperature flash heating, leading to the formation of a microbe-inactivated, dehydrated layer of ~100 µm in thickness. Aerobic mesophilic bacteria, Enterobacteriaceae, yeast and mold on the treated samples are inactivated to a level below the detection limit and remained low during room temperature storage of 5 days. Meanwhile, the product quality, including visual appearance, texture, and nutrient level of the beef, remains mostly unchanged. In contrast, microorganisms grow rapidly on the untreated control samples, along with a rapid deterioration of the meat quality. This method might serve as a promising preservation technology for securing food safety and quality.

Landslide susceptibility assessment using deep learning considering unbalanced samples distribution.

Landslide susceptibility assessment (LSA) is fundamental for managing landslide geological disasters. This study presents a deep learning approach (DNN-MSFM) designed to enhance LSA modeling, particularly addressing limitations caused by the unbalanced distribution of data samples in applied datasets. DNN-MSFM approach combines a deep neural network (DNN) and a mean squared false misclassification loss function (MSFM) to handle unbalanced samples from the algorithmic perspective. The model's performance was evaluated on an unbalanced dataset containing mapping units' records of 293 landslide samples and 653 non-landslide samples from the Baota District, China. Its effectiveness was assessed through statistical metrics and compared against DNN and Support Vector Machine (SVM) basic models. The results demonstrated a significant performance enhancement from the DNN-MSFM (OverallAccuracy = 0.889 and area under the receiver operating characteristic curve (AUC) = 0.84), indicating its effectiveness in learning the underlying landslide susceptibility features and demonstrating its ability to provide improved predictions even in areas with unbalanced landslide samples. Moreover, the study emphasizes the importance of considering balanced loss functions in training DNN under various imbalance degrees and contributes to expanding the applicability of DNN in LSA modeling. Also, this study builds a foundation for further enhancements of deep learning methods for geological disaster assessments.

Pembrolizumab in patients from China with microsatellite instability-high/mismatch repair deficient tumors: KEYNOTE-158.

Aim: To evaluate pembrolizumab in patients of Chinese descent with microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) tumors enrolled in KEYNOTE-158 (Cohort L). Methods: Patients with MSI-H/dMMR advanced tumors received pembrolizumab 200 mg IV Q3W. Primary end point was overall response rate (ORR). Secondary end points were duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: 24 patients were enrolled (20 were evaluable for efficacy). With median follow-up of 12.4 months, the ORR was 70%. DOR, PFS and OS were all not reached. A total of 19 (79%) patients had a treatment-related adverse event (AE; grade ≥3 in 4 [17%]), and 8 (33%) had an immune-mediated AE (grade ≥3 in (4 [17%]). Conclusion: Pembrolizumab provided meaningful and durable responses with manageable safety. These results are consistent with those reported for the global trial.

A Biomimetic "Salting Out-Alignment-Locking" Tactic to Design Strong and Tough Hydrogel.

Recently, hydrogel-based soft materials have demonstrated huge potential in soft robotics, flexible electronics as well as artificial skins. Although various methods are developed to prepare tough and strong hydrogels, it is still challenging to simultaneously enhance the strength and toughness of hydrogels, especially for protein-based hydrogels. Herein, a biomimetic "salting out-alignment-locking" tactic (SALT) is introduced for enhancing mechanical properties through the synergy of alignment and the salting out effect. As a typical example, tensile strength and modulus of initially brittle gelatin hydrogels increase 940 folds to 10.12 ± 0.50 MPa and 2830 folds to 34.26 ± 3.94 MPa, respectively, and the toughness increases up to 1785 folds to 14.28 ± 3.13 MJ m-3. The obtained strength and toughness hold records for the previously reported gelatin-based hydrogel and are close to the tendons. It is further elucidated that the salting out effect engenders hydrophobic domains, while prestretching facilitates chain alignment, both synergistically contributing to the outstanding mechanical properties. It is noteworthy that the SALT demonstrates remarkable versatility across different salt types and polymer systems, thus opening up new avenues for engineering strong, tough, and stiff hydrogels.

Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

Pharmacokinetics, pharmacodynamics and safety of 15 mg-tolvaptan administered orally for 7 consecutive days to Chinese patients with child-Pugh B cirrhosis.

Background: Tolvaptan, a selective vasopressin V2-receptor antagonist, can elicit a diuretic effect without significant electrolyte loss. The aims were to evaluate multiple-dose pharmacokinetics, pharmacodynamics and safety of daily administration of 15 mg tolvaptan in Chinese adult patients with confirmed Child-Pugh Class B cirrhosis accompanied by ascites. Methods: This was an open-label, single-center, single- and multiple-dose study. All patients received a daily 15 mg dose of tolvaptan for 7 consecutive days. The plasma concentrations of tolvaptan and its two metabolites (DM-4103, DM-4107) were measured using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In addition, various pharmacokinetics parameters were calculated. The pharmacodynamic outcomes evaluated changes in serum sodium and potassium concentrations, daily urine volume, daily water consumption, fluid balance and body weight. Safety profiles, including the incidence of treatment-emergent adverse events (TEAEs), were carefully recorded. Results: Eleven patients with Child-Pugh B cirrhosis were eventually enrolled in the study. Plasma concentrations of tolvaptan and DM-4107 reached steady-states after 7 days of consecutive oral administration. No accumulation of tolvaptan or DM-4107 was found, but DM-4103 accumulated 18.2-fold after multiple-dosing. The daily urine volume and daily water consumption were statistically significantly increased after administration of tolvaptan from Day 1 to Day 7 (all p < 0.05), accompanied by an increased serum sodium concentration. Of 11 patients, 9 (81.8%) reported 20 TEAEs, with the majority being mild to moderate in severity. The most commonly occurring TEAEs were thirst (45.5%), pollakiuria (36.4%) and dry mouth (27.3%). Conclusion: Tolvaptan at a daily dose of 15 mg had a diuretic effect but did not increase serum sodium excretion or lead to tolvaptan accumulation. It is therefore can be safely used for short-term treatment of Chinese adult patients with confirmed Child-Pugh B cirrhosis. Clinical Trial Registration: https://clinicaltrials.gov/search?term=NCT01359462, identifier NCT01359462.

Serum Albumin for Short-Term Poor Prognosis in Patients With Acute Pulmonary Embolism: A Clinical Study Based on a Database.

The relationship between serum albumin (ALB) and short-term prognosis in patients with acute pulmonary embolism (APE) remains unclear. We investigated the predictive value of ALB for short-term prognosis in APE patients using our hospital pulmonary embolism (PE) database (384 patients consecutively collected). Logistic regression analysis and nomograms were applied to construct the predictive model, and validation was assessed. A total of 340 APE patients were included, with a 30-day all-cause mortality rate of 8.5%. The incidence of hypoalbuminemia was 15.9%. The odds ratio (OR) for short-term mortality in patients with high ALB was 0.89 (0.886, 95% CI: 0.812-0.967). Additionally, we created a nomogram for individualized mortality risk prediction. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic area under the curve (AUC) of ALB was 0.758 (95% CI 0.683-0.833), and the best cut-off value was 33.85 g/L. Optimal simplified Pulmonary Embolism Severity Index (sPESI) (ALB combined sPESI) AUC was 0.835 (95% CI 0.775-0.896). Baseline hypoalbuminemia may be an independent prognostic indicator of short-term mortality in patients with APE.

HIF­1 and macrophage activation signalling pathways are potential biomarkers of invasive aspergillosis.

Invasive aspergillosis (IA) is a severe disease, the pathogenesis of which remains unclear. The present study aimed to determine the molecular mechanism of IA and to identify potential biomarkers using bioinformatics analysis. The GSE78000 dataset, which includes data from patients with IA and healthy individuals, was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the IA and control groups were identified with the 'affy' package in R software. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases were then used to analyse the function and pathway enrichment of DEGs. The protein-protein interaction network was analysed with the Search Tool for the Retrieval of Interacting Genes (STRING) website. In addition, DEGs were confirmed using reverse transcription-quantitative PCR and western blotting in samples with IA (n=6) and control samples (n=6) collected from the Department of Respiratory and Critical Care Medicine of the First Affiliated Hospital of Henan University of Science and Technology (Luoyang, China). The present study identified 735 DEGs, including 312 upregulated and 423 downregulated genes. Through GO and KEGG analyses of the DEGs, macrophage activation and hypoxia-inducible factor 1 (HIF-1) signalling pathways were revealed to be significantly upregulated and downregulated, respectively, in patients with IA compared with that of the healthy individuals. Subsequently, correlation analysis of macrophage activation and HIF-1 signalling pathways was revealed using correlation as a distance metric for hierarchical clustering correlation analysis. However, there was no protein-protein interaction between the macrophage activity regulation and HIF-1 signalling pathways based on STRING analysis. In summary, the present study identified candidate genes and associated molecules that may be associated to IA and revealed potential biomarkers and therapeutic targets for IA.

Diagnostic accuracy of thoracic CT to differentiate transudative from exudative pleural effusion prior to thoracentesis.

BACKGROUND: Computed tomography (CT) scan is commonly performed for pleural effusion diagnostis in the clinic. However, there are limited data assessing the accuracy of thoracic CT for the separation of transudative from exudative effusions. The study aimed to determine the diagnostic value of thoracic CT in distinguishing transudates from exudates in patients with pleural effusion. METHODS: This is a two-center retrospective analysis of patients with pleural effusion, a total of 209 patients were included from The First Affiliated Hospital of Henan University of Science and Technology as the derivation cohort (Luoyang cohort), and 195 patients from the First Affiliated Hospital of Zhengzhou University as the validation cohort (Zhengzhou cohort). Patients who underwent thoracic CT scan followed by diagnostic thoracentesis were enrolled. The optimal cut-points of CT value in pleural fluid (PF) and PF to blood CT value ratio for predicting a transudative vs. exudative pleural effusions were determined in the derivation cohort and further verified in the validation cohort. RESULTS: In the Derivation (Luoyang) cohort, patients with exudates had significantly higher CT value [13.01 (10.01-16.11) vs. 4.89 (2.31-9.83) HU] and PF to blood CT value ratio [0.37 (0.27-0.53) vs. 0.16 (0.07-0.26)] than those with transudates. With a cut-off value of 10.81 HU, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CT value were 0.85, 88.89%, 68.90%, 43.96%, and 95.76%, respectively. The optimum cut-value for PF to blood CT value ratio was 0.27 with AUC of 0.86, yielding a sensitivity of 61.11%, specificity of 86.36%, PPV of 78.57%, and NPV of 73.08%. These were further verified in the Validation (Zhengzhou) cohort. CONCLUSIONS: CT value and PF to blood CT value ratio showed good differential abilities in predicting transudates from exudates, which may help to avoid unnecessary thoracentesis.

Clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism: a multicenter study report.

BACKGROUND: Clinical characteristics of patients with pulmonary thromboembolism have been described in previous studies. Although very old patients with pulmonary thromboembolism are a special group based on comorbidities and age, they do not receive special attention. OBJECTIVE: This study aims to explore the clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism in a relatively large population. DESIGN AND PARTICIPANTS: The study included a total of 7438 patients from a national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES). Consecutive patients with acute pulmonary thromboembolism were enrolled and were divided into three groups. Comparisons were performed between these three groups in terms of clinical characteristics, comorbidities and in-hospital prognosis. Mortality predictors were analyzed in very old patients with pulmonary embolism. KEY RESULTS: In 7,438 patients with acute pulmonary thromboembolism, 609 patients aged equal to or greater than 80 years (male 354 (58.1%)). There were 2743 patients aged between 65 and 79 years (male 1313 (48%)) and 4095 patients aged younger than 65 years (male 2272 (55.5%)). Patients with advanced age had significantly more comorbidities and worse condition, however, some predisposing factors were more obvious in younger patients with pulmonary thromboembolism. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2, malignancy, anticoagulation as first therapy were mortality predictors for all-cause death in very old patients with pulmonary thromboembolism. The analysis found that younger patients were more likely to have chest pain, hemoptysis (the difference was statistically significant) and dyspnea triad. CONCLUSION: In very old population diagnosed with pulmonary thromboembolism, worse laboratory results, atypical symptoms and physical signs were common. Mortality was very high and comorbid conditions were their features compared to younger patients. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2 and malignancy were positive mortality predictors for all-cause death in very old patients with pulmonary thromboembolism while anticoagulation as first therapy was negative mortality predictors.

Azarshahr travertine compression strength prediction based on point-load index (Is) data using multilayer perceptron.

Azarshahr County in the northwest of Iran is predominantly covered by Azarshahr travertine, a prevailing sedimentary rock. This geological composition has led to extensive open-pit mining activities, particularly in the western and southwestern parts of the county. The rock's drillability and resistance to excavation play a pivotal role in determining its overall durability and hardness, crucial factors that influence the mining process. These attributes are intimately tied to the compressive strength of the rock. Accurate assessment of rock strength is vital for devising reliable excavation methodologies at mining sites. However, conventional approaches for analyzing rock strength have limitations that undermine the precision of strength estimations. In response, this study endeavors to leverage artificial intelligence techniques, specifically the Multilayer Perceptron (MLP), to enhance the prediction of travertine's compressive strength. To formulate a robust model, a comprehensive database containing data from 150 point-load index (Is) tests on Azarshahr travertine was compiled. This dataset serves as the foundation for the development of the MLP-based predictive model, which proves instrumental in projecting rock compressive strength. The model's accuracy and efficacy were rigorously assessed using the Receiver Operating Characteristic (ROC) curve, employing both training and testing datasets. The modeling outcomes reveal impressive results. The estimated R-squared coefficient attained an impressive value of 0.975 for axial strength and 0.975 for diametral strength. The overall accuracy, as indicated by the Area Under the Curve (AUC) metric, stands at an impressive 0.968. These exceptional performance metrics underscore the efficacy of the MLP model in accurately predicting compressive strength based on the point-load index of samples. The implications of this study are substantial. The predictive model, empowered by the MLP approach, has profound implications for excavation planning and drillability assessment within the studied region's travertine deposits. By facilitating accurate forecasts of rock strength, this model equips mining endeavors with valuable insights for effective planning and execution.

Increased expression of ficolin-1 is associated with airway obstruction in asthma.

BACKGROUND: The activated complement cascade is involved in asthmatic airway inflammation. Ficolins are essential for innate immunity and can activate the complement lectin pathway. Despite this, the significance of ficolins in asthma has yet to be determined. This study aimed to explore the presence of ficolins in individuals with asthma and to determine the relationship between ficolins and clinical characteristics. METHODS: For the study, 68 asthmatic patients and 30 healthy control subjects were recruited. Enzyme-linked immunosorbent assay was used to determine plasma ficolin-1, ficolin-2, and ficolin-3 concentrations both before and after inhaled corticosteroid (ICS) therapy. Further, the associations of plasma ficolin-1 level with pulmonary function and asthma control questionnaire (ACQ) score were examined in the asthma patients. RESULTS: Patients with asthma exhibited significantly elevated plasma ficolin-1 levels (median, 493.9 ng/mL; IQR, 330.2-717.8 ng/mL) in comparison to healthy controls (median, 330.6 ng/mL; IQR, 233.8-371.1 ng/mL). After ICS treatment, plasma ficolin-1 (median, 518.1 ng/mL; IQR, 330.2-727.0 ng/mL) in asthmatic patients was significantly reduced (median, 374.7 ng/mL; IQR, 254.8-562.5 ng/mL). Additionally, ficolin-1 expressions in plasma were significantly correlated with pulmonary function parameters and ACQ score in asthmatic patients. Asthma patients with higher plasma ficolin-1 levels demonstrated poorer lung function than those with lower plasma ficolin-1 levels. CONCLUSIONS: The results revealed that asthmatic patients had higher plasma ficolin-1 concentrations, which decreased after ICS treatment and were linked to their lung function, implying a potential involvement of ficolin-1 in asthma pathogenesis.

In Situ Lignin Adhesion for High-Performance Bamboo Composites.

Bamboo composite is an attractive candidate for structural materials in applications such as construction, the automotive industry, and logistics. However, its development has been hindered due to the use of harmful petroleum-derived synthetic adhesives or low-bonding biobased adhesives. Herein, we report a novel bioadhesion strategy based on in situ lignin bonding that can process natural bamboo into a scalable and high-performance composite. In this process, lignin bonds the cellulose fibrils into a strong network via a superstrong adhesive interface formed by hydrogen bonding and nanoscale entanglement. The resulting in situ glued-bamboo (glubam) composite exhibits a record-high shear strength of ∼4.4 MPa and a tensile strength of ∼300 MPa. This in situ lignin adhesion strategy is facile, highly scalable, and cost-effective, suggesting a promising route for fabricating strong and sustainable structural bamboo composites that sequester carbon and reduce our dependence on petrochemical-based adhesives.

Pathogenic Nocardia amamiensis infection: A rare case report and literature review.

Background: To date, only six cases of Nocardia amamiensis infection have been reported, including two ocular cases, three pulmonary cases, and one disseminated case. However, no Nocardia amamiensis pulmonary infection cases have been reported in immunocompetent patients without structural pulmonary disease. This study describes a rare case and provides a detailed review of all previous cases. Methods: A pulmonary infection caused by Nocardia amamiensis in a 64-year-old man with low-grade fever, night sweats, and weight loss was reported. All previously reported cases of Nocardia amamiensis infection were searched and reviewed. Results: The pathogen was identified as Nocardia amamiensis using bronchoalveolar lavage fluid (BALF) mNGS, and the current case was successfully treated with trimethoprim-sulfamethoxazole (ST) monotherapy. mNGS and 16S rRNA PCR are standard tests to identify Nocardia.Conclusion: mNGS has high diagnostic performance for Nocardia amamiensis. Further studies are needed to clarify the clinical characteristics and explore more effective treatment protocols for this rare pathogen.

Stages of psychological change among patients with non-alcoholic fatty liver disease in China: a national cross-sectional study.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. However, treatment of NAFLD is potentially influenced by psychological conditions. Using the simplified version of the University of Rhode Island Change Assessment (URICA-SV) scale, this study aimed to evaluate the stage of psychological change as a prerequisite to refining implementation strategies for psychological change. DESIGN: A multicentre cross-sectional survey. SETTING: Ninety hospitals in China. PARTICIPANTS: 5181 patients with NAFLD were included in this study. OUTCOME MEASURES: All patients completed the URICA-SV questionnaire and were assigned to one of the three stages of change (precontemplation, contemplation or action) according to their readiness scores. A stepwise multivariate logistic regression analysis was used to identify independent factors associated with the stage of psychological change. RESULTS: A total of 4832 (93.3%) patients were included in the precontemplation stage and only 349 (6.7%) considered making a change or preparing to make one. There were significant differences in gender (Cohen's d=0.039, p=0.005), age (Cohen's d=-0.327, p<0.001), waist circumference (Cohen's d=0.143, p=0.003), alanine transaminase (Cohen's d=0.347, p=0.001), triglyceride (Cohen's d=0.351, p=0.002), body mass index (BMI; Cohen's d=0.056, p<0.001), proportion of hyperlipidaemia (Cohen's d=0.068, p<0.001) and cardiovascular disease (Cohen's d=0.032, p=0.029), therapeutic regimen (Cohen's d=0.136, p<0.001), and Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease overall score (Cohen's d=-0.420, p<0.001) between patients with NAFLD in the precontemplation stage and those in the contemplation/action stage. Logistic regression identified BMI (HR 0.659, 95% CI 0.469 to 0.928, p=0.017), cardiovascular disease (HR 2.161, 95% CI 1.089 to 4.287, p=0.027) and triglyceride (HR 0.751, 95% CI 0.591 to 0.955, p=0.020) as independent factors predicting psychological change. CONCLUSIONS: The results demonstrated that very few patients with NAFLD presented psychological condition in the stage of action. Psychological condition was found to be significantly related to BMI, cardiovascular disease and triglyceride factors. Integrated diversity considerations for evaluating psychological change are necessary.

Single-cell RNA sequencing to reveal non-parenchymal cell heterogeneity and immune network of acetaminophen-induced liver injury in mice.

The role of non-parenchymal cells (NPCs) in the early phase of acetaminophen (APAP)-induced liver injury (AILI) remains unclear. Therefore, single-cell sequencing (scRNA-seq) was performed to explore the heterogeneity and immune network of NPCs in the livers of mice with AILI. Mice were challenged with saline, 300 mg/kg APAP, or 750 mg/kg APAP (n = 3 for each group). After 3 h, the liver samples were collected, digested, and subjected to scRNA-seq. Immunohistochemistry and immunofluorescence were performed to confirm the expression of Makorin ring finger protein 1 (Mkrn1). We identified 14 distinct cell subtypes among the 120,599 cells. A variety of NPCs were involved, even in the early stages of AILI, indicating highly heterogeneous transcriptome dynamics. Cholangiocyte cluster 3, which had high deleted in malignant brain tumors 1 (Dmbt1) expression, was found to perform drug metabolism and detoxification functions. Liver sinusoidal endothelial cells exhibited fenestrae loss and angiogenesis. Macrophage cluster 1 displayed a M1 polarization phenotype, whereas cluster 3 tended to exhibit M2 polarization. Kupffer cells (KCs) exhibited pro-inflammatory effects due to the high expression of Cxcl2. qRT-PCR and western blotting verified that the LIFR-OSM axis might promote the activation of MAPK signaling pathway in RAW264.7 macrophages. Mkrn1 was highly expressed in the liver macrophages of AILI mice and AILI patients. Interaction patterns between macrophages/KCs and other NPCs were complex and diverse. NPCs were highly heterogeneous and were involved in the immune network during the early phase of AILI. In addition, we propose that Mkrn1 may serve as a potential biomarker of AILI.

The Role of Bone Morphogenetic Protein 4 in Lung Diseases.

Bone morphogenetic protein 4 (BMP4) is a multifunctional secretory protein that belongs to the transforming growth factor ß superfamily. BMPs transduce their signaling to the cytoplasm by binding to membrane receptors of the serine/threonine kinase family, including BMP type I and type II receptors. BMP4 participates in various biological processes, such as embryonic development, epithelial-mesenchymal transition, and maintenance of tissue homeostasis. The interaction between BMP4 and the corresponding endogenous antagonists plays a key role in the precise regulation of BMP4 signaling. In this paper, we review the pathogenesis of BMP4-related lung diseases and the foundation on which BMP4 endogenous antagonists have been developed as potential targets.

Spatially confined protein assembly in hierarchical mesoporous metal-organic framework.

Immobilization of biomolecules into porous materials could lead to significantly enhanced performance in terms of stability towards harsh reaction conditions and easier separation for their reuse. Metal-Organic Frameworks (MOFs), offering unique structural features, have emerged as a promising platform for immobilizing large biomolecules. Although many indirect methods have been used to investigate the immobilized biomolecules for diverse applications, understanding their spatial arrangement in the pores of MOFs is still preliminary due to the difficulties in directly monitoring their conformations. To gain insights into the spatial arrangement of biomolecules within the nanopores. We used in situ small-angle neutron scattering (SANS) to probe deuterated green fluorescent protein (d-GFP) entrapped in a mesoporous MOF. Our work revealed that GFP molecules are spatially arranged in adjacent nanosized cavities of MOF-919 to form "assembly" through adsorbate-adsorbate interactions across pore apertures. Our findings, therefore, lay a crucial foundation for the identification of proteins structural basics under confinement environment of MOFs.

PU.1-CD23 signaling mediates pulmonary innate immunity against Aspergillus fumigatus infection by driving inflammatory response.

BACKGROUND: Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. PU.1 is critical for innate immunity against Aspergillus fumigatus (AF) in macrophages. However, the molecular mechanism underlying PU.1 mediating immunity against AF infection in human alveolar macrophages (AMs) is still unclear. METHODS: In this study, we detected the expressions of PU.1, CD23, p-ERK, CCL20 and IL-8 and key inflammatory markers IL-1ß, IL-6, TNF-α and IL-12 in human THP-1-derived macrophages (HTMs) or PU.1/CD23-overexpressed immunodeficient mice with AF infection. Moreover, we examined these expressions in PU.1-overexpressed/interfered HTMs. Additionally, we detected the phagocytosis of macrophages against AF infection with altered PU.1 expression. Dual luciferase, ChIP and EMSAs were performed to detect the interaction of PU.1 and CD23. And we invested the histological changes in mouse lung tissues transfected with PU.1/CD23-expressing adenoviruses in AF infection. RESULTS: The results showed that the expressions of PU.1, CD23, p-ERK, CCL20, IL-8, IL-1ß, IL-6, TNF-α and IL-12 increased significantly with AF infection, and PU.1 regulated the later 8 gene expressions in HTMs. Moreover, CD23 was directly activated by PU.1, and overexpression of CD23 in PU.1-interfered HTMs upregulated IL-1ß, IL-6, TNF-α and IL-12 levels which were downregulated by PU.1 interference. PU.1 overexpression strengthened the phagocytosis of the HTMs against AF. And injection of PU.1/CD23-expressing adenoviruses attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Adenovirus (Ad)-PU.1 increased the CD23, p-ERK, CCL20, IL-8 levels. CONCLUSIONS: Our study concluded that PU.1-CD23 signaling mediates innate immunity against AF in lungs through regulating inflammatory response. Therefore, PU.1-CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.

Reliability and validity of the Chinese version of chronic liver disease questionnaire-nonalcoholic fatty liver disease in patients with nonalcoholic fatty liver disease: a multicenter cross-sectional survey in China.

PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.