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.

[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.

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.

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.

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.

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.

Smp24, a Scorpion-Venom Peptide, Exhibits Potent Antitumor Effects against Hepatoma HepG2 Cells via Multi-Mechanisms In Vivo and In Vitro.

Scorpion-venom-derived peptides have become a promising anticancer agent due to their cytotoxicity against tumor cells via multiple mechanisms. The suppressive effect of the cationic antimicrobial peptide Smp24, which is derived from the venom of Scorpio Maurus palmatus, on the proliferation of the hepatoma cell line HepG2 has been reported earlier. However, its mode of action against HepG2 hepatoma cells remains unclear. In the current research, Smp24 was discovered to suppress the viability of HepG2 cells while having a minor effect on normal LO2 cells. Moreover, endocytosis and pore formation were demonstrated to be involved in the uptake of Smp24 into HepG2 cells, which subsequently interacted with the mitochondrial membrane and caused the decrease in its potential, cytoskeleton reorganization, ROS accumulation, mitochondrial dysfunction, and alteration of apoptosis- and autophagy-related signaling pathways. The protecting activity of Smp24 in the HepG2 xenograft mice model was also demonstrated. Therefore, our data suggest that the antitumor effect of Smp24 is closely related to the induction of cell apoptosis, cycle arrest, and autophagy via cell membrane disruption and mitochondrial dysfunction, suggesting a potential alternative in hepatocellular carcinoma treatment.

Multiple Mechanistic Action of Brevinin-1FL Peptide against Oxidative Stress Effects in an Acute Inflammatory Model of Carrageenan-Induced Damage.

Amphibian skin is acknowledged to contain an antioxidant system composed of various gene-encoded antioxidant peptides, which exert significant effects on host defense. Nevertheless, recognition of such peptides is in its infancy so far. Here, we reported the antioxidant properties and underlying mechanism of a new antioxidant peptide, brevinin-1FL, identified from Fejervarya limnocharis frog skin. The cDNA sequence encoding brevinin-1FL was successfully cloned from the total cDNA of F. limnocharis and showed to contain 222 bp. The deduced mature peptide sequence of brevinin-1FL was FWERCSRWLLN. Functional analysis revealed that brevinin-1FL could concentration-dependently scavenge ABTS+, DPPH, NO, and hydroxyl radicals and alleviate iron oxidation. Besides, brevinin-1FL was found to show neuroprotective activity by reducing contents of MDA and ROS plus mitochondrial membrane potential, increasing endogenous antioxidant enzyme activity, and suppressing H2O2-induced death, apoptosis, and cycle arrest in PC12 cells which were associated with its regulation of AKT/MAPK/NF-κB signal pathways. Moreover, brevinin-1FL relieved paw edema, decreased the levels of TNF-α, IL-1ß, IL-6, MPO, and malondialdehyde (MDA), and restored catalase (CAT) and superoxide dismutase (SOD) activity plus glutathione (GSH) contents in the mouse injected by carrageenan. Together, these findings indicate that brevinin-1FL as an antioxidant has potent therapeutic potential for the diseases induced by oxidative damage. Meanwhile, this study will help us further comprehend the biological functions of amphibian skin and the mechanism by which antioxidants protect cells from oxidative stress.

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.

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.

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.

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.

The Co-Expression of Melanoma-Antigen Family a Proteins and New York Esophageal Squamous Cell Carcinoma-1 in Breast Cancer: A Pilot Study.

OBJECTIVE: The aim of this study was to quantify the expression of melanoma-antigen family A proteins (MAGE-A) and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) in breast cancer and establish the prognosis of breast cancer patients with MAGE-A and NY-ESO-1 co-expression. METHODS: A total of 122 patients with breast cancer were recruited for this study. Their clinicopathological data were collected retrospectively, and the MAGE-A and NY-ESO-1 expressions in paraffin-embedded specimens from the 122 patients were evaluated using immunohistochemical analysis. In addition, the survival states of the patients were recorded. RESULTS: Fifty-four patients (44.26%) were MAGE-A positive and 46 (37.70%) were NY-ESO-1 positive. Interestingly, 22 of the 46 NY-ESO-1-positive cases co-expressed MAGE-A. The expression of MAGE-A was positively associated with estrogen-receptor status (χ2 = 4.026, p = 0.045) and human epidermal growth factor receptor 2 status (χ2 = 5.482, p = 0.019), while the expression of NY-ESO-1 was positively associated with p53 expression (χ2 = 4.541, p = 0.033). Of the 122 patients, the lowest survival rate was observed in patients with NY-ESO-1 (+)/MAGE-A (+), with a 5-year survival rate of 59.09% and a median survival of 97 months. CONCLUSION: The results showed that MAGE-A and NY-ESO-1 were frequently expressed in breast cancer patients. The co-expression of MAGE-A and NY-ESO-1 occurred in about 18% of these patients, and it may indicate a poor prognosis.

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.

Wire-in-Wire TiO2/C Nanofibers Free-Standing Anodes for Li-Ion and K-Ion Batteries with Long Cycling Stability and High Capacity.

Wearable and portable mobile phones play a critical role in the market, and one of the key technologies is the flexible electrode with high specific capacity and excellent mechanical flexibility. Herein, a wire-in-wire TiO2/C nanofibers (TiO2 ww/CN) film is synthesized via electrospinning with selenium as a structural inducer. The interconnected carbon network and unique wire-in-wire nanostructure cannot only improve electronic conductivity and induce effective charge transports, but also bring a superior mechanic flexibility. Ultimately, TiO2 ww/CN film shows outstanding electrochemical performance as free-standing electrodes in Li/K ion batteries. It shows a discharge capacity as high as 303 mAh g-1 at 5 A g-1 after 6000 cycles in Li half-cells, and the unique structure is well-reserved after long-term cycling. Moreover, even TiO2 has a large diffusion barrier of K+, TiO2 ww/CN film demonstrates excellent performance (259 mAh g-1 at 0.05 A g-1 after 1000 cycles) in K half-cells owing to extraordinary pseudocapacitive contribution. The Li/K full cells consisted of TiO2 ww/CN film anode and LiFePO4/Perylene-3,4,9,10-tetracarboxylic dianhydride cathode possess outstanding cycling stability and demonstrate practical application from lighting at least 19 LEDs. It is, therefore, expected that this material will find broad applications in portable and wearable Li/K-ion batteries.

Antimicrobial and Anti-inflammatory Effects of a Novel Peptide From the Skin of Frog Microhyla pulchra.

Brevinins are an important antimicrobial peptide (AMP) family identified in the skin of Ranidae frogs and generally contain a characteristic ranabox structure at their C-terminal sequence. Herein a novel AMP named brevinin-2MP has been identified from the skin of the frog Microhyla pulchra by molecular cloning. Brevinin-2MP (GVITDTLKGVAKTVAAELLRKAHCKLTNSC) with a high amphipathic α-helix in sodium dodecyl sulfate solutions can destroy bacterial cell membrane and kill microbes. Furthermore, brevinin-2MP has been found to inhibit the lipopolysaccharide (LPS)-induced expression of pro-inflammatory NO, MCP-1, IL-6, and TNF-α via binding unidentified targets on the cell membrane and consequently suppressing the activation of MAPK/NF-κB signaling cascades induced by LPS in RAW 264.7 cells. Consistently, brevinin-2MP significantly alleviates the acute inflammatory response in carrageenan-induced mice paw. In conclusion, brevinin-2MP with anti-inflammatory and antimicrobial properties will be an ideal candidate drug molecule for bacterial inflammation treatment.

Identification of Mutations Related to Cisplatin-Resistance and Prognosis of Patients With Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common histologic type of non-small cell lung cancer (NSCLC; approximately 60%), and platinum-based chemotherapy is the cornerstone of the treatment for patients with LUAD. However, a considerable number of patients experience tumor recurrence after developing cisplatin (cis-diamminedichloroplatinum(II) or CDDP) resistance. Therefore, it is particularly important to screen primary CDDP-resistant LUAD patient populations, which can maximize the clinical benefits for these patients. Methods: Data for 61 LUAD cell lines were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database to screen for mutations related to CDDP susceptibility, and we conducted whole-exome sequencing (WES) of tumors from 45 LUAD patients from Zhujiang Hospital of Southern Medical University. Subsequently, the clinical prognostic value of these mutations was verified by using The Cancer Genome Atlas (TCGA)-LUAD cohort and our cohort (n = 45). Results: Based on drug sensitivity data for the GDSC-LUAD cell lines and survival analysis of the cohorts TCGA-LUAD and Local-LUAD, we found only one gene (GREB1) with mutations related to decreased CDDP sensitivity as well as worse overall survival (OS) and progression-free survival (PFS) [OS: log-rank p = 0.038, hazard ratio (HR; 95% confidence interval (95% CI)): 2.19 (0.73-6.55); PFS: log-rank p = 0.001; HR: 4.65, 95% CI: 1.18-18.37]. The GREB1-mutant (GREB1-MT) group had a higher frequency of gene mutations. Additionally, gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) suggested reduced accumulation of intracellular drugs in the GREB1-MT group, in addition to increased drug efflux and enhanced DNA damage repair and intracellular detoxification. Conclusion: This study found that GREB1 mutations may mediate the primary resistance and clinical prognosis of LUAD patients undergoing treatment with CDDP. Further functional analysis showed that GREB1 mutations are related to the known mechanism of CDDP resistance. These results suggest that GREB1 mutations are potential biomarkers for screening of CDDP resistance among LUAD patients.

The electrochemical storage mechanism of an In2S3/C nanofiber anode for high-performance Li-ion and Na-ion batteries.

There are only a handful of reports on indium sulfide (In2S3) in the electrochemical energy storage field without a clear electrochemical reaction mechanism. In this work, a simple electrospinning method has been used to synthesize In2S3/C nanofibers for the first time. In lithium-ion batteries (LIBs), the In2S3/C nanofiber electrode can not only deliver a high initial reversible specific capacity of 696.4 mA h g-1 at 50 mA g-1, but also shows ultra-long cycle life with a capacity retention of 80.5% after 600 cycles at 1000 mA g-1. In sodium-ion batteries (SIBs), the In2S3/C nanofibers electrode can exhibit a high initial reversible specific capacity (393.7 mA h g-1 at 50 mA g-1) and excellent cycling performance with a high capacity retention of 97.3% after 300 cycles at 1000 mA g-1. The excellent electrochemical properties mainly benefited from In2S3 being encapsulated by a carbon matrix, which buffers the volume expansion and significantly improves the conductivity of the composite. Furthermore, the structural evolution of In2S3 during the first lithiation/delithiation and sodiation/desodiation processes has been illustrated by ex situ XRD. The results confirm that the reaction mechanism of In2S3 in both LIBs and SIBs can be summarized as conversion reactions and alloying reactions, which provide theoretical support for the development of In2S3 in the field of electrochemistry.

Boosting the charge transfer of Li2TiSiO5 using nitrogen-doped carbon nanofibers: towards high-rate, long-life lithium-ion batteries.

Li2TiSiO5 (LTSO) has a theoretical specific capacity of up to 315 mA h g-1 with a suitable working potential (0.28 V vs. Li/Li+). However, the electronic structure of Li2TiSiO5 is firstly investigated by theoretical calculation based on the first-principles approach, and the results demonstrate that Li2TiSiO5 acts as the insulator for transferring electrons. Therefore, the framework with better conductivity is very essential for Li2TiSiO5 to enhance the charge transfer kinetics. Nitrogen-doped carbon encapsulated Li2TiSiO5 nanofibers (LTSO/NDC nanofibers) are obtained by using carbamide as a nitrogen source through an electrospinning technique. The nitrogen-doped carbon matrix with high electronic conductivity improves the electrochemical properties of LTSO significantly. The diffusion coefficient of lithium ions (DLi+) is greatly improved by manual calculation. The LTSO/NDC nanofiber electrode can deliver 371.7 mA h g-1 at 0.1 A g-1 and 361.1 mA h g-1 at 0.2 A g-1, and also shows a comparable cycle performance which could endure a long cycle over 800 cycles at 0.5 A g-1 almost without capacity decay. Hence, the LTSO/NDC nanofiber anode with a high rate and a long life provides a new direction for the realization of LTSO-based compounds in lithium ion batteries.