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Type I interferon (IFN-I)-induced signaling plays a critical role in host antiviral innate immune responses. Despite this, the mechanisms that regulate this signaling pathway have yet to be fully elucidated. The nucleoporin Ran Binding Protein 2 (RanBP2) (also known as Nucleoporin 358 KDa, Nup358) has been implicated in a number of cellular processes, including host innate immune signaling pathways, and is known to influence viral infection. In this study, we documented that RanBP2 mediates the sumoylation of signal transducers and activators of transcription 1 (STAT1) and inhibits IFN-α-induced signaling. Specifically, we found that RanBP2-mediated sumoylation inhibits the interaction of STAT1 and Janus kinase 1 (JAK1), as well as the phosphorylation and nuclear accumulation of STAT1 after IFN-α stimulation, thereby antagonizing the IFN-α-mediated antiviral innate immune signaling pathway and promoting viral infection. Our findings not only provide insights into a novel function of RanBP2 in antiviral innate immunity but may also contribute to the development of new antiviral therapeutic strategies. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony. [ABSTRACT FROM AUTHOR]

A rationally designed bioreducible ionizable lipid nanoparticle mediates efficient siRNA delivery in retinal cells and significantly inhibits retinal angiogenesis, lack of toxicity in vitro and in vivo. [Display omitted] Small interfering RNA (siRNA) is emerging as a promising treatment for retinal neovascularization due to its specific inhibition of the expression of target genes. However, the clinical translation of siRNA drugs is hindered by the efficiency and safety of delivery vectors. Here, we describe the properties of a new bioreducible ionizable lipid nanoparticle (LNP) 2N12H, which is based on a rationally designed novel ionizable lipid called 2N12B. 2N12H exhibited degradation in response to the mimic cytoplasmic glutathione condition and ionization with a pK a value of 6.5, which remaining neutral at pH 7.4. At a nitrogen to phosphorus ratio of 5, 2N12H efficiently encapsulated and protected siRNA from degradation. Compared to the commercial vehicle Lipofectamine 2000, 2N12H demonstrated similar silencing efficiency and improved safety in the in vitro cell experiments. 2N12H/siVEGFA reduced the expression of VEGFA in retinal pigment epithelium cells and mouse retina, consequently suppressing cell migration and retinal neovascularization. In the mouse model, the therapeutic effect of 2N12H/siVEGFA was comparable to that of the clinical drug ranibizumab. Together, these results suggest the potential of this novel ionizable LNP to facilitate the development of nonviral ocular gene delivery systems. [ABSTRACT FROM AUTHOR]

• Broadband waterborne absorptive metamaterial with hydrostatic pressure resistance is proposed. • Acousto-electric analogy is adopted to determine the equivalent parameters for transfer matrix method. • Oscillators of helical configurations demonstrate strong hydrostatic pressure resistance. • Experimental results confirm the superior performance of the configurations at 3 MPa. Underwater absorptive metamaterials are rapidly developed duo local resonance mechanisms, but they still suffer from the disadvantages of poor hydrostatic resistance. The poor acoustic absorption performance at high hydrostatic pressure mainly attributes to the decreased damping coefficient and increased modulus of substrate at high hydrostatic pressure. Acoustic metastructures with helical oscillators are proposed and optimized with simulating annealing algorithm, where the helical oscillators are beneficial for easing the stress in the polymer substrate and resulting in good acoustic absorption abilities. Four acoustic absorptive metastructures without any oscillators (pure polymer substrate), with cylindrical oscillators, with helical oscillators, with both cylindrical and helical oscillators are proposed and experimentally verified in this study. All three metastructures with oscillators demonstrate excellent acoustic absorption coefficient with the absence of the hydrostatic pressure, while the metastructures with helical oscillators exhibit better hydrostatic pressure resistance compared with the metastructures with cylindrical oscillators. Besides, the coupling of helical oscillators and helical oscillators enhanced the acoustic performance furtherly. It is revealed that the acoustic metamaterials with a combination of cylindrical oscillator and helical oscillator exhibit superior performance under hydrostatic pressure up to 3 MPa in the frequency range of 0.5kHz∼10 kHz compared with the others, demonstrating a new avenue for underwater acoustic metamaterials application. [Display omitted] [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is a major public health problem, and gut microbiota dysbiosis has been implicated in the emergence of T2D in humans. Dietary interventions can indirectly influence the health status of patients with type 2 diabetes through their modulatory effects on the intestinal microbiota. In recent years, fecal microbiota transplantation is becoming familiar as a new medical treatment that can rapidly improve intestinal health. We conducted a 90-day controlled open-label trial to evaluate the health improvement ability of a specially designed diet, and the diet combined with fecal microbiota transplantation (FMT). According to our study, both diet and diet plus FMT treatments showed great potential in controlling blood glucose and blood pressure levels. Sequencing the V4 region of 16S rRNA gene on the Illumina MiniSeq platform revealed a shift of intestinal microbial community in T2D patients, and the changes were also observed in response to the treatments. FMT changed the gut microbiota more quickly than diet. Beneficial bacterium, such as Bifidobacterium, increased along the study and was negatively correlated with blood glucose, blood pressure, blood lipid and BMI. Sulfate-reducing bacteria (SRB), Bilophila and Desulfovibrio, decreased significantly after treatment, showed a positive correlation with blood glucose indices. Thus, the specially designed diet is beneficial to improve blood glucose control in diabetic patients, it also showed the potential to reverse dyslipidemia and dysarteriotony. [ABSTRACT FROM AUTHOR]

Background: Studies have found that high density lipoprotein cholesterol (HDL-C) levels are linked to a variety of diseases. However, evidence for the relationship between stress urinary incontinence (SUI) and HDL-C remain limited. Methods: 590 eligible women were enrolled. Basic characteristic, gynecological examinations and blood sampling were collected. The examination of the possible link between HDL-C and SUI was done using univariate and multivariate logistic regression. Feature importance ranking and Receiver operating characteristic (ROC) curves were performed to further evaluate the association between HDL-C and SUI in women. Results: A significant association was found between HDL-C and SUI in women, revealing higher HDL-C levels were related to a lower risk of SUI (OR 0.238; 95%CI: 0.091–0.623; P < 0.01) after adjustment for potential key confounders. The AUC for the SUI predicted by the combined HDL-C was 0.845 (95%CI: 0.798–0.891, P < 0.001). The feature importance ranking revealed that vaginal delivery, HDL-C were the top two important factors. Conclusions: HDL-C levels were correlated with the development of SUI. In addition to physical and surgical treatments, HDL-C may offer the possibility of potential targeted treatment and prevention of SUI afterwards. [ABSTRACT FROM AUTHOR]

Unmanned Aerial Vehicle (UAV)-Assisted becomes promising prospects for the development of 6G non-terrestrial networks (NTN) due to their low cost, low latency, flexible coverage, and support for emergency response. UAVs utilize close-range multi-point cooperative computing to provide computational, storage, and communication resources for 6G NTN. However, insufficient resources and variable business requirements can lead to node overload or task timeout. Therefore, selecting collaborative nodes and optimizing data transmission paths between non-terrestrial nodes has become a formidable challenge. Due to the capacity constraints, power limitations, time-varying communication links, and increasing terminal demands, existing algorithms face difficulties in meeting the requirements of cooperative computing for non-terrestrial nodes. To solve the issue, this paper proposes a multi-task cooperative computing mechanism that focuses on node selection and path optimization. Furthermore, node selection and path optimization algorithm based on multi-agent proximal policy optimization (NSPO-MAPPO) is designed to optimize the latency-aware multi-task cooperative computing objective, thereby improving computational task execution efficiency and service quality. Experimental comparisons with other algorithms demonstrate the effectiveness of our method in minimizing latency, enhancing the task load balancing degree, and ensuring stable and reliable cooperative computing services for non-terrestrial nodes. [ABSTRACT FROM AUTHOR]

Chronic lung diseases represent a largely global burden whose pathogenesis remains largely unknown. Research increasingly suggests that epigenetic modifications, especially DNA methylation, play a mechanistic role in chronic lung diseases. DNA methylation can affect gene expression and induce various diseases. Of the caveolae in plasma membrane of cell, caveolin‐1 (Cav‐1) is a crucial structural constituent involved in many important life activities. With the increasingly advanced progress of genome‐wide methylation sequencing technologies, the important impact of Cav‐1 DNA methylation has been discovered. The present review overviews the biological characters, functions, and structure of Cav‐1; epigenetic modifications of Cav‐1 in health and disease; expression and regulation of Cav‐1 DNA methylation in the respiratory system and its significance; as well as clinical potential as disease‐specific biomarker and targets for early diagnosis and therapy. [ABSTRACT FROM AUTHOR]

This paper addresses the problem of non-Bayesian learning over multi-agent networks, where agents repeatedly collect partially informative observations about an unknown state of the world, and try to collaboratively learn the true state out of m alternatives. We focus on the impact of adversarial agents on the performance of consensus-based non-Bayesian learning, where non-faulty agents combine local learning updates with consensus primitives. In particular, we consider the scenario where an unknown subset of agents suffer Byzantine faults—agents suffering Byzantine faults behave arbitrarily. We propose two learning rules. In our learning rules, each non-faulty agent keeps a local variable which is a stochastic vector over the m possible states. Entries of this stochastic vector can be viewed as the scores assigned to the corresponding states by that agent. We say a non-faulty agent learns the underlying truth if it assigns one to the true state and zeros to the wrong states asymptotically. In our first update rule, each agent updates its local score vector as (up to normalization) the product of (1) the likelihood of the cumulative private signals and (2) the weighted geometric average of the score vectors of its incoming neighbors and itself. Under reasonable assumptions on the underlying network structure and the global identifiability of the network, we show that all the non-faulty agents asymptotically learn the true state almost surely. We propose a modified variant of our first learning rule whose complexity per iteration per agent is O (m 2 n log n) , where n is the number of agents in the network. In addition, we show that this modified learning rule works under a less restrictive network identifiability condition. [ABSTRACT FROM AUTHOR]

Optically transparent and mechanically strong glass fiber (GF)‐reinforced polycarbonate (PC) composites were fabricated via reacting with biorenewable isosorbide (ISB) moiety. While direct copolymerization of ISB and bisphenol A (BPA) by melt transesterification with diphenyl carbonate remained difficult due to the large discrepancy of reactivity and low thermal stability of ISB, we demonstrated in this work that ISB and BPA copolycarbonates with high molecular weight, low discoloration, and excellent optical transparency can be fabricated at 250 °C within 2.5 min by reactive blending of commercially available ISB‐based PC and BPA‐PC. A systematic study of synthesis, thermal degradation, and reactive blending of ISB‐containing PCs was performed to distinguish the reactivity between ISB and BPA, elucidate the effect of catalyst on chain scission, and testify the reaction mechanism of the unexpected asymmetrical inner–inner carbonate exchange. We clarified that the hydroxyl group on BPA exhibited a low reactivity and Lewis acid‐catalytic transesterification played a key role in preventing from the chain scission during the asymmetrical inner–inner exchange. Another unexpected factor that effectively suppressed the further chain scission was the miscibility of the ISB‐based PC with BPA‐PC once each chain on average was carbonate exchanged with its counterpart to form a "biblock" PC. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1670–1681 [ABSTRACT FROM AUTHOR]

Purpose: High levels of heterogeneity and immunosuppression characterize the HCC immune microenvironment (TME). Unfortunately, the majority of hepatocellular carcinoma (HCC) patients do not benefit from immune checkpoint inhibitors (ICIs) therapy. New small molecule therapies for the treatment of HCC are the goal of our research. Methods: SUMOylation inhibitors (TAK-981 and ML-792) were evaluated for the treatment of preclinical mouse HCC models (including subcutaneous and orthotopic HCC models). We profile immune cell subsets from tumor samples after SUMOylation inhibitors treatment using single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), flow cytometry, and multiple immunofluorescences (mIF). Results: We discover that SUMOylation is higher in HCC patient samples compared to normal liver tissue. TAK-981 and ML-792 decrease SUMOylation at nanomolar levels in HCC cells and also successfully reduced the tumor burden. Analysis combining scRNA-seq and CyTOF demonstrate that treatment with SUMOylation inhibitors reduces the exhausted CD8+T (Tex) cells while enhancing the cytotoxic NK cells, M1 macrophages and cytotoxic T lymphocytes (CTL) in preclinical mouse HCC model. Furthermore, SUMOylation inhibitors have the potential to activate innate immune signals from CD8+T, NK and macrophages while promoting TNFα and IL-17 secretion. Most notably, SUMOylation inhibitors can directly alter the TME by adjusting the abundance of intestinal microbiota, thereby restoring anti-tumor immunity in HCC models. Conclusions: This preclinical study suggests that SUMO signaling inhibitors may be beneficial for the treatment of HCC. [ABSTRACT FROM AUTHOR]

A variety of CTLA4-Fc fusion proteins and anti-CTLA4 monoclonal antibody have been approved. Given the shortcomings of macromolecular antibodies, recombinant proteins derived from the tenth unit of human type III fibronectin (FN3) termed monobody were studied as CTLA4 analogs in this study. A peptide EL16 1 derived from CD80-binding domain (MYPPPY motifs) in the complementarity determining region (CDR) 3 of CTLA4 was found to inhibit the interaction of CTLA4 with CD80 significantly. Afterward, the peptide EL16 as well as the CDR1 of CTLA4 which is also critical for its binding to CD80 were grafted onto FN3 and obtained a novel CD80 binding monobody protein CFN13. 2 CFN13 showed 80% binding affinity compared to CTLA4. In addition, to increase the half-life, CFN13 was fused to human IgG1 Fc to generate CFN13-Fc fusion protein. As expected, CFN13-Fc bound to CD80 in a dosage-dependent manner as CFN13 did, and displayed 41.0% and 31.4% inhibition on the interaction of CTLA4-Fc with CD80 at 200 μg/ml and 100 μg/ml respectively. Moreover, peptide EL16 could inhibit CFN13-Fc binding to CD80 significantly, with the inhibition ratio of 64.3% and 52.8% at 100 and 50 μg/ml respectively, indicating that the peptide EL16 and CFN13-Fc shared the similar binding sites with CD80 and the CDR3 motif of CTLA4 contributed more than CDR1 in binding to CD80. In summary, our study provides insights into small molecular analogs of CTLA4. • Peptide EL16 derived from CDR3 loop of CTLA4 inhibited CTLA4/CD80 interaction. • EL16 and CDR1 of CTLA4 were grafted onto FN3, generating a CTLA4 analog CFN13. • CFN13 and CFN13-Fc had high binding affinity to CD80. • CFN13-Fc inhibited CTLA4/CD80 interaction as the peptide EL16 did. • The binding mode of peptide EL16 and CFN13 with CD80 were proposed. [ABSTRACT FROM AUTHOR]

We are interested in approximate Byzantine consensus problem, wherein all the fault-free processes reach consensus asymptotically (approximately in finite time). In particular, we focus on the algorithms under which each process communicates with other processes that are up to l hops away and maintains minimal states across iterations. For a given l , we identify a necessary and sufficient condition on the network structure for the existence of iterative algorithms of interest. Our necessary and sufficient condition generalizes the tight condition identified in prior work for l = 1 . For l ≥ l ⁎ , where l ⁎ is the length of a longest cycle-free path in the given network, our condition is equivalent to the necessary and sufficient conditions for exact consensus in undirected and directed networks both. [ABSTRACT FROM AUTHOR]

The present study examines the uptake of the heavy metal cadmium (Cd) by Microcystis aeruginosa in the presence of dissolved organic matter (DOM) from different origins. The DOM used in the present study were extracted from soil, sediment taken from Meiliang Bay at Taihu Lake, and from M. aeruginosa cultured in the laboratory. The 3 different DOM samples were characterized using ultraviolet-visible absorption spectroscopy and Fourier transform infrared spectroscopy. The excitation-emission matrix (EEM) fluorescence spectroscopy was used to characterize the interactions of DOM with Cd2+. The results showed that all types of DOM extracted from the 3 sources in the present study exhibited aliphatic and aromatic characteristics and contained hydroxyls, carbonyls, phenols, carboxyls, carbohydrates, amines, and ethers. Humic acids and fulvic acids proved to be the major components of DOM. The sediment DOM had the highest degrees of aromatization and humification among the samples. The results also showed that sediment and soil DOM samples had lower molecular weights than M. aeruginosa DOM. The DOM could react with Cd2+ by complexing to alter Cd speciation. When exposed to Cd, EEM fluorescence intensities of all 3 DOM types had a significant decrease, and the intracellular Cd content improved with increasing Cd concentrations. The addition of DOM greatly enhanced Cd uptake by M. aeruginosa compared with the control group. Environ Toxicol Chem 2017;36:1856-1863. © 2017 SETAC [ABSTRACT FROM AUTHOR]

TiO nanotube arrays (NTAs) with different intertube spaces were fabricated via electrochemical anodization process in the electrolyte with different water contents. Uniform distributed cadmium selenide (CdSe) nanoparticles were deposited onto the TiO NTAs through electrodeposition method. The influence of water contents in electrolyte on the microstructure and photocatalytic property of CdSe/TiO NTAs were studied. The results show that increasing the water content in electrolyte from 2 to 12 vol% can enlarge the intertube space from 0 to 22 nm, which is beneficial for the deposition of CdSe nanoparticles. The photocatalytic activity of CdSe/TiO NTAs was evaluated by measuring the degradation of methyl orange solutions under visible light. When water content was 10 vol%, CdSe nanoparticles distributed uniformly on the inner and outer surface of TiO NTAs. The photocatalytic tests indicated that CdSe/TiO NTAs composites exhibits excellent photocatalytic properties after visible light irradiation for 2 h, the degradation rate reached from 55.7 to 94.5 % when water content increased from 2 to 10 vol%, whereas the degradation rate of the TiO NTAs without CdSe modification is just 4.8 %. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Highly ordered TiO2 nanotube arrays (NTAs) were fabricated on titanium substrate via electrochemical anodization method. CdSe nanoparticles were deposited on the TiO2 NTAs through the electrodeposition process. The influence of electrolyte concentration and deposition time on the visible light photocatalytic performance of CdSe/TiO2 NTAs was studied systematically. The photocatalytic activity of as-prepared samples was evaluated by degradation of methyl orange under visible light irradiation. The results indicated that the CdSe nanoparticles distributed uniformly on the surface of TiO2 NTAs when deposited in the electrolyte containing 0.02M CdCl2, 2mM SeO2 and 0.02M Na2SO4 with time of 600s. After irradiation under visible light for 2h, the degradation rate of CdSe/TiO2 NTAs composite material reached 94.4%, while the degradation rate of unmodified TiO2 NTAs was only 6.2 % under the same condition, demonstrating that the CdSe/TiO2 NTAs exhibited higher photocatalytic activity in visible light region. In addition, a reasonable degradation rate of 80.96% was achieved even after being used for 5 times. [Copyright &y& Elsevier]

Abstract: Yes-associated protein (YAP) is inactivated by the tumour suppressing Hippo pathway. The YAP gene is amplified in human liver cancer, and promotes tumour growth. However, there are contrasting reports about its function in breast cancer. Studies have demonstrated both oncogenic or tumour suppressor functions. Our study aims to clarify the role of YAP in breast cancer. We investigated the expression of YAP in 69 cases of human breast cancer tissue by immunohistochemistry (IHC). The role of YAP on cell growth in vitro and tumourigenesis in vivo were evaluated. We found that YAP was expressed in 75.4% (52/69) of breast cancer samples; amongst these cases YAP was overexpressed in 29% (20/69). There was no YAP expression in the remainder (17/69) cases. Breast cancer cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promotes cell proliferation. This was confirmed in vivo: overexpression of YAP enhanced tumour formation and growth, whereas downregulation of YAP decreased the tumour formation and growth. Our results suggest that YAP acts as an oncogene in a subtype of breast cancer. [Copyright &y& Elsevier]

• A new safety lane change trajectory model for autonomous vehicles. • Minimum safety distances in different steering frequency domain. • Vehicle collision avoidance control strategies are proposed. • Typical lane change scenarios for intelligent vehicles are designed. Lane change maneuvers, are important contributors to road traffic accidents on highway. In this paper, we propose a new safe lane change trajectory model and collision avoidance control method for Society of Automotive Engineers (SAE)-level 2 automatic driving vehicles. First, a Gaussian distribution is used to describe the new trajectory model that uses pure steering and combined braking. According to regional and progressive states, a new safe lane change meaning is defined. Second, we design a new four-level automatic driving mode and an effective decision mechanism that considers safety and ergonomics. Moreover, a new trajectory tracking controller combined with a decision mechanism was designed using feedback linearization, verified using typical lane-change scenarios. Finally, based on a physical simulation platform, PreScan, the hardware-in-the-loop simulation result demonstrate the feasibility and effectiveness of our method. This paper provides a valuable reference on an expert and intelligent system methodology for automatic driving vehicles, which will be helpful for improving highway traffic safety and efficiency. [ABSTRACT FROM AUTHOR]

Positive-sense single-stranded RNA (+ssRNA) viruses, the most abundant viruses of eukaryotes in nature, require the synthesis of negative-sense RNA (−RNA) using their genomic (positive-sense) RNA (+RNA) as a template for replication. Based on current evidence, viral proteins are translated via viral +RNAs, whereas −RNA is considered to be a viral replication intermediate without coding capacity. Here, we report that plant and animal +ssRNA viruses contain small open reading frames (ORFs) in their −RNA (reverse ORFs [rORFs]). Using turnip mosaic virus (TuMV) as a model for plant +ssRNA viruses, we demonstrate that small proteins encoded by rORFs display specific subcellular localizations, and confirm the presence of rORF2 in infected cells through mass spectrometry analysis. The protein encoded by TuMV rORF2 forms punctuate granules that are localized in the perinuclear region and co-localized with viral replication complexes. The rORF2 protein can directly interact with the viral RNA-dependent RNA polymerase, and mutation of rORF2 completely abolishes virus infection, whereas ectopic expression of rORF2 rescues the mutant virus. Furthermore, we show that several rORFs in the −RNA of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have the ability to suppress type I interferon production and facilitate the infection of vesicular stomatitis virus. In addition, we provide evidence that TuMV might utilize internal ribosome entry sites to translate these small rORFs. Taken together, these findings indicate that the −RNA of +ssRNA viruses can also have the coding capacity and that small proteins encoded therein play critical roles in viral infection, revealing a viral proteome larger than previously thought. It is generally accepted that the negative-sense RNA (−RNA) of positive-sense single-stranded RNA (+ssRNA) viruses lacks coding capacity. This study shows that plant and animal +ssRNA viruses contain small open reading frames (ORFs) in their −RNA (rORFs) that display specific subcellular localizations and are important for viral infection. These small rORFs might be translated using internal ribosome entry sites as a translational strategy. [ABSTRACT FROM AUTHOR]

In this study, to reduce secondary sound source pollution in the reference signal of active noise control (ANC), a novel ANC algorithm, based on signal reconstruction, is proposed for vehicle interior noise. This algorithm combines the processes of ear-sides noise reconstruction and ANC. First, to reduce non-stationarity and nonlinearity, multi-source noise signals outside the vehicle are decomposed into a finite number of intrinsic mode function (IMF) components by empirical mode decomposition (EMD). Second, the IMFs are reconstructed by the energy-extreme division method into three components: high-frequency, intermediate-frequency and low-frequency. The radial basis function neural network (RBFNN) parameters are adjusted by the proportions of the components. Model training is performed to obtain the high-precision EMD–RBFNN reconstruction model (EMD–NNRM). The reconstructed noise signal is used as the reference signal of the variable step-size least mean square (VSS-LMS) algorithm, to control the passenger ear-sides noise. The effectiveness of the EMD–NNRM is validated using four noise signals from the outside of a vehicle. The interior noise of a high-speed vehicle is processed by the proposed algorithm and the traditional VSS-LMS algorithm for comparison. The reconstruction results show that the mean absolute error is improved by 77.64% compared with the back propagation neural network reconstruction model. Reconstructed passenger ear-sides noise can be utilized for ANC. The active control results suggest that the proposed algorithm can not only effectively suppress the interior noise but can also avoid pollution from secondary sound sources. [ABSTRACT FROM AUTHOR]

In this study, Al 2 O 3 –TiC composites synergistically reinforced with multi-walled carbon nanotubes (MWCNTs) and graphene nanoplates (GNPs) were prepared via spark plasma sintering (SPS). The effects of the MWCNT and GNP contents on the phase composition, mechanical properties, fracture mode, and toughening mechanism of the composites were systematically investigated. The experimental results indicated that the composite grains became more refined with the addition of MWCNTs and GNPs. The nanocomposites presented high compactness and excellent mechanical properties. The composite with 0.8 wt% MWCNTs and 0.2 wt% GNPs presented the best properties of all analysed specimens, and its relative density, hardness, and fracture toughness were 97.3%, 18.38 ± 0.6 GPa, and 9.40 ± 1.6 MPa m1/2, respectively. The crack deflection, bridging, branching, and drawing effects of MWCNTs and GNPs were the main toughening mechanisms of Al 2 O 3 –TiC composites synergistically reinforced with MWCNTs and GNPs. [ABSTRACT FROM AUTHOR]

Fruit fly optimization algorithm (FOA) is a kind of swarm intelligence optimization algorithm, which has been widely applied in science and engineering fields. The aim of this study is to design an improved FOA, namely evolution FOA (EFOA), which can overcome some shortcomings of basic FOA, including difficulty in local optimization, slow convergence speed, and lack of robustness. EFOA applies a few new strategies which adaptively control the search steps and swarm numbers of the fruit flies. The evolution mechanism used in EFOA can preserve dominant swarms and remove inferior swarms. Comprehensive comparison experiments are performed to compare EFOA with other swarm intelligence algorithms through 14 benchmark functions and a constrained engineering problem. Experimental results suggest that EFOA performs well both in global search ability and in robustness, and it can improve convergence speed. [ABSTRACT FROM AUTHOR]

According to International Diabetes Federation Diabetes Atlas statistics, diabetic retinopathy (DR) is the leading cause of vision loss in blinding diseases. The underlying cause of retinal vasculopathy progression in diabetic patients is hyperglycemia and hypoxia features in microvascular region. Hence, cyanobacteria are used as carriers to load both gold nanoparticles (Au NPs) with glucose oxidase‐like activity and iridium nanoparticles (Ir NPs) with catalase‐like activity, respectively (Cyano@Au@Ir). The Au NPs nanozyme first degrades glucose into hydrogen peroxide, which is further decomposed into H2O and O2 by the Ir NPs to complete the cascade hypoglycemic reaction. Based on the unique light transmittance of eyeball and the accumulation of light in the retinal area, the sustainable O2 production by Cyano greatly alleviates the hypoxia of microenvironment, leading to the decrease of angiogenic growth factor and hypoxia‐inducible factor expressions. Simultaneously, the highly expressed peroxide in the DR microenvironment can also be eliminated by Ir NPs for anti‐inflammatory property. Furthermore, it is demonstrated in DR animal model that Cyano@Au@Ir significantly reduces neovascular progression and vascular leakage. This novel treatment mode fundamentally degrades blood glucose, continuously supplies O2, and scavenges free radicals for comprehensive microenvironment regulation, providing inspirations for solving fundus complications of DR. [ABSTRACT FROM AUTHOR]

Interleukin-2 (IL-2) is a multifunctional cytokine in immune regulation. It is essential for the differentiation, expansion and stability of CD25+Foxp3+ regulatory T (Treg) cells, which is an important factor in immune suppression and self-tolerance. Meanwhile, IL-2 also stimulate effector T (Teff) cells to promote immune responses. The opposite and diverse function of IL-2 impedes its application to boost Treg cell populations in autoimmune disease treatment. Thus, it became focus of the research to modulate IL-2 activities to enhance Treg cell functions selectively. Based on the characteristic properties of Treg cells such as constitutively expression of high affinity IL-2 receptors (IL-2Rs), multiple approaches, including IL-2/mAb complexes, IL-2 muteins and low-dose of IL-2 have emerged in recent years to selectively target Treg cells and treat autoimmunity. These therapeutic approaches have achieved favorable results in both clinical trials and experimental animal models, and provided engineering blueprints to develop novel strategies of IL-2 treatments for autoimmune diseases. • IL-2 is the key cytokine to maintain Treg cell functions and immune homeostasis • Multiple novel therapeutic approaches emerged in recent years to bias IL-2 activities for the treatment of autoimmune diseases • New therapeutic strategies including IL-2/mAb complexes, IL-2 muteins and low-dose IL-2 can selectively enhance Treg function [ABSTRACT FROM AUTHOR]

We first present a generalization of ω⁎-Gâteaux differentiability theorems of Lipschitz mappings from open sets to those closed convex sets admitting nonsupport points and then show that every nonempty bounded closed convex subset of a Banach space has the fixed point property for isometries if it Lipschitz embeds into a super reflexive space. With the application of Baudier-Lancien-Schlumprecht’s theorem, we finally show that every nonempty bounded closed convex subset of a Banach space has the fixed point property for continuous affine mappings if it uniformly embeds into the Tsirelson space T⁎. [ABSTRACT FROM AUTHOR]

Objective We aimed to analyze and predict the risk of white matter lesions (WMLs) in hypertensive patients with different traditional Chinese medicine (TCM) syndromes, and to explore the relationship and influencing factors between them. Methods From September 2019 to December 2021, 309 patients were enrolled from the cardiovascular departments of the Affiliated Hospital of Gansu University of Traditional Chinese Medicine according to the inclusion and exclusion criteria, and they were divided into four syndromes: phlegm and blood stasis syndrome, kidney qi deficiency syndrome, liver fire hyperactivity syndrome, and yin deficiency and yang hyperactivity syndrome. Diastolic blood pressure (DBP), homocysteine acid (Hcy), uric acid (UA), and serum cystatin C (Cys C) were measured. The ARWMC and Fazekas scales were used to assess the site, score, and the degree of WMLs (mild, moderate, or severe) in hypertensive patients with different syndromes, and the correlation between risk factors and different syndromes was summarized. Results There were significant differences in DBP, Hcy, UA, and Cys C among different TCM syndrome types (P<0. 05). WMLs were assessed by the Fazekas and ARWMC scales, and there was no significant difference in the distribution of WMLs sites among different syndrome types. There was no significant difference in the Fazekas scores of WMLs, but there was a significant difference in the ARWMC ratings among different syndrome types (P<0. 05). The WMLs Fazekas and ARWMC risk classification analysis of different TCM syndrome types were significantly different (P<0. 05). According to the Fazekas scale assessment, there were differences in WMLs among all of the syndrome types (P<0. 05). Spearman rank correlation analysis showed that the WMLs degree was positively correlated with age, Hcy, Cys C, and UA in the phlegm and blood stasis syndrome group (rs =0. 22, 0. 23, 0. 18, 0. 24, P<0. 05). The WMLs degree was negatively correlated with HUA and HHcy (rs =-0. 19, -0. 21, P<0. 05). The degree of WMLs was positively correlated with UA (rs =0. 48, P<0. 05), and negatively correlated with HUA (rs = -0. 47, P<0. 05). The degree of WMLs in yin deficiency and yang hyperactivity syndrome group was positively correlated with age, HUA, and Cys C (rs = 0. 37, 0. 27, 0. 27, P <0. 05), and negatively correlated with UA (rs = -0. 32, P < 0. 05). The degree of WMLs in the kidney qi deficiency syndrome group was positively correlated with Hcy (rs = 0. 33, P <0. 05), but negatively correlated with HHcy and DBP (rs = -0. 32, -0. 30, P < 0. 05). The phlegm and blood stasis syndrome had more risk factors with a statistically significant difference (P < 0. 05) compared with the liver fire hyperactivity syndrome, yin deficiency and yang hyperactivity syndrome, and kidney qi deficiency syndrome. According to the ARWMC rating, there were differences in WMLs among all syndrome types (P<0. 05). Spearman rank correlation analysis showed that the WMLs degree was positively correlated with UA (rs =0. 57, P<0. 05) and negatively correlated with HUA (rs =-0. 58, P<0. 05) in patients with hypertension and the ARWMC rating. The degree of WMLs was positively correlated with UA (rs = 0. 34, P <0. 05), and negatively correlated with HUA (rs =-0. 44, P<0. 05). The degree of WMLs in the kidney qi deficiency syndrome group was positively correlated with Cys C (rs =0. 26, P<0. 05), and negatively correlated with diabetes mellitus and HUA (rs =-0. 30, -0. 28, P<0. 05). There were more risk factors with statistically significant differences (P<0. 05) in the kidney qi deficiency syndrome compared with phlegm and blood stasis syndrome, liver fire hyperactivity syndrome, and yin deficiency and yang hyperactivity syndrome. Conclusion The phlegm and blood stasis syndrome and kidney qi deficiency syndrome may be TCM syndrome types with higher incidences of WMLs in hypertensive patients. [ABSTRACT FROM AUTHOR]

Although Interleukin-2 (IL-2) was identified almost 40 years ago, only recently low dosage IL-2 therapy is proved to be an effective approach to treat autoimmune diseases. The underlining mechanism is that IL-2 can fine-tune subsets of CD4 + T cells by promoting the development and maintenance of regulatory T cells (Treg) at low-dosage (ld) and enhance the functions of effector T cells (Teff) at high-dosage (hd). Since the successful clinical trials of IL-2 to treat patients with autoimmune diseases and inflammatory conditions, including Systemic lupus erythematosus (SLE) and Type 1 Diabetes (T1D), ld IL-2 therapy is a promising strategy to treat autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear. Method: We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al. Results: Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy. Conclusions: The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations. [ABSTRACT FROM AUTHOR]

Indoor simulation experiment with 2.76 L microcosms using sediment from Taihu Lake were conducted to investigate the relationship between algae bloom and heavy metals release into a lake aquatic environment. The results showed that Microcystic aeruginosa (M. aeruginosa) growth can enhance cadmium (Cd) mobilization from sediments to overlying water due to increasing pH and DO content of overlying water and changing the redox condition of surface sediment (0–2 cm) from weak oxidation to weak reduction. The dissolved Cd concentration in overlying water can be decreased during algal growth process. The remobilization of Cd from sediment can effectively reduce the ecological risk of total Cd in sediments. The results of this study showed that both I geo and E r i can be used to effectively evaluate the ecological risk of heavy metal Cd in different fractions. [ABSTRACT FROM AUTHOR]

Background: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Herein, we carried out a systematic review and meta-analysis of published literature to identify recipient-related clinical risk factors associated with PGD development. Method: A systematic search of electronic databases (PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus) for studies published from 1970 to 2013 was performed. Cohort, case-control, or cross-sectional studies that examined recipient-related risk factors of PGD were included. The odds ratios (ORs) or mean differences (MDs) were calculated using random-effects models Result: Thirteen studies involving 10042 recipients met final inclusion criteria. From the pooled analyses, female gender (OR 1.38, 95% CI 1.09 to 1.75), African American (OR 1.82, 95%CI 1.36 to 2.45), idiopathic pulmonary fibrosis (IPF) (OR 1.78, 95% CI 1.49 to 2.13), sarcoidosis (OR 4.25, 95% CI 1.09 to 16.52), primary pulmonary hypertension (PPH) (OR 3.73, 95%CI 2.16 to 6.46), elevated BMI (BMI≥25 kg/m2) (OR 1.83, 95% CI 1.26 to 2.64), and use of cardiopulmonary bypass (CPB) (OR 2.29, 95%CI 1.43 to 3.65) were significantly associated with increased risk of PGD. Age, cystic fibrosis, secondary pulmonary hypertension (SPH), intra-operative inhaled nitric oxide (NO), or lung transplant type (single or bilateral) were not significantly associated with PGD development (all P>0.05). Moreover, a nearly 4 fold increased risk of short-term mortality was observed in patients with PGD (OR 3.95, 95% CI 2.80 to 5.57). Conclusions: Our analysis identified several recipient related risk factors for development of PGD. The identification of higher-risk recipients and further research into the underlying mechanisms may lead to selective therapies aimed at reducing this reperfusion injury. [ABSTRACT FROM AUTHOR]

Highlights: [•] TiO2/fly ash beads photocatalyst was prepared by hydrolysis-precipitation method. [•] For N-S-TiO2/FMS, (NH2)2CO and (NH2)2SC were used as N, S source respectively. [•] Visible absorption edge was expanded from 390–500nm after N, S co-doping. [•] N-S-TiO2/FMS samples present obvious visible light photocatalytic activity. [•] Fly ash beads reduced the reunion effect and improved operation recycle ability. [ABSTRACT FROM AUTHOR]

The gene therapy attracted more and more attention for the tumor therapy. To obtain a safe gene therapy system, the new gene vectors beyond the virus were developed for a high gene therapy efficiency. The ultrasound mediated gene therapy was safer and the plasmid DNA could be delivered by the microbubbles and combined with the ultrasound to increase the gene transfection efficiency. In this work, the cationic microbubbles decorated with Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-AspCys) (iRGD peptides) and magnetic Fe 3 O 4 nanoparticles (MB iM) was designed for targeted ultrasound contrast imaging guided gene therapy of tumors. The ultrasound image intensity was dramatically enhanced at the tumor site that received MB iM with the magnet applied, compared to those administrated the non-targeted microbubbles (MB b) or the microbubbles with only one target material on the surface (MB M and MB bi). The pGPU6/GFP/Neo-shAKT2 was used as a sample gene, which down regulate the AKT2 protein expression for the cancer therapy. It illustrated that MB iM /AKT2 had the highest gene transfection efficiency in the studied microbubbles mediated by the ultrasound, leading to the AKT2 protein expression downregulation and the strongest tumor killing effect in vitro and in vivo. In summary, a novel and biocompatible gene delivery platform via MB iM with both the endogenous and external targeting effects for breast cancer theranostics was developed. [Display omitted] • iRGD dual-targeted magnetic microbubbles (MB iM) designed for targeted gene delivery. • The ultrasound image intensity at the tumor site was enhanced by MB iM. • The gene therapy efficiency was improved by MB iM mediated by ultrasound. [ABSTRACT FROM AUTHOR]

• ZIF-8 MOFs were used to load high amount of antibiotics (LEVO) showing pH responsiveness to bacterial infection. • The negatively charged ZIF-8@LEVO@HA nano drug carrier was combined onto CL after amination treatment. • The antibacterial CL has a high drug loading capacity (0.65 mg/cm2) owing to the surface bound ZIF-8. • The ZLHP-CL showed excellent bactericidal effect with inhibitory zone diameter 34 mm. • In infectious keratitis animal, ZLHP-CL efficiently killed bacteria, reduced the inflammation reaction in corneal tissue repair. Eye trauma, ophthalmic surgery and contact lens (CL) wearing cause corneal infection and bacterial biofilms formation, which further lead to corneal ulcer and perforation. In view of the low bioavailability of antibiotic eye drops and the clinical problems that cause bacterial resistance, we used pH sensitive zeolitic imidazolate framework-8 metal–organic frameworks (ZIF-8 MOFs) to load broad-spectrum antibacterial drugs levofloxacin (LEVO). After the surface modification by hyaluronic acid (HA), the nanomaterial surface was negatively charged. A simple amination treatment was used to endow CL surface with amino groups to combine the negatively charged nano drug loading system through electrostatic forces. The bacteriostatic ring of ZIF-8@LEVO@HA-PEI modified CL (ZLHP-CL) was 34 mm, which could be owing to the high drug loading capacity of ZIF-8 (0.65 mg/cm2). The bactericidal function was further confirmed by shake flask method and live/dead bacterial staining assay against S. aureus , S. epidermidis and E. coli. It is worth mentioning that ZLHP-CL showed significant pH sensitivity to the bacterial infection, which released drug rapidly at pH 5.5 and hardly released drug at pH 7.4. In the bacterial biofilm's formation experiment, it was found that ZLHP-CL obviously inhibited bacterial adhesion and biofilms formation. Furthermore, it was proved in infectious keratitis animal that ZLHP-CL could kill the bacteria and reduce the inflammation reaction, which showed advantages in corneal tissue repair and light transmittance maintenance. In this work, based on nanotechnology, a facile CL drug loading technology is developed, which can be used to sustained release of various drugs for ophthalmic diseases treatment. [ABSTRACT FROM AUTHOR]

Depression has become the leading cause of disability worldwide and is a global health burden. Quantitative assessment of depression-related neurotransmitter concentrations in human fluids is highly desirable for diagnosis, monitoring disease, and therapeutic interventions of depression. In this review, we focused on the latest strategies of CD-based electrochemical biosensors for detecting a depression-related neurotransmitter. We began this review with an overview of the microstructure, optical properties and cytotoxicity of CDs. Next, we introduced the development of synthetic methods of CDs, including the "Top-down" route and "Bottom-up" route. Finally, we highlighted detecting an application of CD-based electrochemical sensors in a depression-related neurotransmitter. Moreover, challenges and future perspectives on the recent progress of CD-based electrochemical sensors in depression-related neurotransmitter detection were discussed. [ABSTRACT FROM AUTHOR]

• iPP film crystallized via the mesophase exhibits improved photo-oxidation stability in comparison with melt-crystallized iPP film. • iPP with nodular morphology has higher transparency and lower O 2 diffusivity than the iPP with lamellar morphology. • The relationship between enhanced photo-oxidation stability and nodular morphology of iPP has been established. Photo-oxidation degradation behaviors of isotactic polypropylene (iPP) films with different crystalline morphology were investigated by artificially accelerated aging test. The α form iPP with nodular morphology was obtained by quenching the melt and subsequent annealing process, and its photo-oxidation degradation behavior was compared with that of the melt-crystallized α form iPP sample. Fourier transform infrared spectroscopy (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), X-ray scattering, dynamic mechanical analysis (DMA) and atomic force microscopy (AFM) were utilized to characterize the microstructural variations of these two kinds of iPP films during photo-oxidation degradation process. The results showed that iPP film of nodular morphology exhibits improved photo-oxidation stability compared with that of lamellar and spherulitic structure. UV-Vis spectra and O 2 diffusivity test of unexposed and aged samples demonstrated that the iPP film of nodular morphology has higher transparency and lower O 2 diffusivity than that of lamellar morphology. Combining the microstructural analysis and surface morphology observation, the improved photo-oxidation stability of "nodular" iPP was correlated with its higher UV light transparency, lower O 2 diffusion coefficient as well as the slower segmental mobility in the amorphous phase. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of the immunoglobulin light-chain repertoires with chronic HBV infection, the high-throughput sequencing and IMGT/HighV-QUEST were adapted to analyze the κ (IgK) and λ (IgL) light-chain repertoires from the inactive HBV carriers (IHB) and the healthy adults (HH). The comparative analysis revealed high similarity between the κ light-chain repertoires of the HBV carriers and the healthy adults. Nevertheless, the proportion of IGLV genes with ≥90% identity as the germline genes was higher in the IgL light-chain repertoire of the IHB library compared with that of HH library (74.6% vs. 69.1%). Besides, the frequency of amino acid mutations in the CDR1 regions was significantly lower in the IgL light-chain repertoire of the IHB library than that of the HH library (65.52% vs. 56.0%). These results suggested the lower somatic mutation level in the IgL repertoire of IHB library, which might indicate the biased selection of IGLV genes in the IgL repertoire with chronic HBV infection. These findings might lead to a better understanding of the characteristics of the light-chain repertoires of HBV chronically infected individuals. [ABSTRACT FROM AUTHOR]

Efficient encapsulation of hydrophilic drugs was substantially challenging when using emulsion solvent evaporation approach. The aim of present study was to design palonosetron hydrochloride-loaded PLGA microspheres (Pal-MS) with high encapsulation efficiency (EE) to sustain drug release for over several days. Pal-MS were prepared using emulsion-solvent evaporation method. Results showed that the pH of external phase could significantly affect the EE and the drug release rate of Pal-MS. By increasing the pH of external phase from 5.0 to 10.0, EE of Pal-MS increased from 55.64% to 94.33%. When the pH of external phase was 7.0, an ideal Pal-MS with EE of 86.51% and a zero-order drug release profile was obtained. The improved EE and drug release performance was proved to be associated with possible PLGA degradation, enhanced drug-PLGA interaction and reduced drug diffusion from organic phase to aqueous phase. After subcutaneous injection, such Pal-MS showed more steady drug plasma concentration (0.207–1.238 ng/ml) over the entire 6-day in comparison with those of multiple-day-dosing intravenous palonosetron hydrochloride solution. It was concluded that Pal-MS were successfully designed by the adjustment of the pH of external phase and could be promising for preventing both acute and delayed chemotherapy-induced nausea and vomiting (CINV). [ABSTRACT FROM AUTHOR]

Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes. A resource of >1,500 bacterial reference genomes sheds light on the human gut microbiome. [ABSTRACT FROM AUTHOR]

Background: At present, the predictive ability of the prognostic indicator of hepatocellular carcinoma (HCC) is still limited. This study aims to analyze the relationship between the preoperative high-sensitivity C-reactive protein to lymphocyte ratio (HCLR) and the clinicopathologic characteristics of HCC. Patients and methods: A total of 229 HCC patients undergoing surgical resection were retrospectively analyzed. The majority of the patients (132/229) had tumors larger than 5 cm, and 45 out of 229 had more than one tumor focus. Receiver operating characteristic curve analysis was used to decide the cutoff value of HCLR. The overall survival (OS) and progression-free survival (PFS) rates were evaluated by adopting the Kaplan–Meier method. Results: The cutoff value of HCLR for the best discrimination of HCC prognosis was 1.3 with a sensitivity of 75.5% and a specificity of 71.8%. The area under the receiver operating characteristic curve was 0.791 (95% CI, 0.731–0.840). Preoperative HCLR at a high level (>1.3) was positively correlated with large tumor size, TNM stage, microvascular invasion, and recurrence. The mean OS and PFS in patients with HCLR >1.3 were significantly shorter than in those with HCLR ≤1.3. Univariate and multivariate analyses revealed the HCLR was an independent predictor of OS and PFS. Conclusion: HCLR was an important independent predictor of dismal prognosis in HCC patients and can be used as a sensitive indicator for the dynamic monitoring of postoperative patients. [ABSTRACT FROM AUTHOR]

7α,15α-diOH-Dehydroepiandrosterone (7α,15α-diOH-DHEA) is an important intermediate in the synthesis of steroid pharmaceutical compounds, and can be bioconverted from DHEA by Colletotrichum lini ST-1 . A microemulsion system can improve substrate bioavailability and may also minimize DHEA cellular toxicity as cells and substrate are retained in the water and oil phase respectively. In this study, several microemulsions with a different hydrophile lipophile balance were prepared and evaluated based on their stability and bioconversion efficacy. The yield of the best formula of 7α,15α-diOH-DHEA was 61.2%, which was 3.1 times that of the traditional water phase bioconversion system. This formula was further optimized using the Taguchi orthogonal experimental design, and the yield reached 73.3%. Due to less cellular toxicity of the substrate using the microemulsion system, the repeated-cycle bioconversion based on microemulsion using recycled cells was realized for the first time, and the overall 6-cycle production (41.5 g from 60 g DHEA) was 4.3 times that of the traditional method. This highly efficient microemulsion system, with improved cell sustainability as well as bioreactivity, may be expanded to the bioconversion of other insoluble and toxic substrates. [ABSTRACT FROM AUTHOR]

We address the problem of computing distances between permutations that take into account similarities between elements of the ground set dictated by a graph. The problem may be summarized as follows: Given two permutations and a positive cost function on transpositions that depends on the similarity of the elements involved, find a smallest cost sequence of transpositions that converts one permutation into another. Our focus is on costs that may be described via special metric-tree structures. The presented results include a linear-time algorithm for finding a minimum cost decomposition for simple cycles and a linear-time 4 ∕ 3 -approximation algorithm for permutations that contain multiple cycles. The proposed methods rely on investigating a newly introduced balancing property of cycles embedded in trees, cycle-merging methods, and shortest path optimization techniques. [ABSTRACT FROM AUTHOR]

1,2-Dichloroethane (1,2-DCA) is a common compound found in groundwater contaminated with organics. This compound is difficult to remove from groundwater and has the potential to inflict significant harm on human health and the environment. This study used sodium persulfate (Na 2 S 2 O 8) activated by sodium hydroxide (NaOH) to remove 1,2-DCA from aqueous solutions. Density functional theory was employed to calculate the potential energy surface of the reactants, intermediates, transient states, and products to thoroughly analyze the degradation pathways. The computations were performed in combination with in situ remediation of a 1,2-DCA plume from a point source to verify the industrial applicability of the technology. The results showed the 1,2-DCA removal efficiency was impacted considerably by the Na 2 S 2 O 8 dosage and the dosing sequence of Na 2 S 2 O 8 and NaOH, with the mean removal ratio reaching 96.24%. A free radical reaction was the main pathway of 1,2-DCA degradation; superoxide radical (O 2 •–) existed stably and played a key role in the reaction, and the main transformation proceeded via a vinyl chloride intermediate. The maximum removal of 1,2-DCA reached 91.79% in the in situ remediation. The developed technology exhibits important advantages in enabling flexible control over chemical dosages, long durations of effective activity, and rapid full-cycle remediation. • SPASH was in situ pilot-scale tested to remediate 1,2-DCA in groundwater. • A free radical reaction was the main pathway of 1,2- DCA degradation. • The transformation involving vinyl chloride comprised the main pathway. • The technology exhibits important advantages in rapid full-cycle remediation. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is characterized by chronic transmural inflammation. The symptom of the mice model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) is closed to human under CD condition, so this kind of animal is widely used in the related researches. Although the dysbiosis of the fecal microbiota has been proved to play an important role in the patients with CD, the composition of the gastrointestinal microbiota in the mouse model under disease condition is still unclear. In the current study, male 7-week BALB/c mice were anesthetized and intrarectal administrated by ethanol (ET group), TNBS in ethanol (TN group), and phosphate buffered saline (PBS) (CK group) as control. The symptoms of individuals under the CD condition were observed, and the changes of the bacterial taxonomic structure and functional composition were revealed by next-generation sequencing (NGS) 16S sequencing. The BALB/c mice in TN group demonstrated CD-like symptoms and the damages in the intestinal tract. The NGS 16S results exhibited that the diversity and microbial composition under CD condition are significantly different with those in ET group. The KEGG Orthology (KO) profile were generated from PICRUSt, and function modules such as methanogenesis (M00347) and microcin C transport system (M00349) were found enriched in the individuals in the TN group. This study proved that mouse model induced by TNBS could develop the similar symptom to CD patient, and we firstly showed the significant intestinal microbe changes on both taxonomic structure and functional composition in this mouse model. [ABSTRACT FROM AUTHOR]

Based on tropical cyclone yearbook data from 1949 to 2006, climate characteristics, such as interdecadal variation, period of tropical cyclone frequency, rainstorm and strong wind, intensity characteristics, were analyzed. Main results were as follows: tropical cyclone affecting Shandong Province was mainly from the last ten-day of July to the last ten-day of August, and its interdecadal variation was obvious. The marked periodic variation of every 2. 4 and 5 years was found according to power spectrum analysis. It showed obvious weakening tendency about tropical cyclone's intensity by using Kendall test. It also showed that August was the strongest month among a year for rainstorm frequency and intensity, and flood disaster was more easily/ to occur during this month. It was distinct for frequency's interdecadal variation of tropical cyclone causing rainstorm and strong wind. Marked period was existed about annual average precipitation and strong wind. At the same time, the cause of the variation was discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] Traditional encapsulated microbubbles are recently used as delivery carriers for drugs and genes, but they have low efficiency. If the local microbubble concentration could be increased, this might be able to improve the therapeutic efficacy of diseases. In this study, we developed novel cationic magnetic microbubbles (MB M), which could simultaneously realize targeted aggregation under a magnetic field as well as ultrasonographic real-time visualization. Their physicochemical properties, biocompatibility, ultrasonography, magnetic response characteristics, and biodistribution were systematically evaluated. Here, the MB M were 2.55 ± 0.14 µm in size with a positive zeta potential, and had a good biocompatibility. They were able to enhance ultrasonographic contrast both in vitro and in vivo. MB M could be attracted by an external magnet for directional movement and aggregation in vitro. We confirmed that MB M also had a great magnetic response in vivo, by means of fluorescence imaging and contrast-enhanced ultrasound imaging. Following intravenous injection into tumor-bearing mice, MB M showed excellent stability in the internal circulation, and could accumulate in the tumor vasculature through magnetic targeting. With the excellent combination of magnetic response and acoustic properties, cationic magnetic microbubbles (MB M) have promising potential for use as a new kind of drug/gene carrier for theranostics in the future. [ABSTRACT FROM AUTHOR]

Abstract: Ethylene propylene diene monomer rubber composites reinforced with micro- and nano-sized short fibers were made by mechanically blending of silanized fibrillar silicate (FS) nanofibers and polyamide 66 (PA-66) microfibers. A synergistic reinforcement on static and dynamic mechanical properties was revealed. When FS nanofibers and PA-66 microfibers were used together in an appropriate volume ratio, static and dynamic mechanical properties (such as tensile stress, mechanical anisotropy, compression modulus, dynamic storage modulus and tensile fatigue property) of the resulting composites were substantially improved. The co-reinforcement mechanism of nano- and micro-sized fibers was discussed in terms of composite fracture morphology. The synergetic reinforcement effect on the dynamic fatigue properties is attributed to the result of competitive factors including stress transfer, crack initiation and propagation, and matrix reinforcement, whereas the synergetic reinforcement effect on the static tensile properties is achieved due to the strong interfacial adhesion between FS nanofibers and rubber. [Copyright &y& Elsevier]