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Summer rainfall is an important contributor to water budgets in western North American deserts, where intense rainfall sustains ecosystems while also causing flash floods and damaging erosion. A better understanding of Grand Canyon palaeoclimate and the long-term history of the summer monsoon from summer-sensitive palaeoclimate records will improve our ability to project future hydroclimatic changes under warmer conditions. Here we show multi-proxy evidence for an intensification of the Early Holocene (11,700–8,200 years ago) hydrological cycle linked to a stronger and expanded summer North American Monsoon from calcite oxygen and uranium isotopes in a uranium-series precisely dated stalagmite from a Grand Canyon cave. Our results suggest that subsurface infiltration was greater in the Early Holocene than today at Grand Canyon. A data–model comparison with an isotope-enabled climate model suggests that enhanced infiltration was due to an Early Holocene monsoon intensification associated with rising atmospheric temperature. Projections of a future increase in precipitation intensity or more frequent and expanded North American monsoon rain events may paradoxically result in increased subsurface infiltration at Grand Canyon and other high-altitude plateaus, even within the context of western North American aridification in a hotter climate.

Drug–Drug interaction (DDI) prediction is essential in pharmaceutical research and clinical application. Existing computational methods mainly extract data from multiple resources and treat it as binary classification. However, this cannot unambiguously tell the boundary between positive and negative samples owing to the incompleteness and uncertainty of derived data. A granular computing method called three-way decision is proved to be effective in making uncertain decision, but it relies on supplementary information to make delay decision. Recently, biomedical knowledge graph has been regarded as an important source to obtain abundant supplementary information about drugs. This paper proposes a three-way decision-based method called 3WDDI, in combination with knowledge graph embedding as supplementary features to enhance DDI prediction. The drug pairs are divided into positive, negative and boundary regions by Convolutional Neural Network (CNN) according to drug chemical structure feature. Further, delay decision is made for objects in the boundary region by integrating knowledge graph embedding feature to promote the accuracy of decision-making. The empirical results show that 3WDDI yields up to 0.8922, 0.9614, 0.9582, 0.8930 for Accuracy, AUPR, AUC and F1-score, respectively, and outperforms several baseline models.

•Lane changing issue for bus exiting is explored with the incomplete information game.•The new model has high accuracy for predicting drivers’ behaviors and strategies.•The driving styles have significant impacts on drivers’ behavioral decision makings.•Various rates for driving styles make drivers’ strategic choices different.•The passenger car and bus drivers both have obvious strategic tendencies.

The removal of endocarp, which has great effects on protein properties, is indispensable during developing pecan kernel protein. The effect of different removal methods, namely alkaline peeling (AP), enzymatic peeling (EP), and mechanical peeling (MP), on the physicochemical, structural, and functional properties of pecan kernel protein was investigated. The obtained proteins by three peeling methods had similar molecular weight (14–66 kDa) and amino acids (18 in all) composition. The average particle size of obtained protein samples in series of EP, AP, MP were 0.89, 0.74, and 0.80 μm respectively, the protein contents were 70.34%, 74.72%, and 73.12% respectively, and the L* values (representative of lightness) were 49.21, 65.18, 59.78 respectively. The protein structure of AP and EP samples was greatly changed, behaving as the reduction of the α-helix and β-sheet in secondary structure and the red-shift of the maximum wavelength in the endogenous fluorescence, while the MP was beneficial to maintain the structure. The AP sample presented better solubility, oil absorption capacity, and emulsification; The MP sample showed the best foaming property. These results confirmed that different peeling methods could greatly influence the physicochemical, structural, and functional properties of pecan protein. This research would provide a useful guideline for the production and applications of pecan protein.

Proanthocyanidins are the most abundant phenols with high biological activities in chokeberry. The effects of ultrasonic-microwave assisted extraction (UMAE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and traditional solvent extraction (TSE) on the yield, purity, antioxidant and antibacterial activities of crude chokeberry proanthocyanidins (CCP) were evaluated in this study. Results showed that UMAE exhibited the maximum yield (31.52 ± 0.8 mg/g fresh weight) and purity (16.34 ± 0.59%). The method of UMAE not only significantly aggravated the destruction of cells but also accelerated the release rate of proanthocyanidins from cells. Moreover, the CCP extracted by UMAE had the greatest antioxidant and antibacterial activities in the four methods. The IC50of ABTS·+, DPPH, superoxide anion scavenging abilities were 102.52 ± 0.84, 22.03 ± 0.55, 214.93 ± 1.33 μg/mL, respectively, and the MBC and MIC of Staphylococcus aureus, Streptococcus mutans, Pseudomonas aeruginosa, and Escherichia coliwere 5, 5, 10, 5 mg/mL, and 1.25, 1.25, 2.5, 1.25 mg/mL, respectively. According to the analysis of high performance liquid chromatography-mass spectrometry (HPLC-MS), the main proanthocyanidins in purified chokeberry proanthocyanidins (PCP) were B-type procyanidins, including procyanidin B2, B5 dimer, and procyanidin C1 trimer, with the degree of polymerization (DP) of 14. Therefore, UMAE is an effective extraction to obtain chokeberry proanthocyanidins, which is a potential antioxidant or antibacterial agent.

Phenolic compounds are bioactive metabolites in plants. The phenolic compounds in husks and seeds of areca nut (AN) were extracted via conventional liquid–solid extraction and ultrasonic-microwave synergistic extraction (UMSE), and abbreviated as CHP, CSP, UHP, and USP, respectively. The extraction conditions of UHP and USP were optimized (solid/solvent ratio of 1:40 and 1:50, the ethanol concentration of 50%, microwave power of 600 and 300 W, and extraction time of 360 and 540 s, respectively). The total phenolic content (TPC) yield, purity, antioxidant activity, and antibacterial activity of four samples were determined and compared. The USP has excellent TPC yield (270.92 mg GAE/g DW), purity (42.84%), antioxidant activities (the IC50of DPPH, ABTS, and Superoxide anion were 55.40, 81.87, 138.65 µg/mL, respectively), and antibacterial activities (the MIC of Streptococcus mutans, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosawere 2.50, 5.00, 15.00, and 25.00 mg/mL, respectively). The HPLC–MS showed that USP rich in phenolic compounds, especially proanthocyanidin polymers. Moreover, we speculated that the antibacterial and antioxidant activity might be due to proanthocyanidin polymers. Therefore, UMSE is an efficient method to obtain phenolic compounds of AN, and USP is a potential antibacterial agent and antioxidant.

Based on its excellent visible light absorption and photoelectric response capabilities, SbSI has attracted significant research attention for a wide range of applications. Despite the fact that interesting physical properties can be induced from the sophisticated band structures of SbSI, that is, either with direct or indirect band gaps, its nonlinear optical (NLO) properties are not yet fully explored. In the present work, the NLO response of SbSI nanorods is investigated by the combination of open-aperture (OA) Z-scan, pump–probe, and spatial self-phase modulation (SSPM). It is found that the synthesized SbSI nanorods possess a relatively large nonlinear absorption coefficient and a small saturable optical intensity at a wavelength of 400 nm, compared to those of other materials. More importantly, the OA Z-scan experiments suggest that the direct band gap of SbSI plays a dominant role on the NLO effects, which is further verified by the SSPM experiments. The present work suggests that the SbSI nanorods may have great potentials for optical switches and saturable absorbers.

Pancreatic cancer is one of the world’s leading causes of cancer-related death. Activation of STAT3 has been reported as a major contributor in pancreatic cancer tumorigenesis and chemoresistance. However, treatment of advanced pancreatic cancer patients with STAT3 inhibitors often meets drug resistance and heterogeneous response. We found that EGFR activation is a main cause for resistance to STAT3 inhibitors in pancreatic cancer cells, regardless of KRAS mutation status. Mechanistically, inhibition of STAT3 promotes STAT1- and STAT4-mediated TGF-α expression, leading to activation of the EGFR pathway. Combined treatment of pancreatic cancer cells with EGFR and STAT3 inhibitors persistently blocks EGFR and STAT3 signaling, and exerts synergistic antitumor activity both in vitro and in vivo, with or without KRAS mutation. Our results indicate that reciprocal cross-talk between STAT3 and EGFR pathways is a key molecular mechanism leading to resistance in pancreatic cancer cells. Furthermore, the study shows that combined inhibition of both EGFR and STAT3 might overcome drug resistance encountered during treatment with single agent alone. This study suggests an improved therapeutic strategy, through combined treatment with STAT3 and EGFR inhibitors, for pancreatic cancer patients.

The Asian summer monsoon (ASM) is teleconnected to the El Niño Southern Oscillation (ENSO), but this relationship is nonstationary and has shifted significantly in recent decades. Characterizing the drivers of such shifts is crucial for improving ASM prediction and extreme event preparedness. Paleoclimate records indicate a link between ASM strength and solar activity on multidecadal‐to‐centennial timescales, but 20th‐century data are too short to test mechanisms. Here we evaluate how solar irradiance influences the ASM‐ENSO relationship using last‐millennium paleoclimate data assimilation reconstructions and model simulations. We find that high solar irradiance weakens the ENSO‐East Asian summer monsoon (EASM) correlation, but strengthens the ENSO‐South Asian summer monsoon (SASM) correlation. Solar irradiance likely influences the strength of the ENSO‐EASM and ENSO‐SASM teleconnections via changes in the Western Pacific Subtropical High and the amplitude of ENSO events, respectively. We suggest a need for considering solar activity in decadal ASM rainfall predictions under global warming scenarios. The Asian summer monsoon (ASM) affects over one‐third of the world's population, with significant environmental and economic impacts. The ASM is influenced by the El Niño Southern Oscillation (ENSO), but the ENSO‐ASM relationship has undergone notable changes in recent decades. Understanding the drivers of these changes is essential for improving ASM prediction. Previous studies based on individual records of past climate change have indicated a connection between ASM strength and solar activity over long periods, but 20th‐century instrumental data are too short to fully understand this link. In this study, we investigated the influence of solar activity on the ENSO‐ASM relationship using past climate records and model simulations spanning the last 1,000 years. We find that high solar irradiance weakens the ENSO‐East Asian summer monsoon relationship while strengthening the ENSO‐South Asian summer monsoon relationship. Solar irradiance might impact the strength of the ENSO‐ASM relationship by causing changes in the air pressure systems over the western Pacific and the intensity of ENSO events. These findings imply that solar activity, combined with global warming, will affect rainfall in the ASM region. It is crucial to consider solar activity in the long‐term prediction of ASM rainfall as the climate continues to warm. Solar irradiance altered the El Niño‐Southern Oscillation (ENSO) and Asian summer monsoon relationship during the past millenniumHigh solar irradiance weakens (strengthens) the ENSO‐East Asian (South Asian) summer monsoon correlationSolar irradiance modulates the ENSO‐ASM teleconnection through changes in the Western Pacific Subtropical High and ENSO event amplitude Solar irradiance altered the El Niño‐Southern Oscillation (ENSO) and Asian summer monsoon relationship during the past millennium High solar irradiance weakens (strengthens) the ENSO‐East Asian (South Asian) summer monsoon correlation Solar irradiance modulates the ENSO‐ASM teleconnection through changes in the Western Pacific Subtropical High and ENSO event amplitude

The aim of this study was to summarize the evidence of health literacy and health outcomes in hypertensive patients.

The purpose of this study is to assess the awareness on cardiac rehabilitation (CR) in patients with coronary heart disease (CHD).

(−)-Epicatechin gallate (ECG), as a natural α-amylase inhibitor, has received extensive attention. However, poor liposolubility of ECG limits its application. In this study, lipophilic derivatives of ECG (1A-ECG, 2A-ECG, 1B-ECG, and 2B-ECG) were synthesized by Lipozyme TLIM (Thennomyces lanuginosus) and their mechanism on delaying starch digestion was investigated. The results showed that the conversion of ECG exceeded 70% under optimal conditions. Interestingly, compared with ECG, the inhibitory activities of ECG derivatives on α-amylase decreased, while the inhibitory activity of 1A-ECG on α-amylase increased. Though the main force between ECG and 1A-ECG with α-amylase was induced by hydrogen bond, hydrophobic interaction was the main force between other derivatives with α-amylase. However, the addition of four ECG derivatives can effectively reduce the proportion of rapidly digestible starch, and delay the digestion of starch. This study may expand the applications of ECG and provide a theoretical basis for 1A-ECG to delay the digestion of starch.

Supplemental Digital Content is available in the text.Fibroblast growth factor 2 (FGF2) is closely involved in a variety of tumors, including gastric cancer (GC). FGF2 inhibitors exert good antitumor activity, but no FGF2 inhibitor has been employed for clinical use. To obtain a low-toxicity, stable peptidomimetic (called P29) target to FGF2, the affinity between P29 and FGF2 was detected by surface plasmon resonance. The stability of P29 was measured by high performance liquid chromatography. MTT assay and transwell assay were used to access the proliferative and invasive ability of GC cells, respectively. Western blot assay and flow cytometric analysis were applied to study the mechanism of P29. P29 possessed high affinity with FGF2 and a longer half-life in vitro. P29 suppressed the FGF2-induced proliferation of GC cells. It also inhibited the phosphorylation of FRS2, ERK1/2, and AKT triggered by FGF2 in GC. In addition, P29 blocked GC cell transformation from the G1/G0 phase to the S phase and weakened the invasive capability of GC cells. In this paper, we present a novel FGF2 inhibitor that could exert improved anticancer effect in GC in vitro.

Sedimentary and diagenetic processes control the distribution of clay minerals in sedimentary basins, although these processes have seldom been studied continuously in continental sedimentary basins. The Songliao Basin, northeast China, is a large continental, petroleum-bearing basin, and provides a unique study site to understand the sedimentary and diagenetic processes that influence clay assemblages. In this paper, the clay mineralogy of a 2500 m-thick Late Cretaceous (late Turonian to Maastrichtian) terrestrial sedimentary succession (SK-1s and SK-1n cores), retrieved by the International Continental Scientific Drilling Program in the Songliao Basin, was examined. The objective was to determine the diagenetic and paleoenvironmental variations that controlled the formation of clay mineral assemblages, and to determine the thermal and paleoenvironmental evolution of the basin. The results from both cores show that illite is ubiquitous through the succession, smectite is frequently encountered in the upper strata, and ordered mixed-layer illite-smectite (I-S), chlorite, and kaolinite are abundant in the lower strata. Burial diagenesis is the primary control on the observed decrease of smectite and increasing illite, I-S, and chlorite with depth. Observations of clay-mineral diagenesis are used to reconstruct the paleotemperatures and maximum burial depths to which the sediments were subjected. The lowermost sediments could have reached a maximum burial of ~1000 m deeper than today and temperatures ~50°C higher than today in the latest Cretaceous. The transition of smectite to I-S in the SK-1 cores and the inferred paleotemperatures provide new constraints for basin modeling of oil maturation at elevated temperatures in the Songliao Basin. Authigenic kaolinite and smectite are enriched in sandstones with respect to the coeval mudstones from the SK-1n core, as a result of early diagenesis with the participation of primary aluminosilicates and pore fluids. In the upper part of both SK-1 cores, variations in smectite and illite were controlled primarily by paleoenvironmental changes. Increases in smectite and decreases in illite from the late Campanian to Maastrichtian are interpreted as resulting from increasing humidity, a conclusion consistent with previous paleoenvironmental interpretations.

Variations of the sea surface temperature (SST) and primary productivity in the northeast Pacific have far‐reaching implications. In addition to influencing the regional and global temperature and hydroclimate, these conditions also control marine ecosystems and their services, which subsequently impact regional economies. Yet, our understanding of the variability and controls of northeast Pacific SST and productivity on timescales exceeding observational records remains limited. Here, we use marine sediment records from seven locations, spanning 25.2°N–59.6°N, in the northeast Pacific to characterize the millennial‐scale variability of SST and productivity from 9,000 to 1,000 years BP. We explore the dynamics of their spatiotemporal evolution and compare these data with transient climate model outputs to identify potential drivers. Through a heat budget analysis and optimal fingerprinting analysis, we characterize the spatial pattern of forcings. We find that SST varied spatially in the northeast Pacific, with higher latitudes exhibiting greater magnitude changes than lower latitudes, which differs from previous work suggesting regional synchronicity and coherence during the Holocene. Our analysis did not find evidence for coherent variability of primary producer community nor carbon export, highlighting the difficulty of identifying the complex interactions between environmental conditions, producers, and carbon export. Model‐proxy disagreement demonstrates the need for higher resolution model frameworks, but shows nonetheless that observed variability in the proxy records can be explained by a combination of greenhouse gas and orbital forcing. We suggest that the complex SST variations and marine ecosystem responses to forced changes are important factors that can drive disagreements in model projections. Holocene temperature and productivity changes in the northeast Pacific are spatially variableTemperature change in proxies is amplified poleward, and productivity is decoupled from temperatureComparison with TraCE21ka model simulations suggests that multiple forcings and dynamical processes are responsible for these changes Holocene temperature and productivity changes in the northeast Pacific are spatially variable Temperature change in proxies is amplified poleward, and productivity is decoupled from temperature Comparison with TraCE21ka model simulations suggests that multiple forcings and dynamical processes are responsible for these changes

Previous studies showed that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. In the current study, we aimed to investigate whether the compound L6123, a novel non-ATP-competitive FGFR1 inhibitor, could show better antitumor activity than the leading compound, nordihydroguaiaretic acid (NDGA), in FGFR1-overexpressing gastric cancer cells. Using an MTT assay, we investigated the inhibitory effect of L6123 on the viability of three gastric cancer cells (MGC-803, SGC-7901, and BGC-823) overexpressing FGFR1, wild-type mouse embryonic fibroblast (MEF-WT), and MEF expressing FGFR1, FGFR2, and FRS2 gene knockout (MEF-FGFR1-FGFR2-FRS2-ko). We studied the antitumor mechanism of L6123 against the gastric cancer cell line SGC-7901 by western blot analysis. The antitumor effects of L6123 on the gastric cancer cell line SGC-7901 were detected by flow cytometry, Hoechst staining, western blot analysis, and Transwell invasion assay. L6123 had lower IC50in all three gastric cancer cells than NDGA and showed better inhibitory activity against MEF-WTcells than against MEF-FGFR1-FGFR2-FRS2-kocells. In the SGC-7901 gastric cell, L6123 inhibited the FGF2-induced phosphorylation of FGFR1FRS2ERK12 in a dose-dependent manner, induced the activation of the apoptosis-related proteins, cleaved-PARP and cleaved-caspase-3, decreased the expression of pro-caspase-3 and Bcl-2, and induced tumor cell apoptosis. L6123 also dose-dependently reduced cell invasion ability, and showed better activity than NDGA at the same concentration. A novel non-ATP-competitive inhibitor L6123 showed excellent antigastric cancer activity by inhibiting the FGFR1 signaling pathway. Thus, we discovered a potential agent for the treatment of FGFR1-overexpressing gastric cancer.

The benefits of physical activity are well known, but little is known about the views of elderly Chinese people regarding physical activity, and what factors affect this. This qualitative study aims to explore the experiences and perceptions of the elderly community regarding physical activity and to gain a better understanding of these. A qualitative study of 12 elderly Chinese people was undertaken using the Colaizzi phenomenological approach and using semi-structured interviews to gather data. Three key themes emerged relating to current physical activity status, beliefs about physical activity and factors influencing physical activity.This study provides new knowledge about the elderly community's experiences and perceptions of physical activity. By understanding these, we may show that promoting active lifestyles and building physical activity into and around day-to-day activities are important strategies in increasing levels of activity. Furthermore, the need for appropriate activity facilities, available space, peer motivation and general social support could promote activity beliefs and subsequent adherence among the elderly community.

A simple, accurate and inexpensive high performance liquid chromatography with electrochemical detection (HPLC-ECD) method for the simultaneous separation and determination of the three synthetic estrogens including diethylstilbestrol, dienestrol, and hexestrol in milk was established. For the sample treatment procedure, acetonitrile was added to the milk sample, the mixture was vortex mixed, centrifuged, concentrated by evaporation and determined by HPLC-ECD. The detection and quantification limits of the three estrogens obtained with ECD were lower than those obtained by diode array detection (DAD). Calibration curves, limit of detection and recoveries of diethylstilbestrol, dienestrol, and hexestrol with ECD ranged from 0.04 to 24 μg ml−1, 4.7 × 10−3to 7.1 × 10−3μg ml−1, and 83 to 103%, respectively. Meanwhile, the effect of thermal treatment on the stability of the estrogens was investigated, and the results showed that these compounds initially decreased by 26% for diethylstilbestrol, 32% for dienestrol, and 41% for hexestrol after five minutes of heat treatment, then remained stable with increasing duration of heat treatment. The method was applied to the determination of the three synthetic estrogens in authentic milk samples.

The article offers information on the technological innovations in the evolution of synthetic leather, and the development of superfine fiber synthetic leather and the necessary high-efficient, high-productive needle punching equipment for its production.

The discovery that mutations in the EGFRgene are detected in up to 50% of lung adenocarcinoma patients, along with the development of highly efficacious epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has revolutionized the treatment of this frequently occurring lung malignancy. Indeed, the clinical success of these TKIs constitutes a critical milestone in targeted cancer therapy. Three generations of EGFR-TKIs are currently approved for the treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). The first-generation TKIs include erlotinib, gefitinib, lapatinib, and icotinib; the second-generation ErbB family blockers include afatinib, neratinib, and dacomitinib; whereas osimertinib, approved by the FDA on 2015, is a third-generation TKI targeting EGFR harboring specific mutations. Compared with the first- and second-generation TKIs, third-generation EGFR inhibitors display a significant advantage in terms of patient survival. For example, the median overall survival in NSCLC patients receiving osimertinib reached 38.6 months. Unfortunately, however, like other targeted therapies, new EGFR mutations, as well as additional drug-resistance mechanisms emerge rapidly after treatment, posing formidable obstacles to cancer therapeutics aimed at surmounting this chemoresistance. In this review, we summarize the molecular mechanisms underlying resistance to third-generation EGFR inhibitors and the ongoing efforts to address and overcome this chemoresistance. We also discuss the current status of fourth-generation EGFR inhibitors, which are of great value in overcoming resistance to EGFR inhibitors that appear to have greater therapeutic benefits in the clinic.

Southern California's Mediterranean‐type hydroclimate is highly variable on interannual time scales due to teleconnected climate forcings such as the El Niño–Southern Oscillation (ENSO). Here we present subannually resolved scanning X‐ray fluorescence Ti counts from deep‐sea cores in Santa Barbara Basin, California, recording 2,000 years of hydroclimate variability. The reconstructed Southern California precipitation record contains interannual variability in the 2‐ to 7‐year band that could be driven by changes in tropical Pacific ENSO variability and/or the strength of the ENSO teleconnection modulated by extratropical pressure systems. Observed interannual precipitation variance increased and was associated with longer periodicities (5–7 years) when the Intertropical Convergence Zone migrated southward (1370–1540 CE) and the Aleutian Low strengthened creating a robust ENSO teleconnection. Weak interannual precipitation variance with shorter periodicity (2–3 years) was observed when the Intertropical Convergence Zone shifted northward (700–900 CE) and/or the Aleutian Low was weak (1540–1680 CE). El Niños occur when the rising branch of atmospheric circulation in the tropical Pacific shifts eastward, driving changes in air temperature and rainfall around the globe. Rainfall in Southern California often increases during El Niño events causing rivers to carry extra sediment to the ocean. We reconstructed Southern California rainfall for every year of the last 2,000 years using the elemental signature of river sediment deposited in Santa Barbara Basin. We found that after ~1350 CE, when the Aleutian Low was strong, interannual rainfall in Southern California varied more and with longer cycles (5 to 7 years). During this time, the region of rising air at the equator was further south and storms over the North Pacific Ocean were stronger and occurred further east. Both of these changes in atmospheric circulation increased the Southern California rainfall response to El Niño events in the tropical Pacific Ocean. The interannual (2‐ to 7‐year band) precipitation in Southern California is closely related to ENSO variance originating from the tropical PacificExtratropical pressure systems modulate the interannual precipitation changes in Southern California by influencing the ENSO teleconnectionThe magnitude and frequency of interannual precipitation variance in Southern California changes throughout the past 2,000 years