Mesenchymal stem cells prevent H7N9 virus infection via rejuvenating immune environment to inhibit immune-overactivity.

BACKGROUND: Influenza is a clinically important infectious disease with a high fatality rate, which always results in severe pneumonia. Mesenchymal stem cells (MSCs) exhibit promising therapeutic effects on severe viral pneumonia, but whether MSCs prevent virus infection and contribute to the prevention of influenza remains unknown. METHODS: ICR mice were pretreated with human umbilical cord (hUC) MSCs and then infected with the influenza H7N9 virus. Weight, survival days, and lung index of mice were recorded. Serum antibody against influenza H7N9 virus was detected according to the hemagglutination inhibition method. Before and after virus infection, T cell and B cell subtypes in the peripheral blood of mice were evaluated by flow cytometry. Cytokines in the supernatants of MSCs, innate immune cells, and mouse broncho alveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay (ELISA) or Luminex Assay. RESULTS: Pretreatment with MSCs protected mice against influenza H7N9 virus infection. Weight loss, survival rate, and structural and functional damage to the lungs of infected mice were significantly improved. Mechanistically, MSCs modulated T lymphocyte response in virus-infected mice and inhibited the cGAS/STING pathway. Importantly, the protective effect of MSCs was mediated by cell-to-cell communications and attenuation of cytokine storm caused by immune overactivation.

Hollow structure molecularly imprinted ratiometric fluorescence sensor for the selective and sensitive detection of dopamine.

Developing hollow-structure quantum dot carriers to increase quantum luminous efficiency is a creative idea for designing a novel sensor. A ratiometric hollow CdTe@H-ZIF-8/CDs@MIPs sensor was developed for the sensitive and selective detection of dopamine (DA). CdTe QDs and CDs were used as the reference signal and recognition signal, respectively, and thus showed a visual effect. MIPs provided high selectivity toward DA. The TEM image demonstrated that the sensor was a hollow structure, which could have ample opportunity to excite quantum dots to emit light through multiple light scattering through holes. In the presence of DA, the fluorescence intensity of the optimum CdTe@H-ZIF-8/CDs@MIPs was remarkably quenched by DA, achieving a linear range of 0-600 nM and a limit of detection of 12.35 nM. The developed ratiometric fluorescence sensor showed an obvious and meaningful color change with a gradual increase in DA concentration under a UV lamp. Moreover, the optimum CdTe@H-ZIF-8/CDs@MIPs was remarkably sensitive and selective in detecting DA among various analogs and showed good anti-interference ability. The HPLC method also further confirmed that CdTe@H-ZIF-8/CDs@MIPs shows good practical application prospects.

Selective and ratiometric fluorescence sensing of bisphenol A in canned food based on portable fluorescent test strips.

In this study, a conversion method and molecular imprinting technology were used to design molecularly imprinted polymers (MIP)-based ratiometric fluorescence test papers. The ZnO quantum dots (ZnO QDs) acted as the background quantum dots and ZIF-8 raw material. Carbon dots (CDs) were used as the identification signals. The imprinting layer achieved a selective function. Therefore, a ZnO@ZIF-8/CDs@MIPs sensor was designed for the detection of Bisphenol A (BPA). The sensor exhibited a fast response time for BPA detection. In addition, the sensor demonstrated that effective detection of BPA can still be achieved in complex environments. The detection limit of this sensor was 0.778 nM with a linear range of 0-60 nM. The corresponding test solutions exhibited clear changes from blue to yellow. The selectivity experiments results demonstrated that ZnO@ZIF-8/CDs@MIPs only exhibit excellent selective recognition effect for BPA. ZnO@ZIF-8/CDs@MIPs-2 was used for the detection of BPA in canned food and compared with the results of HPLC detection of BPA. The two spiked recovery ranges were 96.58-102.04% and 97.43-103.82%, respectively. In addition, the prepared ZnO@ZIF-8/CDs@MIPs-2 test paper visually recognized BPA under ultraviolet light. This study provides guidelines for the design and application of fluorescent test papers for quick detection in practical applications.

Constructing hollow ZIF-8/CDs@MIPs fluorescent sensor from Osmanthus leaves to specifically recognize bovine hemoglobin.

To develop non-toxic, highly efficient and selective fluorescence sensors was a significance research. In this work, a novel hollow fluorescence sensor was designed with biomass carbon dots (CDs), ZIF-8 and molecularly imprinted polymers (MIPs) via aqueous polymerization. The results demonstrated such unique structure fluorescence sensor exhibited fast response time, excellent stability and highly selectively towards bovine hemoglobin (BHb). Even in a complex environment, the hollow fluorescence sensor (H-ZIF-8/CDs@MIPs) still has a good recognition effect on BHb. Under an optimized condition, the hollow fluorescence sensor was quenched linearly with BHb concentration in the range of 0.058-4.5 µM with the detection limit of 15.6 nM. In addition, a possible quenching mechanism of hollow fluorescence towards BHb was confirmed resonance energy transfer (FRET). In the actual application process, the hollow fluorescence sensor showed a better detection performance towards BHb with the recoveries ranged of 98.6-101.1 %. This work provided a strategy to design green and unique hollow fluorescence sensor for practical application.

Global, regional, and national burdens of hip osteoarthritis from 1990 to 2019: estimates from the 2019 Global Burden of Disease Study.

BACKGROUND: Hip osteoarthritis is a common disabling condition of the hip joint and is associated with a substantial health burden. We assessed the epidemiological patterns of hip osteoarthritis from 1990 to 2019 by sex, age, and socio-demographic index (SDI). METHODS: Age-standardized rates (ASRs) were obtained for the incidence and disability-adjusted life years (DALYs) of hip osteoarthritis from 1990 to 2019 for 21 regions, encompassing a total of 204 countries and territories. The estimated annual percentage changes (EAPCs) of ASRs were calculated to evaluate the trends in the incidence and DALYs of hip osteoarthritis over these 30 years. RESULTS: Globally, from 1990 to 2019, the age-standardized incidence rate (ASIR) of hip osteoarthritis increased from 17.02 per 100,000 persons to 18.70 per 100,000 persons, with an upward trend in the EAPC of 0.32 (0.29-0.34), whereas the age-standardized DALY rate increased from 11.54 per 100,000 persons to 12.57 per 100,000 persons, with an EAPC of 0.29 (0.27-0.32). In 2019, the EAPCs of the ASIR and age-standardized DALY rate of hip osteoarthritis were positively associated with the SDI of hip osteoarthritis. In 1990 and 2019, the incidence of hip osteoarthritis was unimodally distributed across different age groups, with a peak incidence in the 60-64-year-old age group, whereas the DALYs increased with age. CONCLUSIONS: The incidence and DALYs of hip osteoarthritis have been increasing globally. The EAPCs of the ASIR and age-standardized DALY rate were particularly significant in developed regions and varied across nations and regions, indicating the urgent need for governments and medical institutions to increase the awareness regarding risk factors, consequences of hip osteoarthritis.

Potential Role of S-Palmitoylation in Cancer Stem Cells of Lung Adenocarcinoma.

S-palmitoylation, catalyzed by a family of 23 zinc finger Asp-His-His-Cys (DHHC) domain-containing (ZDHHC) protein acyltransferases localized on the cell membrane. However, stemness genes modulated by ZDHHCs in lung adenocarcinoma (LUAD) remain to be defined. Previously, we have constructed a network of cancer stem cell genes, including INCENP, based on mRNA stemness indices (mRNAsi) of LUAD. INCENP has the function of a chromosomal passenger complex locating to centromeres, which is performed by the conserved region of its N-terminal domain. INCENP protein with a deletion of the first non-conserved 26 amino acid sequence failed to target centromeres. However, the exact function of the deleted sequence has not been elucidated. To identify novel cancer stem cell-relevant palmitoylated proteins and responsible ZDHHC enzymes in LUAD, we analyzed multi-omics data obtained from the database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and the Human Protein Atlas (HPA). ZDHHC5 is distinguished from the ZDHHC family for being up-regulated in mRNA and protein levels and associated with malignant prognosis. ZDHHC5 was positively associated with INCENP, and the correlation score increased with LUAD stages. CSS-Palm results showed Cys15 was the S-palmitoylation site of INCENP. Interestingly, Cys15 locates in the 1-26 aa sequence of INCENP, and is a conserved site across species. As INCENP is a nuclear protein, we predicted that the nuclear localization signal of ZDHHC5 was specific to the importin αß pathway, and the result of immunofluorescence proves that ZDHHC5 is located in the nucleoplasm, in addition to the plasma membrane. Therefore, our study indicates the S-palmitoylation of INCENP mediated by ZDHHC5 as a potential mechanism of S-palmitoylation to modulate CSCs in LUAD.

Identification of biomarkers for acute leukemia via machine learning-based stemness index.

Traditional methods to understand leukemia stem cell (LSC)'s biological characteristics include constructing LSC-like cells and mouse models by transgenic or knock-in methods. However, there are some potential pitfalls in using this method, such as retroviral insertion mutagenesis, non-physiological level gene expression, non-physiological expansion, and difficulty to construct. The mRNAsi index for each sample of the Cancer Genome Atlas (TCGA) could avoid these potential pitfalls by machine learning. In this work, we aimed to construct a network of LSC genes utilizing the mRNAsi. First, mRNAsi value was analyzed with expressions distributions, survival analysis, age, and gender in acute myeloid leukemia (AML) samples. Then, we used the weighted gene co-expression network analysis (WGCNA) to construct modules of stemness genes. The correlation of the LSC genes transcription and interplay among LSC proteins was analyzed. We performed functional and pathway enrichment analysis to annotate stemness genes. Survival analysis further identified prognostic biomarkers by clinical data of TCGA and the Gene Expression Omnibus (GEO) database. We found that the result of mRNAsi overall survival is not significant, which may be due to the heterogeneity of AML in the stage of myeloid differentiation, French-American-British (FAB) classification systems. Enrichment analysis indicated that the stemness genes were biologically clustered as a group and mainly associated with cell cycle and mitosis. Moreover, 10 key genes (SNRNP40, RFC4, RFC5, CDC6, HSPE1, PA2G4, SNAP23P, DARS2, MIS18A, and HPRT1) were screened by survival analysis with the data from TCGA and GEO. Among them, RFC4 and RFC5 were the distinguished biomarkers for their double-validated prognostic value in both databases. Additionally, the expression of RFC4 and RFC5 had the same trend as mRNAsi score in FAB subtypes. In conclusion, our result demonstrated that mRNAsi based LSC-related genes were found to have strong interactions as a cluster. These genes, especially RFC4 and RFC5, could be the therapeutic targets for inhibiting the stemness characteristics of AML. This work is also a comprehensive pipeline for future cancer stem cell studies.

Clinical and molecular characteristics of Staphylococcus aureus isolated from Chinese children: association among the agr groups and genotypes, virulence genes and disease types.

BACKGROUND: This study was aimed to investigate the clinical and molecular epidemiology of Staphylococcus aureus (S. aureus) isolated from Chinese children and determine the possible relationship among the accessory gene regulator (agr) groups and genotypes, as well as among the virulence genes and disease types. METHODS: S. aureus strains were isolated from Beijing Children's Hospital between October 2017 and October 2019. The isolates and 19 virulence genes were characterized using multi-locus sequence typing, staphylococcal protein A (spa), staphylococcal cassette chromosome mec, and agr typing. RESULTS: A total of 191 non-repetitive S. aureus clinical isolates were divided into 33 sequence types (STs), 18 clonal complexes (CCs), and 59 spa types. ST59 (39.8%), t437 (37.7%), and agr I (84.8%) were the predominant types. CC59, CC25, CC22, CC951, CC8, and CC398 belonged to agr I. CC5 and CC15 were assigned to agr II, and CC30 was characterized as agr III. CC121 was classified under agr IV. The eta, etb, and bbp genes were more prevalent in agr IV (P < 0.001 for each), while tst was more prevalent in agr group III compared to the other groups (P < 0.001). Nearly all isolates that harbored lukS/F-PV belonged to agr I (P = 0.005). However, the correlation between disease types and agr groups was not significant (P > 0.05). CONCLUSIONS: An association among the agr groups and genotypes, as well as specific toxin genes, was observed among the S. aureus strains isolated from Chinese children. However, a statistical correlation was not found among the agr groups and disease types.

Visual monitoring of trace water in organic solvents based on ecofriendly b/r-CDs ratiometric fluorescence test paper.

Developing a green, non-toxic and easy to synthesize of fluorescence probe for fast and visual detecting trace water in various organic solvents was an important task. Here, a novel dual-emission fluorescence probe (b/r-CDs) was designed based on the red CDs (r-CDs) and blue CDs (b-CDs) to detect the trace water and enhance the visualization for naked-eye observation in different organic solvents. Among, the red fluorescence carbon dots (CDs) was found to have the capability to monitor trace amounts of water, which synthesized with green tea by facile ultrasonic method. Further, Such a dual-emission probe could fast monitor trace water in various organic solvents with high stability and fast response. Importantly, a synergistic mechanism of the dynamic process (b-CDs) and static quenching (r-CDs) was proved for the study of water detection. Moreover, the test paper was made for detecting trace water in different organic solvents, achieving convenient and effective detection.

LRRC19-A Bridge between Selenium Adjuvant Therapy and Renal Clear Cell Carcinoma: A Study Based on Datamining.

Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.

Molecularly imprinted polymers-captivity ZnO nanorods for sensitive and selective detecting environmental pollutant.

To develop the semiconductor of ZnO nanomaterials as the fluorescence sensor without leakage toxicity. Here, a molecularly imprinted polymer captivity ZnO nanorods (NRs) (MIPs-captivity ZnO NRs) was fabricated by precipitation polymerization. Such traditional technology was not only achieved the specific recognition for direct fluorescent quantification of the target tetracycline (TC) through fluorescence quenching, but also formed the shield to reduce the toxic effects of ZnO towards organisms. Under the optimized experimental conditions, the MIPs-captivity ZnO NRs were effectively applied to the direct fluorescence quantification of TC with excellent stability. Moreover, the practical analytical performance of the MIPs-captivity ZnO NRs was assayed by appraising the detection effects of TC in water sample from the Yangtze River with satisfactory results.

Biomass derived the V-doped carbon/Bi2O3 composite for efficient photocatalysts.

This work focused on the utilization of biological extract for the preparation of lignin-based carbon composites materials and used in the field of photocatalysis. A straightforward one-step carbonization way has been developed to prepare vanadium-doped lignin-based carbon/Bi2O3 composites photocatalyst by using sodium lignosulfonate as the carbon source and catalyst. The application of lignin as the carbon source to form photocatalyst support tends to control the uniform distribution. At the same time, sodium lignosulfonate as the catalyst could break down the BiVO4 during carbonization process. A series of characterizations demonstrated the BiVO4 was transformed into Bi2O3 and vanadium-doped lignin-based carbon. The possible synthesis process was proposed. Moreover, the novel V-doped carbon/Bi2O3 composites photocatalyst displayed higher photocatalytic activity than bare BiVO4. A possible photocatalytic mechanism was also discussed. This work provided new insight into the lignin-based carbon materials.

Photocatalytic removal using g-C3N4 quantum dots/Bi2Ti2O7 composites.

In this work, a simple method to load of g-C3N4 quantum dots (CN QDs) onto Bi2Ti2O7 (BTO) microsphere with the amount of CN QDs (3, 7, 10 and 15%). The photocatalyst was used for the treatment of water pollutants under visible-light illumination, which proved that CNBTO composites showed improved photocatalytic activity matched up to pure BTO. Reformation of BTO with CN QDs enhanced the light assimilation capacity, and promoted the isolation of photo-induced electron-hole pairs. The trapping experiments and ESR were announced the holes (h+) and superoxide oxide (O2-) played the key role, and the relative mechanism of the photocatalytic process was proposed. Meanwhile, the effects of CN QDs content, pH and initial pollutant concentration on the removal efficiency of ciprofloxacin (CIP) were studied. Results showed that the CN QDs loaded on BTO presented higher photocatalytic efficiency, and an optimum value for the dosage of photocatalytic in pH 8.0.

Preparation of a self-cleanable molecularly imprinted sensor based on surface-enhanced Raman spectroscopy for selective detection of R6G.

Novel molecularly imprinted polymers (MIPs) based on the technique of surface-enhanced Raman scattering (SERS) were successfully prepared. Firstly, ZnO nanorods were fabricated with Ag by reduction of Ag+ on the surface of the ZnO nanorods. Then, ZnO/Ag heterostructures were used as the substrate, rhodamine 6G was used as the template molecule, acrylamide was used as the functional monomer, ethylene glycol dimethacrylate was used as the cross-linker, and 2,2'-azobis(2-methylpropionitrile) was used as the initiator to prepare the ZnO/Ag MIPs (ZOA-MIPs). Through characterization analysis, it was proved that the novel ZOA-MIPs exhibited excellent SERS properties and selectivity. Under the optimal conditions, there was a good linear relationship (R 2 = 0.996) between the Raman signal (at 1654 cm-1) and the concentration of the templates, and the detection limit was 10-13 mol L-1. It was also proved that the ZOA-MIPs had the property of self-cleaning, resulting in good reusability. It is envisaged that the sensitivity of SERS coupled with the selectivity of MIPs could result in a promising chemosensor for practical applications.

A high performance and highly-controllable core-shell imprinted sensor based on the surface-enhanced Raman scattering for detection of R6G in water.

A novel, sensitive sensor material combined the technique of surface enhance Raman scattering (SERS) and molecular imprinting was prepared. It was used the amino-functionalized SiO2 nanospheres as the supporting materials and anchored Ag nanoparticles on the surface by the function of coordination between Ag+ and NH2-. Then, it was used that the Rhodamine 6G (R6G) as the template, acrylamide (AM) as functional monomer, ethyleneglycol dimethacrylate (EGDMA) as cross-linker, 2,2'-azobis(2-methylpropionitrile) (AIBN) as initiator to prepare the core-shell molecular imprinted polymers. Prominently, the shell thickness could be controlled by the regulation of cross-linker dosage and it was found that the SERS detection signal was most obvious when the shell thickness was about 40nm. Under the optimal condition, it was presented good linear relationship (R2=0.93) between the Raman signal (at 1505cm-1) and the concentration of the templates and the limit of detection was 10-12molL-1. Meanwhile, the selective experiment was proved that this materials owned specific selectivity to the template. It was confirmed that the core-shell molecular imprinted polymers were a kind of highly sensitive and selective sensor materials in the field of R6G detection.

Prognostic factors for severe acute respiratory syndrome: a clinical analysis of 165 cases.

This study analyzes single factors that affect the prognosis of severe acute respiratory syndrome (SARS) and establishes a prognosis model by multivariate analysis. We retrospectively analyzed the clinical features of SARS in 165 clinically confirmed severe cases. Both age and existence of other diseases before SARS were significantly correlated with prognosis (r=0.506 and r=0.457, respectively; P<.001). During the acute phase of SARS, lactate dehydrogenase level, degree of hypoxemia, respiratory rate, alpha -hydroxybutyric dehydrogenase level, creatine kinase isoenzyme-MB, platelet count, and number of involved lobes noted on chest radiographs, and so on, correlated markedly with the prognosis (r=0.257-0.788; P<.05). The multivariate prognosis regression model was associated with degree of hypoxemia and platelet count. The model was defined by the formula Py=1=es/(1+es), where S is [2.490 x degree of hypoxemia]-[0.050 x number of platelets], and it had a high sensitivity (91.67%), specificity (98.33%), and accuracy (96.42%). The model could be used to effectively judge the state of illness and the prognosis.