COX6C expression driven by copy amplification of 8q22.2 regulates cell proliferation via mediation of mitosis by ROS-AMPK signaling in lung adenocarcinoma.

Copy number variations (CNVs) play a vital role in regulating genes expression and tumorigenesis. We explored the copy number alterations in early-stage lung adenocarcinoma using high-throughput sequencing and nucleic acid flight mass spectrometry technology, and found that 8q22.1-22.2 is frequently amplified in lung adenocarcinoma tissues. COX6C localizes on the region and its expression is notably enhanced that driven by amplification in lung adenocarcinoma. Knockdown of COX6C significantly inhibits the cell proliferation, and induces S-G2/M cell cycle arrest, mitosis deficiency and apoptosis. Moreover, COX6C depletion causes a deficiency in mitochondrial fusion, and impairment of oxidative phosphorylation. Mechanistically, COX6C-induced mitochondrial deficiency stimulates ROS accumulation and activates AMPK pathway, then leading to abnormality in spindle formation and chromosome segregation, activating spindle assemble checkpoint, causing mitotic arrest, and ultimately inducing cell apoptosis. Collectively, we suggested that copy amplification-mediated COX6C upregulation might serves as a prospective biomarker for prognosis and targeting therapy in patients with lung adenocarcinoma.

Aptamer-functionalized two-photon SiO2@GQDs hybrid-based signal amplification strategy for targeted cancer imaging.

Targeted imaging is playing an increasingly important role in the early detection and precise diagnosis of cancer. This need has motivated research into sensory nanomaterials that can be constructed into imaging agents to serve as biosensors. Graphene quantum dots (GQDs) as a valuable nanoprobe show great potential for use in two-photon biological imaging. However, most as-prepared GQDs exhibit a low two-photon absorption cross-section, narrow spectral coverage, and "one-to-one" signal conversion mode, which greatly hamper their wide application in sensitive early-stage cancer detection. Herein, a versatile strategy has been employed to fabricate an aptamer Sgc8c-functionalized hybrid as a proof-of-concept of the signal amplification strategy for targeted cancer imaging. In this study, GQDs with two-photon imaging performance, and silica nanoparticles (SiO2 NPs) as nanocarriers to provide amplified recognition events by high loading of GQD signal tags, were adopted to construct a two-photon hybrid-based signal amplification strategy. Thus, the obtained hybrid (denoted SiO2@GQDs) enabled extremely strong fluorescence with a quantum yield up to 0.49, excellent photostability and biocompatibility, and enhanced bright two-photon fluorescence up to 2.7 times that of bare GQDs (excitation at 760 nm; emission at 512 nm). Moreover, further modification with aptamer Sgc8c showed little disruption to the structure of the SiO2@GQDs-hybrid and the corresponding two-photon emission. Hence, SiO2@GQDs-Sgc8c showed specific responses to target cells. Moreover, it could be used as a signal-amplifying two-photon nanoprobe for targeted cancer imaging with high specificity and great efficiency, which exhibits a distinct green fluorescence compared to that of GQDs-Sgc8c or SiO2@GQDs. This signal amplification strategy holds great potential for the accurate early diagnosis of tumors and offers new tools for the detection a wide variety of analytes in clinical application.

Network characterization linc1393 in the maintenance of pluripotency provides the principles for lncRNA targets prediction.

Long non-coding RNAs (lncRNAs) have been implicated in diverse biological processes. However, the functional mechanisms have not yet been fully explored. Characterizing the interactions of lncRNAs with chromatin is central to determining their functions but, due to precise and efficient approaches lacking, our understanding of their functional mechanisms has progressed slowly. In this study, we demonstrate that a nuclear lncRNA linc1393 maintains mouse ESC pluripotency by recruiting SET1A near its binding sites, to establish H3K4me3 status and activate the expression of specific pluripotency-related genes. Moreover, we characterized the principles of lncRNA-chromatin interaction and transcriptional regulation. Accordingly, we developed a computational framework based on the XGBoost model, LncTargeter, to predict the targets of a given lncRNA, and validated its reliability in various cellular contexts. Together, these findings elucidate the roles and mechanisms of lncRNA on pluripotency maintenance, and provide a promising tool for predicting the regulatory networks of lncRNAs.

RRP15 deficiency induces ribosome stress to inhibit colorectal cancer proliferation and metastasis via LZTS2-mediated ß-catenin suppression.

Ribosome biogenesis (RiBi) plays a pivotal role in carcinogenesis by regulating protein translation and stress response. Here, we find that RRP15, a nucleolar protein critical for RiBi and checkpoint control, is frequently upregulated in primary CRCs and higher RRP15 expression positively correlated with TNM stage (P < 0.0001) and poor survival of CRC patients (P = 0.0011). Functionally, silencing RRP15 induces ribosome stress, cell cycle arrest, and apoptosis, resulting in suppression of cell proliferation and metastasis. Overexpression of RRP15 promotes cell proliferation and metastasis. Mechanistically, ribosome stress induced by RRP15 deficiency facilitates translation of TOP mRNA LZTS2 (Leucine zipper tumor suppressor 2), leading to the nuclear export and degradation of ß-catenin to suppress Wnt/ß-catenin signaling in CRC. In conclusion, ribosome stress induced by RRP15 deficiency inhibits CRC cell proliferation and metastasis via suppressing the Wnt/ß-catenin pathway, suggesting a potential new target in high-RiBi CRC patients.

HOXA13 serves as a biomarker to predict neoadjuvant therapy efficacy in advanced colorectal cancer patients.

Neoadjuvant therapy (NAT) for advanced colorectal cancer (ACRC) is a kind of well-evidenced therapy, yet a portion of ACRC patients have poor therapeutic response. To date, no suitable biomarker used for assessing NAT efficacy has been reported. Here, we collect 72 colonoscopy biopsy tissue specimens from ACRC patients before undergoing NAT and investigate the relationship between HOXA13 expression and NAT efficacy. The results show that HOXA13 expression in pretreated tumor specimens is negatively associated with tumor regression ( P<0.001) and progression-free survival ( P<0.05) in ACRC patients who underwent NAT. Silencing of HOXA13 or its regulator HOTTIP significantly enhances the chemosensitivity of colorectal cancer (CRC) cells, leading to an increase in cell apoptosis and the DNA damage response (DDR) to chemotherapeutic drug treatment. In contrast, HOXA13 overexpression causes a significant increase in chemoresistance in CRC cells. In summary, we find that the HOTTIP/HOXA13 axis is involved in regulating chemotherapeutic sensitivity in CRC cells by modulating the DDR and that HOXA13 serves as a promising marker for NAT efficacy prediction in ACRC patients.

Kif4A mediates resistance to neoadjuvant chemoradiotherapy in patients with advanced colorectal cancer via regulating DNA damage response.

More and more patients with advanced colorectal cancer (CRC) have benefited from surgical resection or ablation following neoadjuvant chemoradiotherapy (nCRT), but nCRT may be ineffective and have potential risks to some patients. Therefore, it is necessary to discover effective biomarkers for predicting the nCRT efficacy in CRC patients. Chromokinesin Kif4A plays a critical role in mitosis, DNA damage repair and tumorigenesis, but its relationship with nCRT efficacy in advanced CRC remains unclear. Here, we find that Kif4A expression in pretreated tumor tissue is positively correlated with poorer tumor regression after receiving nCRT ( P=0.005). Knockdown of endogenous Kif4A causes an increased sensitivity of CRC cells to chemotherapeutic drugs 5-fluorouracil (5-FU) and Cisplatin (DDP), while overexpression of Kif4A enhances resistance of CRC cells to the chemotherapeutic drugs. Furthermore, depending on its motor domain and tail domain, Kif4A regulates DNA damage response (DDR) induced by 5-FU or DDP treatment in CRC cells. In conclusion, we demonstrate that Kif4A may be a potential independent biomarker for predicting the nCRT efficacy in advanced CRC patients, and Kif4A regulates chemosensitivity of CRC cells through controlling DDR.

Improvement of the Interface between the Lithium Anode and a Garnet-Type Solid Electrolyte of Lithium Batteries Using an Aluminum-Nitride Layer.

The next generation of all-solid-state batteries can feature battery safety that is unparalleled among conventional liquid batteries. The garnet-type solid-state electrolyte Li7La3Zr2O12 (LLZO), in particular, is widely studied because of its high Li-ion conductivity and stability in air. However, the poor interface-contact between Li and the electrolyte (garnet) severely limits the development of solid electrolytes. In this study, we synthesize cubic phase Li6.4La3Zr1.4Ta0.6O12 (LLZTO) using a secondary sintering method. In addition, a thin aluminum nitride (AlN) layer is introduced between the metal (Li) and the solid electrolyte. Theoretical calculations show that AlN has a high affinity for Li. Furthermore, it is shown that the AlN coating can effectively reduce the interface impedance between Li and the solid electrolyte and improve the lithium-ion transport. The assembled symmetric Li cells can operate stably for more than 3600 h, unlike the symmetric cells without AlN coating, which short-circuited after only a few cycles. The hybrid solid-state battery with a modified layer, which is assembled using LiFePO4 (LFP), still has a capacity of 120 mAh g-1 after 200 cycles, with a capacity retention rate of 98%. This shows that the introduction of an AlN interlayer is very helpful to obtain a stable Li/solid-electrolyte interface, which improves the cycling stability of the battery.

NiFe2O4/Ketjen Black Composites as Efficient Membrane Separators to Suppress the Shuttle Effect for Long-Life Lithium-Sulfur Batteries.

Lithium-sulfur batteries exhibit great potential as one of the most promising energy storage devices due to their high theoretical energy density and specific capacity. However, the shuttle effect of the soluble polysulfide intermediates could lead to a severe self-discharge effect that hinders the development of lithium-sulfur batteries. In this paper, a battery separator has been prepared based on NiFe2O4/Ketjen Black (KB) modification by a simple method to solve the shuttle effect and improve the battery performance. The as-modified separator with the combination of small-size KB and NiFe2O4 nanoparticles can effectively use the physical and chemical double-layer adsorption to prevent polysulfide from the shuttle. Moreover, it can give full play to its catalytic effect to improve the conversion efficiency of polysulfide and activate the dead sulfur. The results show that the NiFe2O4/KB-modified separator battery still maintains a discharge capacity of 406.27 mAh/g after 1000 stable cycles at a high current density of 1 C. Furthermore, the coulombic efficiency remains at 99%, and the average capacity attenuation per cycle is only 0.051%. This simple and effective method can significantly improve the application capacity of lithium-sulfur batteries.

Assessment of Spectra of the Atmospheric Infrared Ultraspectral Sounder on GF-5 and Validation of Water Vapor Retrieval.

Atmospheric Infrared Ultraspectral Sounder (AIUS) aboard the Chinese GaoFen-5 satellite was launched on 9 May 2018. It is the first hyperspectral occultation spectrometer in China. The spectral quality assessment of AIUS measurements at the full and representative spectral bands was presented by comparing the transmittance spectra of measurements with that of simulations. AIUS measurements agree well with simulations. Statistics show that more than 73% of the transmittance differences are within ±0.05 and more than 91% of the transmittance differences are within ±0.1. The spectral windows for O3, H2O, temperature, CO, CH4, and HCl were also analyzed. The comparison experiments indicate that AIUS data can provide reliable data for O3, H2O, temperature, CO, CH4, and HCl detection and dynamic monitoring. The H2O profiles were then retrieved from AIUS measurements, and the precision, resolution, and accuracy of the H2O profiles are discussed. The estimated precision is less than 1.3 ppmv (21%) below 57 km and about 0.9-2.4 ppmv (20-31%) at 60-90 km. The vertical resolution of H2O profiles is better than 5 km below 32 km and about 5-8 km at 35-85 km. Comparisons with MLS Level 2 products indicate that the mean H2O profiles of AIUS have a good agreement with those of MLS. The relative differences are mostly within ±10% at 16-75 km and about 10-15% at 16-20 km in 60∘-80∘ S. For 60∘-65 ∘ S in December, the relative differences are within ±5% between 22 km and 80 km. The H2O profiles retrieved from AIUS measurements are credible for scientific research.

Two-photon imaging of aptamer-functionalized Copolymer/TPdye fluorescent organic dots targeted to cancer cells.

Fluorescent organic dots (O-dots) recently have emerged as a new class of promising contrast reagents for two-photon fluorescence (TPF) imaging. However, most of these developed two-photon absorption (TPA) O-dots have no tumor-targeting group, which hampers their wide application for targeted tumor imaging. Herein, we fabricated Sgc8c aptamer-mediated TPA O-dots as a proof-of-concept of the sensing platform for targeted imaging in live cells or deep tissues. The O-dots composed of trans-4-[p-(N, N-diethylamino)styryl]-4'-(dimethyl amino) stilbene (DEAS) emerged as TPA organic emissive cores and encapsulation by using poly (methyl methacrylate-co-methacrylic acid) (PMMA-co-MAA) as polymeric encapsulating matrix to form DEAS/PMMA-co-MAA O-dots via a co-precipitation strategy. The obtained O-dots enabled an extremely high TPA absorption cross-section, bright two-photon fluorescence (excitation at 720 nm; emission at 412 nm and 434 nm), excellent cell-permeability and high penetration depth. Sgc8c aptamer, as a protein tyrosine kinase-7 (PTK7) receptor-targetable ligand, was further anchored on the surface of O-dots to obtain DEAS/PMMA-co-MAA@Sgc8c nanoprobes by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC)-mediated coupling reaction. Guided by Sgc8c aptamer, DEAS/PMMA-co-MAA@Sgc8c nanoprobes could be rapidly internalized into target acute lymphoblastic leukemia cells (CEM) cells with high specificity and great efficiency. It was also performed that two-photon images of TPA nanoprobes exhibited high two-photon brightness not only in target CEM cells, but also in mouse liver tissue slices even a depth of up to 210 µm. In our perception, it is highly promising that this nanoprobe provides a valuable tool for in vivo targeted imaging.

Reliable and simple spectrophotometric determination of sun protection factor: A case study using organic UV filter-based sunscreen products.

BACKGROUND: Current in vitro SPF screening method for plant oil body (oleosome)-based SPF products possesses significant inconsistency and low reliability in the SPF rating. OBJECTIVES: The primary objective of this study was to evaluate the reliability and reproducibility of spectrophotometrically determined sun protection factor (SPF) from oleosome-based SPF products. The secondary objective was the data comparison of the spectrophotometric measurements against in vivo SPF testing to establish a reliable in vitro test method as a screening assay. METHODS: Octyl methoxycinnamate (UVB filter) and avobenzone (UVA filter) were loaded into safflower oil bodies and formulated into oil-in-water emulsion-based finished products. To evaluate the reliability between in vivo and spectrophotometric test methods, samples were dispatched to a clinical laboratory, and the reported SPF values were compared with spectrophotometric test results. RESULTS: The observed SPF from the in vivo and spectrophotometric test results demonstrated a high correlation for SPF 30 products. Proportional correlation between the two evaluation methods was observed for SPF 15 and 50 products with slightly lesser accuracy with a smaller number of population tested in the clinical studies. CONCLUSIONS: A reliable spectrophotometric screening method for oil body-based SPF formulas has been developed using two broadly used organic UV sunscreen actives as a case study. The results demonstrated a high level of reproducibility and reliability compared to the US FDA-guided in vivo SPF testing method.

Generation of biallelic knock-out sheep via gene-editing and somatic cell nuclear transfer.

Transgenic sheep can be used to achieve genetic improvements in breeds and as an important large-animal model for biomedical research. In this study, we generated a TALEN plasmid specific for ovine MSTN and transfected it into fetal fibroblast cells of STH sheep. MSTN biallelic-KO somatic cells were selected as nuclear donor cells for SCNT. In total, cloned embryos were transferred into 37 recipient gilts, 28 (75.7%) becoming pregnant and 15 delivering, resulting in 23 lambs, 12 of which were alive. Mutations in the lambs were verified via sequencing and T7EI assay, and the gene mutation site was consistent with that in the donor cells. Off-target analysis was performed, and no off-target mutations were detected. MSTN KO affected the mRNA expression of MSTN relative genes. The growth curve for the resulting sheep suggested that MSTN KO caused a remarkable increase in body weight compared with those of wild-type sheep. Histological analyses revealed that MSTN KO resulted in muscle fiber hypertrophy. These findings demonstrate the successful generation of MSTN biallelic-KO STH sheep via gene editing in somatic cells using TALEN technology and SCNT. These MSTN mutant sheep developed and grew normally, and exhibited increased body weight and muscle growth.

Intermolecular interactions during complex coacervation of pea protein isolate and gum arabic.

The nature of intermolecular interactions during complexation between pea protein isolate (PPI) and gum arabic (GA) was investigated as a function of pH (4.30-2.40) by turbidimetric analysis and confocal scanning microscopy in the presence of destabilizing agents (100 mM NaCl or 100 mM urea) and at different temperatures (6-60 degrees C). Complex formation followed two pH-dependent structure-forming events associated with the formation of soluble and insoluble complexes and involved interactions between GA and PPI aggregates. Complex formation was driven by electrostatic attractive forces between complementary charged biopolymers, with secondary stabilization by hydrogen bonding. Hydrophobic interactions were found to enhance complex stability at lower pH (pH 3.10), but not with its formation.

Effect of pH, salt, and biopolymer ratio on the formation of pea protein isolate-gum arabic complexes.

Turbidity measurements were used to study the formation of soluble and insoluble complexes between pea protein isolate (PPI) and gum arabic (GA) mixtures as a function of pH (6.0-1.5), salt concentration (NaCl, 0-50 mM), and protein-polysaccharide weight mixing ratio (1:4 to 10:1 w/w). For mixtures in the absence of salt and at a 1:1 mixing ratio, two structure-forming transitions were observed as a function of pH. The first event occurred at a pH of 4.2, with the second at pH 3.7, indicating the formation of soluble and insoluble complexes, respectively. Sodium chloride (7.5 mM) due to substantial PPI aggregation. The pH at which maximum PPI-GA interactions occurred was 3.5 and was independent of NaCl levels. As PPI-GA ratios increased, structure-forming transitions shifted to higher pH.