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Abstract A practical fixed‐time composite learning control scheme, by combining dynamic regressor extension and mixing (DREM) parameter identification algorithm and adaptive dynamic surface control (DSC) technique, is proposed for a class of strict‐feedback non‐linear systems subjected to linear‐in‐parameters uncertainties and full‐state constraint. To address the problem of state constraint, a non‐linear transformation function is introduced to convert the originally constrained non‐linear system into an unconstrained one. Meanwhile, the hyperbolic tangent function is employed to avoid singularity issues that often appeared in the traditional fixed‐time (FXT) control designs. In order to relax the requirement of persistency of excitation condition, a modified FXT‐DREM parameter identification approach with an interval excitation condition is constructed by introducing a three‐layer transformation technique derived from the classical DREM algorithm. Then, the modified FXT‐DREM parameter identification algorithm is seamlessly integrated into the adaptive DSC framework, resulting in a composite‐learning control scheme. By employing Lyapunov stability analysis, the fixed‐time convergence of both the parameter estimation error and the trajectory tracking error is proved. Finally, the effectiveness of the proposed design is demonstrated through simulation test.

X-ray scattering/diffraction tensor tomography techniques are promising methods to acquire the 3D texture information of heterogeneous biological tissues at micrometre resolution. However, the methods suffer from a long overall acquisition time due to multi-dimensional scanning across real and reciprocal space. Here, a new approach is introduced to obtain 3D reciprocal information of each illuminated scanning volume using mathematic modeling, which is equivalent to a physical scanning procedure for collecting the full reciprocal information required for voxel reconstruction. The virtual reciprocal scanning scheme was validated by a simulated 6D wide-angle X-ray diffraction tomography experiment. The theoretical validation of the method represents an important technological advancement for 6D diffraction tensor tomography and a crucial step towards pervasive applications in the characterization of heterogeneous materials.

Macadamia nuts, scientifically designated as Macadamia integrifolia, are a highly valuable crop that originated in Australia. This study provides a comprehensive examination of the symbiotic relationships between various macadamia root systems and arbuscular mycorrhizal fungi (AMF). The four principal macadamia-producing regions in Yunnan Province were selected for investigation on the basis of meticulous criteria. To determine the AMF infection rate, the roots were stained. Furthermore, high-throughput sequencing was employed to conduct a comprehensive analysis of the fungal diversity in the rhizosphere soil. The findings were definitive, indicating that both normal and cluster roots are capable of establishing a symbiotic relationship with AMF. Secondary forests exhibited significantly elevated fungal diversity relative to normal roots, while cluster roots demonstrated the lowest diversity and notable regional variation, indicating that the environment exerts a considerable influence on inter-root fungi and AMF. The analysis of the fungal community composition revealed that the predominant groups were Ascomycetes and Basidiomycetes. The FUNGuild function prediction clearly indicated distinct differences in the fungal functions of secondary forests, cluster roots, and normal roots. This study provides a scientific foundation for the sustainable development of macadamia nuts and significantly contributes to a deeper comprehension of the intricate interactions between macadamia and AMF, thereby fostering the long-term stable and healthy growth of the macadamia nut industry.

The bilateral teleoperation system is susceptible to model parameter uncertainty and unknown disturbances in both the master and slave manipulators, resulting in instability and inaccuracies in the force and position tracking performance. To address these issues, a novel nonlinear model reference adaptive impedance controller has been designed to achieve coordinated force and position synchronization of dual manipulators. The adaptive control laws, based on sliding mode functions, have been designed to compensate for the uncertainty of the manipulator model. Furthermore, an adaptive estimation law has been employed to appraise the unknown upper bound of external disturbances. This ensures that the closed-loop model parameters of the dual manipulator converge to the reference impedance model respectively. Simultaneously, it enables the position error between the reference model response and the end-effector task space position to asymptotically converge to zero. To verify the effectiveness of the proposed controller, simulations have been conducted on the MATLAB platform and experiments on a single degree of freedom teleoperation system have been performed. The results demonstrate that the controller exhibits strong robustness and has the capability of force-position tracking ability.

Abstract Lymphatic vessels, comprising the secondary circulatory system in human body, play a multifaceted role in maintaining homeostasis among various tissues and organs. They are tasked with a serious of responsibilities, including the regulation of lymph absorption and transport, the orchestration of immune surveillance and responses. Lymphatic vessel development undergoes a series of sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into the highly specialized lymphatic vessel networks. Lymphangiogenesis, as defined by new lymphatic vessels sprouting from preexisting lymphatic vessels/embryonic veins, is the main developmental mechanism underlying the formation and expansion of lymphatic vessel networks in an embryo. However, abnormal lymphangiogenesis could be observed in many pathological conditions and has a close relationship with the development and progression of various diseases. Mechanistic studies have revealed a set of lymphangiogenic factors and cascades that may serve as the potential targets for regulating abnormal lymphangiogenesis, to further modulate the progression of diseases. Actually, an increasing number of clinical trials have demonstrated the promising interventions and showed the feasibility of currently available treatments for future clinical translation. Targeting lymphangiogenic promoters or inhibitors not only directly regulates abnormal lymphangiogenesis, but improves the efficacy of diverse treatments. In conclusion, we present a comprehensive overview of lymphatic vessel development and physiological functions, and describe the critical involvement of abnormal lymphangiogenesis in multiple diseases. Moreover, we summarize the targeting therapeutic values of abnormal lymphangiogenesis, providing novel perspectives for treatment strategy of multiple human diseases.

Abstract Lymphangiogenesis in tumors provides an auxiliary route for cancer cell invasion to drainage lymph nodes, facilitating the development of lymphatic metastasis (LM). However, the mechanisms governing tumor lymphangiogenesis and lymphatic permeability in gastric cancer (GC) remain largely unknown. Here, the unprecedented role and mechanism of cysteine‐rich intestinal protein‐1 (CRIP1) in mediating the development of GC LM is uncovered. A series of assays are performed to identify downstream targets of CRIP1, and rescue experiments are performed to confirm the effects of this regulatory axis on LM. CRIP1 overexpression facilitates LM in GC by promoting lymphangiogenesis and lymphatic vessel permeability. CRIP1 promotes phosphorylation of cAMP responsive element binding protein 1(CREB1), which then mediates vascular endothelial growth factor C (VEGFC) expression necessary for CRIP1‐induced lymphangiogenesis and transcriptionally promotes C‐C motif chemokine ligand 5 (CCL5) expression. CCL5 recruits macrophages to promote tumor necrosis factor alpha (TNF‐α) secretion, eventually enhancing lymphatic permeability. The study highlights CRIP1 regulates the tumor microenvironment to promote lymphangiogenesis and LM in GC. Considering the current limited understanding of LM development in GC, these pathways provide potential targets for future therapeutics.

Amorphous metal catalysts often exhibit appealing catalytic properties, however, accurate control synthesis of amorphous nano-metal catalysts is a challenge. Here, the authors report a feasible strategy to prepare the amorphous Cu catalysts by supercritical CO2 treatment followed by electroreduction. The resulted catalyst shows high selectivity towards multi-carbon products for CO2 electroreduction.

Disordered linkers (DLs) are intrinsically disordered regions that facilitate movement between adjacent functional regions/domains, contributing to many key cellular functions. The recently completed second Critical Assessments of protein Intrinsic Disorder prediction (CAID2) experiment evaluated DL predictions by considering a rather narrow scenario when predicting 40 proteins that are already known to have DLs. We expand this evaluation by using a much larger set of nearly 350 test proteins from CAID2 and by investigating three distinct scenarios: (1) prediction residues in DLs vs. in non-DL regions (typical use of DL predictors); (2) prediction of residues in DLs vs. other disordered residues (to evaluate whether predictors can differentiate residues in DLs from other types of intrinsically disordered residues); and (3) prediction of proteins harboring DLs. We find that several methods provide relatively accurate predictions of DLs in the first scenario. However, only one method, APOD, accurately identifies DLs among other types of disordered residues (scenario 2) and predicts proteins harboring DLs (scenario 3). We also find that APOD’s predictive performance is modest, motivating further research into the development of new and more accurate DL predictors. We note that these efforts will benefit from a growing amount of training data and the availability of sophisticated deep network models and emphasize that future methods should provide accurate results across the three scenarios.

As a candidate anode material for Li-ion batteries, Bi-based materials have attracted extensive attention from researchers due to their high specific capacity, environmental friendliness, and simple synthesis methods. However, Bi-based anode materials are prone to causing large volume changes during charging and discharging processes, and the effect of these changes on lithium storage performance is still unclear. This work introduces that Bi/C nanocomposites are prepared by the Bi-based MOF precursor calcination method, and that the Bi/C nanocomposite maintains a high specific capacity (931.6 mAh g−1) with good multiplicative performance after 100 cycles at a current density of 100 mA g−1. The structural evolution of Bi/C anode material during the first cycle of charging and discharging is investigated using in situ synchrotron radiation SAXS. The SAXS results indicate that the multistage scatterers of Bi/C composite, used as an anode material during the first lithiation, can be classified into mesopores, interspaces, and Bi nanoparticles. The different nanostructure evolutions of three types of Bi nanoparticles were observed. It is believed that this result will help to further understand the complex reaction mechanism of Bi-based anode materials in Li-ion batteries.

The microminiaturization of detectors used to record the intensity of X-ray beams is very favorable for combined X-ray experimental techniques. In this paper, chemical-vapor-deposited (CVD) polycrystalline diamond film was used to fabricate a micro-detector owing to its well controlled size, good thermostability, and appropriate conductivity. The preparation process and the main components of the CVD diamond micro-detector are described. The external dimensions of the packaged CVD diamond micro-detector are 15 mm × 7.8 mm × 5.8 mm. To demonstrate the performance of the detector, K-edge X-ray absorption fine-structure (XAFS) spectra of Cr, Fe, Cu, and Se foils were collected using the CVD diamond micro-detector and routine ion chamber. These XAFS measurements were performed at beamline 1W2B of Beijing Synchrotron Radiation Facility, covering an energy range from 5.5 to 13.5 keV. By comparison, it can be seen that the CVD diamond micro-detector shows a more excellent performance than the routine ion-chamber in recording these XAFS spectra. The successful application of the CVD diamond micro-detector in XAFS measurements shows its feasibility in recording X-ray intensity.

The increasing energy consumption in backbone networks has been one of crucial concerns in Information and Communications Technology (ICT) sector. From a viewpoint of intelligent adaption, we propose Green Routing in Backbone networks with Bundled links, which is referred to as GRB2, to investigate the substantial power saving in a bundled link based backbone network for above enormous challenges from severe alarming statistics of the issues on economy, energy and environment. We formulate the above problems as Mixed Integer Linear Programming (MILP) models and develop power-aware greedy heuristics to solve them. We have investigated and compared the different characterizations of the solutions to the proposed problems by evaluating network power consumption including Power Saving Ratio (PSR) profile over time, PSR profile under different Maximum Cable Utilization (MCU) and PSR profile under different Bundled Sizes (BSs) and network performance including Powered-Off Cable Rate (POCR), Mean State Switching Times (MSST) and Mean Running Time (MRT) for various traffic demands during PPs and OPPs under different real backbone network topology scenarios compared with MSPF, SSPF, and HDEER. Experiment results show the different power-saving potential of these solutions once applied in the backbone network.

The authors present flDPnn, a computational tool for disorder and disorder function predictions from protein sequences. flDPnn was assessed with the data from the “Critical Assessment of Protein Intrinsic Disorder Prediction” experiment and on an independent and low-similarity test dataset, which show that flDPnn offers accurate predictions of disorder, fully disordered proteins and four common disorder functions.

Ciprofloxacin is ubiquitous and poses a potential threat to aquatic ecosystems. However, the comprehensive effect of prolonged ciprofloxacin exposure on the submerged clonal plant Vallisneria natans (Lour.) Hara remains unknown. Growth and physiological responses in V. natans exposed to ciprofloxacin at concentrations of 0, 0.05, 0.25, 1.25, 2.5, 5 and 10 mg/L were repeatedly evaluated on Days 7, 14, 28, 42 and 56. V. natans maintained good growth properties under 0.05–0.25 mg/L ciprofloxacin treatments, while the inhibition effect on plant growth induced by higher-concentration treatments increased over time. The IC50 values of ciprofloxacin for growth endpoints ranged from 1.6 mg/L to 5.3 mg/L and displayed time-dependent decreases. Pigment contents were significantly stimulated by ciprofloxacin on Day 7 but decreased to varying degrees as the exposure time was extended. Soluble protein and hydrogen peroxide content rose significantly over the first 14 days of treatment with 0.25–10 mg/L ciprofloxacin but decreased under 1.25–10 mg/L ciprofloxacin treatments since Day 28. Antioxidants including superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase and proline functioned well in mitigating oxidative stress under different ciprofloxacin concentrations, lowering the comprehensive toxic effects of ciprofloxacin on V. natans during the period from Day 14 to Day 42, as evidenced by decreased IBR (integrated biomarker response) values. However, the toxic pressure of ciprofloxacin on V. natans peaked on Day 56. These findings suggest that exposure time can influence the responses of V. natans exposed to ciprofloxacin and that IBR can be employed to evaluate the integrated impacts of prolonged ciprofloxacin contamination in aquatic settings.

The electrochemical CO2 reduction reaction (CO2RR) is a promising approach for mitigating the greenhouse effect arising from anthropogenic CO2 emission. Nonetheless, poor product selectivity associated with electrochemical catalysts is the main technical problem for the application of CO2RR technology. The catalytic performance of nano-catalysts is strongly dependent on their microstructural features. Anomalous small-angle X-ray scattering (ASAXS) is one of the most effective techniques for studying nanostructural change in an operando way, especially for complex systems and mixed-element catalyst situations. Furthermore, based on the research results of ASAXS, appropriate catalyst components and nanostructures can be designed to achieve stable catalytic performance of the catalyst, promote catalytic reaction rate, or improve catalytic reaction selectivity. In this paper, the basic concept, principle, and applications in different systems of ASAXS are reviewed thoroughly. Finally, the development prospect of ASAXS in the field of electrocatalysis is prospected. It is hoped that this review will further promote ASAXS technology to play a more far-reaching impact in the field of electrocatalytic CO2RR.

A recent advance in the disorder prediction field is the development of the quality assessment (QA) scores. QA scores complement the propensities produced by the disorder predictors by identifying regions where these predictions are more likely to be correct. We develop, empirically test and release a new QA tool, QUARTERplus, that addresses several key drawbacks of the current QA method, QUARTER. QUARTERplus is the first solution that utilizes QA scores and the associated input disorder predictions to produce very accurate disorder predictions with the help of a modern deep learning meta-model. The deep neural network utilizes the QA scores to identify and fix the regions where the original/input disorder predictions are poor. More importantly, the accurate QUATERplus’s predictions are accompanied by easy to interpret residue-level QA scores that reliably quantify their residue-level predictive quality. We provide these interpretable QA scores for QUARTERplus and 10 other popular disorder predictors. Empirical tests on a large and independent (low similarity) test dataset show that QUARTERplus predictions secure AUC = 0.93 and are statistically more accurate than the results of twelve state-of-the-art disorder predictors. We also demonstrate that the new QA scores produced by QUARTERplus are highly correlated with the actual predictive quality and that they can be effectively used to identify regions of correct disorder predictions. This feature empowers the users to easily identify which parts of the predictions generated by the modern disorder predictors are more trustworthy. QUARTERplus is available as a convenient webserver at http://biomine.cs.vcu.edu/servers/QUARTERplus/.

While collaborative curriculum design (CCD) has gained increasing attention in the field of education, there is scant research as to how EFL teachers implement it in authentic design contexts. The present case study places particular emphasis on teacher activities during collaborative EFL curriculum development in China. The researchers adopt Activity Theory as an analytical tool to understand the relationships between EFL teachers, reform goals, and various aspects of the sociocultural context in which CCD is advocated, highlighting the pivotal role that mediation of knowledge/experience plays in the teacher learning community. Research findings indicate that the TDTs’ collaborative process is a socially constructed and culturally mediated activity that promotes EFL teacher development. Moreover, in-service teachers are prone to take challenges through educational reforms out of teacher motives and external stimuli. Limitations of the CCD model are also discussed to shed light on future research.

Abstract Background Immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of several kinds of malignancies. Some clinical demographic characteristics were reported to be associated with the ICIs efficacy. The purpose of our current meta-analysis was to clearly evaluated the relationship between BMI and ICIs efficacy for cancer patients receiving immunotherapy. Methods A systematic search of Pubmed, EMBASE and conference proceedings was performed to investigate the influence of BMI on ICIs efficacy. Pooled analysis for overall survival (OS), progression-free survival (PFS) and immune-related adverse effects (IRAEs) were analyzed in current study. Results A total of 13 eligible studies comprising 5279 cancer patients treated with ICIs were included in the analysis. The pooled analysis showed there is positive association between high BMI and improved OS and PFS among patients with ICIs treatment (OS: HR = 0.62, 95% CI 0.55–0.71, P

This paper presents a dynamic surface fixed-time fault-tolerant control strategy for the longitudinal dynamic model of fixed-wing unmanned aerial vehicles (UAVs). Firstly, a novel disturbance observer is constructed to precisely estimate the lumped disturbance. Secondly, without fractional power terms in the designed fixed-time fault-tolerant controller, the potential singular value problem is tactfully avoided, which often exists in the stability analysis of the traditional fixed-time controller design. Thirdly, a novel fixed-time filter is proposed to overcome the phenomenon of “differential explosion” in the backstepping control scheme. Lyapunov stability analysis guarantees that the tracking errors can converge to the neighborhood of the origin in the fixed time. The simulation results verify the effectiveness of the proposed control scheme.

The decision-maker obtains the pairwise comparisons matrix by comparing two entities. In the process of comparing the two entities, the relationship between the two entities and other entities is not considered. In this way, the judgment may be illogical. This paper mainly studies the satisfactory consistency of the interval number pairwise comparisons matrix based on cyclic matrix. Firstly, the illogical judgment entity in the process of the decision-maker’s judgment is expressed by the cyclic matrix. There are three entities and four entities to form the cyclic matrix. The relationship and various forms of the cyclic cycle formed by the four entities and the three entities are discussed; then, the satisfactory consistency of the interval number pairwise comparisons matrix is determined by judging whether there is a cyclic matrix in the submatrix of the interval number pairwise comparisons matrix. Finally, two examples are given to verify the rationality and effectiveness of the method.

Illeis bistigmosa (Mulsant, 1850) is a potential biological control agent of powdery mildews. We have determined the first mitochondrial genome of I. bistigmosa. The circular mitogenome of I. bistigmosa consists of 17,840 bp including 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a control region (D-loop). The base composition was AT-biased (78.44%). Maximum-likelihood phylogenetic trees strongly supported the monophyly of Coccinellinae. Illeis bistigmosa is the sister group of Halyzia sedecimguttata and Halyziini species (unclassified Halyziini), within fungivorous coccinellids. Illeis bistigmosa mitochondrial genome will be a fundamental resource for understanding the molecular phylogenetic relationships of the species-rich family Coccinellidae of Coleoptera.

Abstract Background As mosquitoes are one of the most harmful creatures in the world, recent high-frequency interceptions of invasive mosquito species have emphasized the need to enhance the biological security of the Zhejiang Province in China. As such, an integrated management system should be implemented to monitor the vectors of mosquito-borne diseases during data digitization and the processing of permanent E-forms and provide an online one-stop identification service. Methods This system is a semi-open network built on the latest Microsoft.NET Framework, Active Server Page.NET (ASP.NET) and Internet Information Services (IIS) for the Windows 2000 service as a basic infrastructure platform. This creates a physical separation between the data input as the back-page intranet and the online automated Lucid identification as the front-page internet through the digital interchange platform and security firewall. Results This system mainly comprises three core modules: automated statistical analysis of operational data, online vector identification and digital specimen storage management, in addition to accessory modules. The joint analysis of invasive and native data collected between 2011 and 2017 at 14 surveillance points in the Zhejiang Province, excluding Ningbo Port, provided insights into the geographical differences in species abundance and the dynamic nature of seasonal interception within the statistical analysis module. Most importantly, multi-access keys to mosquitoes based on Lucid software were loaded in the module for vector identification. Subscribers can utilize this procedure for the online identification of 2 subfamilies, 10 genera and 33 mosquitoes by selecting any typical morphological feature in the classification system that matches the current images at hand. Conclusions Our report suggests that this system can enhance the ability to master the basic information on invasive mosquitoes and satisfy the increasing requirements for public health safety in the integrated management of vector-borne diseases.

Electrocatalytic reduction of carbon dioxide is attractive for obtaining multicarbon products, but conversion efficiency is low. Here the authors use copper complex materials for electrochemical reduction of carbon dioxide to ethanol and acetic acid with high efficiencies and activities.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (p < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (p < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042–2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115–3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562–4.442) were independent risk factors affecting the OS of ccRCC patients (all, p < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.

tRNA-derived fragments (tRFs) are a new classification of small non-coding RNAs (sncRNAs) derived from the specific cleavage of precursors and mature tRNAs. Accumulating recent evidence has shown that tRFs are frequently abnormal in several cancers. Nevertheless, the role of tRFs in gastric cancer and its mechanism remain unclear. In this study, we found abnormal expression of tRF-3017A (derived from tRNA-Val-TAC) in gastric cancer tissues and cell lines and confirmed its effect on promoting the invasion and migration of gastric cancer cells through functional experiments in vitro. Analysis of clinicopathologic data showed patients with higher tRF-3017A were associated with significantly higher lymph node metastasis. Mechanistic investigation implies that tRF-3017A regulates the tumor suppressor gene NELL2 through forming the RNA-induced silencing complex (RISC) with Argonaute (AGO) proteins. In this study, we found that higher tRF-3017A were associated with significantly higher lymph node metastasis in gastric cancer patients and the tRF-3017A may play a role in promoting the migration and invasion of gastric cancer cells by silencing tumor suppressor NELL2.

Background: Patients with locally advanced rectal cancer (LARC) are more likely to suffer local recurrence and distant metastases, contributing to worse prognoses. Considering the provided dramatic reduction of local recurrences, neoadjuvant CRT (nCRT) followed by curative resection with total mesorectal excision (TME) and adjuvant chemotherapy has been established as standard therapy for LARC patients. However, the efficacy of adding bevacizumab in neoadjuvant therapy, especially in induction therapy-containing nCRT for LARC patients remains uncertain. Materials: PubMed, Embase, and Web of Science were searched to retrieve records on the application of bevacizumab in a neoadjuvant setting for LARC patients. The endpoints of interest were pCR and the rates of patients suffering Grade 3/4 bevacizumab-specific adverse events, namely bleeding, wound healing complications, and gastrointestinal perforation. Results: 29 cohorts covering 1134 subjects were included in this systematic review. The pooled pCR rate for bevacizumab-relevant cohorts was 21% (95% confidence interval (95% CI), 17–25%; I2 = 61.8%), the pooled estimates of Grade 3/4 bleeding, Grade 3/4 wound healing complication, Grade 3/4 gastrointestinal perforation were 1% (95% CI, 0–3%; I2 = 0%), 2% (95% CI, 1–5%; I2 = 4.7%), and 2% (95% CI, 0–5%; I2 = 0%), respectively. Conclusion: The addition of bevacizumab in the nCRT, especially in the TNT, for LARC patients provides promising efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by future studies.

Background: Aspirin is one of the most commonly prescribed drugs worldwide and has been reported to possess anti-cancer properties in addition to antipyretic and analgesic effects. This umbrella review summarizes systematic reviews and meta-analyses that investigate the association between aspirin and cancer risk, aiming to help clinical and public health decision-makers interpret the results of these studies when re-positioning aspirin.Methods: An umbrella review of systematic reviews and meta-analyses.Results: The associations that reached statistical significance (17 in total) indicated potential preventive effects of aspirin on certain cancers or precancerous lesions. We found that no association was supported by strong evidence. Only one association (aspirin and overall cancer risk) was supported by highly suggestive evidence. The evidence supporting the association between aspirin and the risk of breast cancer, non-cardia gastric cancer, or prostate cancer was considered to be highly suggestive. The remaining 23 associations were supported by weak (13) or not suggestive evidence (10).Conclusions: The association between aspirin and a reduced risk of esophageal squamous cell carcinoma is supported by strong evidence, researchers and policy makers should pay more attention to the potential merit of repositioning aspirin to prevent esophageal squamous cell carcinoma.

Abstract Patients with locally advanced rectal cancer (LARC) are at tremendous risk of metastatic diseases. To improve the prognoses of LARC patients, the efficacy of adding targeted agents to neoadjuvant therapy has been investigated by many researchers but remains controversial. A literature search of relevant databases was conducted through December 2016, 804 studies were identified and 32 investigations were ultimately included. A total of 1196 patients from 31 cohorts of 29 studies were eligible for quantitative synthesis in this single‐arm setting meta‐analysis. As pathologic complete response (pCR) shows promise as a prognosis indicator, we focused on pCR rates to evaluate whether adding targeted agents to neoadjuvant therapies improves the outcome of LARC patients. In our study, we revealed pooled estimates of pCR of 27% (95%CI, 21–34%) and 14% (95%CI, 9–21%) for bevacizumab‐relevant cohorts and cetuximab‐relevant cohorts, respectively. The safety of adding targeted agents to neoadjuvant therapy was also evaluated by pooling the data of Grade 3/4 toxicity. In conclusion, our study revealed that adding bevacizumab to the neoadjuvant therapy regimens provides appreciable pCR for LARC patients. Meanwhile, the efficacy of cetuximab remains inconclusive, RCTs with larger scale and better study design that stress more on mutational status are needed.

The synthesis of patchy colloids is limited by poor control over the location and shape of ligand domains. Here, the authors use adaptable polymer masks to protect select areas of the particle during functionalization, allowing them to create patchy colloids with unconventional surface morphologies.

Crystallization kinetics of metal-organic frameworks in conventional organic solvents are usually very slow. Here, the authors show that an ionic liquid medium accelerates considerably the formation of Zr-based metal-organic frameworks that are active catalysts in the Meerwein-Ponndorf-Verley reaction.

Abstract Background F-18- fluorodeoxyglucose Positron emission tomography (18FDG-PET) has been widely used in clinical practice. However, the prognostic value of the pretreatment standardized uptake value (SUV) for patients with gastric cancer remains controversial. Methods Major databases were systematically searched. The quality of the included studies was assessed using the Newcastle–Ottawa scale; the PET protocols were also evaluated. The pooled hazard ratio (HR) for overall survival (OS) and recurrence-free survival (RFS) were used to estimate the effect size. Data from the included studies were analyzed using Review Manager Software version 5.2. Results Eight studies with 1080 patients were included. The pooled HR for OS of six studies including 672 patients was 1.72 (95% CI [1.28–2.3], p = 0.0004, I2 = 0%), indicating that patients with high SUVs may have poor prognosis. The pooled HR for RFS was 1.70 (95% CI [1.20–2.39], p = 0.003, I2 = 0%). Subgroup analysis based on the cutoff values determining method indicated that the receiver operating characteristic (ROC) method could better define the cutoff value. Subgroup analysis based on the therapeutic strategies used subsequently indicated the significant prognostic value of SUV. Conclusion In conclusion, our meta-analysis indicated that pretreatment SUV in primary lesions can be an important prognostic factor for overall survival and recurrence-free survival in patients with gastric cancer. High SUVs may indicate poor prognosis.

Introduction: Biomarkers are biological molecules entirely or partially participating in cancerous processes that function as measurable indicators of abnormal changes in the human body microenvironment. Aiming to provide an overview of associations between prognostic biomarkers and gastric cancer (GC), we performed this umbrella review analyzing currently available meta-analyses and grading the evidence depending on the credibility of their associations.Methods: A systematic literature search was conducted by two independent investigators of the PubMed, Embase, Web of Science, and Cochrane Databases to identify meta-analyses investigating associations between prognostic biomarkers and GC. The strength of evidence for prognostic biomarkers for GC were categorized into four grades: strong, highly suggestive, suggestive, and weak.Results: Among 120 associations between prognostic biomarkers and GC survival outcomes, only one association, namely the association between platelet count and GC OS, was supported by strong evidence. Associations between FITC, CEA, NLR, foxp3+ Treg lymphocytes (both 1- and 3-year OS), CA 19-9, or VEGF and GC OS were supported by highly suggestive evidence. Four associations were considered suggestive and the remaining 108 associations were supported by weak or not suggestive evidence.Discussion: The association between platelet count and GC OS was supported by strong evidence. Associations between FITC, CEA, NLR, foxp3+ Treg lymphocytes (both 1- and 3-year OS), CA 19-9, or VEGF and GC OS were supported by highly suggestive evidence, however, the results should be interpreted cautiously due to inadequate methodological quality as deemed by AMSTAR 2.0.

The prognosis of stage IV gastric cancer (GC) is poor, with palliative chemotherapy remaining the main therapeutic option. Studies increasingly indicate that patients with unresectable stage IV GC, who undergo gastrectomy with radical intention after responding to several regimens of combined chemotherapy, can achieve good survival outcomes. Thus, surgery aiming at radical resection for unresectable stage IV GC after combined chemotherapy has received increasing attention in recent years. This novel therapeutic strategy was defined as conversion surgery in patients with unresectable stage IV GC and it can associate with significant improved survival when R0 resection can be achieved. Despite the recent advances in conversion surgery for patients with unresectable stage IV GC, selection criteria for combination chemotherapy regimens, indications for conversion surgery, optimal timing to surgery, and postoperative chemotherapy all remain controversial. This article reviews the current state of conversion surgery for unresectable stage IV GC.

In this article, oxygen doped boron nitride (OBNNS) was selected and introduced into PI to form OBNNS/PI composite films. The thermal, electrical, optical and mechanical properties of the OBNNS/PI composite films were all improved compared to pure PI. Our experimental results shown that the synthesized OBNNS/PI composite with a low OBNNS content (0.25 wt%) have thermal conductivity of 0.291 W·m−1·K−1, tensile strength of 127.1 MPa, elongation at break of 13.3%, and corona resistant life of 9.50 h, all were significantly enhanced compared with that of a pure PI film. This can be attributed the homogeneous and ordered dispersion of OBNNS in PI matrix. The successful preparation of the OBNNS/PI composites will pave a way for the development of multifunctional polyimide-based composites for applications. Keywords: Polyimide, Boron nitride, Multifunctional, Application

Background: Metformin has been reported to possess anti-cancer properties in addition to glucose-lowering activity and numerous systematic reviews and meta-analyses have studied the association between metformin use and cancer incidence or survival outcomes. We performed an umbrella review to assess the robustness of these associations to facilitate proper interpretation of these results to inform clinical and policy decisions.Methods: We searched PubMed and Embase systematic reviews and meta-analyses investigating the effect of metformin use on cancer incidence or survival outcomes published from inception to September 2, 2018. We estimated the summary effect size, the 95% CI, and the 95% prediction interval, heterogeneity, evidence of small-study effects, and evidence of excess significance bias.Results: We included 21 systematic reviews and meta-analyses covering 11 major anatomical sites and 33 associations. There was strong evidence for the association between metformin use and decreased pancreatic cancer incidence. The association between metformin use and improved colorectal cancer overall survival (OS) was supported by highly suggestive evidence. Seven associations (all cancer incidence, all cancer OS, breast cancer OS, colorectal cancer incidence, liver cancer incidence, lung cancer OS, and pancreatic cancer OS) presented only suggestive evidence. The remaining 24 associations were supported by weak or not-suggestive evidence.Conclusions: Associations between metformin use and pancreatic cancer incidence or colorectal cancer OS are supported by strong or highly suggestive evidence, respectively. However, these results should be interpreted with caution due to the poor methodological quality of the systematic reviews and meta-analyses.

With close to 30 sequence-based predictors of RNA-binding residues (RBRs), this comparative survey aims to help with understanding and selection of the appropriate tools. We discuss past reviews on this topic, survey a comprehensive collection of predictors, and comparatively assess six representative methods. We provide a novel and well-designed benchmark dataset and we are the first to report and compare protein-level and datasets-level results, and to contextualize performance to specific types of RNAs. The methods considered here are well-cited and rely on machine learning algorithms on occasion combined with homology-based prediction. Empirical tests reveal that they provide relatively accurate predictions. Virtually all methods perform well for the proteins that interact with rRNAs, some generate accurate predictions for mRNAs, snRNA, SRP and IRES, while proteins that bind tRNAs are predicted poorly. Moreover, except for DRNApred, they confuse DNA and RNA-binding residues. None of the six methods consistently outperforms the others when tested on individual proteins. This variable and complementary protein-level performance suggests that users should not rely on applying just the single best dataset-level predictor. We recommend that future work should focus on the development of approaches that facilitate protein-level selection of accurate predictors and the consensus-based prediction of RBRs.

A robust adaptive neural control scheme based on a back-stepping technique is developed for the longitudinal dynamics of a flexible hypersonic flight vehicle, which is able to ensure the state tracking error being confined in the prescribed bounds, in spite of the existing model uncertainties and actuator constraints. Minimal learning parameter technique–based neural networks are used to estimate the model uncertainties; thus, the amount of online updated parameters is largely lessened, and the prior information of the aerodynamic parameters is dispensable. With the utilization of an assistant compensation system, the problem of actuator constraint is overcome. By combining the prescribed performance function and sliding mode differentiator into the neural back-stepping control design procedure, a composite state tracking error constrained adaptive neural control approach is presented, and a new type of adaptive law is constructed. As compared with other adaptive neural control designs for hypersonic flight vehicle, the proposed composite control scheme exhibits not only low-computation property but also strong robustness. Finally, two comparative simulations are performed to demonstrate the robustness of this neural prescribed performance controller.

Background and objective Our previous in vivo experiment (paper has been published) has confirmed Feiyanning’s regulation effect on epithelial cell markers Alpha-catenin, beta-catenin, E-Cadherin and mesenchymal cell markers N-cadherin, Fibronectin, vimentin. Based on previous study, the objective of this study is to further investigate the expression of epithelial-mesenchymal cell marker gene and protein intervened by Feiyanning in highly metastatic lung cancer cells 95-D in vitro. Methods Human highly metastatic lung cancer 95-D cells were treated with different concentrations of Feiyanning in vitro, and then Real-time PCR and Western blot methods were used to detect mRNA and protein expression of epithelial-mesenchymal cell marker factor Alpha-catenin, beta-catenin, E-Cadherin, N-cadherin, Fibronectin and vimentin. Results Real-time PCR results showed that compared with the control group, Feiyanning at 20% concentration remarkably up-regulated the expression of Alpha-catenin (P

Some of the intrinsically disordered proteins and protein regions are promiscuous interactors that are involved in one-to-many and many-to-one binding. Several studies have analyzed enrichment of intrinsic disorder among the promiscuous hub proteins. We extended these works by providing a detailed functional characterization of the disorder-enriched hub protein-protein interactions (PPIs), including both hubs and their interactors, and by analyzing their enrichment among disease-associated proteins. We focused on the human interactome, given its high degree of completeness and relevance to the analysis of the disease-linked proteins. We quantified and investigated numerous functional and structural characteristics of the disorder-enriched hub PPIs, including protein binding, structural stability, evolutionary conservation, several categories of functional sites, and presence of over twenty types of posttranslational modifications (PTMs). We showed that the disorder-enriched hub PPIs have a significantly enlarged number of disordered protein binding regions and long intrinsically disordered regions. They also include high numbers of targeting, catalytic, and many types of PTM sites. We empirically demonstrated that these hub PPIs are significantly enriched among 11 out of 18 considered classes of human diseases that are associated with at least 100 human proteins. Finally, we also illustrated how over a dozen specific human hubs utilize intrinsic disorder for their promiscuous PPIs.

Helium status is the primary effect of material properties under radiation. 10B-doped aluminum samples were prepared via arc melting technique and rapidly cooled with liquid nitrogen to increase the boron concentration during the formation of compounds. An accumulated helium concentration of ~6.2 × 1025 m−3 was obtained via reactor neutron irradiation with the reaction of 10B(n, α)7Li. Temperature-stimulated helium evolution was observed via small-angle X-ray scattering (SAXS) and was confirmed via transmission electron microscopy (TEM). The SAXS results show that the volume fraction of helium bubbles significantly increased with temperature. The amount of helium bubbles reached its maximum at 600°C, and the most probable diameter of the helium bubbles increased with temperature until 14.6 nm at 700°C. A similar size distribution of helium bubbles was obtained via TEM after in situ SAXS measurement at 700°C, except that the most probable diameter was 3.9 nm smaller.

BACKGROUND: Chikungunya (CHIK) virus is a mosquito-borne emerging pathogen presenting great health challenges worldwide, particularly in tropical zones. Here we report a newly detected strain of CHIK, Zhejiang/chik-sy/2012, in China, a nonindigenous region for CHIK, using a modified approach based on the classic cDNA-AFLP. We then performed etiological and phylogenetic analyses to better understand its molecular characterization and phylogenetic pattern, and also to aid in further evaluating its persistence in Southeast Asia. METHODS: By using this modified procedure, we determined for the first time the complete genome sequence of the chikungunya virus strain, Zhejiang/chik-sy/2012, isolated in 2012 from a patient in Zhejiang, China. Sequence analyses revealed that this positive single strand of RNA is 12,017 bp long. We found no single amino acid mutation in A226V, D284E and A316V. Phylogenetic analysis showed that our strain shared the greatest homology with a strain isolated in Taiwan, which was derived from a strain from Indonesia. Chik-sy/2012 is in a different clade from other CHIK viruses found in China previously. CONCLUSIONS: A modified cDNA-AFLP in virus discovery was used to isolate the first CHIK and the first complete genome sequence of virus strain chik-sy/2012 in 2012 from a patient with CHIK fever in Zhejiang, China. The infection displayed great phylogenetic distance from viruses detected in Guangdong, China, in 2008 and 2010, since they were derived from another evolutionary lineage. Additional molecular epidemiology data are needed to further understand, monitor and evaluate CHIK in China.

BackgroundThe H1N1 pandemic in 2009 and the H5N1 pandemic in 2005 demonstrated that the drugs approved to treat influenza A viruses have low efficacy. This provided a stimulus for new studies of influenza A viruses in the context of the methods used in drug design developed over the past 100 years. Finding new universal drugs is the ultimate goal but its long time horizon is incompatible with emergency situations created by reoccurring influenza outbreaks. Therefore, we propose a computer-aided method for finding efficacious drugs and drug complexes based on the use of the DrugBank database.Methods(1) We start by assembling a panel of target proteins. (2) We then assemble a panel of drugs. (3) This is followed by a selection of benchmark binding pockets based on the panel of target proteins and the panel of drugs. (4) We generate a set of computational features, which measure the efficacy of a drug. (5) We propose a universal program to search for drugs and drug complexes. (6) A case study we report here illustrates how to use this universal program for finding an optimal drug and a drug complex for a given target. (7) Validation of the Azirchromycin and Aspirin complex is provided mathematically. (8) Finally, we propose a simple strategy to validate our computational prediction that the Azirchromycin and Aspirin complex should prove clinically effective.ResultA set of computable features are mined and then based on these features, a universal program for finding the potential drug &drug complexes is proposed. Using this universal program, the Azirchromycin and Aspirin complex is selected and its efficacy is predicted mathematically. For clinical validation of this finding, future work is still required.

We have successfully synthesized the new S = 1/2 anisotropic kagome antiferromagnet ZnCu _3 (OH) _6 SO _4 and determined its structure by synchrotron x-ray diffraction. No magnetic ordering is observed down to 50 mK, despite a moderately high Weiss temperature of Θ _w ∼ −79 K, indicating that the compound is a new quantum spin liquid (QSL) candidate. A linear temperature dependence of the magnetic heat capacity is found at 6 ∼ 15 K and below 0.6 K. Temperature-independent intrinsic susceptibilities are observed exactly in both temperature ranges. This consistently suggests a gapless QSL below 0.6 K, which may evolve from an unconventional quantum spin state at higher temperatures (6 ∼ 15 K).