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Background. Many studies have demonstrated the promising utility of DNA methylation and miRNA as biomarkers for colorectal cancer (CRC) early detection. However, mRNA is rarely reported. This study aimed to identify novel fecal-based mRNA signatures. Methods. The differentially expressed genes (DEGs) were first determined between CRCs and matched normal samples by integrating multiple datasets. Then, Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to reduce the number of candidates of aberrantly expressed genes. Next, the potential functions were investigated for the candidate signatures and their ability to detect CRC and pan-cancers was comprehensively evaluated. Results. We identified 1841 common DEGs in two independent datasets. Functional enrichment analysis revealed they were mainly related to extracellular structure, biosynthesis, and cell adhesion. The CRC classifier was established based on six genes screened by LASSO regression. Sensitivity, specificity, and area under the ROC curve (AUC) for CRC detection were 79.30%, 80.40%, and 0.85 (0.76–0.92) in the training set, and these indexes achieved 93.20%, 41.80%, and 0.73 (0.65–0.83) in the testing set. For validation set, the sensitivity, specificity, and AUC were 98.90%, 98.00%, and 0.97 (0.94–0.99). The average sensitivities exceeded 90.00% for CRCs with different clinical features. For adenomas detection, the sensitivity and specificity were 74.50% and 64.00%. Besides, the six genes obtained an average AUC of 0.855 for pan-cancer detection. Conclusion. The six-gene signatures showed ability to detect CRC and pan-cancer samples, which could be served as potential diagnostic markers.

The accuracy of traffic noise prediction models (TNMs) is impaired by affecting factors and system errors. In addition, the traditional traffic noise source cannot be tested as the sound source is generated in the centreline of the road. To address these limitations, a TNM based on the equivalent sound source at the road shoulder was developed. First, the equivalent traffic flow based on the acoustic-equivalent conversion coefficient was calculated and the traffic noise source intensity model was deduced. The shoulder's sound pressure level (SPL) data were then used to formulate a single-vehicle equivalent SPL model and correct the traffic noise source intensity model. The propagation model was fitted according to the attenuation law that traffic noise strength attenuates gradually from the shoulder to the road outside and fluctuates periodically. The results of a case study showed that the absolute percentage error of the proposed model's prediction was 2·3% compared with the measured value, which was better than the performance of the current model suggested in the Chinese specification. The proposed prediction model provides a friendly and less time-consuming approach for city planners and traffic engineers to conduct freeway traffic noise prediction and assessment.

Introduction: With prevalent and increased attention to driver inattention (DI) behavior, this research provides a comprehensive investigation of the influence of built environment and roadway characteristics on the DI-related vehicle crash frequency per year. Specifically, a comparative analysis between DI-related crash frequency in rural road segments and urban road segments is conducted. Method: Utilizing DI-related crash data collected from North Carolina for the period 2013–2017, three types of models: (1) Poisson/negative binomial (NB) model, (2) Poisson hurdle (HP) model/negative binomial hurdle (HNB) model, and (3) random intercepts Poisson hurdle (RIHP) model/random intercepts negative binomial hurdle (RIHNB) model, are applied to handle excessive zeros and unobserved heterogeneity in the dataset. Results: The results show that RIHP and RIHNB models distinctly outperform other models in terms of goodness-of-fit. The presence of commercial areas is found to increase the probability and frequency of DI-related crashes in both rural and urban regions. Roadway characteristics (such as non-freeways, segments with multiple lanes, and traffic signals) are positively associated with increased DI-related crash counts, whereas state-secondary routes and speed limits (higher than 35 mph) are associated with decreased DI-related crash counts in rural and urban regions. Besides, horizontal curved and longitudinal bottomed segments and segments with double yellow lines/no passing zones are likely to have fewer DI-related crashes in urban areas. Medians in rural road segments are found to be effective to reduce DI-related crashes. Practical Applications: These findings provide a valuable understanding of the DI-related crash frequency for transportation agencies to propose effective countermeasures and safety treatments (e.g., dispatching more police enforcement or surveillance cameras in commercial areas, and setting more medians in rural roads) to mitigate the negative consequences of DI behavior.

Pyroptosis, as a novel mode of cell death, has been proven to have impressive antitumor effects. Dying cells undergoing pyroptosis can elicit antitumor immunity by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Accordingly, developing an effective, stable, and controllable nanoplatform that can promote these two side effects is a promising option for cancer therapy. In this study, we designed a carrier-free chemo-photodynamic nanoplatform (A-C/NPs) using a co-assembly strategy with cytarabine (Ara-C) and chlorin e6 (Ce6) to induce pyroptosis and a subsequent immune response against breast cancer. Mechanistically, A-C/NPs can trigger GSDME-mediated pyroptosis in a controllable manner through reactive oxygen species (ROS) accumulation, causing immunogenic cell death (ICD), in which dying cells release high-mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and calcitonin (CRT). Additionally, Ara-C can stimulate the maturation of cytotoxic T lymphocytes to act synergistically with Ce6-mediated immunogenic cell death (ICD), collectively augmenting the anticancer effect of A-C/NPs. The A-C/NPs showed excellent suppressive effects on the growth of orthotopic, abscopal, and recurrent tumors in a breast cancer mouse model. The chemo-photodynamic therapy (PDT) using the proposed nanomedicine strategy could be a novel strategy for triggering pyroptosis and improving the global anticancer immune response.

In the forensic investigation, recognizing and locating the multiple diatom objects in an image is a challenging issue due to the interferences of the highly complex backgrounds. To address this issue, a coarse to fine diatom recognition and a localization framework based on the deep learning network is proposed in this paper. Firstly, the diatom images are obtained by performing the anatomic study on the cadavers. Next, a high definition electron microscope is scanned. Then, a coarse to fine deep learning framework is constructed to locate and recognize the diatom objects. Unlike the existing diatom classification and recognition methods, which used light microscopy with low resolution and completed under a simple backgrounds, our framework utilizes the high definition electron scanning microscopy with much higher resolution and suffers from the complex backgrounds interferences. To demonstrate the effectiveness of the proposed framework, 4 diatom image datasets with different background interference degrees are constructed. Also, 3 computer numerical simulation analysis are performed. They are (1) the limitations of the traditional methods in the diatom recognition, (2) the optimized composition of the training strategies and the network models, and (3) the performance of the proposed framework. The computer numerical simulation results show that the proposed framework achieves a recognition accuracy of 0.852. This is greater than 0.758 achieved by the AlexNet. Moreover, it can overcome the problem of the highly complex backgrounds interferences in the forensic investigation. Furthermore, it can locate and recognize the multiple objects in various diatom images simultaneously.

The problem of urban crashes brings huge challenges and threats to local police and governments, especially in many cities in developing countries such as China. To reduce the frequency and severit...

Potassium-ion batteries (KIBs) are competitive alternatives to lithium-ion batteries (LIBs) due to the abundant K resources and high energy density. As an indispensable part of the battery, the electrolyte affects the battery capacity, rate capability, cycle life, and safety. Nevertheless, the researches on electrolytes and corresponding solid electrolyte interfaces (SEI) in KIB are still in its infancy and require further attention. In this review, recent progresses of various K+ containing electrolytes for KIBs are summarized comprehensively. Additionally, the effects of salts, solvents, additives, and concentrations on the properties of various electrolyte systems are discussed in detail. Thereafter, interface chemistry between electrode and electrolyte, as well as rational modification strategies for high-performance KIB are reviewed. Finally, the major challenges and the future perspectives are estimated for advanced KIB. This review will provide good directions for the development of high-performance KIB.

Introduction: With the increasing trend of pedestrian deaths among all traffic fatalities in the past decade, there is an urgent need for identifying and investigating hotspots of pedestrian-vehicle crashes with an upward trend. Method: To identify pedestrian-vehicle crash locations with aggregated spatial pattern and upward temporal pattern (i.e., hotspots with an upward trend), this paper first uses the average nearest neighbor and the spatial autocorrelation tests to determine the grid distance and the neighborhood distance for hotspots, respectively. Then, the spatiotemporal analyses with the Getis-Ord Gi* index and the Mann-Kendall trend test are utilized to identify the pedestrian-vehicle crash hotspots with an annual upward trend in North Carolina from 2007 to 2018. Considering the unobserved heterogeneity of the crash data, a latent class model with random parameters within class is proposed to identify specific contributing factors for each class and explore the heterogeneity within classes. Significant factors of the pedestrian, vehicle, crash type, locality, roadway, environment, time, and traffic control characteristics are detected and analyzed based on the marginal effects. Results: The heterogeneous results between classes and the random parameter variables detected within classes further indicate the superiority of latent class random parameter model. Practical Applications: This paper provides a framework for researchers and engineers to identify crash hotspots considering spatiotemporal patterns and contribution factors to crashes considering unobserved heterogeneity. Also, the result provides specific guidance to developing countermeasures for mitigating pedestrian-injury at pedestrian-vehicle crash hotspots with an upward trend.

Potassium (K) metal batteries are identified as some of the most potential candidates for next-generation energy storage devices due to the abundant reserves, low redox potential and high theoretical capacity of K metal. However, the practical application of K metal batteries is severely hindered by the uncontrollable growth of K dendrites. Herein, a dendrite-free and high-performance K metal anode was obtained by constraining K metal on SnO2-modified commercial carbon cloth (K-CC@SnO2). In the K-CC@SnO2 structure, K metal wraps the SnO2 particles and forms a closely connected structure with the carbon cloth. CC@SnO2 not only shows excellent potassiophilicity, but also possesses high electronic conductivity and large void spaces, which can induce the homogeneous deposition of K metal and accommodate the large volume changes of K during the plating/stripping processes. Consequently, the as-constructed K-CC@SnO2 anodes exhibit low polarization and long cycling life with a dendrite-free morphology in symmetric cells with a carbonate-based electrolyte. In addition, a perylene-3,4,9,10-tetracarboxylic diimide (PTCDI)‖K-CC@SnO2 full cell shows excellent rate performance (112.5 mA h g−1 @ 5 A g−1) and ultralong cycling life (up to 10 000 cycles). A PTCDI‖K-CC@SnO2 pouch cell was successfully assembled and it delivers a long cycling life of 500 cycles with an energy density of 274 W h kg−1. These results indicate that a simple and effective strategy has been proposed for the development of K metal anodes with commercialization potential.

Hepatocellular carcinoma (HCC) is a major threat to human health due to its high lethality. Our previous studies suggested that Fuzheng Xiaozheng prescription (FZXZP), an effective Chinese medicine, demonstrated significant suppressive effects on HCC. However, its underlying mechanism remains largely unclear.This study aimed to investigate the anti-HCC mechanisms of FZXZP from transcriptomic sequencing based on a holistic perspective.Rat HCC model was induced by diethylnitrosamine, and then the model was administered with two doses of FZXZP, high and low. Sodium demethylcantharidate was used as a positive control. Subsequently, microarrays of circRNA, miRNA and mRNA were performed on the blank, model, high and low dose groups, respectively, and the competitive binding mechanisms among them were further analyzed by bioinformatics. Then, the circRNA-miRNA-mRNA networks were constructed to mine the targeted-RNAs of FZXZP in HCC, as well as to explore their potential regulatory mechanisms. Finally, functions and pathways of the FZXZP targeted genes in rat HCC were annotated with GO and KEGG, and qRT-PCR was performed to validate the accuracy of the above analyses in this study.The results showed that FZXZP significantly inhibited the development and progression of HCC in rats, improved the pathological conditions and suppressed the proliferation of HCC cells. Subsequently, after a series of screening, the competing endogenous RNA networks (circRNA-miRNA-mRNA), consisting of 2 circRNAs, 7 miRNAs and 104 mRNAs, were finally established. KEGG and GO analyses of the networks revealed that lipid metabolism related pathways, such as fatty acid metabolism, bile secretion and PPAR pathway, were significantly enriched. In the further hubgene network analysis, in addition to lipid metabolism, aberrant glucose metabolism was found to be ameliorated by G6pc and Pklr in hubgenes. Finally, the qRT-PCR analyses confirmed that the expression tendencies of the above targeted genes were correct and believable in transcriptomic sequencings, and qRT-PCR results of the genes closely related to proliferation, invasion and apoptosis of HCC also indicated the inhibitory effects of FZXZP on HCC obviously.FZXZP demonstrated significant anti-HCC effects through improving lipid and glucose metabolism, restoring the metabolic homeostasis of the liver via circRNA-miRNA-mRNA networks.

Loss of E-cadherin (ECAD), often caused by epigenetic inactivation, is closely associated with tumor metastasis. However, how ECAD is regulated in response to oxidative stress during tumorigenesis is largely unknown. Here we identify RNF25 as a new E3 ligase of ECAD, whose activation by oxidative stress leads to ECAD protein degradation in hepatocellular carcinoma (HCC). Loss of ECAD activates YAP, which in turn promotes the transcription of RNF25, thus forming a positive feedback loop to sustain the ECAD downregulation. YAP activation mitigates oxidative stress in detached HCC cells by upregulating antioxidant genes, protecting detached HCC cells from ferroptosis, resulting in anoikis resistance. Mechanistically, we found that protein kinase A (PKA) senses oxidative stress by redox modification in its β catalytic subunit (PRKACB) at Cys200 and Cys344, which increases its kinase activity towards RNF25 phosphorylation at Ser450, facilitating RNF25-mediated degradation of ECAD. Moreover, RNF25 expression is associated with HCC metastasis and depletion of RNF25 is sufficient to diminish HCC invasion and metastasis in vitro and in vivo. Together, these results identify a dual role of RNF25 as a critical regulator of ECAD protein turnover, promoting both anoikis resistance and metastasis, and PKA is a necessary redox sensor to enable this process. Our study provides mechanistic insight into how tumor cells sense oxidative stress signals to spread while escaping cell death.

Fuzheng Xiaozheng prescription (FZXZP), a traditional Chinese medicine, which was derived from the famous decoction, Sanjiasan, in the book of "Wenyilun" in Ming dynasty. Due to its function of invigorating the circulation of blood in Chinese medicine, it was usually used for treating the liver cirrhosis, hepatocellular carcinoma (HCC), etc. Clinical application found that FZXZP exhibited satisfactory therapeutic effects in HCC treatments. However, we still know little about the underlying mechanisms.In this study, we aim to gain a deeper insight into the inhibiting effects of FZXZP on HCC rats and preliminarily elucidate the underlying intervention effects.Two doses of FZXZP were adopted to evaluate the therapeutic effects on rat HCC, and then the intervention effects were evaluated from different aspects. High performance liquid chromatography (HPLC) was used for the active compounds prediction in FZXZP. Finally, the mRNA-Seq was conducted to reveal the intervention mechanisms and the mechanisms were further validated by quantitative Real-time PCR (qRT-PCR) and lipid contents analyses.The results showed that FZXZP significantly alleviated the serum biochemical indicators and improved the pathological characteristics of HCC rats. Mechanistically, FZXZP could regulate some lipid related metabolisms, including arachidonic acid, linoleic acid and retinol, as well as improving the steroid hormone biosynthesis, to improve the inflammatory statuses and restoring ability of HCC livers, and these were further confirmed by our following analyses on serum lipid contents and cytokine expressions. In addition, FZXZP could also negatively regulate four extracellular growth factors which could result in the blocking of two cancer-related signaling pathways, Ras/MAPK and Ras/PI3K-Akt.Our results suggested that FZXZP demonstrated significant inhibiting effects on rat HCC progresses, and these may be realized by improving the inflammatory statuses and blocking the Ras/MAPK and Ras/PI3K-Akt signaling pathways.

VOPO4·2H2O, as a new cathode material for Ca-ion batteries, exhibits a discharge capacity of 100.6 mA h g-1, excellent cycling stability (200 cycles) and good rate performance (42.7 mA h g-1 at 200 mA g-1). In situ X-ray diffraction and in situ Raman results demonstrate the calcium-ion-storage mechanism of VOPO4·2H2O is a single-phase reaction based on asymmetric Ca2+ insertion and deinsertion.

Oxygen evolution reaction (OER)-induced reconstruction on precatalysts generally results in surface-reconstructed catalysts with less active species and thus low mass activity. Herein, the deeply r...

As an important part of traffic safety analysis, crash prediction models using road geometric alignments and traffic data (CPM-GAs) have been regarded as the most classic way and can be used in sta...

The calcium-ion battery is an emerging energy storage system that has attracted considerable attention recently. However, the absence of high-performance cathode materials is one of the main challe...

Solid-state lithium-ion batteries with high safety are the encouraging next-generation rechargeable electrochemical energy storage devices. Yet, low Li

Cancer is a disease which frequently has a poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments frequently impedes the clinical outcomes. Besides the active resistance driven by genetic and epigenetic alterations in tumor cells, the tumor microenvironment (TME) has also been reported to be a crucial regulator in tumorigenesis, progression, and resistance. Here, we propose that the adaptive mechanisms of tumor resistance are closely connected with the TME rather than depending on non-cell-autonomous changes in response to clinical treatment. Although the comprehensive understanding of adaptive mechanisms driven by the TME need further investigation to fully elucidate the mechanisms of tumor therapeutic resistance, many clinical treatments targeting the TME have been successful. In this review, we report on recent advances concerning the molecular events and important factors involved in the TME, particularly focusing on the contributions of the TME to adaptive resistance, and provide insights into potential therapeutic methods or translational medicine targeting the TME to overcome resistance to therapy in clinical treatment.

With the popularity of smartphones and the increasing dependence on cellphones, cellphone-use-involved distracted driving has become a global traffic safety concern. Calling, texting, or watching videos while driving could have harmful impacts on driving abilities and increase crash-injury severities. To investigate the temporal stability and the heterogeneity of cellphone-involved crash injury severity determinants, a series of likelihood ratio tests and random parameters logit models with heterogeneity in means and variances are estimated. Cellphone-involved single-vehicle crash datasets of Pennsylvania from 2004 to 2019 are utilized. Marginal effects are also applied to investigate the impact of explanatory variables on injury severity outcomes. The results indicate an overall temporal instability of cellphone-involved crashes across different periods. However, driving without seatbelts and overturns are observed to produce relatively stable and positive influence on the increased injury severities of cellphone-involved crashes. Besides, it is noteworthy that a combination of cellphone usage with risky driving behaviors (aggressive driving, alcohol- or drug-related driving, speeding, or fatigue driving) significantly increase driver injury-severities. This finding highlights the necessity of identifying drivers with multiple risk-taking behaviors and enacting laws to prohibit these drivers from using cellphones while driving. Applications of smartphones provide another feasible approach to prevent using cellphones while driving. Insights and suggestions of this study would be valuable to mitigate the negative outcomes of cellphone-involved crashes and prevent the crashes caused by cellphone-involved distracted driving in the future.

N-doped carbon-confined transition metal nanocatalysts display efficient oxygen reduction reaction (ORR) performance comparable to commercial Pt/C electrocatalysts because of their efficient charge transfer from metal atoms to active N sites. However, the sheathed active sites inside the electrocatalysts and relatively large-size confined metal particles greatly restrict their activity improvement. Here, we develop a facile and efficient "MOFs plus ZIFs" synthesis strategy to successfully construct ultrafine sub-5 nm Co nanodots confined into superficial N-doped carbon nanowires (Co@C@NC) via a well-designed synthesis process. The unique synthesis mechanism is based on low-pressure vapor superassembly of thin zeolitic imidazolate framework (ZIF) coatings on metal-organic framework substrates. During the successive pyrolysis, the preferential formation of the robust N-doped carbon shell from the ZIF-67 shell keeps the core morphology without shrinkage and limits the growth of Co nanodots. Benefiting from this architecture with accessible and rich active N sites on the surface, stable carbon confined architecture, and large surface area, the Co@C@NC exhibits excellent ORR performance, catching up to commercial Pt/C. Density functional theory demonstrates that the confined Co nanodots efficiently enhance the charge density of superficial active N sites by interfacial charge transfer, thus accelerating the ORR process.

Highlights A facile self-etching strategy was used to obtain mesoporous carbon (meso-C) nanowires with zinc-catalyzed short-range ordered structure.Meso-C anode showed high initial Coulombic efficiency (76.7%) and excellent cycling stability (1000 cycles) for potassium-ion batteries.In/ex situ characterizations revealed the reversible structural changes, and the kinetic analyses revealed the rapid K+ diffusion in electrode. Electronic supplementary material The online version of this article (10.1007/s40820-020-00481-7) contains supplementary material, which is available to authorized users., Amorphous carbon shows great potential as an anode material for high-performance potassium-ion batteries; however, its abundant defects or micropores generally capture K ions, thus resulting in high irreversible capacity with low initial Coulombic efficiency (ICE) and limited practical application. Herein, pore engineering via a facile self-etching strategy is applied to achieve mesoporous carbon (meso-C) nanowires with interconnected framework. Abundant and evenly distributed mesopores could provide short K+ pathways for its rapid diffusion. Compared to microporous carbon with highly disordered structure, the meso-C with Zn-catalyzed short-range ordered structure enables more K+ to reversibly intercalate into the graphitic layers. Consequently, the meso-C shows an increased capacity by ~ 100 mAh g−1 at 0.1 A g−1, and the capacity retention is 70.7% after 1000 cycles at 1 A g−1. Multiple in/ex situ characterizations reveal the reversible structural changes during the charging/discharging process. Particularly, benefiting from the mesoporous structure with reduced specific surface area by 31.5 times and less defects, the meso-C generates less irreversible capacity with high ICE up to 76.7%, one of the best reported values so far. This work provides a new perspective that mesopores engineering can effectively accelerate K+ diffusion and enhance K+ adsorption/intercalation storage. Electronic supplementary material The online version of this article (10.1007/s40820-020-00481-7) contains supplementary material, which is available to authorized users.

Unique interfacial properties within heterostructures play vital roles in enhancing hydrogen evolution reaction (HER) electrocatalysis. On the basis of the MoO2-Ni heterostructure, we hereby propos...

Two-dimensional (2D) nanostructure engineering and surface modification with functional groups are of great importance to anode materials for rechargeable lithium-ion batteries. Herein, stacked NiO nanosheets@carbon (denoted as NiO@C) and 3 nm-ultrathin NiO nanosheets@functionalized carbon with surface functional groups NO3-, CO32-, OH-, and COOH- (denoted as NiO@FC) were prepared via a facile one-pot reaction and topotactic conversion. Specifically, NiO@FC exhibits excellent lithium storage performance: the capacity of NiO@FC is 489.2 mA h g-1, higher than that of NiO@C (1018.7 mA h g-1 at 0.2 A g-1), and maintains a capacity of 1133 mA h g-1 after 800 cycles, which exceed that of all previously reported NiO anodes. The enhanced lithium storage performance is attributed to the sufficient void space, which offers buffer space for volume change and speeds up the diffusion of Li+ ions. In addition, the surface functional groups were proved to not only hinder the agglomeration of nanosheets but also further donate active sites and improve storage capacity. These advantageous features achieved by designing such a stacked structure with functionalized carbon modification provide a promising strategy for the preparation of high-performance anode materials and other 2D functional materials.

Urban junctions usually present significant safety concerns, and the majority of all crashes in urban areas occur in or near junctions. Factors contributing to crash severity at junctions have been explored, but crash risk levels and crash severity patterns of different junction types have hardly been investigated. In order to fill this gap, this study analyzed the safety performance of six junction types and the factors contributing to crash severity, in order to assist city transportation authorities to implement effective countermeasures. Fault tree analysis (FTA) was applied for the risk evaluation of urban junctions and association rules (AR) algorithm was employed for the crash severity pattern analysis based on data from the U.K. STATS19 database from 2012 to 2016. Overall, four types of urban junctions with high crash risk level and over 4,000 AR contributing to crash severity are identified in the present paper. The results show that: (a) roundabouts and mini-roundabouts have the lowest fatality and casualty rates while T-junctions or staggered junctions and crossroads have the highest crash risk levels; (b) FTA may produce inaccurate outcomes because of incorrect logic gates, but AR can generate real potential relationships between crash severity and risk factors; (c) crash severity patterns are quite complex and the interdependence between risk factors is different for each junction type; (d) risk factors such as male driver, no physical crossing facilities within 50 meters, and give way or uncontrolled junction are common in high-risk junctions at night.

VOPO

Ethnopharmacological relevance Fuzheng Xiaozheng prescription (FZXZP) is a traditional Chinese medicine (TCM) that was derived from Sanjiasan, a famous decoction documented in the book of Wenyilun in Ming dynasty. Based on our years' clinic application, FZXZP demonstrated satisfactory therapeutic effects in cirrhosis and hepatocellular carcinoma (HCC) treatments. However, the underlying mechanisms are still largely unknown. Aim of study In this study, we aim to systematically evaluate the intervention effects of FZXZP on rat HCC and deeply elucidate the underlying regulative mechanisms on rat HCC. Materials and methods The HCC rats were induced by using diethylnitrosamine (DEN) and two doses of FZXZP were adopted to treat the HCC rats. Liver phenotype, blood chemistry and liver histopathology were used to evaluate the intervention effects. High performance liquid chromatography (HPLC) was conducted to analyze the components of FZXZP. Finally, miRNA-Seq and mRNA-Seq were performed to investigate the regulative mechanisms of FZXZP on rat HCC and qRT-PCR was carried out to verify the accuracies of the two RNA-Seqs. Results Results of liver phenotypes, blood chemistry and liver histopathology demonstrated that FZXZP significantly alleviated the liver damage, inhibited the progresses of HCC. Nine potential components were identified from FZXZP, and anti-cancer prediction suggested that almost all of them were reported to show an anti-cancer effect. Mechanistically, FZXZP was found to promote the lipid related metabolisms, improve the anti-inflammation ability by activating PPAR signaling pathway, arachidonic acid metabolism, bile secretion, etc. CONCLUSION: our results suggested that FZXZP significantly alleviated the rat HCC, mechanistically by improving the anti-inflammation ability and promoting the lipid related metabolisms.

The manipulation of recombinant DNA has been an integral step in molecular biology to date. A number of strategies have been developed over the years, as traditional cloning methods are time consuming, have high backgrounds and low efficiency and are often limited by the number of suitable restriction sites available. Here, we constructed a series of new positive-selection-based cloning vectors that overcome most of the above mentioned drawbacks and can be applied in both eukaryotic and prokaryotic systems. This strategy is based on the extreme toxicity of DpnI in wild-type E. coli and the inactivation of this lethality by the introduction of target gene within multiple cloning sites. There are no rapid approaches for identifying soluble proteins for high-throughput screening. In this study, we combined this highly efficient cloning strategy with rapid identification of soluble proteins to construct vectors with multiple fusion tags, such as MBP, GST, CBD, NusA, and Sumo, to generate enzymes with potential diagnostic, industrial or therapeutic applications. Thus, this versatile positive-selection-based technology is appropriate for routine cloning, DNA library construction, and high-throughput screening for the expression of proteins of interest.

Realizing stable cycling performance with high areal capacity is a great challenge for metal-ion battery anodes. Achieveing high areal capacity generally requires the electrode in a high active loading with increased electrode thickness, which is not beneficial to the cycling stability. In this work, novel nanosheet-assembled compact CaV4O9 microflowers are firstly synthesized through a facile method, which exhibit both high areal capacity and stable cycling performance at high mass loadings. The compact microflower structure leads to an increased tap density of the electrode materials, benefiting to reduce the anode thickness at high mass loadings. Meanwhile, the assembled nanosheets maintain the nano-effects of the active materials for favorable electrochemical reactions. These merits together with the intrinsic superior electrochemical properties of CaV4O9, result in the outstanding electrochemical performance. When used as Li-ion battery anodes, a high areal capcity of ~2.5 mAh cm−2 at a high mass loading of 4.4 mg cm−2 is obtained, and a stable cycling over 400 cycles with the areal capacity over 1.5 mAh cm−2 is demonstrated. Besides, the superior electrochemical performance at high mass loadings is also observed for Na storage. These achievements may pave the way for constructing applicable high-capacity and stable anode materials in metal-ion batteries.

Vulnerable road users (VRUs)-related crashes are recognized as an important public safety problem. However, few macro-level studies of VRUs-involved crashes have considered the long-term spatial, temporal, or spatiotemporal effects in the crash risk. This study analyzes the bicycle and pedestrian crash risk in different injury severities by using three multivariate Bayesian space–time models. These models address different spatiotemporal effects to account for possible correlations across injury severities over space and time. Various explanatory variables are used to examine the contributory risk factors, including socio-demographic features, roadway structures, and weather characteristics. Spatio-temporal conditional autoregression with an ANOVA style (ST-CARanova) models outperform other two space–time models in most circumstances. The long-term spatiotemporal effects, such as relatively high temporal autocorrelations, significant spatial heterogeneity, and weak spatiotemporal interactions, are found in this study. The increase of female ratios, young people ratios, unemployment rates, and annual average high temperatures could increase the county-level crash risk of cyclists and pedestrians. The findings provide useful insights for policy makers to improve the safety of cyclists and pedestrians.

Metal oxides are considered as attractive candidates as anode materials for lithium ion batteries (LIBs) due to their high capacities compared to commercialized graphite. However, fast capacity fading, which is caused by inherent large volume expansions and agglomeration of active particles upon cycling, is a great challenge. Herein, we propose the design of porous CaFe2O4 electrode material to address the above issue. Compared to pristine iron oxides, CaFe2O4 exhibits a distinct trade-off in terms of high capacity and long-term stability, which is beneficial to the potential practical applications. Such a trade-off effect is attributed to the synergistic effect between the porous structure and the in situ formed CaO nanograins during charging/discharging processes. This work provides an effective strategy in achieving anode materials with high capacity and long-term stability for next-generation LIBs.

Powering device for miniaturized electronics is highly desired with well-maintained capacity and high-rate performance. Though Ni-Zn microbattery can meet the demand to some extent with intrinsic fast kinetic, it still suffers irreversible structure degradation due to the repeated lattice strain. Herein, a stable Ni-Zn microbattery with ultrahigh-rate performance is rationally constructed through in situ electrochemical approaches, including the reconstruction of nanoporous nickel and the introduction of epitaxial Zn(OH)2 nanophase. With the enhanced ionic adsorption effect, the superior reactivity of the superficial nickel-based nanostructure is well stabilized. Based on facile miniaturization and electrochemical techniques, the fabricated nickel microelectrode exhibits 63.8% capacity retention when the current density is 500 times folded, and the modified hydroxides contribute to the great stability of the porous structure (92% capacity retention after 10 000 cycles). Furthermore, when the constructed Ni-Zn microbattery is measured in a practical metric, excellent power density (320.17 mW cm-2 ) and stable fast-charging performance (over 90% capacity retention in 3500 cycles) are obtained. This surface reconstruction strategy for nanostructure provides a new direction for the optimization of electrode structure and enriches high-performance output units for integrated microelectronics.

Transition metal phosphides or partially phosphatized oxides usually suffer from surface reconstruction during oxygen evolution reaction (OER), but still possess enhanced catalytic activity than directly synthesized oxides, which has aroused great interest in exploring the causes of such high catalytic activity. To monitor electronic property of catalyst during the OER can provide crucial insights into catalytic ability. Here we design a planar electrochemical microdevice based on individual thin-film catalyst, and for the first time explore the continuous electric conductance evolution of lattice P-doped oxides during the electrochemical activation process. Moreover, combining on-chip electrochemical impedance spectra measurements, in situ I-V measurements, and theoretical simulations of reconstructed lattice P-doped oxides, the effect of P–O groups on new-formed oxides is clarified. The induced electronic coupling between new-formed oxides and P-O groups has been studied and demonstrated. The coupled P–O groups effectively promote the metal–oxygen covalency of new-formed oxides, which accelerates electron transfer between active metallic center and oxygen adsorbates, thus leading to the enhanced electrocatalytic activity. Our study highlights the role of surface P–O groups in Co3O4 during the OER, and such unique on-chip electrochemical microdevice platform can also be applied in other related fields to understand the dynamic behavior of energy materials at nanoscale.

To systematically account for the spatiotemporal features and unobserved heterogeneity within pedestrian-vehicle crashes, this paper employs the spatiotemporal analysis and hierarchical Bayesian random-effects models to explore the factors contributing to pedestrian-injury severities of pedestrian-vehicle crashes involving single vehicle in North Carolina from 2007 to 2018. Ten spatiotemporal patterns of the crashes are identified by applying an improved spatiotemporal analysis. Significant temporal instability and the spatiotemporal instability of the factors to the pedestrian-injury crashes are identified by the likelihood ratio tests. A hierarchical Bayesian random intercept logit model with random-effects across the spatiotemporal groups is firstly employed for the whole dataset. The comparison between different hierarchical models indicates that addressing random-effects across observations and increasing the number of random parameters could both improve the model performance. Then a hierarchical Bayesian random-effects-only logit model, which allows all parameters to be randomly distributed across observations, is developed to further investigate the unobserved heterogeneity in spatiotemporal segmented datasets. The significant improvements in terms of model fit and the hit accuracy underscore the superiority of the random-effects-only model. The marginal effects of the human, vehicle, crash, locality, roadway, environment, time, and traffic control factors for each spatiotemporal dataset also provide insights into possible inherent reasons for the spatiotemporal instability/tendency of the crash and correlated factors. Meanwhile, specific countermeasures are given to locations especially in which the spatially aggregated patterns of the crashes have new, consecutive, and intensifying temporal tendencies. This study provides a framework for engineers and researchers to identify spatiotemporal patterns of the crashes and explore the factors affecting pedestrian-injury severities especially in those existing crash-prone areas.

Summary Fundamental investigations of reconstruction of oxygen evolution reaction (OER) pre-catalysts and performance evaluation under realistic conditions are vital for practical water electrolysis. Here, we capture dynamic reconstruction, including the geometric/phase structure, of hydrate molybdates at oxidized potentials. Etching-reconstruction engineering endows the formed NiOOH with a sub-5-nm particle-interconnected structure, as revealed by multi-angle electron tomography. The key to complete reconstruction is the multicomponent co-leaching-induced loose reconstruction layer, conductive to solution penetration and mass transport. This unique structure avoids particle agglomeration in catalysis and promotes complete exploitation of the catalyst with 1,350 h of durability to meet industrial requirements. Upon addition of iron during reconstruction, mainstream Fe-NiOOH with a retained structure forms. Coupled with MoO2-Ni arrays in a membrane-free and two-electrode cell, it achieves stable electrolysis in industrial-concentration KOH for 260 h. This work highlights the reconstruction chemistry of hydrate oxygen-evolving systems and their performance evaluation under industrial conditions.