Tuning the optoelectronic properties of emerging solar absorbers through cation disorder engineering.

Chalcogenide solar absorbers, such as AgBiS2 and kesterites, have gained a resurgence of interest recently, owing to their high stability compared to metal-halide compounds, as well as their rising efficiencies in photovoltaic devices. Although their optical and electronic properties are conventionally tuned through the composition and structure, cation disorder has increased in prominence as another important parameter that influences these properties. In this minireview, we define cation disorder as the occupation of a cation crystallographic site with different species, and the homogeneity of this cation disorder as how regular the alternation of species in this site is. We show that cation disorder is not necessarily detrimental, and can lead to increases in absorption coefficient and reductions in bandgap, enabling the development of ultrathin solar absorbers for lightweight photovoltaics. Focusing on kesterites and ABZ2 materials (where A = monovalent cation, B = divalent cation, and Z is a chalcogenide anion), we discuss how the degree and homogeneity of cation disorder influences the optical properties, charge-carrier transport and photovoltaic performance of these materials, as well as how cation disorder could be tuned and quantified. We finish with our perspectives on the important questions moving forward in making use of cation disorder engineering as a route to achieve more efficient solar absorbers.

Simulation research on aerodynamic noise characteristics of a compressor under different working conditions.

The shear stress transport turbulence model is employed to conduct a detailed study of flow characteristics at the highest efficiency point and near-stall point in a full-channel 1.5-stage compressor in this paper. The simulation results for the compressor's total pressure ratio and efficiency exhibit good agreement with experimental data. Emphasis is placed on examining the internal flow structure in the tip area of the compressor rotor under near-stall conditions. The results reveal that significant differences in flow structure primarily occur in the tip area as the compressor approaches stall. Specifically, a reduction in turbulent kinetic energy is observed in a region spanning approximately 20%-60% of the chord length on the rotor suction face near-stall conditions. Two additional peak frequencies, at 0.8 and 1.6 times the blade passage frequency, are observed, and the intricate flow phenomena are elaborated at the near-stall point. The near-stall point exhibits greater noise levels than the highest efficiency point, where the intensity of the surface source increases by more than 10 dB, peaking at 20 dB. This additional peak serves as a significant supplementary noise source near the stall point, leading to a maximum increase of 33.3 dB in the free radiated sound power. The acoustic response within the duct indicates that the compressor operating at the near-stall point continues to produce substantial noise on the actual test bench, showing an average increase of 6 dB in noise levels, and the distribution of the additional peak single-tone noise at the entrance significantly differs from that observed at the highest efficiency point.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Resolving electron and hole transport properties in semiconductor materials by constant light-induced magneto transport.

The knowledge of minority and majority charge carrier properties enables controlling the performance of solar cells, transistors, detectors, sensors, and LEDs. Here, we developed the constant light induced magneto transport method which resolves electron and hole mobility, lifetime, diffusion coefficient and length, and quasi-Fermi level splitting. We demonstrate the implication of the constant light induced magneto transport for silicon and metal halide perovskite films. We resolve the transport properties of electrons and holes predicting the material's effectiveness for solar cell application without making the full device. The accessibility of fourteen material parameters paves the way for in-depth exploration of causal mechanisms limiting the efficiency and functionality of material structures. To demonstrate broad applicability, we further characterized twelve materials with drift mobilities spanning from 10-3 to 103 cm2V-1s-1 and lifetimes varying between 10-9 and 10-3 seconds. The universality of our method its potential to advance optoelectronic devices in various technological fields.

Grain Engineering of Sb2 S3 Thin Films to Enable Efficient Planar Solar Cells with High Open-Circuit Voltage.

Sb2 S3 is a promising environmentally friendly semiconductor for high performance solar cells. But, like many other polycrystalline materials, Sb2 S3 is limited by nonradiative recombination and carrier scattering by grain boundaries (GBs). This work shows how the GB density in Sb2 S3 films can be significantly reduced from 1068 ± 40 to 327 ± 23 nm µm-2 by incorporating an appropriate amount of Ce3+ into the precursor solution for Sb2 S3 deposition. Through extensive characterization of structural, morphological, and optoelectronic properties, complemented with computations, it is revealed that a critical factor is the formation of an ultrathin Ce2 S3 layer at the CdS/Sb2 S3 interface, which can reduce the interfacial energy and increase the adhesion work between Sb2 S3 and the substrate to encourage heterogeneous nucleation of Sb2 S3 , as well as promote lateral grain growth. Through reductions in nonradiative recombination at GBs and/or the CdS/Sb2 S3 heterointerface, as well as improved charge-carrier transport properties at the heterojunction, this work achieves high performance Sb2 S3 solar cells with a power conversion efficiency reaching 7.66%. An impressive open-circuit voltage (VOC ) of 796 mV is achieved, which is the highest reported thus far for Sb2 S3 solar cells. This work provides a strategy to simultaneously regulate the nucleation and growth of Sb2 S3 absorber films for enhanced device performance.

Fast Near-Infrared Photodetectors Based on Nontoxic and Solution-Processable AgBiS2.

Solution-processable near-infrared (NIR) photodetectors are urgently needed for a wide range of next-generation electronics, including sensors, optical communications and bioimaging. However, it is rare to find photodetectors with >300 kHz cut-off frequencies, especially in the NIR region, and many of the emerging inorganic materials explored are comprised of toxic elements, such as lead. Herein, solution-processed AgBiS2 photodetectors with high cut-off frequencies under both white light (>1 MHz) and NIR (approaching 500 kHz) illumination are developed. These high cut-off frequencies are due to the short transit distances of charge-carriers in the ultrathin photoactive layer of AgBiS2 photodetectors, which arise from the strong light absorption of this material, such that film thicknesses well below 120 nm are sufficient to absorb >65% of NIR to visible light. It is also revealed that ion migration plays a critical role in the photo-response speed of these devices, and its detrimental effects can be mitigated by finely tuning the thickness of the photoactive layer, which is important for achieving low dark current densities as well. These outstanding characteristics enable the realization of air-stable, real-time heartbeat sensors based on NIR AgBiS2 photodetectors, which strongly motivates their future integration in high-throughput systems.

Characterization of an Emergent Chicken H3N8 Influenza Virus in Southern China: a Potential Threat to Public Health.

Although influenza A viruses of several subtypes have occasionally infected humans, to date only those of the H1, H2, and H3 subtypes have led to pandemics and become established in humans. The detection of two human infections by avian H3N8 viruses in April and May of 2022 raised pandemic concerns. Recent studies have shown the H3N8 viruses were introduced into humans from poultry, although their genesis, prevalence, and transmissibility in mammals have not been fully elucidated. Findings generated from our systematic influenza surveillance showed that this H3N8 influenza virus was first detected in chickens in July 2021 and then disseminated and became established in chickens over wider regions of China. Phylogenetic analyses revealed that the H3 HA and N8 NA were derived from avian viruses prevalent in domestic ducks in the Guangxi-Guangdong region, while all internal genes were from enzootic poultry H9N2 viruses. The novel H3N8 viruses form independent lineages in the glycoprotein gene trees, but their internal genes are mixed with those of H9N2 viruses, indicating continuous gene exchange among these viruses. Experimental infection of ferrets with three chicken H3N8 viruses showed transmission through direct contact and inefficient transmission by airborne exposure. Examination of contemporary human sera detected only very limited antibody cross-reaction to these viruses. The continuing evolution of these viruses in poultry could pose an ongoing pandemic threat. IMPORTANCE A novel H3N8 virus with demonstrated zoonotic potential has emerged and disseminated in chickens in China. It was generated by reassortment between avian H3 and N8 virus(es) and long-term enzootic H9N2 viruses present in southern China. This H3N8 virus has maintained independent H3 and N8 gene lineages but continues to exchange internal genes with other H9N2 viruses to form novel variants. Our experimental studies showed that these H3N8 viruses were transmissible in ferrets, and serological data suggest that the human population lacks effective immunological protection against it. With its wide geographical distribution and continuing evolution in chickens, other spillovers to humans can be expected and might lead to more efficient transmission in humans.

PTPRO suppresses lymph node metastasis of esophageal carcinoma by dephosphorylating MET.

Protein tyrosine phosphatase receptor-type O (PTPRO) is a membrane-bound tyrosine phosphatase. Notably, epigenetically silenced PTPRO due to promoter hypermethylation is frequently linked to malignancies. In this study, we used cellular and animal models, and patient samples to demonstrate that PTPRO can suppress the metastasis of esophageal squamous cell carcinoma (ESCC). Mechanistically, PTPRO can inhibit MET-mediated metastasis by dephosphorylating Y1234/1235 in the kinase activation loop of MET. Patients with PTPROlow/p-METhigh had significantly poor prognosis, suggesting that PTPROlow/p-METhigh can serve as an independent prognostic factor for patients with ESCC.

Genome-wide DNA methylation profiling of gastric cardia cancer.

BACKGROUND AND AIM: Aberrant DNA methylation has been found in various cancer types including gastric cancer, yet the genome-wide DNA methylation profile of gastric cardia cancer (GCC) remains unclear. Therefore, we aimed to profile the DNA methylation pattern of GCC and identify promising diagnostic epigenetic biomarkers. METHODS: We investigated the genome-wide DNA methylation pattern in eight pairs of GCC and adjacent normal tissues using Illumina 850K microarrays. Subsequently, bisulfite-pyrosequencing and quantitative real-time PCR were performed on eight pairs of GCC-adjacent normal tissues for validation. Finally, we performed immunohistochemistry to examine ADHFE1 expression on 126 pairs of GCC-adjacent normal samples. RESULTS: DNA methylome analysis showed global hypomethylation and local hypermethylation of promoter cytosine-phosphate-guanine (CpG) islands (CGIs) in GCC tissues compared with gastric cardia normal mucosa (P < 2.2 × 10-16 ). Differential methylation analysis identified a total of 91 723 differentially-methylated probes (DMPs), and the candidate gene with the largest average DNA methylation difference mapped to ADHFE1 (mean Δß = 0.53). Subsequently, three DMPs in the ADHFE1 promoter were validated by pyrosequencing. Notably, the mean methylation level of the three candidate DMPs (ADHFE1_cg08090772, ADHFE1_cg19283840, and ADHFE1_cg20295442) was negatively associated with ADHFE1 mRNA expression level (Spearman rho = -0.64, P = 0.01). Moreover, both mRNA (P = 0.0213) and protein (P < 0.0001) expression of ADHFE1 were significantly decreased in GCCs compared with the adjacent normal tissues. CONCLUSIONS: Our results reveal DNA methylation aberrations in GCC and that ADHFE1 gene DNA methylation contributes to the risk of GCC, thus providing novel mechanistic insights into gastric cardia cancer carcinogenesis.

Adipose tissue levels of polybrominated diphenyl ethers in relation to prognostic biomarkers and progression-free survival time of breast cancer patients in eastern area of southern China: A hospital-based study.

Evidence indicates that individual or groups of polybrominated diphenyl ethers (PBDEs) are associated with risk of breast cancer (BC). Epidemiological studies of PBDEs and BC progression are scarce. This study aimed to investigate the relationships between PBDE burdens in adipose tissues and prognostic biomarkers of BC as well as progression-free survival (PFS) of patients for the first time. The concentrations of 14 PBDE congeners in breast adipose tissues of 183 cases from the eastern area of southern China were analyzed by gas chromatography-mass spectrometry (GC-MS). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models for the associations between PBDE levels and prognostic biomarkers. Kaplan-Meier and Cox regression analyses were conducted to identify the correlations between PBDEs and PFS. The results showed that BDE-99 and 190 levels were positively associated with clinical stage and N stage respectively (OR = 2.61 [1.26-5.40], OR = 2.78 [1.04-7.46]). Concentrations of BDE-28 and BDE-183 were negatively associated with the expression of estrogen receptor (ER) (OR = 0.30 [0.11-0.81]; 0.39 [0.15-0.99]) and progesterone receptor (PR) (OR = 0.36 [0.14-0.92]; 0.37 [0.15-0.91]), and increased BDE-47 was associated with lower human epidermal growth factor receptor 2 (HER2) expression (OR = 0.44 [0.23-0.86]). Adipose levels of BDE-71, 99, 138, 153, 154 and total PBDEs were positively associated with p53 expression (all P < 0.05). Finally, BDE-47, 99 and 183 were considered as independent prognostic factors for shorter PFS in the Cox models (adjusted hazard ratios = 3.14 [1.26-7.82]; 2.25 [1.03-4.94]; 2.60 [1.08-6.25], respectively). The recurrence risk and prognosis of BC may be closely bound to the body burdens of certain PBDE congeners. Further epidemiological and experimental studies are needed for confirmation.

Strong absorption and ultrafast localisation in NaBiS2 nanocrystals with slow charge-carrier recombination.

I-V-VI2 ternary chalcogenides are gaining attention as earth-abundant, nontoxic, and air-stable absorbers for photovoltaic applications. However, the semiconductors explored thus far have slowly-rising absorption onsets, and their charge-carrier transport is not well understood yet. Herein, we investigate cation-disordered NaBiS2 nanocrystals, which have a steep absorption onset, with absorption coefficients reaching >105 cm-1 just above its pseudo-direct bandgap of 1.4 eV. Surprisingly, we also observe an ultrafast (picosecond-time scale) photoconductivity decay and long-lived charge-carrier population persisting for over one microsecond in NaBiS2 nanocrystals. These unusual features arise because of the localised, non-bonding S p character of the upper valence band, which leads to a high density of electronic states at the band edges, ultrafast localisation of spatially-separated electrons and holes, as well as the slow decay of trapped holes. This work reveals the critical role of cation disorder in these systems on both absorption characteristics and charge-carrier kinetics.

Elucidating the Role of Antisolvents on the Surface Chemistry and Optoelectronic Properties of CsPbBrxI3-x Perovskite Nanocrystals.

Colloidal lead-halide perovskite nanocrystals (LHP NCs) have emerged over the past decade as leading candidates for efficient next-generation optoelectronic devices, but their properties and performance critically depend on how they are purified. While antisolvents are widely used for purification, a detailed understanding of how the polarity of the antisolvent influences the surface chemistry and composition of the NCs is missing in the field. Here, we fill this knowledge gap by studying the surface chemistry of purified CsPbBrxI3-x NCs as the model system, which in itself is considered a promising candidate for pure-red light-emitting diodes and top-cells for tandem photovoltaics. Interestingly, we find that as the polarity of the antisolvent increases (from methyl acetate to acetone to butanol), there is a blueshift in the photoluminescence (PL) peak of the NCs along with a decrease in PL quantum yield (PLQY). Through transmission electron microscopy and X-ray photoemission spectroscopy measurements, we find that these changes in PL properties arise from antisolvent-induced iodide removal, which leads to a change in halide composition and, thus, the bandgap. Using detailed nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR) measurements along with density functional theory calculations, we propose that more polar antisolvents favor the detachment of the oleic acid and oleylamine ligands, which undergo amide condensation reactions, leading to the removal of iodide anions from the NC surface bound to these ligands. This work shows that careful selection of low-polarity antisolvents is a critical part of designing the synthesis of NCs to achieve high PLQYs with minimal defect-mediated phase segregation.

ECRG4 acts as a tumor suppressor in nasopharyngeal carcinoma by suppressing the AKT/GSK3ß/ß-catenin signaling pathway.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a poor prognosis. Studies have shown that esophageal carcinoma related gene 4 (ECRG4) is hypermethylated and significantly downregulated in NPC tissues. However, the role of ECRG4 in NPC, and in particular the underlying molecular mechanism, is largely unclear. In this study, using immunohistochemical staining of ECRG4 in NPC and normal specimens, we confirmed that ECRG4 was downregulated in human NPC tissues. In addition, various biological and molecular studies were carried out and the results showed that ECRG4 exerted anticancer effect in NPC, including inhibiting cell growth, migration, and invasion of NPC cells in vitro. Moreover, restoring ECRG4 expression suppressed the in vivo tumorigenesis of CNE2 cells. ECRG4 inhibited AKT/GSK3ß/ß-catenin signaling, as well as the downstream targets of ß-catenin. LiCl treatment, which reduced GSK3ß phosphorylation and upregulated ß-catenin expression, restored the invasive ability of ECRG4-overexpressing NPC cells. Furthermore, we showed that the DNA methylation inhibitor 5-aza-dC reduced ECRG4 methylation and the invasive ability of negative control cells, but not that of ECRG4-overexpressing cells, suggesting that the inhibitory effect of 5-aza-dC depends on low expression of ECRG4. Collectively, our results demonstrated that ECRG4 downregulation contributed to NPC growth and invasion by activating AKT/GSK3ß/ß-catenin signaling pathway. ECRG4 could be a promising therapeutic target for the treatment of NPC. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00520-8.

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma.

Cadmium (Cd) exposure has been implicated in the etiology of esophageal squamous cell carcinoma (ESCC), albeit with inconsistent results from epidemiologic studies and without causal evidence. In this study, we explore the relationship of Cd exposure and the development, progression and therapeutic resistance of ESCC. A total of 150 ESCC patients and 177 matched controls from a coastal region with a high incidence of ESCC in China were included in the study. It was found that the median blood Cd level (BCL) was significantly higher in ESCC patients than that in the controls. Odds ratios for ESCC risk were 3.12 (95% CI 1.54-6.30) and 3.71 (95% CI 1.84-7.48) in the third and fourth quartiles of Cd distribution, respectively. Notably, BCL above 4.71 µg/L was strongly associated with shorter progression-free survival time compared to that below 1.60 µg/L (p < 0.001). The chronic Cd-treated ESCC cells (CCT-ESCC) CCT-EC109 and CCT-EC9706 exhibited increased cell proliferation and tumorigenesis, enhanced migration and invasion, and upregulated EMT biomarkers following 12 weeks of exposure to 5 µM cadmium chloride. Furthermore, Cd treatment attenuated the efficacy of 5-fluorouracil, cisplatin and irradiation treatment in CCT-ESCC cells both in vitro and in vivo. Moreover, we revealed that Cd stimulated the cancer cell stemness and Wnt/ß-catenin signaling pathway in the CCT-ESCC cells. Additionally, 5-aza-2-deoxy-cytidine treatment resulted in suppression of the Wnt/ß-catenin signaling pathway and rescue of the Cd-induced cell radioresistance. These results offer new insights into the role of environmental Cd exposure in the development, progression and chemoradioresistance of ESCC.

Endothelial colony-forming cell-derived exosomal miR-21-5p regulates autophagic flux to promote vascular endothelial repair by inhibiting SIPL1A2 in atherosclerosis.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) represents an efficient therapeutic method for atherosclerosis but conveys a risk of causing restenosis. Endothelial colony-forming cell-derived exosomes (ECFC-exosomes) are important mediators during vascular repair. This study aimed to investigate the therapeutic effects of ECFC-exosomes in a rat model of atherosclerosis and to explore the molecular mechanisms underlying the ECFC-exosome-mediated effects on ox-LDL-induced endothelial injury. METHODS: The effect of ECFC-exosome-mediated autophagy on ox-LDL-induced human microvascular endothelial cell (HMEC) injury was examined by cell counting kit-8 assay, scratch wound assay, tube formation assay, western blot and the Ad-mCherry-GFP-LC3B system. RNA-sequencing assays, bioinformatic analysis and dual-luciferase reporter assays were performed to confirm the interaction between the miR-21-5p abundance of ECFC-exosomes and SIPA1L2 in HMECs. The role and underlying mechanism of ECFC-exosomes in endothelial repair were explored using a high-fat diet combined with balloon injury to establish an atherosclerotic rat model of vascular injury. Evans blue staining, haematoxylin and eosin staining and western blotting were used to evaluate vascular injury. RESULTS: ECFC-exosomes were incorporated into HMECs and promoted HMEC proliferation, migration and tube formation by repairing autophagic flux and enhancing autophagic activity. Subsequently, we demonstrated that miR-21-5p, which is abundant in ECFC-exosomes, binds to the 3' untranslated region of SIPA1L2 to inhibit its expression, and knockout of miR-21-5p in ECFC-exosomes reversed ECFC-exosome-decreased SIPA1L2 expression in ox-LDL-induced HMEC injury. Knockdown of SIPA1L2 repaired autophagic flux and enhanced autophagic activity to promote cell proliferation in ox-LDL-treated HMECs. ECFC-exosome treatment attenuated vascular endothelial injury, regulated lipid balance and activated autophagy in an atherogenic rat model of vascular injury, whereas these effects were eliminated with ECFC-exosomes with knockdown of miR-21-5p. CONCLUSIONS: Our study demonstrated that ECFC-exosomes protect against atherosclerosis- or PTCA-induced vascular injury by rescuing autophagic flux and inhibiting SIAP1L2 expression through delivery of miR-21-5p. Video Abstract.

Reducing N6AMT1-mediated 6mA DNA modification promotes breast tumor progression via transcriptional repressing cell cycle inhibitors.

DNA N6-methyladenosine (6mA) is a novel epigenetic signaling modification in humans and has been implicated in the progression and tumorigenesis of several cancers. However, the function and mechanism of 6mA in breast cancer (BC), the most common cancer among women, are unclear. Here, we found that decreases in N6AMT1 correlated with the extent of 6mA in clinical BC tissues and predicted a worse survival of BC patients. Functionally, knockdown of N6AMT1 markedly reduced 6mA in DNA and promoted colony formation and migration of BC cells, whereas overexpression of N6AMT1 had the opposite effect. Moreover, silencing of N6AMT1 reduced 6mA modification and enhanced the growth of BC cells in vitro and tumors in vivo. 6mA immunoprecipitation sequencing (6mA-IP-seq), RNA-seq, 6mA-IP-PCR, and bioinformatics analysis indicated that N6AMT1 was a functional methyltransferase for genomic 6mA DNA modifications and related to gene transcriptional activity. Critical negative regulators of the cell cycle, such as RB1, P21, REST, and TP53 were identified as targets of N6AMT1 in BC. These results suggest N6AMT1 enhances DNA 6mA levels to repress tumor progression via transcriptional regulation of cell cycle inhibitors.

Development of a multi-arm polyrotaxanes modified mesoporous silica-coated gold nanoplatform for protecting endothelial progenitor cells against high glucose environment.

Recent study reported that endothelial progenitor cells (EPCs) have potential to treat diabetic macroangiopathy. High glucose environment of diabetes can affect the adhesion of EPCs by decreasing the expression of CXC chemokine receptor 4 (CXCR4) and affect the proliferation of EPCs by decreasing the expression of miR-126. The results showed that the cytotoxicity of GNR@MSNs@PEI to EPCs was significantly lower than PEI; the temperature of GNR@MSNs@PEI solution can be controlled between 38-40°C under 808 nm laser irradiation. 25.67 µg of pcDNA3.1-GFP-CXCR4 and 5.36 µg of FITC-miR-126 could be loaded in 1 mg of GNR@MSNs@PEI; GNR@MSNs@PEI has gene transfection almost the same as Lipofectamine 3000. Subsequent in vitro studies showed that pcDNA3.1-GFP-CXCR4 and miR-126 loaded GNR@MSNs@PEI can significantly increase the adhesion and proliferation and decrease the apoptosis of EPCs treated with high glucose under 808 nm laser irradiation. In conclusion, nano-carriers (GNR@MSNs@PEI) with high pcDNA3.1-CXCR4 and miR-126 loading capacity, high biocompatibility, well cell internalization, and controllable release ability were constructed to transfer CXCR4 expression plasmid (pcDNA3.1-CXCR4) and miR-126 into EPCs efficiently. Further in vitro studies indicated that pcDNA3.1-CXCR4 and miR-126-loaded GNR@MSNs@PEI could protect EPCs against high glucose-induced injury.

Investigation into the role of Stmn2 in vascular smooth muscle phenotype transformation during vascular injury via RNA sequencing and experimental validation.

This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.

A Platinum Resistance-Related lncRNA Signature for Risk Classification and Prognosis Prediction in Patients with Serous Ovarian Cancer.

Accurate risk stratification for patients with serous ovarian cancer (SOC) is pivotal for treatment decisions. In this study, we identified a lncRNA-based signature for predicting platinum resistance and prognosis stratification for SOC patients. We analyzed the RNA-sequencing data and the relevant clinical information of 295 SOC samples obtained from The Cancer Genome Atlas (TCGA) database and 180 normal ovarian tissues from the Genotype-Tissue Expression (GTEx) database. A total of 284 differentially expressed lncRNAs were screened out between platinum-sensitive and platinum-resistant groups by univariate Cox regression analysis. Then, a signature consisting of eight prognostic lncRNAs was used to construct a lncRNA score model by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The ROC analysis showed that this signature had a good predictive performance for chemotherapy response in the training set (AUC = 0.8524) and the testing and whole sets with 0.8142 and 0.8393 of AUC, respectively. Dichotomized by the risk score of lncRNAs (lncScore), the high-risk patients showed significantly shorter progression-free survival (PFS) and overall survival (OS). Based on the final Cox model, a nomogram comprising the 8-lncRNA signature and 3 clinicopathological risk factors was then established for clinical application to predict the 1, 2, and 3-year PFS of SOC patients. The gene set enrichment analysis (GSEA) revealed that genes in the high-risk group were active in ATP synthesis, coupled electron transport, and mitochondrial respiratory chain complex assembly. Overall, our findings demonstrated the potential clinical significance of the 8-lncRNA-based classifier as a novel biomarker for outcome prediction and therapy decisions in SOC patients with platinum treatment.

The Novel Non-coding Transcriptional Regulator Gm18840 Drives Cardiomyocyte Apoptosis in Myocardial Infarction Post Ischemia/Reperfusion.

BACKGROUND: Ischemia/reperfusion-mediated myocardial infarction (MIRI) is a major pathological factor implicated in the progression of ischemic heart disease, but the key factors dysregulated during MIRI have not been fully elucidated, especially those essential non-coding factors required for cardiovascular development. METHODS: A murine MIRI model and RNA sequencing (RNA-seq) were used to identify key lncRNAs after myocardial infarction. qRT-PCR was used to validate expression in cardiac muscle tissues and myocardial cells. The role of Gm18840 in HL-1 cell growth was determined by flow cytometry experiments in vitro. Full-length Gm18840 was identified by using a rapid amplification of cDNA ends (RACE) assay. The subcellular distribution of Gm18840 was examined by nuclear/cytoplasmic RNA fractionation and qRT-PCR. RNA pulldown and RNA immunoprecipitation (RIP)-qPCR assays were performed to identify Gm18840-interacting proteins. Chromatin isolation by RNA purification (ChIRP)-seq (chromatin isolation by RNA purification) was used to identify the genome-wide binding of Gm18840 to chromatin. The regulatory activity of Gm18840 in transcriptional regulation was examined by a luciferase reporter assay and qRT-PCR. RESULTS: Gm18840 was upregulated after myocardial infarction in both in vivo and in vitro MIRI models. Gm18840 was 1,471 nt in length and localized in both the cytoplasm and the nucleus of HL-1 cells. Functional studies showed that the knockdown of Gm18840 promoted the apoptosis of HL-1 cells. Gm18840 directly interacts with histones, including H2B, highlighting a potential function in transcriptional regulation. Further ChIRP-seq and RNA-seq analyses showed that Gm18840 is directly bound to the cis-regulatory regions of genes involved in developmental processes, such as Junb, Rras2, and Bcl3. CONCLUSION: Gm18840, a novel transcriptional regulator, promoted the apoptosis of myocardial cells via direct transcriptional regulation of essential genes and might serve as a novel therapeutic target for MIRI.