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Abstract Recent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in the human population. The present study aims to assess the causal relationship from the gut microbiota to CRC and to identify specific causal microbe taxa via genome-wide association study (GWAS) summary statistics based two-sample Mendelian randomization (MR) analyses. Microbiome GWAS (MGWAS) in the TwinsUK 1,126 twin pairs was used as discovery exposure sample, and MGWAS in 1,812 northern German participants was used as replication exposure sample. GWAS of CRC in 387,156 participants from the UK Biobank (UKB) was used as the outcome sample. Bacteria were grouped into taxa features at both family and genus levels. In the discovery sample, a total of 30 bacteria features including 15 families and 15 genera were analyzed. Five features, including 2 families (Verrucomicrobiaceae and Enterobacteriaceae) and 3 genera (Akkermansia, Blautia, and Ruminococcus), were nominally significant. In the replication sample, the genus Blautia (discovery beta=-0.01, P = 0.04) was successfully replicated (replication beta=-0.18, P = 0.01) with consistent effect direction. Our findings identified genus Blautia that was causally associated with CRC, thus offering novel insights into the microbiota-mediated CRC development mechanism.

Abstract Background Single nucleotide polymorphisms (SNPs) located in microRNA (miRNA) binding sites can affect the interactions between miRNAs and target genes, which is related to cancer susceptibility and tumorigenesis. However, the association between SNPs located in miR-17-92 cluster binding sites and ESCC risk remains unclear. Therefore, we aimed to explore the relationship between polymorphisms in miR-17-92 cluster binding sites and ESCC susceptibility. Methods Six SNPs in the binding sites of miR-17-92 cluster were selected using bioinformatics databases, and their association with ESCC risk was investigated in a case-control study (including 488 cases and 512 controls) based on the population from high incidence areas of ESCC in China. We evaluated the SNP-SNP and SNP-smoking interactions using generalized multifactor dimensionality reduction (GMDR). Moreover, the expression of the miR-17-92 cluster and its target genes was determined in ESCC and adjacent normal tissues by quantitative real-time polymerase chain reaction (qRT-PCR). The dual-luciferase reporter assay was conducted to verify the effect of SNPs on the binding affinity between miRNAs and target genes. Results We found that the SNP rs1804506 C > T had a significant association with the decreased ESCC risk. The SNP rs1804506 T allele was associated with a significantly decreased risk of ESCC in the additive model (OR = 0.817, 95% CI = 0.681–0.981, P = 0.030). The rs1804506 T allele had more striking effects on reducing ESCC risk in older individuals, female or non-smoker subgroups. We also found a significant interaction effect between rs1366600 and smoking by GMDR methods (P = 0.011). Additionally, the expression levels of miR-19a-3p and TGFBR3 were significantly downregulated in ESCC tissues compared with normal tissues, and the carriers of rs1804506 TT genotype had lower expression level of TGFBR3 than those of rs1804506 CC/CT genotype. Following dual-luciferase reporter assay showed that the rs1804506 T allele reduced the binding of miR-19a-3p and TGFBR3 3′-UTR. Conclusions Our findings suggest that the rs1804506 polymorphism in miR-17-92 cluster binding sites contributes to the susceptibility of ESCC, which might provide new clues and scientific evidence for the etiology and biomarkers for the prevention and treatment of ESCC.

SIRT1 (Sir2) is an NAD+-dependent deacetylase that plays critical roles in a broad range of biological events, including metabolism, the immune response and ageing1-5. Although there is strong interest in stimulating SIRT1 catalytic activity, the homeostasis of SIRT1 at the protein level is poorly understood. Here we report that macroautophagy (hereafter referred to as autophagy), a catabolic membrane trafficking pathway that degrades cellular components through autophagosomes and lysosomes, mediates the downregulation of mammalian SIRT1 protein during senescence and in vivo ageing. In senescence, nuclear SIRT1 is recognized as an autophagy substrate and is subjected to cytoplasmic autophagosome-lysosome degradation, via the autophagy protein LC3. Importantly, the autophagy-lysosome pathway contributes to the loss of SIRT1 during ageing of several tissues related to the immune and haematopoietic system in mice, including the spleen, thymus, and haematopoietic stem and progenitor cells, as well as in CD8+CD28- T cells from aged human donors. Our study reveals a mechanism in the regulation of the protein homeostasis of SIRT1 and suggests a potential strategy to stabilize SIRT1 to promote productive ageing.

Supercapacitors are extensively used in urban rail transit, electric vehicles, renewable energy storage, electronic products, and the military industry due to its long cycle life and high power density. Porous carbon materials are regarded as promising anode materials for supercapacitors due to their high specific surface areas and well-developed pore structures. However, the over-developed pore structure often results in poor conductivity and reduced cycle stability due to the destruction of a carbon skeleton. Herein, we introduce an advanced strategy for preparing porous carbon with high specific surface areas (3333 m2 g−1), high electrical conductivity (68.6 S m−1), and fast ion transport channels through secondary high-temperature carbonization treatment. As a result, the fabricated porous carbon anode delivers a high specific capacitance (199.2 F g−1 at 1 A g−1) and outstanding rate performance (136.3 F g−1 at 20 A g−1) in organic electrolyte. Furthermore, the assembled symmetrical supercapacitor achieves an energy density of 43.2 Wh kg−1 at 625.0 W kg−1, highlighting the potential of a secondary high-temperature carbonization strategy in practical applications.

AbstractObjective To compare the efficacy and safety of 1470-nm diode laser enucleation of the prostate (DiLEP) with that of plasmakinetic resection of the prostate (PKRP) in treating patients with large benign prostatic hyperplasia (BPH > 80ml).Methods The clinical data from 211 cases of BPH (>80 ml) were collected for analysis. The patients were divided into two groups: the PKRP group (n = 118) and the DiLEP group (n = 93), based on the surgical method used.Result The DiLEP group demonstrated significantly lower surgical time (p

Modular multilevel converter (MMC)-based high-voltage DC (HVDC) systems have found rapid growth in power grids. To reduce the inrush current, it is necessary to precharge the submodule (SM) capacitors to the rated voltage before normal operation. In this paper, an optimized pre-charging strategy for MMC is proposed based on power balancing . First, the charging power is obtained by a designed closed-loop control of the SM capacitors. Then the total power released by the AC or DC side could be calculated by power conservation and feedback by controlling the charging current. At the same time, the power difference between the upper and lower bridge arm of each phase and the internal voltage balancing of bridge arms are also considered by the proposed bridge arm and SM voltage algorithms. By comparing with conventional closed-loop pre-charging strategies, the pre-charging speed is greatly enhanced as the achievement of synchronous charging of upper and lower bridge arm SMs. Moreover, as the same voltage and current double closed-loop control applied in both MMC pre-charging and normal state, the state transition time could be reduced. Finally, a series of simulations and prototype experiments are conducted to verify the feasibility of the proposed pre-charging strategy.

Increasing interest in high-energy lithium-ion batteries has triggered the demand to clarify the reaction mechanism in battery cathodes during high-potential operation. However, the reaction mechanism often involves both transition-metal and oxygen activities that remain elusive. Here we report a comprehensive study of both cationic and anionic redox mechanisms of LiNiO2 nearly full delithiation. Selection of pure LiNiO2 removes the complication of multiple transition metals. Using combined X-ray absorption spectroscopy, resonant inelastic X-ray scattering, and operando differential electrochemical mass spectrometry, we are able to clarify the redox reactions of transition metals in the bulk and at the surface, reversible lattice oxygen redox, and irreversible oxygen release associated with surface reactions. Many findings presented here bring attention to different types of oxygen activities and metal-oxygen interactions in layered oxides, which are of crucial importance to the advancement of a Ni-rich layered oxide cathode for high capacity and long cycling performance.

Plant genotype alone appears to be insufficient to explain trait variations. This study integrates GWAS, MWAS and mGWAS in 827 foxtail millet cultivars, revealing that root-associated microbiota affect plant phenotypes in a host genotype-dependent manner.

Abstract The joint design problem for the coexistence of multiple‐input multiple‐output (MIMO) radar and multi‐user multiple‐input‐single‐output (MU‐MISO) communication is investigated. Different from the conventional design schemes, which require defining the primary function, we consider designing the transmit waveform, precoding matrix and receive filter to maximize the radar SINR and the minimal SINR of communication users, simultaneously. By doing so, the promising overall performance for both sensing and communication is achieved without requiring parameter tuning for the threshold of communication or radar. However, the resulting optimization problem which contains the maximin objective function and the unit sphere constraint, is highly nonconvex and hence difficult to attain the optimal solution directly. Towards this end, the epigraph‐form reformulation is first adopted, and then an alternating maximisation (AM) method is devised, in which the Dinkelbach’s algorithm is used to tackle the nonconvex fractional‐programing subproblem. Simulation results indicate that the proposed method can achieve improved performance compared with the benchmarks.

Mixtures of soft rock and sand have been applied extensively in the Mu Us Sandy Land (MUSL, also known as the Mu Us Desert) to limit the loss of top soil by wind erosion. In this study, the efficacy of sand-fixing technology was investigated in a series of experiments. The sand-fixing effect of seven different mixtures (ratios) on soft rock and sand was evaluated in a wind tunnel. The results indicated that the MUSL soils are susceptible to wind erosion, as the textural composition of sand is dominated by coarse particles. MUSL soils dominated by silt and clay particle sizes are more resistant to wind erosion. Each soft rock and sand combination experiences severe wind erosion. However, wind erosion was significantly reduced when soft rock and sand were mixed. An increase in particle size was associated with an increase in the resistance of soft rock and sand mixtures to wind erosion. The ability to resist wind erosion was greatest when the ratio of soft rock and sand was between 1:2 and 1:5. This study provided data to support the approaches to sand-fixing commonly used at present in the MUSL. The results of this study have important practical significance for the improvement of agricultural land potential in dry sandy areas.

Research has shown that intrapersonal, interpersonal, and stress factors are associated with development in marital satisfaction. However, the unique contributions of early predictors and changes in these factors to the development of marital satisfaction have been overlooked. Based on data from 268 Chinese newlywed couples (M[subscript age] = 29.59, SD = 3.25 for husbands; M[subscript age] = 28.08, SD = 2.51 for wives), the current study used latent growth curve model to examine (a) the development of marital satisfaction and the unique contributions of the intrapersonal, interpersonal, and stress predictors to the developmental trajectories (i.e., the initial level and change) of marital satisfaction; (b) whether the intrapersonal, interpersonal, and stress predictors develop over time; and (c) how trajectories of these predictor domains are associated with changes in marital satisfaction. The results indicated that interpersonal variables, rather than intrapersonal or stress predictors at baseline, were associated with both the initial levels of and changes in marital satisfaction; in contrast, only the changes in the stress levels were found to be related to changes in marital satisfaction. The theoretical implications and future directions for this research are discussed.

RAS mutations are among the most prevalent oncogenic drivers in cancers. RAS proteins propagate signals only when associated with cellular membranes as a consequence of lipid modifications that impact their trafficking. Here, we discovered that RAB27B, a RAB family small GTPase, controlled NRAS palmitoylation and trafficking to the plasma membrane, a localization required for activation. Our proteomic studies revealed RAB27B upregulation in CBL- or JAK2-mutated myeloid malignancies, and its expression correlated with poor prognosis in acute myeloid leukemias (AMLs). RAB27B depletion inhibited the growth of CBL-deficient or WRAS-mutant cell lines. Strikingly, Rab27b deficiency in mice abrogated mutant but not WT NRAS-mediated progenitor cell growth, ERK signaling, and NRAS palmitoylation. Further, Rab27b deficiency significantly reduced myelomonocytic leukemia development in vivo. Mechanistically, RAB27B interacted with ZDHHC9, a palmitoyl acyltransferase that modifies NRAS. By regulating palmitoylation, RAB27B controlled c-RAF/MEK/ERK signaling and affected leukemia development. Importantly, RAB27B depletion in primary human AMLs inhibited oncogenic NRAS signaling and leukemic growth. We further revealed a significant correlation between RAB27B expression and sensitivity to MEK inhibitors in AMLs. Thus, our studies presented a link between RAB proteins and fundamental aspects of RAS posttranslational modification and trafficking, highlighting future therapeutic strategies for RAS-driven cancers., Introduction CBL family proteins, including C-CBL (also called CBL), CBL-B, and CBL-C, are RING domain-containing E3 ubiquitin ligases, among which CBL and CBL-B are widely expressed in hematopoietic cells. CBL [...]