Collider bias correction for multiple covariates in GWAS using robust multivariable Mendelian randomization.

Genome-wide association studies (GWAS) have identified many genetic loci associated with complex traits and diseases in the past 20 years. Multiple heritable covariates may be added into GWAS regression models to estimate direct effects of genetic variants on a focal trait, or to improve the power by accounting for environmental effects and other sources of trait variations. When one or more covariates are causally affected by both genetic variants and hidden confounders, adjusting for them in GWAS will produce biased estimation of SNP effects, known as collider bias. Several approaches have been developed to correct collider bias through estimating the bias by Mendelian randomization (MR). However, these methods work for only one covariate, some of which utilize MR methods with relatively strong assumptions, both of which may not hold in practice. In this paper, we extend the bias-correction approaches in two aspects: first we derive an analytical expression for the collider bias in the presence of multiple covariates, then we propose estimating the bias using a robust multivariable MR (MVMR) method based on constrained maximum likelihood (called MVMR-cML), allowing the presence of invalid instrumental variables (IVs) and correlated pleiotropy. We also established the estimation consistency and asymptotic normality of the new bias-corrected estimator. We conducted simulations to show that all methods mitigated collider bias under various scenarios. In real data analyses, we applied the methods to two GWAS examples, the first a GWAS of waist-hip ratio with adjustment for only one covariate, body-mass index (BMI), and the second a GWAS of BMI adjusting metabolomic principle components as multiple covariates, illustrating the effectiveness of bias correction.

Two Birds with One Stone: V4 C3 MXene Synergistically Promoted VS2 Cathode and Zinc Anode for High-Performance Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (AZIBs) are considered to be a rising star in the large-scale energy storage area because of their low cost and environmental friendliness properties. However, the limited electrochemical performance of the cathode and severe zinc dendrite of the anode severely hinder the practical application of AZIBs. Herein, a novel 3D interconnected VS2 ⊥V4 C3 Tx heterostructure material is prepared via one-step solvothermal method. Morphological and structural characterizations show that VS2 nanosheets are uniformly and dispersedly distributed on the surface of the V4 C3 MXene substrate, which can effectively suppress volume change of the VS2 . Owing to the open heterostructure along with the high conductivity of V4 C3 MXene, the VS2 ⊥V4 C3 Tx cathode shows a high specific capacity of 273.9 mAh g-1 at 1 A g-1 and an excellent rate capability of 143.2 mAh g-1 at 20 A g-1 . The V4 C3 MXene can also effectively suppress zinc dendrite growth when used as protective layer for the Zn anode, making the V4 C3 Tx @Zn symmetric cell with a stable voltage profile for ≈1700 h. Benefitting from the synergistic modification effect of V4 C3 MXene on both the cathode and anode, the VS2 ⊥V4 C3 Tx ||V4 C3 Tx @Zn battery exhibits a long cycling lifespan of 5000 cycles with a capacity of 157.1 mAh g-1 at 5A g-1 .

1,25(OH)2 D3 inhibits Lewis lung cancer cell migration via NHE1-sensitive metabolic reprograming.

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.

Formaldehyde exacerbates inflammation and biases T helper cell lineage commitment through IFN-γ/STAT1/T-bet pathway in asthma.

The correlation between formaldehyde (FA) exposure and prevalence of asthma has been widely reported. However, the underlying mechanism is still not fully understood. FA exposure at 2.0 mg/m3 was found to exacerbate asthma in OVA-induced murine models. IFN-γ, the cytokine produced by T helper 1 (Th1) cells, was significantly induced by FA in serum and bronchoalveolar lavage fluid (BALF) of asthmatic mice, which was different from cytokines secreted by other Th cells. The observation was also confirmed by mRNA levels of Th marker genes in CD4+ T cells isolated from BALF. In addition, increased production of IFN-γ and expression of T-bet in Jurkat T cells primed with phorbol ester and phytohaemagglutinin were also observed with 100 µM FA treatment in vitro. Upregulated STAT1 phosphorylation, T-bet expression and IFN-γ production induced by FA was found to be restrained by STAT1 inhibitor fludarabine, indicating that FA promoted Th1 commitment through the autocrine IFN-γ/STAT1/T-bet pathway in asthma. This work not only revealed that FA could bias Th lineage commitment to exacerbate allergic asthma, but also identified the signaling mechanism of FA-induced Th1 differentiation, which may be utilized as the target for development of interfering strategies against FA-induced immune disorders.

Ion-Specific Nanoconfinement Effect in Multilayered Graphene Membranes: A Combined Nuclear Magnetic Resonance and Computational Study.

Ion adsorption within nanopores is involved in numerous applications. However, a comprehensive understanding of the fundamental relationship between in-pore ion concentration and pore size, particularly in the sub-2 nm range, is scarce. This study investigates the ion-species-dependent concentration in multilayered graphene membranes (MGMs) with tunable nanoslit sizes (0.5-1.6 nm) using nuclear magnetic resonance and computational simulations. For Na+-based electrolytes in MGMs, the concentration of anions in graphene nanoslits increases in correlation with their chaotropic properties. As the nanoslit size decreases, the concentration of chaotropic ion (BF4-) increases, whereas the concentration of kosmotropic ions (Cit3-, PO43-) and other ions (Ac-, F-) decreases or changes slightly. Notably, anions remain more concentrated than counter Na+ ions, leading to electroneutrality breakdown and unipolar anion packing in MGMs. A continuum modeling approach, integrating molecular dynamic simulation with the Poisson-Boltzmann model, elucidates these observations by considering water-mediated ion-graphene non-electrostatic interactions and charge screening from graphene walls.

Carbon Foam-Supported VS2 Cathode for High-Performance Flexible Self-Healing Quasi-Solid-State Zinc-Ion Batteries.

As the new generation of energy storage systems, the flexible battery can effectively broaden the application area and scope of energy storage devices. Flexibility and energy density are the two core evaluation parameters for the flexible battery. In this work, a flexible VS2 material (VS2 @CF) is fabricated by growing the VS2 nanosheet arrays on carbon foam (CF) using a simple hydrothermal method. Benefiting from the high electric conductivity and 3D foam structure, VS2 @CF shows an excellent rate capability (172.8 mAh g-1 at 5 A g-1 ) and cycling performance (130.2 mAh g-1 at 1 A g-1 after 1000 cycles) when it served as cathode material for aqueous zinc-ion batteries. More importantly, the quasi-solid-state battery VS2 @CF//Zn@CF assembled by the VS2 @CF cathode, CF-supported Zn anode, and a self-healing gel electrolyte also exhibits excellent rate capability (261.5 and 149.8 mAh g-1 at 0.2 and 5 A g-1 , respectively) and cycle performance with a capacity of 126.6 mAh g-1 after 100 cycles at 1 A g-1 . Moreover, the VS2 @CF//Zn@CF full cell also shows good flexible and self-healing properties, which can be charged and discharged normally under different bending angles and after being destroyed and then self-healing.

New insights into the biology and development of lung cancer in never smokers-implications for early detection and treatment.

Lung cancer is the leading cause of cancer deaths worldwide. Despite never smokers comprising between 10 and 25% of all cases, lung cancer in never smokers (LCNS) is relatively under characterized from an etiological and biological perspective. The application of multi-omics techniques on large patient cohorts has significantly advanced the current understanding of LCNS tumor biology. By synthesizing the findings of multi-omics studies on LCNS from a clinical perspective, we can directly translate knowledge regarding tumor biology into implications for patient care. Primarily focused on never smokers with lung adenocarcinoma, this review details the predominance of driver mutations, particularly in East Asian patients, as well as the frequency and importance of germline variants in LCNS. The mutational patterns present in LCNS tumors are thoroughly explored, highlighting the high abundance of the APOBEC signature. Moreover, this review recognizes the spectrum of immune profiles present in LCNS tumors and posits how it can be translated to treatment selection. The recurring and novel insights from multi-omics studies on LCNS tumor biology have a wide range of clinical implications. Risk factors such as exposure to outdoor air pollution, second hand smoke, and potentially diet have a genomic imprint in LCNS at varying degrees, and although they do not encompass all LCNS cases, they can be leveraged to stratify risk. Germline variants similarly contribute to a notable proportion of LCNS, which warrants detailed documentation of family history of lung cancer among never smokers and demonstrates value in developing testing for pathogenic variants in never smokers for early detection in the future. Molecular driver subtypes and specific co-mutations and mutational signatures have prognostic value in LCNS and can guide treatment selection. LCNS tumors with no known driver alterations tend to be stem-like and genes contributing to this state may serve as potential therapeutic targets. Overall, the comprehensive findings of multi-omics studies exert a wide influence on clinical management and future research directions in the realm of LCNS.

"Blue-free" orange ZnO-related light-emitting diode based on a natural interface layer of Ga2O3 and ZnGa2O4.

To fabricate a ZnO-related light-emitting diode (LED) with zero emission at blue wavelengths ("blue-free"), an ingenious strategy is employed. Specifically, for the first time to the best of our knowledge, a natural oxide interface layer, possessing remarkable visible emission potential, is introduced into the Au/i-ZnO/n-GaN metal-insulator-semiconductor (MIS) structure. The unique Au/i-ZnO/interface layer/n-GaN structure successfully eliminated the harmful blue emissions (400-500 nm) from the ZnO film, and the remarkable orange electroluminescence is mainly attributed to the impact ionization process of the natural interface layer at high electric field. It is worth mentioning that the device achieved ultra-low color temperature (2101 K) and excellent color rendering index (92.8) under electrical injection, indicating that the device could fulfill the requirements of electronic display systems and general illumination, and might even play unexpected roles in special lighting domains. The results obtained provide a novel and effective strategy for the design and preparation of ZnO-related LEDs.

Molecular-level uniform graphene/polyaniline composite film for flexible supercapacitors with high-areal capacitance.

To increase the specific capacitance of supercapacitors, polyaniline (PANI) has been chosen as additive electrode material for the pseudocapacitive performance. Here, we synthesize a molecular-level uniform reduced graphene oxide/PANI (rGO/PANI) composite film with high flexibility and conductivity via self-assembly and specific thermal reduction, which performs great potential in flexible supercapacitors with high areal capacitance. Particularly, the electrode of rGO/PANI-42.9% exhibits a high specific areal capacitance (1826 mF cm-2at 0.2 mA cm-2), and it also presents a good cycling stability (it remains 76% of its initial capacitance after 10 500 cycles). Moreover, the specific gravimetric capacitance of rGO/PANI-33.3% reaches up to 256.4 F g-1at 0.2 A g-1, showing greatly enhanced performance compared with the pure rGO electrode (183 F g-1). The results of various characteristic analysis demonstrate that electrochemical performance of the as-prepared rGO/PANI film is closely associated with the uniform distribution of PANI in rGO/PANI composite. Overall, our reported method is convenient and environmental-friendly, and could be beneficial for the development of high-performance capacitive energy storage materials.

HIGH-DIMENSIONAL FACTOR REGRESSION FOR HETEROGENEOUS SUBPOPULATIONS.

In modern scientific research, data heterogeneity is commonly observed owing to the abundance of complex data. We propose a factor regression model for data with heterogeneous subpopulations. The proposed model can be represented as a decomposition of heterogeneous and homogeneous terms. The heterogeneous term is driven by latent factors in different subpopulations. The homogeneous term captures common variation in the covariates and shares common regression coefficients across subpopulations. Our proposed model attains a good balance between a global model and a group-specific model. The global model ignores the data heterogeneity, while the group-specific model fits each subgroup separately. We prove the estimation and prediction consistency for our proposed estimators, and show that it has better convergence rates than those of the group-specific and global models. We show that the extra cost of estimating latent factors is asymptotically negligible and the minimax rate is still attainable. We further demonstrate the robustness of our proposed method by studying its prediction error under a mis-specified group-specific model. Finally, we conduct simulation studies and analyze a data set from the Alzheimer's Disease Neuroimaging Initiative and an aggregated microarray data set to further demonstrate the competitiveness and interpretability of our proposed factor regression model.

Minimizing thermal damage using self-cooling jaws for radiofrequency intestinal tissue fusion.

INTRODUCTION: Radiofrequency (RF)-induced tissue fusion shows great potential in sealing intestinal tissue without foreign materials. To improve the performance of RF-induced tissue fusion, a novel self-cooling jaw has been designed to minimize thermal damage during the fusion. MATERIAL AND METHODS: The prototype of self-cooling jaws was developed and manufactured. A total number of 60 mucosa-to-mucosa fusions were conducted using ex-vivo porcine intestinal segments with the proposed design and conventional bipolar jaws. The effects of intestinal fusion were evaluated based on temperature curves, burst pressure, thermal damage, and histological appearances. RESULTS: The self-cooling jaws showed significant decrease in temperature during the fusion process. An optimal burst pressure (5.7 ± 0.5 kPa) and thermal damage range (0.9 ± 0.1 mm) were observed when the applied RF power was 100 W. The thermal damage range of the prototype has almost decreased 36% in comparison with the conventional bipolar jaws (1.4 ± 0.1 mm). The histological observation revealed that a decrease of thermal damage was achieved through the application of self-cooling jaws. CONCLUSIONS: The self-cooling jaws were proved to be effective for reducing the thermal damage during RF-induced tissue fusion, which could potentially promote the clinical application of tissue fusion techniques in the future.

Cigarette smoke augments CSF3 expression in neutrophils to compromise alveolar-capillary barrier function during influenza infection.

BACKGROUND: Cigarette smokers are at increased risk of acquiring influenza, developing severe disease and requiring hospitalisation/intensive care unit admission following infection. However, immune mechanisms underlying this predisposition are incompletely understood, and therapeutic strategies for influenza are limited. METHODS: We used a mouse model of concurrent cigarette smoke exposure and H1N1 influenza infection, colony-stimulating factor (CSF)3 supplementation/receptor (CSF3R) blockade and single-cell RNA sequencing (scRNAseq) to investigate this relationship. RESULTS: Cigarette smoke exposure exacerbated features of viral pneumonia such as oedema, hypoxaemia and pulmonary neutrophilia. Smoke-exposed infected mice demonstrated an increase in viral (v)RNA, but not replication-competent viral particles, relative to infection-only controls. Interstitial rather than airspace neutrophilia positively predicted morbidity in smoke-exposed infected mice. Screening of pulmonary cytokines using a novel dysregulation score identified an exacerbated expression of CSF3 and interleukin-6 in the context of smoke exposure and influenza. Recombinant (r)CSF3 supplementation during influenza aggravated morbidity, hypothermia and oedema, while anti-CSF3R treatment of smoke-exposed infected mice improved alveolar-capillary barrier function. scRNAseq delineated a shift in the distribution of Csf3 + cells towards neutrophils in the context of cigarette smoke and influenza. However, although smoke-exposed lungs were enriched for infected, highly activated neutrophils, gene signatures of these cells largely reflected an exacerbated form of typical influenza with select unique regulatory features. CONCLUSION: This work provides novel insight into the mechanisms by which cigarette smoke exacerbates influenza infection, unveiling potential therapeutic targets (e.g. excess vRNA accumulation, oedematous CSF3R signalling) for use in this context, and potential limitations for clinical rCSF3 therapy during viral infectious disease.

A Facile Approach for Anisotropic Hydrogel with Light-Regulated Stiffness and Its Application to Achieve Mechanical Toughening.

Many load-bearing tissues in nature obtain high toughness by fabricating anisotropic structures with spatially regulated composition and modulus at the macroscale. This inspires a toughening strategy for hydrogels based on the controlling of modulus heterogeneity. Herein, a facile approach to realize light-regulated spatial modulus heterogeneity with large contrast in hydrogels is proposed. Ferric citric acid complex (Fe3+ /CA-complex) is used as a light-responsive ionic cross-linker, which can first stiffen an alginate/polyacrylamide (Alg/PAAm) hydrogel by coordinating with the Alg to form another network, then realize light-triggered softening through photoreduction of ferric ions (Fe3+ ). Based on this, a stripe-patterned hydrogel with alternating stiff and soft segments can be fabricated through photopatterning. The modulus contrast between the stiff and soft phases can be adjusted by control of several influence factors and the maximum modulus contrast can reach up to 87 times. As a result, the toughness of the stripe-patterned hydrogel is enhanced by 3.5 times comparing to that hydrogel without a pattern. This approach shows great potential in the synthesis of smart hydrogels with light-programmable mechanical performances, and may be widely applicable for the hydrogels with functional groups that can coordinate with metal ions.

Design and performance evaluation of a powered stapler for gastrointestinal anastomosis.

OBJECTIVE: This paper reports the design of a powered stapler for gastrointestinal anastomosis and evaluates its performance. The proposed stapling instrument is intended to simplify and optimize the current procedure of mechanical stapling, while providing controllable operation for the powered stapling procedure, such as conditioning the tissue to the right stage before firing of the stapler. MATERIAL AND METHODS: The feasibility and efficacy of the prototype were assessed by ex vivo experiments with porcine small intestine segments, where the tissue conditioning operation, burst pressure of the stapled intestine samples, and staple malformation rate were examined. RESULTS: The functionality of the developed powered stapler was validated, where the theoretical, numerical, and experimental results agree well with each other. The preliminary results indicated that the proposed tissue conditioning operation could lower the clamping pressure with a maximum level of 1.35 g/mm2. The average burst pressure of the stapled segments (16 samples) is 6.37 kPa, and the maximum malformation rate of the tested groups (five groups, each group with 90 staplers) was 5.56%. CONCLUSION: The developed novel tissue conditioning procedure could reduce the pressure response of the intestine tissue samples. The proposed powered stapler proves effective for performing gastrointestinal anastomosis procedures.

microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer.

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.

Cancer-associated fibroblast-derived exosomal microRNA-24-3p enhances colon cancer cell resistance to MTX by down-regulating CDX2/HEPH axis.

MicroRNA-24-3p (miR-24-3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer-associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF-derived exosomal miR-24-3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF-derived exosomal miR-24-3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR-24-3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR-24-3p was verified using ChIP and dual-luciferase reporter gene assays. Exosomes were isolated from miR-24-3p inhibitor-treated CAFs (CAFs-exo/miR-24-3p inhibitor), which were used in combination with gain-of-function and loss-of-function experiments and MTX treatment. CCK-8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR-24-3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR-24-3p and could up-regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down-regulated miR-24-3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR-24-3p was transferred into CC cells via CAF-derived exosomes. CAF-derived exosomal miR-24-3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF-derived exosomal miR-24-3p accelerated resistance of CC cells to MTX by down-regulating CDX2/HEPH axis.

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation.

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition.

BACKGROUND: Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. METHODS: Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. RESULTS: LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. CONCLUSION: Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

Effects of Different Land Use Types on Active Autotrophic Ammonia and Nitrite Oxidizers in Cinnamon Soils.

Land use types with different disturbance gradients show many variations in soil properties, but the effects of different land use types on soil nitrifying communities and their ecological implications remain poorly understood. Using 13CO2-DNA-based stable isotope probing (DNA-SIP), we examined the relative importance and active community composition of ammonia-oxidizing archaea (AOA) and bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in soils under three land use types, forest, cropland, and greenhouse vegetable soil, representing three interference gradients. Soil net nitrification rate was in the order forest soil > cropland soil > greenhouse vegetable soil. DNA-SIP showed that active AOA outcompeted AOB in the forest soil, whereas AOB outperformed AOA in the cropland and greenhouse vegetable soils. Cropland soil was richer in NOB than in AOA and AOB. Phylogenetic analysis revealed that ammonia oxidation in the forest soil was predominantly catalyzed by the AOA Nitrosocosmicus franklandus cluster within the group 1.1b lineage. The 13C-labeled AOB were overwhelmingly dominated by Nitrosospira cluster 3 in the cropland soil. The active AOB Nitrosococcus watsonii lineage was observed in the greenhouse vegetable soil, and it played an important role in nitrification. Active NOB communities were closely affiliated with Nitrospira in the forest and cropland soils, and with Nitrolancea and Nitrococcus in the greenhouse vegetable soil. Canonical correlation analysis showed that soil pH and organic matter content significantly affected the active nitrifier community composition. These results suggest that land use types with different disturbance gradients alter the distribution of active nitrifier communities by affecting soil physicochemical properties. IMPORTANCE Nitrification plays an important role in the soil N cycle, and land use management has a profound effect on soil nitrifiers. It is unclear how different gradients of land use affect active ammonia-oxidizing archaea and bacteria and nitrite-oxidizing bacteria. Our research is significant because we determined the response of nitrifiers to human disturbance, which will greatly improve our understanding of the niche of nitrifiers and the differences in their physiology.

Rate Performance Modification of a Lithium-Rich Manganese-Based Material through Surface Self-Doping and Coating Strategies.

Lithium-rich manganese-based materials are currently considered to be highly promising cathode materials for next-generation lithium-ion batteries due to their high specific capacity (>250 mA h g-1) and low cost. A key challenge for the commercialization of these lithium-rich manganese-based materials is their poor rate performance, which is caused by the low electronic conductivity and increasing interface charge transfer resistance produced by the side reaction during the cycling procedure. In this work, we try to improve the rate performance of a lithium-rich manganese-based material Li1.2Mn0.54Co0.13Ni0.13O2 using a collaborative approach with Co-doping and NaxCoO2-coating methods. Cobalt doping can improve the electronic conductivity, and NaxCoO2 coating provides a convenient lithium-ion diffusion channel and moderately alleviates the inevitable decrease in cycling stability caused by cobalt doping. Under the synergistic effect of these two modification strategies, the surface and internal dynamics of the Li1.2Mn0.54Co0.13Ni0.13O2 material are enhanced and its rate performance is considerably improved without decay of the cycle stability.