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Traffic flow forecasting, as one of the important components of intelligent transport systems (ITS), plays an indispensable role in a wide range of applications such as traffic management and city planning. However, complex spatial dependencies and dynamic changes in temporal patterns exist between different routes, and obtaining as many spatial-temporal features and dependencies as possible from node data has been a challenging task in traffic flow prediction. Current approaches typically use independent modules to treat temporal and spatial correlations separately without synchronously capturing such spatial-temporal correlations, or focus only on local spatial-temporal dependencies, thereby ignoring the implied long-term spatial-temporal periodicity. With this in mind, this paper proposes a long-term spatial-temporal graph convolutional fusion network (LSTFGCN) for traffic flow prediction modeling. First, we designed a synchronous spatial-temporal feature capture module, which can fruitfully extract the complex local spatial-temporal dependence of nodes. Second, we designed an ordinary differential equation graph convolution (ODEGCN) to capture more long-term spatial-temporal dependence using the spatial-temporal graph convolution of ordinary differential equation. At the same time, by integrating in parallel the ODEGCN, the spatial-temporal graph convolution attention module (GCAM), and the gated convolution module, we can effectively make the model learn more long short-term spatial-temporal dependencies in the processing of spatial-temporal sequences.Our experimental results on multiple public traffic datasets show that our method consistently obtained the optimal performance compared to the other baselines.

Two new prenylated flavonoids named sinoflavonoids NJ and NK (1–2), along with ten known compounds were isolated from the fruits of Podophyllum hexandrum Royle. The chemical structures were determined through NMR spectroscopic data and MS analysis. Sinoflavonoid NJ (1) with an unusual 5,11-dioxabenzo[b]fluoren-10-one skeleton was firstly reported from Berberidaceae. The isolated flavonoids were tested with LPS-induced RAW 264.7 mouse macrophages model for their anti-inflammatory activity. Sinoflavonoid NJ (1) showed the most potent inhibition on nitric oxide production with IC50 value as 0.06 μM.

Charge compensation on anionic redox reaction (ARR) has been promising to realize extra capacity beyond transition metal redox in battery cathodes. The practical development of ARR capacity has been hindered by high-valence oxygen instability, particularly at cathode surfaces. However, the direct probe of surface oxygen behavior has been challenging. Here, the electronic states of surface oxygen are investigated by combining mapping of resonant Auger electronic spectroscopy (mRAS) and ambient pressure X-ray photoelectron spectroscopy (APXPS) on a model LiCoO

Twelve guaianolide-type sesquiterpene oligomers with diverse structures were isolated from the whole plants of Ainsliaea fragrans, including a novel trimer (1) and two new dimers (2, 3). The chemical structures of the new compounds were elucidated through spectroscopic data interpretation and computational calculations. Ainsfragolide (1) is an unusual guaianolide sesquiterpene trimer generated with a novel C-C linkage at C2'-C15″, which may be biosynthesized prospectively through a further Michael addition. Cytotoxicity results showed that ainsfragolide (1) was the most potent compound against five cancer cell lines with IC50 values in the range of 0.4-8.3 μM.

Objective: Shaanxi is the most highly populated province with high burdens of tuberculosis in northwestern China. The aim of this study was to investigate the molecular characteristics and drug res...

A single-crystalline Ni-rich (SCNR) cathode with a large particle size can achieve higher energy density, and is safer, than polycrystalline counterparts. However, synthesizing large SCNR cathodes (>5 μm) without compromising electrochemical performance is very challenging due to the incompatibility between Ni-rich cathodes and high temperature calcination. Herein, we introduce Vegard's Slope as a guide for rationally selecting sintering aids, and we successfully synthesize size-controlled SCNR cathodes, the largest of which can be up to 10 μm. Comprehensive theoretical calculation and experimental characterization show that sintering aids continuously migrate to the particle surface, suppress sublattice oxygen release and reduce the surface energy of the typically exposed facets, which promotes grain boundary migration and elevates calcination critical temperature. The dense SCNR cathodes, fabricated by packing of different-sized SCNR cathode particles, achieve a highest electrode press density of 3.9 g cm−3 and a highest volumetric energy density of 3000 Wh L−1. The pouch cell demonstrates a high energy density of 303 Wh kg−1, 730 Wh L−1 and 76% capacity retention after 1200 cycles. SCNR cathodes with an optimized particle size distribution can meet the requirements for both electric vehicles and portable devices. Furthermore, the principle for controlling the growth of SCNR particles can be widely applied when synthesizing other materials for Li-ion, Na-ion and K-ion batteries.

The reactivity of garnet solid electrolytes toward humid air hinders their practical application despite their attractive, superior properties such as high Li+ conductivity and wide electrochemical window. Sealing garnets with organic solvents can not only prevent them from reacting with humid air but also render them compatible with other processing technologies. Therefore, the chemical and structural stability of garnets in organic solvents must be studied. In this study, we selected several commonly used organic solvents with different representative functional groups to investigate their stability with garnets and reaction mechanisms. The experiments and theoretical calculations revealed that all of the solvents reacted with garnets through Li-H exchange, and solvent acidity determined the reaction strength. Furthermore, the solvent acidity was closely correlated to the functional groups connected to H atoms, which can affect charge distribution. Solvents or the tautomer of the solvents with hydroxyl groups such as alcohol, acetone, and N-methyl pyrrolidone, which are relatively more acidic, can lead to a violent reaction with changes in the lattice parameters of garnets. Ether compounds and saturated aliphatic hydrocarbons with relatively low acidity are highly stable against garnets. The proposed reaction mechanisms and rules may help in selecting appropriate solvents for different applications of garnets.

Two new cadinane sesquiterpenes named myrrhterpenes A and B (1, 2), along with eighteen known analogs were isolated from the resin of Commiphora myrrha. Their structures were determined by various NMR and MS spectrometry analysis, as well as by comparison with related compounds. Anti-inflammatory activity with LPS-induced RAW 264.7 macrophages revealed that two new compounds displayed potent inhibition on nitric oxide production.

Genome-wide association studies (GWASs) have revealed that genetic variants at the 22q13.2 risk locus were robustly associated with schizophrenia. However, the causal variants at this risk locus and their roles in schizophrenia remain elusive. Here we identify the risk missense variant rs1801311 (located in the 1st exon of NDUFA6 gene) as likely causal for schizophrenia at 22q13.2 by disrupting binding of YY1, TAF1, and POLR2A. We systematically elucidated the regulatory mechanisms of rs1801311 and validated the regulatory effect of this missense variant. Intriguingly, rs1801311 physically interacted with NAGA (encodes the alpha-N-acetylgalactosaminidase, which is mainly involved in regulating metabolisms of glycoproteins and glycolipids in lysosome) and showed the most significant association with NAGA expression in the human brain, with the risk allele (G) associated with higher NAGA expression. Consistent with eQTL analysis, expression analysis showed that NAGA was significantly upregulated in brains of schizophrenia cases compared with controls, further supporting that rs1801311 may confer schizophrenia risk by regulating NAGA expression. Of note, we found that NAGA regulates important neurodevelopmental processes, including proliferation and differentiation of neural stem cells. Transcriptome analysis corroborated that NAGA regulates pathways associated with neuronal differentiation. Finally, we independently confirmed the association between rs1801311 and schizophrenia in a large Chinese cohort. Our study elucidates the regulatory mechanisms of the missense schizophrenia risk variant rs1801311 and provides mechanistic links between risk variant and schizophrenia etiology. In addition, this study also revealed the novel role of coding variants in gene regulation and schizophrenia risk, i.e., genetic variant in coding region of a specific gene may confer disease risk through regulating distal genes (act as regulatory variant for distal genes).

Recent large-scale integrative analyses (including Transcriptome-Wide Association Study [TWAS] and Summary-data-based Mendelian Randomization [SMR]) have identified multiple genes whose cis-regulated expression changes may confer risk of schizophrenia. Nevertheless, expression quantitative trait loci (eQTL) data and genome-wide associations used for integrative analyses were mainly from populations of European ancestry, resulting in potential missing of pivotal biological insights in other continental populations due to population heterogeneity. Here we conducted TWAS and SMR integrative analyses using blood eQTL (from 162 subjects) and GWAS data (22 778 cases and 35 362 controls) of schizophrenia in East Asian (EAS) populations. Both TWAS (P = 2.89 × 10–14) and SMR (P = 6.04 × 10–5) analyses showed that decreased TMEM180 mRNA expression was significantly associated with risk of schizophrenia. We further found that TMEM180 was significantly down-regulated in the peripheral blood of schizophrenia cases compared with controls (P = 8.63 × 10–4 in EAS sample), and its expression was also significantly lower in the brain tissues of schizophrenia cases compared with controls (P = 1.87 × 10–5 in European sample from PsychENCODE). Functional explorations suggested that Tmem180 knockdown affected neurodevelopment, ie, proliferation and differentiation of neural stem cells. RNA sequencing showed that pathways regulated by Tmem180 were significantly enriched in brain development and synaptic transmission. In conclusion, our study provides convergent lines of evidence for the involvement of TMEM180 in schizophrenia, and highlights the potential and importance of resource integration and sharing at this big data era in bio-medical research.

Since the impoundment of the Three Gorges Reservoir area in 2003, the potential risks of geological disasters in the reservoir area have increased significantly, among which the hidden dangers of landslides are particularly prominent. To reduce casualties and damage, efficient and precise landslide susceptibility evaluation methods are important. Multiple ensemble models have been used to evaluate the susceptibility of the upper part of Badong County to landslides. In this study, EasyEnsemble technology was used to solve the imbalance between landslide and nonlandslide sample data. The extracted evaluation factors were input into three bagging, boosting, and stacking ensemble models for training, and landslide susceptibility mapping (LSM) was drawn. According to the importance analysis, the important factors affecting the occurrence of landslides are altitude, terrain surface texture (TST), distance to residences, distance to rivers and land use. The influences of different grid sizes on the susceptibility results were compared, and a larger grid was found to lead to the overfitting of the prediction results. Therefore, a 30 m grid was selected as the evaluation unit. The accuracy, area under the curve (AUC), recall rate, test set precision, and kappa coefficient of a multi-grained cascade forest (gcForest) model with the stacking method were 0.958, 0.991, 0.965, 0.946, and 0.91, respectively, which a significantly better than the values produced by the other models.

Zeolitic imidazolate frameworks (ZIFs) have attracted extensive research interests because of their porosity, large specific area, and adjustable aperture. In particular, a series of nanomaterials derived from ZIF-67 precursor has broad application prospects in energy and environment. In this paper, Co-ZIF nanocrystal was synthesized by solvothermal method, by introducing a second kind of transition metal Ni, the NixCo1-x-ZIF nanocrystals with single metal Co-ZIF structure were synthesized. NixCo1-x-O composites were obtained by oxidation of NixCo1-x-ZIF nanocrystals, and the electrocatalytic hydrogen evolution activity of composites modified glassy carbon electrode in 1 M KOH solution was tested. It is found that the Ni0.5Co0.5-O composites have the lowest overpotential compared with similar composites.

Hydroisomerization dewaxing is an advantageous process to improve lubricating oil quality. The bifunctional catalyst used in the hydrogenation isomerization reaction provides the isomerization function with the acidic site supported by molecular sieve, and the precious metals such as Pt and Pd provide the hydrogenation function for the metal site, which has the advantages of high activity, low production cost, and mature synthesis process. The ZSM-22 zeolite was hydrothermal synthesized using 1,6-diamino hexane (DAH) as templates in the presence of the seed, XRD, N2 adsorption-desorption and NH3-TPD Cha adsorption-desorption times. Finally, the hydroisomerization dewaxing performance of the Pt/ZSM-22 and Pt-Pd/ZSM-22 bifunctional catalysts were investigated on a high-pressure fixed-bed hydrogenation reactor. The results show that the hydroisomerization dewaxing performance of the Pt-Pd/ZSM-22 catalyst is better.

Schizophrenia is a severe mental disease characterized with positive symptoms, negative symptoms, and cognitive impairments. Although recent genome-wide association studies (GWASs) have identified over 145 risk loci for schizophrenia, pinpointing the causal variants and genes at the reported loci and elucidating their roles in schizophrenia remain major challenges. Here we identify a functional single-nucleotide polymorphism (SNP; rs213237) in ZNF323 promoter by using functional fine-mapping. We found that allelic differences at rs213237 affected the ZNF323 promoter activity significantly. Consistently, expression quantitative trait loci (eQTL) analysis showed that rs213237 was significantly associated with ZNF323 expression in diverse human brain tissues, suggesting that rs213237 may contribute to schizophrenia risk through regulating ZNF323 expression. Interestingly, we found that ZNF323 protein was localized in the nucleus and knockdown of ZNF323 in macaque neural stem cells (mNSCs) significantly impaired proliferation and survival of mNSCs. We further showed that stable knockdown of ZNF323 in SH-SY5Y cells resulted in significant decrease of the tyrosine hydroxylase (TH) protein expression. Finally, transcriptome analysis revealed that ZNF323 may regulate pivotal schizophrenia risk genes (including VIPR2 and NPY) and schizophrenia-associated pathways (including PI3K-AKT and NOTCH signaling pathways), suggesting that ZNF323 may be a major regulator of schizophrenia risk genes. Our study reveals how a genetic variant in ZNF323 promoter contributes to schizophrenia risk through regulating ZNF323 expression. More importantly, our findings demonstrate that ZNF323 may have a pivotal role in schizophrenia pathogenesis through regulating schizophrenia risk genes and schizophrenia-associated biological processes (including neurodevelopment, PI3K-AKT, and NOTCH signaling pathways).

Titanium cermet combining metallic toughness with ceramic wear resistance has been proven to be a potential candidate for implanted joint material. In this work, titanium cermet was synthesized by means of the elevated temperature solid carburizing technology. The Ti13Nb13Zr alloy surface was found to be converted into TiC ceramic layer combined with a carbon strengthened diffusion zone underneath. The overall thickness of the carburized region grew to about 100 µm after 120 min carburization at 1,500 K. In order to clarify the growth behaviors of TiC ceramic layer, a growth mechanism is proposed. At the beginning of carburizing process, carbonaceous gas decomposed from carburizer due to high temperature and then converted to free atomic carbons through reduction reaction. Then, in-situ generated TiC ceramic layer possessing certain thickness formed on the surface, meanwhile, the inner carbon diffusion zone also grew inwards due to physical diffusion of carbon, and finally forming a gradient carbon distribution. In addition, the tribological behaviors of the new materials were evaluated through reciprocating ball-on-plate sliding wear tests in bovine calf serum. Although there was an increase in friction coefficient, the wear rate decreased by 59.6% due to the formation of the wear-resistant TiC ceramic layer. The wear mechanisms evolved from severe abrasive wear for bare Ti13Nb13Zr alloy to mild adhesive wear for titanium cermet.

Veterans have become one of China’s largest and most vocal protest groups. Studies on the country’s veterans have focused on their grievances and have identified these individuals as “unlucky” victims of economic reforms who suffer because of the state’s inadequate attention and local governments’ poor policy implementation. However, this article argues that the difficulties veterans face are the product of piecemeal policies adopted by central authorities. These policies have been inherited from the Maoist era’s principle of local resettlement of demobilized soldiers. Local governments have tried to reduce the heavy burden this resettlement policy imposes on them. Drawing on a review of a large number of policy documents, as well as interviews with dozens of veterans, this article presents a comprehensive picture of the resettlement system and the way piecemeal reforms have spurred various forms of unrest among veterans. It also shows that the differential treatment of various veteran groups in similar situations, as a result of the fragmented system and accumulated policy changes, has exacerbated veterans’ grievances. Finally, the article explores the conundrum of reforming the resettlement system. While the local resettlement of veterans is guaranteed and remains a cornerstone of civil/party-military relations, it has become impossible for the government to locally resettle all veterans. The resettlement system’s internal fragmentation also allows different authorities to shirk responsibility and eventually puts the burden on the veterans themselves. The elusive reforms proposed by the current leadership are unlikely to resolve these tensions.

Summary Real-world industry-relevant battery composite electrodes are hierarchically structured. In particular for active cathode particles, there is a consensus that their structural and chemical defects could have a profound impact on battery performance. An in-depth understanding of the underlying mechanisms could critically inform cathode material engineering, which remains a daunting challenge at present. Herein, we tackle this question by studying LiCoO2 (LCO) with trace doping of Ti, which exhibits low solubility in the LCO-layered lattice. We observed the spontaneous and heterogeneous segregation of the dopant (Ti), which modified the particle surface and the buried grain boundaries while inducing a significant amount of lattice distortions. These multiscale structural defects promote the robustness of the LCO lattice at a deeply charged state (above 4.5 V). Our result formulates a multiscale defect-engineering strategy that could be applicable to the synthesis of a broad range of energy materials.

The employment of lithium metal anode in rechargeable lithium batteries has been hindered by the safety concerns which are associated with the uncontrolled lithium dendrite growth and the unceasing side reactions with liquid electrolytes. In this work, we report that the use of Ti-containing solid electrolyte-coated separators can greatly enhance the cycle performances of lithium metal anode in cells using liquid electrolytes. The detailed morphologic studies indicate that more uniform lithium deposition is achieved in cells using Ti-containing solid electrolyte-coated separators than that using Al2O3-coated separators, which is likely due to the modified anode and electrolyte interfacial properties induced by the reactive nature of Ti-containing solid electrolytes with metallic lithium. This work demonstrates an effective strategy to enhance the homogeneity of lithium deposition, which leads to the stable cycling of lithium metal anode in rechargeable lithium-ion batteries. Texture intensity decreases by the increase in the amount of alloying elements

Summary All-solid-state lithium-metal batteries are regarded as promising next-generation battery systems. While thermal runaway in conventional Li-ion batteries is known to cause safety hazards, the thermal issues posed by highly reactive metallic lithium (Li) with non-flammable ceramic solid electrolytes (SEs) have been less studied but are critical for the safety of all-solid-state Li-metal batteries. Here, we quantify the thermal stability of four prevalent oxide SEs with metallic Li using the accelerating rate calorimeter (ARC). Thermal runaway is observed during ARC tests for four widely used SEs when contacting with Li, while no obvious heat releases from garnet with Li. The oxygen generation from SEs at elevated temperatures is found to be responsible for the thermal runaway with Li. Our results indicate potential safety issues in all solid-state batteries (ASSBs) brought by highly reactive metallic Li and oxygen from SEs at increased temperatures, emphasizing the need for investigating thermal safety issues in ASSBs.

Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders and a leading cause of disability worldwide. Though recent genome-wide association studies (GWAS) have identified multiple risk variants for MDD, how these variants confer MDD risk remains largely unknown. Here we systematically characterize the regulatory mechanism of MDD risk variants using a functional genomics approach. By integrating chromatin immunoprecipitation sequencing (ChIP-Seq) (from human brain tissues or neuronal cells) and position weight matrix (PWM) data, we identified 34 MDD risk SNPs that disrupt the binding of 15 transcription factors (TFs). We verified the regulatory effect of the TF binding-disrupting SNPs with reporter gene assays, allelic-specific expression analysis, and CRISPR-Cas9-mediated genome editing. Expression quantitative trait loci (eQTL) analysis identified the target genes that might be regulated by these regulatory risk SNPs. Finally, we found that NEGR1 (regulated by the TF binding-disrupting MDD risk SNP rs3101339) was dysregulated in the brains of MDD cases compared with controls, implying that rs3101339 may confer MDD risk by affecting NEGR1 expression. Our findings reveal how genetic variants contribute to MDD risk by affecting TF binding and gene regulation. More importantly, our study identifies the potential MDD causal variants and their target genes, thus providing pivotal candidates for future mechanistic study and drug development.

Nickel-rich layered cathode materials have aroused widespread interest due to their high discharge capacity, which is a basic requirement for next-generation high energy density lithium batteries. However, with the increase of nickel content, cathode materials face the serious challenge of capacity degradation, which is attributed to the formation of rock salt-type oxides such as NiO on the surface of cathode particles. To overcome this shortcoming, a novel Ni concentration gradient LiNi0.8Co0.15Al0.05O2 (NCG-NCA) cathode material was successfully synthesized using the characteristic reaction of Ni2+ and dimethylglyoxime. The final synthesized nickel concentration gradient material combines the advantages of high discharge capacity and excellent stability, which are attributed to the high nickel content in the core and high cobalt content on the surface of the material particles. The cycling stability of the NCG material is remarkably improved, exhibiting an excellent capacity retention of 75% after 200 cycles at a current density of 10C (1C = 160 mA g-1) under a high cut-off voltage of 4.5 V, much higher than that of a pristine NCA (P-NCA) cathode without NCG (50%). The excellent cycling stability of NCG-NCA is due to formation of a stable surface, which is not prone to serious atomic rearrangement on the surface. More importantly, with the structural analysis of NCA materials by neutron diffraction, we find that the proportion of Li/Ni mixing of NCA is reduced by utilizing the NCG structure; in turn, the rate performance of NCG-NCA cathode materials is improved greatly.

Recent genome-wide association studies have reported multiple schizophrenia risk loci, yet the functional variants and their roles in schizophrenia remain to be characterized. Here we identify a functional single nucleotide polymorphism (rs2270363: G>A) at the schizophrenia risk locus 16p13.3. rs2270363 lies in the E-box element of the promoter of NMRAL1 and disrupts binding of the basic helix–loop–helix leucine zipper family proteins, including USF1, MAX and MXI1. We validated the regulatory effects of rs2270363 using reporter gene assays and electrophoretic mobility shift assay. Besides, expression quantitative trait loci analysis showed that the risk allele (A) of rs2270363 was significantly associated with elevated NMRAL1 expression in the human brain. Transcription factors knockdown and CRISPR-Cas9-mediated editing further confirmed the regulatory effects of the genomic region containing rs2270363 on NMRAL1. Intriguingly, NMRAL1 was significantly downregulated in the brain of schizophrenia patients compared with healthy subjects, and knockdown of Nmral1 expression affected proliferation and differentiation of mouse neural stem cells, as well as genes and pathways associated with brain development and synaptic transmission. Of note, Nmral1 knockdown resulted in significant decrease of dendritic spine density, revealing the potential pathophysiological mechanisms of NMRAL1 in schizophrenia. Finally, we independently confirmed the association between rs2270363 and schizophrenia in the Chinese population and found that the risk allele of rs2270363 was the same in European and Chinese populations. These lines of evidence suggest that rs2270363 may confer schizophrenia risk by regulating NMRAL1, a gene whose expression dysregulation might be involved in the pathogenesis of schizophrenia by affecting neurodevelopment and synaptic plasticity.

Based on hybridization chain reaction (HCR) and fluorescence synergism, a novel aptasensor for tobramycin was successfully constructed. Tobramycin competed with cDNA-FAM to bind aptamers immobilized on magnetic beads. After magnetic separation, the released cDNA-FAM acted as initiator to trigger HCR amplification, thus the fluorescence was significantly enhanced due to binding of SYBR Green Ⅰ (SGI) to the formed long double-stranded DNA and the synergistic fluorescence of FAM. In the absence of tobramycin, the initiator was magnetically separated and no HCR occurred, more importantly, graphene oxide can quench the fluorescence of excessive hairpins/SGI and cDNA-FAM, so almost no background signal was detected. This aptasensor can monitor tobramycin in the range of 0.3-50 μM with low detection limit of 17.37 nM. Due to the potential generality of structure-switching aptamers and effectiveness of fluorescence synergism, this enzyme-free amplification strategy can be extended to other applications by rational design of nucleic acid sequences.

Genome-wide association studies have identified 3p21.1 as a robust risk locus for schizophrenia. However, the underlying molecular mechanisms remain elusive. Here a functional regulatory variant (rs2535629) is identified that disrupts CTCF binding at 3p21.1. It is confirmed that rs2535629 is also significantly associated with schizophrenia in Chinese population and the regulatory effect of rs2535629 is validated. Expression quantitative trait loci analysis indicates that rs2535629 is associated with the expression of three distal genes (GLT8D1, SFMBT1, and NEK4) in the human brain, and CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of rs2535629 on GLT8D1, SFMBT1, and NEK4. Interestingly, differential expression analysis of GLT8D1, SFMBT1, and NEK4 suggested that rs2535629 may confer schizophrenia risk by regulating SFMBT1 expression. It is further demonstrated that Sfmbt1 regulates neurodevelopment and dendritic spine density, two key pathological characteristics of schizophrenia. Transcriptome analysis also support the potential role of Sfmbt1 in schizophrenia pathogenesis. The study identifies rs2535629 as a plausibly causal regulatory variant at the 3p21.1 risk locus and demonstrates the regulatory mechanism and biological effect of this functional variant, indicating that this functional variant confers schizophrenia risk by altering CTCF binding and regulating expression of SFMBT1, a distal gene which plays important roles in neurodevelopment and synaptic morphogenesis.

Twelve guaianolide-type sesquiterpene oligomers with diverse structures were isolated from the whole plants of

Based on the high recognition ability and flexible programmability of GR5 DNAzyme, two fluorescent biosensors were engineered for amplified detection of Pb

In recent years, traffic flow forecasting has attracted the great attention of many researchers with increasing traffic congestion in metropolises. As a hot topic in the field of intelligent city computing, traffic flow forecasting plays a vital role, since predicting the changes in traffic flow can timely alleviate traffic congestion and reduce the occurrence of accidents by vehicle scheduling. The most difficult challenges of traffic flow prediction are the temporal feature extraction and the spatial correlation extraction of nodes. At the same time, graph neural networks (GNNs) show an excellent ability in dealing with spatial dependence. Existing works typically make use of graph neural networks (GNNs) and temporal convolutional networks (TCNs) to model spatial and temporal dependencies respectively. However, how to extract as much valid information as possible from nodes is a challenge for GNNs. Therefore, we propose a multi-mode spatial-temporal convolution of mixed hop diffuse ODE (MHODE) for modeling traffic flow prediction. First, we design an adaptive spatial-temporal convolution module that combines Gate TCN and graph convolution to capture more short-term spatial-temporal dependencies and features. Secondly, we design a mixed hop diffuse ordinary differential equation(ODE) spatial-temporal convolution module to capture long-term spatial-temporal dependencies using the receptive field of the mixed hop diffuse ODE. Finally, we design a multi spatial-temporal fusion module to integrate the different spatial-temporal dependencies extracted from two different spatial-temporal convolutions. To capture more spatial-temporal features of traffic flow, we use the multi-mode spatial-temporal fusion module to get more abundant traffic features by considering short-term and long-term two different features. The experimental results on two public traffic datasets (METR-LA and PEMS-BAY) demonstrate that our proposed algorithm performs better than the existing methods in most of cases.

Rechargeable battery technologies have revolutionized electronics, transportation and grid energy storage. Many materials are being researched for battery applications, with layered transition metal oxides (LTMO) the dominating cathode candidate with remarkable electrochemical performance. Yet, daunting challenges persist in the quest for further battery developments targeting lower cost, longer lifespan, improved energy density and enhanced safety. This is, in part, because of the intrinsic complexity of real-world batteries, featuring sophisticated interplay among microstructural, compositional and chemical heterogeneities, which has motivated tremendous research efforts using state-of-the-art analytical techniques. In this research field, synchrotron techniques have been identified as a suite of effective methods for advanced battery characterization in a non-destructive manner with sensitivities to the lattice, electronic and morphological structures. This article provides a holistic overview of cutting-edge developments in synchrotron-based research on LTMO battery cathode materials. We discuss the complexity and evolution of LTMO’s material properties upon battery operation and review recent synchrotron-based research works that address the frontier challenges and provide novel insights in this field. Finally, we formulate a perspective on future directions of synchrotron-based battery research, involving next-generation X-ray facilities and advanced computational developments.

The numerical solution of differential equations can be formulated as an inference problem to which formal statistical approaches can be applied. However, nonlinear partial differential equations (PDEs) pose substantial challenges from an inferential perspective, most notably the absence of explicit conditioning formula. This paper extends earlier work on linear PDEs to a general class of initial value problems specified by nonlinear PDEs, motivated by problems for which evaluations of the right-hand-side, initial conditions, or boundary conditions of the PDE have a high computational cost. The proposed method can be viewed as exact Bayesian inference under an approximate likelihood, which is based on discretisation of the nonlinear differential operator. Proof-of-concept experimental results demonstrate that meaningful probabilistic uncertainty quantification for the unknown solution of the PDE can be performed, while controlling the number of times the right-hand-side, initial and boundary conditions are evaluated. A suitable prior model for the solution of PDEs is identified using novel theoretical analysis of the sample path properties of Matérn processes, which may be of independent interest.

Iridin, one of the main bioactive components isolated from Belamcanda chinensis (L.) DC, exerts various pharmacological activities, such as anti-inflammation, antioxidant, and antitumor. However, the metabolism and pharmacokinetics of iridin are still unknown. After 100 mg/kg administration of iridin orally, the plasma, urine, and fecal bio-samples from Sprague–Dawley (SD) rats were collected and detected by ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). The pharmacokinetics of the major metabolite irigenin (aglycon of iridin) and a total of thirteen metabolites of iridin were identified, including five metabolites in plasma, ten metabolites in urine, and six metabolites in feces. The most principal metabolic pathway of iridin was glucuronidation after demethylation and was mediated by UDP-glucuronosyltransferases (UGTs) 1A7, 1A8, 1A9 and 1A10. This study highlights the first-time investigation of the metabolism of iridin in vivo, and the pharmacokinetics of irigenin (the major metabolite of iridin) in rats. These results provide robust evidence for further research and clinical application of iridin.

A fluorescent aptasensor based on sensitized terbium(III) luminescence was constructed to detect melamine in milk. Tb

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC., Graphical abstract C16-N hydrogel containing triptolide was created as an intraperitoneal depot for the treatment of orthotopic hepatocellular carcinoma. After intraperitoneal injection, the hydrogel retained in the peritoneal cavity for more than 2 weeks with preferential drug accumulation in the liver, and doubled the median survival time of tumor-bearing mice without noticeable side effects to major organs.Image 1

The long progression-free survival (PFS) of patients with inoperable hepatocellular carcinoma (HCC) tumors is an unmet clinical need. Imaging-guided in situ ablation and vaccination with nanoplatforms could be a promising way to achieve durable disease control and long PFS. In the present work, we show that a biomimetic nanoplatform, namely, synthetic high-density lipoprotein (sHDL), can transport photothermal agent DiR and other drugs preferentially into the cytosol of HCC cells, enabling imaging-guided combination therapy for HCC in vivo. With a single injection, the sHDLs reduced the tumor burden, triggered immunogenic cell death (ICD), promoted dendritic cell (DC) maturation, and induced CD8

The urgency of extending functionalities of current advanced driver assistance systems (ADAS), and eventually progressing to highly automated highway driving necessitates the design of automatic lane change system. This paper presents an automatic lane change system targeting on discretional lane change scenario in highway driving. Assuming motion signals of all participants to be available, the MOBIL model is employed as the decision module. The functionality of the adaptive cruise controller is extended to realize dual-target tracking, so as to prevent abrupt acceleration change provoked by the sudden switch of the leading vehicle during the lane change. For the lateral part, a hierarchical trajectory planning algorithm, which combines parametric function and learning-based technique, is proposed to account for uncertainties of driver characteristics in different traffic situations. The trajectory is then tracked by a low-level controller based on model predictive control (MPC) theory, which employs a force input model to predict the motion of the vehicle, and formulates environment envelope and handling limits as constraints. The proposed algorithm is validated through simulations of typical scenarios. Overall, this paper lays a solid foundation for the prototype of ADAS regarding lane change.

Apolipoprotein E (ApoE) ε4 allele and cerebral blood flow (CBF) changes are related to the increased risk of cognitive impairment independently. However, whether there are interactions between ApoE ε4 and CBF on memory performance in older adults with normal cognition remains unknown. This study determined whether the association between CBF and memory performance could be moderated by ApoE ε4 within a sample of cognitively normal older adults from the ADNI. 62 participants, including 23 with ApoE ε4 (ApoE ε4+) and 39 without ApoE ε4 (ApoE ε4−), underwent resting CBF measurement and memory testing. CBF was measured by arterial spin labeling MRI and memory performance was evaluated by the Rey Auditory Verbal Learning Test. By using linear regression models, CBF was negatively associated with memory function in ApoE ε4+ group, whereas positively in ApoE ε4− group by contrast. This study suggests that different CBF-memory relationships can be detected in cognitively normal ApoE ε4 carriers compared to ApoE ε4 non-carriers. Associations between hyperperfusion and worse memory performance in ApoE ε4 carriers may reflect vascular and/or cellular dysfunction.

Introduction The US Food and Drug Administration (FDA) has undertaken efforts to promote representation of women in clinical trials. The objectives of this research are to assess women's participation in clinical trials from a global perspective and to analyze the demographic characteristics of clinical trial participants. Methods FDA's Center for Drug Evaluation and Research-Professional Affairs and Stakeholder Engagement (CDER/PASE) and Office of Women's Health (OWH) collaborated to evaluate demographic data (race, ethnicity, gender, and age) of pivotal trials of New Molecular Entities (NMEs) approved in 2015–2016 by geographic location. One hundred fifty-four pivotal clinical trials supporting 66 NMEs were identified, and the research team analyzed demographic characteristics of 131,749 participants from 70 countries. Results U.S. sites contributed 31% of the 131,749 study participants. On the country level, the United States contributed the largest number of participants and other individual countries contributed 5% or less of the total trial population. Overall, 43% (n = 56,272) of the 131,747 clinical trial participants were women. Of the 40,833 U.S. participants, 49% were women as compared to 40% of the 90,914 non-U.S. participants. Similar levels of participation were seen after the exclusion of sex-specific drug indications, and by therapeutic area for U.S. and non-U.S. sites. Conclusions Clinical trials are becoming increasingly multi-national, and the increasing representation of women across countries is promising. FDA approval processes ensure that global data used in the drug approval process meets regulatory standards and that data can be generalized to the U.S. population.

The Warburg effect in tumor cells involves the uptake of high levels of glucose, enhanced glycolysis, and the metabolism of pyruvate to lactic acid rather than oxidative phos-phorylation to generate energy under aerobic conditions. This effect is closely related to the occurrence, invasion, metastasis, drug resistance, and poor prognosis of gastric cancer (GC). Current research has further demonstrated that the Warburg effect in GC cells is not only mediated by the glycolysis pathway, but also includes roles for mitochondria, noncoding RNAs, and other proteins that do not directly regulate metabolism. As a result, changes in the glycolysis pathway not only lead to abnormal glucose metabolism, but they also affect mitochondrial functions, cellular processes such as apoptosis and cell cycle regulation, and the metabolism of lipids and amino acids. In this review, we discuss metabolic reprogramming in GC based on glycolysis, a possible link between glucose metabolism, lipid metabolism, and amino acid metabolism, and we clarify the role of mitochondria. We also examine recent studies of metabolic inhibitors in GC.

A time-resolved operando X-ray absorption spectroscopy experiment was successfully designed to explore the sulfur reaction dynamics in lithium-sulfur (Li-S) batteries. It presents direct real-time experimental evidence for the distinct sulfur dynamics at different discharge rates, deepening the understanding of reaction mechanisms in Li-S batteries.

Background Mild cognitive impairment (MCI) is a transition state between asymptomatic stage and dementia. Amnestic MCI (aMCI) patients who mainly present with memory deficits are highly likely to progress to Alzheimer’s disease (AD). At present, no broadly effective drug therapy is available to prevent the progression from memory deficit to dementia. Cognitive control training, which has transfer effects on multiple cognitive capacities including memory function in healthy old adults, has not yet been applied to aMCI. Methods/Design In this single-center, randomized double-blind placebo-controlled study, 70 aMCI patients will be recruited and randomly assigned to the training and control groups. The intervention is an Internet-based cognitive control training program performed for 30 min daily, five days per week, for 12 consecutive weeks. Neuropsychological assessment and structural and functional magnetic resonance imaging (MRI) will be performed at baseline and outcome. Primary outcomes are changes of episodic memory retrieval function. Secondary outcome measures are neuroplasticity changes measured by functional and structural MRI. Discussion In this study, an Internet-based cognitive control training program is adopted to investigate whether cognitive control training can enhance the retrieval of episodic memory in aMCI patients. The combination of multi-modal MRI and neuropsychological tests could have a good sensitivity in evaluating the effects of cognitive control training and could also uncover the underlying neural underpinning. Trial registration ClinicalTrials.gov, NCT03133052. Registered on 21 April 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-3143-0) contains supplementary material, which is available to authorized users.