Temporal-spatial distributions of road silt loadings and fugitive road dust emissions in Beijing from 2019 to 2020.

Road silt loading (sL) is an important parameter in the fugitive road dust (FRD) emissions. In this study, the improved Testing Re-entrained Aerosol Kinetic Emissions from Roads (TRAKER) combined with the AP-42 method was firstly developed to quickly measure and estimate the sLs of paved roads in Beijing, China. The annual average sLs in Beijing was 0.59±0.31 g/m2 in 2020, and decreased by 22.4% compared with that in 2019. The seasonal variations of sLs followed the order of spring > winter > summer > autumn in the two years. The seasonal mean road sLs on the same type road in the four seasons presented a decline trend from 2019 to 2020, especially on the Express way, decreasing 47.4%-72.7%. The road sLs on the different type roads in the same season followed the order of Major arterial ∼ Minor arterial ∼ Branch road > Express road, and Township road ∼ Country highway > Provincial highway ∼ National highway. The emission intensities of PM10 and PM2.5 from FRD in Beijing in 2020 were lower than those in 2019. The PM10 and PM2.5 emission intensities at the four planning areas in the two years all presented the order of the capital functional core area > the urban functional expansion area > the urban development new area > the ecological conservation and development area. The annual emissions of PM10 and PM2.5 from FRD in Beijing in 2020 were 74,886 ton and 18,118 ton, respectively, decreasing by ∼33.3% compared with those in 2019.

Genome-wide identification of Tomato Golden 2-Like transcription factors and abiotic stress related members screening.

BACKGROUND: Golden 2-Like (G2-like) transcription factors play an important role in plant development. However, the roles of these G2-like regulatory genes in response to abiotic stresses in tomato are not well understood. RESULTS: In this study, we identified 66 putative G2-like genes in tomato (Solanum lycopersicum) and classified them into 5 groups (I to V) according to gene structure, motif composition and phylogenetic analysis. The G2-like genes were unevenly distributed across all 12 chromosomes. There were nine pairs of duplicated gene segments and four tandem duplicated SlGlk genes. Analysis of the cis-regulatory elements (CREs) showed that the promoter regions of SlGlks contain many kinds of stress- and hormone-related CREs. Based on RNA-seq, SlGlks were expressed in response to three abiotic stresses. Thirty-six differentially expressed SlGlks were identified; these genes have multiple functions according to Gene Ontology (GO) analysis and are enriched mainly in the zeatin biosynthesis pathway. Further studies exhibited that silencing SlGlk16 in tomato would reduce drought stress tolerance by earlier wilted, lower superoxide dismutase (SOD), peroxidase (POD) activities, less Pro contents and more MDA contents. CONCLUSIONS: Overall, the results of this study provide comprehensive information on G2-like transcription factors and G2-like genes that may be expressed in response to abiotic stresses.

Increasing the bioactivity of kynurenine by ultraviolet irradiation via resonance energy transfer in vitro.

Kynurenine (Kyn) is involved in a variety of physiological/pathological reactions via activating aryl hydrocarbon receptor (Ahr). However, how to activate Ahr by Kyn under physiological/pathological conditions is still unclear. Here, we presented that Kyn (8 µM, a concentration less than the dose of Kyn-induced Ahr activation) significantly induced the nuclear transfer of Ahr and the expression of cytochrome P450 1A1 (CYP1A1, a classic biomarker for Ahr activation) when co-administered with ultraviolet (UV) irradiation in 95D cells, which were transfected transiently with siRNA against indoleamine 2,3-dioxygenase 1 (IDO 1) and cultured in cell medium supplemented with bovine serum containing bovine serum albumin (BSA), in vitro. Additionally, we found that the fluorescence intensity of BSA was attenuated by Kyn (2, 4, 6, 8, 10, 12 and 14 µM) mainly through quenching the fluorescence of tryptophan (Trp) residues in the pattern of dynamic quenching related to molecular diffusion. More important, resonance energy transfer from excited-state BSA to Kyn was confirmed, leading to the generation "energetic" Kyn that might be ability of hyperactivity according to the theory of photochemical reaction. These data indicate that UV irradiation is contributable for Kyn to function, and present a novel pattern of altering the activity of biomolecules to some degree.

Emodin inhibits viability, proliferation and promotes apoptosis of hypoxic human pulmonary artery smooth muscle cells via targeting miR-244-5p/DEGS1 axis.

OBJECTIVE: This study aimed to determine the effects of emodin on the viability, proliferation and apoptosis of human pulmonary artery smooth muscle cells (PASMCs) under hypoxia and to explore the underling molecular mechanisms. METHODS: PASMCs were cultured in a hypoxic environment (1% oxygen) and then treated with emodin. Cell viability, proliferation and apoptosis were evaluated using CCK-8 assay, EdU staining assay, western blot and Mito-tracker red CMXRos and Annexin V-FITC apoptosis detection assay. The microRNA (miRNA)/mRNA and protein expression levels were assessed by quantitative real-time PCR and western blotting, respectively. Based on transcriptomics and proteomics were used to identify potential signaling pathways. Luciferase reporter assay was utilized to examine the interaction between miR-244-5p and DEGS1. RESULTS: Emodin at 40 and 160 µM concentration-dependently suppressed cell viability, proliferation and migration, but enhanced cell apoptosis of PASMCs under hypoxia. Transcriptomic and proteomic analysis revealed that emodin could attenuate the activity of PI3K/Akt signaling in PASMCs under hypoxia. In addition, delta 4-desaturase, sphingolipid 1 (DEGS1) was found to be a direct target of miR-244-5p. Emodin could significantly up-regulated miR-244-5p expression and down-regulated DEGS1 expression in PASMCs under hypoxia. Furthermore, emodin-mediated effects on cell viability, migration, apoptosis and PI3K/Akt signaling activity of PASMCs under hypoxia were significantly attenuated by miR-244-5p knockdown. CONCLUSIONS: Our results indicated that emodin suppressed cell viability, proliferation and migration, promoted cell apoptosis of PASMCs under hypoxia via modulating miR-244-5p-mediated DEGS1/PI3K/Akt signaling pathway. MiR-244-5p/DEGS1 axis was initially investigated in this current study, which is expected to further the understanding of the etiology of pulmonary arterial hypertension.

Intercellular Bridge Mediates Ca2+ Signals between Micropatterned Cells via IP3 and Ca2+ Diffusion.

Intercellular bridges are plasma continuities formed at the end of the cytokinesis process that facilitate intercellular mass transport between the two daughter cells. However, it remains largely unknown how the intercellular bridge mediates Ca2+ communication between postmitotic cells. In this work, we utilize BV-2 microglial cells planted on dumbbell-shaped micropatterned assemblies to resolve spatiotemporal characteristics of Ca2+ signal transfer over the intercellular bridges. With the use of such micropatterns, considerably longer and more regular intercellular bridges can be obtained than in conventional cell cultures. The initial Ca2+ signal is evoked by mechanical stimulation of one of the daughter cells. A considerable time delay is observed between the arrivals of passive Ca2+ diffusion and endogenous Ca2+ response in the intercellular-bridge-connected cell, indicating two different pathways of the Ca2+ communication. Extracellular Ca2+ and the paracrine pathway have practically no effect on the endogenous Ca2+ response, demonstrated by application of Ca2+-free medium, exogenous ATP, and P2Y13 receptor antagonist. In contrast, the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin and inositol trisphosphate (IP3) receptor blocker 2-aminoethyl diphenylborate significantly inhibit the endogenous Ca2+ increase, which signifies involvement of IP3-sensitive calcium store release. Notably, passive Ca2+ diffusion into the connected cell can clearly be detected when IP3-sensitive calcium store release is abolished by 2-aminoethyl diphenylborate. Those observations prove that both passive Ca2+ diffusion and IP3-mediated endogenous Ca2+ response contribute to the Ca2+ increase in intercellular-bridge-connected cells. Moreover, a simulation model agreed well with the experimental observations.

Resequencing core accessions of a pedigree identifies derivation of genomic segments and key agronomic trait loci during cotton improvement.

Upland cotton (Gossypium hirsutum) is the world's largest source of natural fibre and dominates the global textile industry. Hybrid cotton varieties exhibit strong heterosis that confers high fibre yields, yet the genome-wide effects of artificial selection that have influenced Upland cotton during its breeding history are poorly understood. Here, we resequenced Upland cotton genomes and constructed a variation map of an intact breeding pedigree comprising seven elite and 19 backbone parents. Compared to wild accessions, the 26 pedigree accessions underwent strong artificial selection during domestication that has resulted in reduced genetic diversity but stronger linkage disequilibrium and higher extents of selective sweeps. In contrast to the backbone parents, the elite parents have acquired significantly improved agronomic traits, with an especially pronounced increase in the lint percentage. Notably, identify by descent (IBD) tracking revealed that the elite parents inherited abundant beneficial trait segments and loci from the backbone parents and our combined analyses led to the identification of a core genomic segment which was inherited in the elite lines from the parents Zhong 7263 and Ejing 1 and that was strongly associated with lint percentage. Additionally, SNP correlation analysis of this core segment showed that a non-synonymous SNP (A-to-G) site in a gene encoding the cell wall-associated receptor-like kinase 3 (GhWAKL3) protein was highly correlated with increased lint percentage. Our results substantially increase the valuable genomics resources available for future genetic and functional genomics studies of cotton and reveal insights that will facilitate yield increases in the molecular breeding of cotton.

Simultaneous energy transfer from molecular-like silver nanoclusters to Sm3+/Ln3+ (Ln = Eu or Tb) in glass under UV excitation.

Molecular-like silver nanoclusters (ML-Ag NCs) with size dependent tunable luminescence properties and high-quantum yield has been explored as a new type of sensitizer for rare earth (RE) ions in glasses recently. In this research, the borosilicate glasses containing ML-Ag NCs and RE3+ (RE = Sm, Eu, Tb) ions were prepared with melt-quenching method. The absorption, TEM and steady spectra measurements indicated that compare with Sm3+ and Tb3+, the introduction of Eu3+ can more effectively promote the formation of luminescent ML-Ag NCs and their further aggregation. Besides the predictable efficient energy transfer from ML-Ag NCs to a single type of RE3+ ion in the codoped glasses, the simultaneously sensitization of Sm3+/Eu3+ and Sm3+/Tb3+ couples by ML-Ag NCs were further realized in the tri-doped glasses. Benefited from the excitation wavelength dependence of energy transfer from ML-Ag NCs to Sm3+/Eu3+ and Sm3+/Tb3+ couples and excitation efficiency on ML-Ag NCs and RE3+ ions, the tri-doped glasses exhibit broad tunable emission simply by changing the excitation wavelength, and the white light emission was achieved in GAgSmEu under UV excitation.

Interleukin-7 Resensitizes Non-Small-Cell Lung Cancer to Cisplatin via Inhibition of ABCG2.

Treatment with cisplatin (DDP) is one of the standard therapies used to treat non-small-cell lung cancer (NSCLC) and fundamentally causes resistance in cancer cells, which eventually poses as an obstacle to the efficacy of chemotherapy in NSCLC. Efforts are on all over the world to explore a sensitizer of NSCLC to DDP. Here, we studied the effect of IL-7 on the resistance of NSCLC to chemotherapy. We observed that IL-7 treatment significantly enhanced DDP-induced effects in A549 and A549/DDP cells (DDP-resistant cells), including decreased cell viability and proliferation, as well as increased cell apoptosis and S arrest, indicating that IL-7 treatment resensitized DDP-resistant NSCLC cells to DDP. Subsequently, IL-7 enhanced the sensitivity of PI3K/AKT signaling and expressions of ABCG2 to DDP. By inhibiting IL-7 signaling via IL-7R knockdown or activating PI3K/AKT signaling via PI3K activation, the resensitization to DDP by IL-7 was abrogated, and the expression levels of ABCG2, p-PI3K, and p-AKT were found to be significantly higher. In vivo results also confirmed that IL-7 only in combination with DDP could remarkably induce tumor regression with reduced levels of ABCG2 in tumorous tissues. These findings indicate that IL-7, apart from its adjuvant effect, could overcome multidrug resistance of DDP to restore its chemotherapy sensitivity.

Physiological and RNA-seq analyses provide insights into the response mechanism of the Cf-10-mediated resistance to Cladosporium fulvum infection in tomato.

KEY MESSAGE: Based on the physiological and RNA-seq analysis, some progress has been made in elucidating the Cf-10-mediated resistance responses to C. fulvum infection in tomato. GO and KEGG enrichment analysis revealed that the DEGs were significantly associated with defense-signaling pathways like oxidation-reduction processes, oxidoreductase activity and plant hormone signal transduction. Leaf mold, caused by the fungus Cladosporium fulvum, is one of the most common diseases affecting tomatoes worldwide. Cf series genes including Cf-2, Cf-4, Cf-5, Cf-9 and Cf-10 play very important roles in resisting tomato leaf mold. Understanding the molecular mechanism of Cf gene-mediated resistance is thus the key to facilitating genetic engineering of resistance to C. fulvum infection. Progress has been made in elucidating two Cf genes, Cf -19 and Cf -12, and how they mediate resistance responses to C. fulvum infection in tomato. However, the mechanism of the Cf-10- mediated resistance response is still unclear. In the present study, RNA-seq was used to analyze changes in the transcriptome at different stages of C. fulvum infection. A total of 2,242 differentially expressed genes (DEGs) responsive to C. fulvum between 0 and 16 days post infection (dpi) were identified, including 1,501 upregulated and 741 downregulated genes. The majority of DEGs were associated with defense-signaling pathways including oxidation-reduction processes, oxidoreductase activity and plant hormone signal transduction. Four DEGs associated with plant-pathogen interaction were uniquely activated in Cf-10 tomato and validated by qRT-PCR. In addition, physiological indicators including reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were measured at 0-21 dpi, and hormone expression [Jasmonic acid (JA) and salicylic acid (SA)] was estimated at 0 and 16 dpi to elucidate the mechanism of the Cf-10-mediated resistance response. C. fulvum infection induced the activities of POD, CAT and SOD, and decreased ROS levels. JA was determined to participate in the resistance response to C. fulvum during the initial infection period. The results of this study provide accountable evidence for the physiological and transcriptional regulation of the Cf-10-mediated resistance response to C. fulvum infection, facilitating further understanding of the molecular mechanism of Cf-10-mediated resistance to C. fulvum infection.

Enhancing the Sensing Properties of TiO2 Nanosheets with Exposed {001} Facets by a Hydrogenation and Sensing Mechanism.

Hydrogenation is successfully employed to improve sensing performances of the gas sensors based on TiO2 nanosheets with exposed {001} facets for the first time. The hydrogenated TiO2 nanosheets show a significantly higher response toward ethanol, acetone, triethylamine, or formaldehyde than the samples without hydrogenation, and the response further increases with an increase of the hydrogenation temperature. The excellent sensing performances are ascribed to an increase of the density of unsaturated Ti5c atoms on the {001} surface resulting from the hydrogenation process. The unsaturated Ti5c atoms are considered to serve as sensing reaction active sites. They can generate noncontributing (free) electrons and adsorb oxygen molecules, and the detailed sensing mechanism is described at atomic and molecule level. The hydrogenated strategy may be employed to enhance the sensing performances of other metal oxide sensors and catalytic reaction activities of catalyst. The concept of the surface unsaturated metal atoms serving as sensing reaction active sites not only deepens the understanding of the sensing reaction and catalytic reaction mechanism but also provides new insights into the design of advanced gas sensing materials, catalysts, and photoelectronic devices.

Hemorrhagic events in cancer patients treated with aflibercept: a meta-analysis.

Aflibercept (Ziv-aflibercept, VEGF Trap, AVE005) is an engineered protein that functions as a decoy receptor to bind vascular endothelial growth factor A (VEGF-A). Hemorrhagic events, including epistaxis, gastrointestinal bleeding, and pulmonary bleeding, is one of its major adverse effects, but the incidence rate and overall risk has not been systematically studied. Therefore, we conducted a meta-analysis of published clinical trials to investigate the incidence and relative risk of hemorrhagic events in cancer patients treated with aflibercept. Electronic databases including PubMed, Embase, Cochrane databases, and American Society of Clinical Oncology abstracts were searched. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with aflibercept with toxicity profile on hemorrhagic events. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies. A total of 4,538 patients with a variety of solid tumors from 13 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade hemorrhagic events in cancer patients were 22.1 % (95 % CI, 16.5-29.7 %) and 4.2 % (95 % CI, 3.9-4.6 %), respectively. The relative risks of hemorrhagic events of aflibercept compared to control were increased for all-grade (RR = 2.63; 95 % CI, 2.07-3.34) and high-grade (RR = 2.45, 95 % CI, 1.62-3.72) hemorrhagic events. The risk of developing high-grade hemorrhagic events with aflibercept was comparable to that of bevacizumab (RR = 1.26; 95 % CI, 0.89-1.79). Aflibercept is associated with an increased risk of developing hemorrhagic events in patients with solid tumors. Close monitoring and management of hemorrhagic events are recommended.

Enhanced Sensing Performance of SnX Ti1-X O2 -TiX Sn1-X O2 Core-Shell Heterostructure via Increasing the Density of Unsaturated Sn and Ti Atoms.

The strategy of combining different semiconductor materials is adjudged an effective approach to improve the sensing performances of semiconductor materials. However, the specific synergistic mechanism for the excellent gas-sensitive performances of composite materials has not been elucidated. Herein, a facile solvothermal method is employed to synthesize SnX Ti1-X O2 -TiX Sn1-X O2 core-shell heterostructures using SnCl4 •5H2 O and tetrabutyl titanate (TBOT) as raw materials. When the molar ratio of SnCl4 •5H2 O/TBOT is 1.8/3.0, the afforded composite exhibited the highest gas sensing performances compared with other composites prepared with other molar ratios. The enhanced sensing performance is attributed to the simultaneous incorporation of Sn and Ti ions into each other's lattice, leading to an increase in the density of unsaturated Sn and Ti atoms on the surface. Ultimately, more oxygen vacancies are formed by the unsaturated Sn and Ti atoms, which benefits electron capture and the redox reaction of adsorbed gases. Thus, the concept of increased unsaturated metal atoms and oxygen vacancy resulting from the doping of different metal ions into each other's lattice has deepened the understanding of gas sensing and the catalytic reaction mechanisms. The lattice synergy of different metals provides a pathway for the design of advanced gas-sensing materials and catalysts.

[Clinical analysis of patients with cardiopulmonary resuscitation in emergency department and establishment of prediction model of restoration of spontaneous circulation in hospital].

OBJECTIVE: To screen the independent influencing factors of restoration of spontaneous circulation (ROSC) in patients after cardiopulmonary resuscitation (CPR) and establish a predictive model, and explore its clinical value. METHODS: A retrospective case control study was conducted. The clinical data of cardiac arrest patients admitted to the emergency department of Tangdu Hospital of Air Force Military Medical University and received CPR from January to July 2023 were analyzed, including general information, blood biochemical indicators, main cause of cardiac arrest, whether it was defibrillation rhythm, duration from admission to CPR, and whether ROSC was achieved. The clinical data between the patients whether achieved ROSC or not were compared. The binary multivariate Logistic regression analysis was used to screen the independent influencing factors of ROSC in in-hospital CPR patients. According to the above influencing factors, the ROSC prediction model was established, and the receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of the model for ROSC. RESULTS: A total of 235 patients who received CPR in the emergency department were enrolled, including 153 cases (65.11%) of in-hospital CPR and 82 cases (34.89%) of out-of-hospital CPR. The ROSC ratio was 30.21% (71/235). Among all patients, the majority were aged 61-80 years [40.43% (95/235)], and cardiogenic disease was the main cause of cardiac arrest [32.77% (77/235)]. Among 153 patients with in-hospital CPR, 89 were non-ROSC and 64 were ROSC with ROSC rate of 41.83%. Compared with the non-ROSC group, the patients in the ROSC group had lower blood lactic acid (Lac), N-terminal pro-brain natriuretic peptide (NT-proBNP), Lac/albumin (Alb) ratio (LAR), and ratio of non-defibrillation rhythm [Lac (mmol/L): 5.50 (2.33, 9.65) vs. 7.10 (3.50, 13.35), NT-proBNP (µg/L): 0.87 (0.20, 8.68) vs. 3.00 (0.58, 20.17), LAR: 0.14 (0.07, 0.29) vs. 0.19 (0.10, 0.43), non-defibrillation rhythm ratio: 68.75% (44/64) vs. 93.26% (83/89)], higher actual base excess (ABE) and Alb [ABE (mmol/L): -3.95 (-12.75, 0.23) vs. -7.50 (-13.50, -3.35), Alb (g/L): 38.13±7.03 vs. 34.09±7.81], and shorter duration from admission to CPR [hours: 3.25 (1.00, 14.00) vs. 8.00 (2.00, 27.50)], the differences were statistically significant (all P < 0.05). Binary multivariate Logistic regression analysis showed that LAR [odds ratio (OR) = 0.037, 95% confidence interval (95%CI) was 0.005-0.287], non-defibrillation rhythm (OR = 0.145, 95%CI was 0.049-0.426), and duration from admission to CPR (OR = 0.984, 95%CI was 0.972-0.997) were independent influencing factors for ROSC in hospitalized CPR patients (all P < 0.05). Based on the above influencing factors, a ROSC prediction model was constructed through regression analysis results. The ROC curve analysis showed that the area under the ROC curve (AUC) for predicting ROSC in in-hospital CPR patients was 0.757 (95%CI was 0.680-0.834), Yoden index was 0.429, sensitivity was 76.6%, and specificity was 66.3. CONCLUSIONS: LAR, non-defibrillation rhythm and duration from admission to CPR were independent influencing factors for ROSC in patients with in-hospital CPR. The ROSC prediction model established based on the above influencing factors has a good predictive value for ROSC of CPR patients in hospital, and can guide clinicians to evaluate the prognosis of patients through relevant indicators as early as possible.

Osteogenically committed hUCMSCs-derived exosomes promote the recovery of critical-sized bone defects with enhanced osteogenic properties.

Low viability of seed cells and the concern about biosafety restrict the application of cell-based tissue-engineered bone (TEB). Exosomes that bear similar bioactivities to donor cells display strong stability and low immunogenicity. Human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-Exos) show therapeutic efficacy in various diseases. However, little is known whether hUCMSCs-Exos can be used to construct TEB to repair bone defects. Herein, PM-Exos and OM-Exos were separately harvested from hUCMSCs which were cultured in proliferation medium (PM) or osteogenic induction medium (OM). A series of in-vitro studies were performed to evaluate the bioactivities of human bone marrow mesenchymal stem cells (hBMSCs) when co-cultured with PM-Exos or OM-Exos. Differential microRNAs (miRNAs) between PM-Exos and OM-Exos were sequenced and analyzed. Furthermore, PM-Exos and OM-Exos were incorporated in 3D printed tricalcium phosphate scaffolds to build TEBs for the repair of critical-sized calvarial bone defects in rats. Results showed that PM-Exos and OM-Exos bore similar morphology and size. They expressed representative surface markers of exosomes and could be internalized by hBMSCs to promote cellular migration and proliferation. OM-Exos outweighed PM-Exos in accelerating the osteogenic differentiation of hBMSCs, which might be attributed to the differentially expressed miRNAs. Furthermore, OM-Exos sustainably released from the scaffolds, and the resultant TEB showed a better reparative outcome than that of the PM-Exos group. Our study found that exosomes isolated from osteogenically committed hUCMSCs prominently facilitated the osteogenic differentiation of hBMSCs. TEB grafts functionalized by OM-Exos bear a promising application potential for the repair of large bone defects.

Construction of a TFs-miRNA-mRNA network related to idiopathic pulmonary fibrosis.

Background: The transcription factors (TFs)-microRNA (miRNA)-messenger RNA (mRNA) network plays an important role in a variety of diseases. However, the relationship between the TFs-miRNA-mRNA network and idiopathic pulmonary fibrosis (IPF) remains unclear. Methods: The GSE110147 and GSE53845 datasets from the Gene Expression Omnibus (GEO) database were used to process differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), as well as Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The GSE13316 dataset was used to perform differentially expressed miRNAs (DEMs) analysis and TFs prediction. Finally, a TFs-miRNA-mRNA network related to IPF was constructed, and its function was evaluated by Gene Ontology (GO) and KEGG analyses. Also, 19 TFs in the network were verified by quantitative real time polymerase chain reaction (qRT-PCR). Results: Through our analysis, 53 DEMs and 2,630 DEGs were screened. The GSEA results suggested these genes were mainly related to protein digestion and absorption. The WGCNA results showed that these DEGs were divided into eight modules, and the GO and KEGG analyses results of blue module genes showed that these 86 blue module genes were mainly enriched in cilium assembly and cilium organization. Moreover, a TFs-miRNA-mRNA network comprising 25 TFs, 11 miRNAs, and 60 mRNAs was constructed. Ultimately, the functional enrichment analysis showed that the TFs-miRNA-mRNA network was mainly related to the cell cycle and the phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling pathway. Furthermore, experimental verification of the TFs showed that ARNTL, TRIM28, EZH2, BCOR, and ASXL1 were sufficiently up-regulated in the transforming growth factor (TGF)-ß1 treatment groups, while BCL6, BHLHE40, FOXA1, and EGR1 were significantly down-regulated. Conclusions: The novel TFs-miRNA-mRNA network that we constructed could provide new insights into the underlying molecular mechanisms of IPF. ARNTL, TRIM28, EZH2, BCOR, ASXL1, BCL6, BHLHE40, FOXA1, and EGR1 may play important roles in IPF and become effective biomarkers for diagnosis and treatment.

Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study.

BACKGROUND AND AIMS: Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival. METHODS: This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality. RESULTS: Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (ΔCLIF-OF ≥2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D). CONCLUSION: This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.

[Inhibition of lipopolysaccharide-induced myeloid-derived suppressor cells in the proliferation of spleen T lymphocytes].

OBJECTIVE: To explore the effects of lipopolysaccharide (LPS)-induced myeloid-derived suppressor cells (MDSCs) on the proliferation of spleen T lymphocytes. METHODS: BALB/c mice were randomly divided into two groups: LPS group and normal control group. They were injected intraperitoneally with LPS and normal saline solution respectively. MDSCs were separated with CD11b immunomagnetic beads from the spleen extract of mice. The morphological characteristics of MDCSs were observed by Wright-Giemsa staining and the characteristic molecules on cell surface identified by flow cytometry. And the effects of MDSCs on the in vitro proliferation of T cells were determined by methyl-thiazolyl-tetrazolium bromide (MTT). RESULTS: The proportion of MDSCs in the spleen of the LPS group was much more than that of the normal control group (27.4% ± 6.6% vs 5.1% ± 3.8%; t = 5.06, P = 0.007). CD11b(+)Gr-1(+)MDSCs could be separated by CD11b immunomagnetic beads from the spleen of mice injected with LPS at a high purity of 84.0% ± 4.2%. MTT method showed that the proliferation of T cells decreased significantly after a co-cultivation with CD11b(+)MDSCs versus the control group. And it was positively correlated with the number of MDSCs (F = 46.26, P = 0.000). CONCLUSIONS: A high purity of LPS-induced myeloid-derived suppressor cells may be separated with CD11b immunomagnetic beads. And it has dose-dependent inhibitory effects on the proliferation of the spleen T lymphocytes.

Scorpion Peptide Smp24 Exhibits a Potent Antitumor Effect on Human Lung Cancer Cells by Damaging the Membrane and Cytoskeleton In Vivo and In Vitro.

Smp24, a cationic antimicrobial peptide identified from the venom gland of the Egyptian scorpion Scorpio maurus palmatus, shows variable cytotoxicity on various tumor (KG1a, CCRF-CEM and HepG2) and non-tumor (CD34+, HRECs, HACAT) cell lines. However, the effects of Smp24 and its mode of action on lung cancer cell lines remain unknown. Herein, the effect of Smp24 on the viability, membrane disruption, cytoskeleton, migration and invasion, and MMP-2/-9 and TIMP-1/-2 expression of human lung cancer cells have been evaluated. In addition, its in vivo antitumor role and acute toxicity were also assessed. In our study, Smp24 was found to suppress the growth of A549, H3122, PC-9, and H460 with IC50 values from about 4.06 to 7.07 µM and show low toxicity to normal cells (MRC-5) with 14.68 µM of IC50. Furthermore, Smp24 could induce necrosis of A549 cells via destroying the integrity of the cell membrane and mitochondrial and nuclear membranes. Additionally, Smp24 suppressed cell motility by damaging the cytoskeleton and altering MMP-2/-9 and TIMP-1/-2 expression. Finally, Smp24 showed effective anticancer protection in a A549 xenograft mice model and low acute toxicity. Overall, these findings indicate that Smp24 significantly exerts an antitumor effect due to its induction of membrane defects and cytoskeleton disruption. Accordingly, our findings will open an avenue for developing scorpion venom peptides into chemotherapeutic agents targeting lung cancer cells.

Lipid-mediated biosynthetic labeling strategy for in vivo dynamic tracing of avian influenza virus infection.

Monitoring the infection behavior of avian influenza viruses is crucial for understanding viral pathogenesis and preventing its epidemics among people. A number of viral labeling methods have been utilized for tracking viral infection process, but most of them are laborious or decreasing viral activity. Herein we explored a lipid biosynthetic labeling strategy for dynamical tracking the infection of H5N1 pseudotype virus (H5N1p) in host. Biotinylated lipids (biotinyl Cap-PE) were successfully incorporated into viral envelope when it underwent budding process by taking advantage of host cell-derived lipid metabolism. Biotin-H5N1p virus was effectively in situ-labeled with streptavidin-modified near-infrared quantum dots (NIR SA-QDs) using streptavidin-biotin conjugation with well-preserved virus activities. Dual-labeled imaging obviously shows that H5N1p viruses are primarily taken up in host cells via clathrin-mediated endocytosis. In animal models, Virus-conjugated NIR QDs displayed extraordinary photoluminescence, superior stability, and tissue penetration in lung, allowing us to long-term monitor respiratory viral infection in a noninvasive manner. Importantly, the co-localization of viral hemagglutinin protein and QDs in infected lung further conformed the dynamic infection process of virus in vivo. Hence, this in situ QD-labeling strategy based on cell natural biosynthesis provides a brand-new and reliable tool for noninvasion visualizing viral infection in body in a real-time manner.

Durable response to crizotinib in an advanced lung adenocarcinoma patient harboring rare CD47-MET fusion: a case report.

Background: MET fusion is a rare type of structure rearrangement, reported only in 0.26% of non-small cell lung cancer (NSCLC). Some uncommon genomic variants, including MET fusions, have been detected with advanced detection technology. Therapeutic option for MET-rearranged NSCLC remains largely uncovered. Case Description: Herein, we described a 72-year-old male patient with a 10-year history of smoking who presented to our hospital with coughing, blood-tinged sputum, chest distress, and anhelation. He was diagnosed with stage IV lung adenocarcinoma harboring a CD47 (EX7)-MET (EX15) fusion, detected by next-generation sequencing (NGS). After one month of crizotinib treatment, the patient showed partial re-expansion of the collapsed right lower lobe, shrinkages of lymph node lesions, and reduced right pleural effusion. The patient achieved partial response (PR) to first-line treatment of crizotinib with a progression-free survival (PFS) of 8 months. Cabozantinib was subsequently administrated, and a short-term PR of fewer than three months was observed. The patient retained CD47-MET fusion and acquired MET D1228E at cabozantinib progression. Conclusions: This case provided the first clinical evidence for the efficacy of crizotinib in CD47-MET rearranged NSCLC and suggested MET D1228E as a resistance mechanism. NGS is a powerful tool for identifying rare MET gene variants in patients with NSCLC, which should be encouraged in clinical practice.