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Abstract The RON receptor tyrosine kinase is critical in the pathogenesis of various cancer types, however, its role in bladder cancer invasive growth is still largely unknown. Here, we found that over 90% of bladder cancer samples exhibit elevated levels of RON expression, with significantly higher expression levels observed in invasive bladder cancer compared to non-invasive bladder cancer. In vitro, RON activation resulted in increased bladder cancer cell migration and invasiveness. Results from mRNA sequencing and transcriptome analysis further demonstrated that MMP12, a downstream molecule of RON, is functionally involved in regulating RON-mediated bladder cancer cell migration and invasiveness. The underlying mechanism appeared to be the RON-mediated inhibition of HIF-2α ubiquitination, which is channeled through the activation of the JNK signaling pathway. Consequently, the activated JNK pathway increased MMP12 expression, ultimately driving bladder cancer cell migration and invasion. As evident in bioinformatics and dual-luciferase reporter assays, the RON mRNA at its 3′-untranslated regions specifically interacted with hsa-miR-659-3p. The binding of hsa-miR-659-3p downregulated the RON gene expression, attenuating the receptor-mediated tumorigenic activities of bladder cancer cells in vitro and in vivo. In conclusion, aberrant RON expression in bladder cancer cells and MMP12 and HIF-2α activities form a functional axis that causes increased bladder cancer cell migration and invasion. The fact that hsa-miR-659-3p downregulates RON expression indicates its critical role in attenuating RON-mediated tumorigenic effect on bladder cancer cells. These findings highlight the importance of RON targeting as a therapeutic means for potential bladder cancer therapy.

Abstract Purpose This study aims to investigate whether adding fosaprepitant to palonosetron and dexamethasone is effective in preventing postoperative nausea and vomiting (PONV) in high-risk patients undergoing gynecologic surgery. Methods Eligible patients undergoing gynecological surgery were randomized into two groups (1:1). One group received fosaprepitant (150 mg) and the other (control) received a placebo infusion. Both groups received a single dose of palonosetron (0.25 mg) and dexamethasone (5 mg) together with therapeutic medication. The primary endpoint was the absence of vomiting and no use of rescue antiemetics during the first 24 h after surgery; complete response rate (CRR). Results CRR was significantly higher in the fosaprepitant group compared to the control group 0–24 h after surgery (P = 0.037; relative risk [RR], 1.116; 95% confidence interval [CI], 1.007 to 1.235). Moreover, CRR was also significantly higher during the 24–48 h (P = 0.004; RR, 1.148; 95% CI, 1.045 to 1.261) and 48–72 h (P = 0.039; RR, 1.083; 95% CI, 1.005 to 1.168) observation periods respectively. The complete control rate was higher in the fosaprepitant group than in the control group during the 0–24 h observation period (P = 0.012; RR, 1.367; 95% CI, 1.067 to 1.751). Nausea and rescue antiemetic use were comparable between the two groups. The severity of vomiting was significantly higher in the fosaprepitant group than in the control group on the second day (P = 0.016). Dynamic pain visual analog scale score was lower in the fosaprepitant group and quality of recovery-15 scores were significantly higher in the same group during 0–24 h observation period (P = 0.018 and 0.005, respectively). Conclusions The triple combination of fosaprepitant, palonosetron, and dexamethasone was superior in the prevention of PONV after gynecologic surgery in high-risk patients. We suggest that for high-risk patients, a triple combination therapy may be a better choice. Trial registration Registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=171741 ) with No. ChiCTR2200060890 on June 13, 2022. Principal investigator: Jingdun Xie.

Abstract Heat extremes pose pronounced threats to social-ecological systems and are projected to become more intense, frequent, and longer. However, the mechanisms driving heatwaves vary across heatwave types and are not yet fully understood. Here we decompose perturbations in the surface energy budget to categorize global heatwave-days into four distinct types: sunny–humid (38%), sunny-dry (26%), advective (18%), and adiabatic (18%). Notably, sunny-dry heatwave-days decrease net ecosystem carbon uptake by 0.09 gC m−2 day−1 over harvested areas, while advective heatwave-days increase the thermal stress index by 6.20 K in populated regions. In addition, from 2000 to 2020, sunny-dry heatwaves have shown the most widespread increase compared to 1979 to 1999, with 67% of terrestrial areas experiencing a doubling in their occurrence. Our findings highlight the importance of classifying heatwave-days based on their underlying mechanisms, as this can enhance our understanding of heatwaves and improve strategies for heat adaptation.

Abstract Lane line images have the essential attribute of large-scale variation and complex scene information, and the similarity between adjacent lane lines is high, which can easily cause classification errors. And remote lane lines are difficult to recognize due to visual angle changes in width. To address this issue, this paper proposes an effective lane detection framework, which is a hybrid feature fusion network that enhances multiple spatial features and distinguishes key features throughout the entire lane line segment. It enhances and fuses lane line features at multiscale to enhance the feature representation of lane line images, especially at the far end. Firstly, in order to enhance the correlation of multiscale lane features, a multi-head self attention is used to construct a multi-space attention enhancement module for feature enhancement in multispace. Secondly, a spatial separable convolutional branch is designed for the jumping layer structure connecting multiscale lane line features. While retaining feature information of different scales, important lane areas in multiscale feature information are emphasized through the allocation of spatial attention weights. Finally, considering that lane lines are elongated areas in the image, and the background information in the image is much more abundant than lane line information, the flexibility of traditional pooling operations in capturing widely existing anisotropic contexts in actual environments is limited. Therefore, before embedding feature output branches, strip pooling is introduced to refine the representation of lane line information and optimize model performance. The experimental results show that the accuracy on the TuSimple dataset reaches 96.84%, and the F1 score on the CULane dataset reaches 75.9%.

The Yellow River Basin (YRB) has experienced severe floods and continuous riverbed elevation throughout history. Global climate change has been suggested to be driving a worldwide increase in flooding risk. However, owing to insufficient evidence, the quantitative correlation between flooding and climate change remains ill-defined. We present a long time series of maximum flood discharge in the YRB dating back to 1843 compiled from historical documents and instrument measurements. Variations in yearly maximum flood discharge show distinct periods: a dramatic decreasing period from 1843 to 1950, and an oscillating gentle decreasing from 1950 to 2021, with the latter period also showing increasing more extreme floods. A Mann-Kendall test analysis suggests that the latter period can be further split into two distinct sub-periods: an oscillating gentle decreasing period from 1950 to 2000, and a clear recent increasing period from 2000 to 2021. We further predict that climate change will cause an ongoing remarkable increase in future flooding risk and an ∼44.4 billion US dollars loss of floods in the YRB in 2100.

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Abstract Cell bionic culture requires the construction of cell growth microenvironments. In this paper, mechanical force and electrical stimulations are applied to the cells cultured on the surface of the piezoelectric laminated micro-beam driven by an excitation voltage. Based on the extended dielectric theory, the electromechanical microenvironment regulating model of the current piezoelectric laminated micro-beam is established. The variational principle is used to obtain the governing equations and boundary conditions. The differential quadrature method and the iterative method are used to solve two boundary value problems for cantilever beams and simply supported beams. In two cases, the mechanical force and electrical stimulations applied to the cells are analyzed in detail and the microscale effect is investigated. This study is meaningful for improving the quality of cell culture and promoting the cross-integration of mechanics and biomedicine.

Abstract Compound droughts with low soil moisture (SM) and high vapor pressure deficit (VPD) pose significant threats to terrestrial carbon sink and agricultural production. However, the frequency and intensity of compound droughts and their adverse impacts on the carbon cycle remain highly uncertain. Here, we define and identify vegetation compound droughts (VCDs) when low SM and high VPD severely limit and adversely affect vegetation carbon uptake. We find frequent and severe VCDs and their considerable adverse impacts on carbon uptake in mid- and low-latitude regions, particularly in drylands. Risks of VCDs have been greatly underestimated as the widely adopted quantile-based approach identifies only 11% of VCDs and 26% of global GPP anomalies due to VCDs. The frequency and intensity of VCDs and their adverse impacts on carbon uptake are projected to increase further, irrespective of whether the CO2 fertilization effect on vegetation growth and photosynthesis is considered or not. These findings improve our understanding of current and future risks of VCDs and underline the importance of adaptation measures to cope with the adverse impacts of ever-increasing compound droughts.

Background: Human-treated dentin matrix (hTDM) has recently been studied as a natural extracellular matrix-based biomaterial for dentin pulp regeneration. However, porcine-treated dentin matrix (pTDM) is a potential alternative scaffold due to limited availability. However, there is a dearth of information regarding the protein composition and underlying molecular mechanisms of pTDM.Methods: hTDM and pTDM were fabricated using human and porcine teeth, respectively, and their morphological characteristics were examined using scanning electron microscopy. Stem cells derived from human exfoliated deciduous teeth (SHEDs) were isolated and characterized using flow cytometry and multilineage differentiation assays. SHEDs were cultured in three-dimensional environments with hTDM, pTDM, or biphasic hydroxyapatite/tricalcium phosphate. The expression of odontogenesis markers in SHEDs were assessed using real-time polymerase chain reaction and immunochemical staining. Subsequently, SHEDs/TDM and SHEDs/HA/TCP complexes were transplanted subcutaneously into nude mice. The protein composition of pTDM was analyzed using proteomics and compared to previously published data on hTDM.Results: pTDM and hTDM elicited comparable upregulation of odontogenesis-related genes and proteins in SHEDs. Furthermore, both demonstrated the capacity to stimulate root-related tissue regeneration in vivo. Proteomic analysis revealed the presence of 278 protein groups in pTDM, with collagens being the most abundant. Additionally, pTDM and hTDM shared 58 identical proteins, which may contribute to their similar abilities to induce odontogenesis. Conclusions: Both hTDM and pTDM exhibit comparable capabilities in inducing odontogenesis, potentially owing to their distinctive bioactive molecular networks.

Glaucomatous optic neuropathy(GON)is the difficulty of glaucoma treatment. In recent years, a variety of theories have been put forward about the pathogenesis of GON, but none of them can explain the principle of optic neuropathy caused by all types of glaucoma, which makes the disease difficult to treat in clinical treatment and is not conducive to early intervention. The latest research found that the transient receptor potential channel vanillic acid subfamily 4(TRPV4)in the retina plays an important role in various pathogenesis of GON. This article will review TRPV4 and its role in the occurrence and development of GON in order to find a common “connection point” for the multiple mechanism theories of GON, which will contribute to further understanding and clinical treatment of the disease.

Continuous electroencephalogram (cEEG) plays a crucial role in monitoring and postoperative evaluation of critical patients with extensive EEG abnormalities. Recently, the temporal variability of dynamic resting-state functional connectivity has emerged as a novel approach to understanding the pathophysiological mechanisms underlying diseases. However, little is known about the underlying temporal variability of functional connections in critical patients admitted to neurology intensive care unit (NICU). Furthermore, considering the emerging field of network physiology that emphasizes the integrated nature of human organisms, we hypothesize that this temporal variability in brain activity may be potentially linked to other physiological functions. Therefore, this study aimed to investigate network variability using fuzzy entropy in 24-hour dynamic resting-state networks of critical patients in NICU, with an emphasis on exploring spatial topology changes over time. Our findings revealed both atypical flexible and robust architectures in critical patients. Specifically, the former exhibited denser functional connectivity across the left frontal and left parietal lobes, while the latter showed predominantly short-range connections within anterior regions. These patterns of network variability deviating from normality may underlie the altered network integrity leading to loss of consciousness and cognitive impairment observed in these patients. Additionally, we explored changes in 24-hour network properties and found simultaneous decreases in brain efficiency, heart rate, and blood pressure between approximately 1 pm and 5 pm. Moreover, we observed a close relationship between temporal variability of resting-state network properties and other physiological indicators including heart rate as well as liver and kidney function. These findings suggest that the application of a temporal variability-based cEEG analysis method offers valuable insights into underlying pathophysiological mechanisms of critical patients in NICU, and may present novel avenues for their condition monitoring, intervention, and treatment.

China is a big producer and consumer of grains and oils. The development of high-yield grains is closely related to chemicals such as pesticides. With the improvement of people’s living standards, residents’ requirements for foods have changed from ‘security of output’ to ‘equal emphasis on quality and output’. In order to strengthen the management of grain quality and safety, it is urgent to comprehensively understand the status of pesticide pollution in grains and develop more efficient, convenient and rapid detection technologies. This paper briefly summarizes the characteristics of pesticides and pesticide residues, analyzes the current status of the use and residues of pesticides in raw materials for grains and oils in China, reviews the existing rapid detection methods and technologies for pesticide residues in grains, and compares the advantages and disadvantages of various rapid detection methods and products. This review is expected to provide a reference for quality inspection during grain purchase.

COVID-19 harms health and income generation activities. The pandemic caused poverty, and food crisis in the most vulnerable and underprivileged segments. Economic turbulence and massive poverty during epidemic period probably resulted in short-term food insecurity and low food consumption. Based on these concerns, the current study examined how COVID-19 has impacted Pakistan's cost of purchasing food. The study surveyed total 1067 Punjab and Sindh residents in Pakistan, from July to October 2021. A structural equation model was used to examine the interrelationship among food intake, food purchasing cost, and health effects. We investigated whether people experienced substantial effects from the loss of a source of income, work hours, debt burden, and food inflation on their food intake. These circumstances all negatively affected food intake, reducing food consumption. Besides COVID-19′s effects on direct income, 41% more people fall into poverty and 23% can't afford healthy food. People's socioeconomic circumstances affects poverty levels and affordable healthy food costs. The cost of purchasing food is significantly correlated with health outcomes. A significant and positive correlation between COVID-19 and income effects, and a negative correlation between food consumption and adverse income effects was explored. In addition, people increased their demand for food assistance during COVID-19 to mitigate negative income shocks. People who cannot afford minimal food costs should be offered food through mobile vehicles or delivery channels in the short term. Cash transfers or subsidies could also be provided to the needy during crisis time.

The Earth is experiencing unprecedented climate change. Vegetation phenology has already showed strong response to the global warming, which alters mass and energy fluxes on terrestrial ecosystems. With technology and method developments in remote sensing, computer science and citizen science, many recent phenology-related studies have been focused on macrophenology. In this perspective, we 1) reviewed the responses of vegetation phenology to climate change and its impacts on carbon cycling, and reported that the effect of shifted phenology on the terrestrial carbon fluxes is substantially different between spring and autumn; 2) elaborated how vegetation phenology affects ecohydrological processes at different scales, and further listed the key issues for each scale, i.e., focusing on seasonal effect, local feedbacks and regional vapor transport for individual, watershed and global respectively); 3) envisioned the potentials to improve current hydrological models by coupling vegetation phenology-related processes, in combining with machine learning, deep learning and scale transformation methods. We propose that comprehensive understanding of climate-macrophenology-hydrology interactions are essential and urgently needed for enhancing our understanding of the ecosystem response and its role in hydrological cycle under future climate change.

Immunosuppression as a result of severe infection impairs pathogen clearance and can increase susceptibility to secondary infection. Here, the authors dissect how T cell aging and the thymic involution that occurs during this process contribute to immunosuppression and find a key role for IL-33.

Microbial degradation has been confirmed as effective and environmentally friendly approach to remediate phthalates from the environment, and hydrolase is an effective element for contaminant degradation. In the present study, a novel dibutyl phthalate (DBP)-hydrolyzing carboxylesterase (named PS06828) from Pseudomonas sp. PS1 was heterogeneously expressed in E. coli, which was identified as a new member of the lipolytic family VI. Purified PS06828 could efficiently degrade DBP with a wide range of temperature (25–37 °C) and pH (6.5–9.0). Multi-spectroscopy methods combined with molecular docking were employed to study the interaction of PS06828 with DBP. Fluorescence and UV–visible absorption spectra revealed the simultaneous presence of static and dynamic component in the fluorescence quenching of PS06828 by DBP. Synchronous fluorescence and circular dichroism spectra showed inconspicuous alteration in micro-environmental polarity around amino acid residues but obvious increasing of α-helix and reducing of β-sheet and random coil in protein conformation. Based on the information on exact binding sites of DBP on PS06828 provided by molecular docking, the catalytic mechanism mediated by key residues (Ser113, Asp166, and His197) was proposed and subsequently confirmed by site-directed mutagenesis. The results can strengthen our mechanistic understanding of family VI esterase involved in hydrolysis of phthalic acid esters, and provide a solid foundation for further enzymatic modification.

The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A–D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L−1. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00–100.00% insecticidal activity even at a concentration as low as 0.625 mg·L−1. As determined by structure–activity relationship (SAR) analysis, compounds with R1 = CH3 and R2 = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L−1, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds.

Compound hot-dry (CHD) and compound hot-wet (CHW) extremes have both intensified under global warming, posing exacerbated socio-economic threats compared to univariate extremes. This study presents a comprehensive assessment and comparison of the historical changes and driving factors behind CHD and CHW using observational data and climate model simulations. Findings indicate a notable surge in CHD and CHW occurrences, with CHW experiencing a higher increasing rate. Our investigation further reveals that anthropogenic climate change predominantly drives the increase in both types of compound extremes, especially for CHW. In contrast, land-atmosphere feedbacks have a limited impact on CHW at a global scale, but substantially contributes to the rise in CHD by reinforcing the negative precipitation-temperature coupling. This influence even surpasses that of anthropogenic climate change in specific regions. Understanding these variations and underlying causes is crucial for improving prediction accuracy and mitigating the impacts of compound extremes.

Here, the authors find increased dry–season and decreased wet–season water availability over subtropical regions and the Amazon. This is caused by seasonally varying soil moisture–atmosphere feedbacks under global warming.

Changes in vegetation responses to precipitation may be hydroclimate dependent. Here the authors reveal contrasting trends of vegetation sensitivity to precipitation in drylands vs. wetter ecosystems over the last 4 decades and identify increased CO2 as a major contributing factor.

Magnetic-fluorescent microbeads have been widely used in the multiplex detection of biological molecules. The traditional method relies on flow cytometry to decode and analyze the microbeads. Alternative strategies that employ immobilized microbeads on a plane and involve fluorescence imaging to analyze the microbeads have been proposed. Among these strategies, an integrated chip that controls magnetic field contribution using nickel powder pillars and captured microbeads has attracted great attention. Despite its unique advantages such as low manufacturing costs, reusability and high capture efficiency, existing research had been limited by the inability to precisely capture a single microbead, and the overlapping of microbeads has made multiplex immunoassays based on this strategy impossible. In this work, low-density microbeads were prepared in a microfluidic chip using IBOMA as the main monomer. The low density of the microbeads made the preparation of an aqueous suspension easier. An integration of nickel patterns, magnets and channels was carried out and demonstrated the capacity of capturing single microbeads precisely. Fluorescence coding further empowered this method with the ability of multiplex immunoassay, which was verified using three types of IgG, and a calibration curve for the detection of anti-human IgG was established using a sandwich immunoassay. These results show the promising potential of this strategy for biomedical detection. [ABSTRACT FROM AUTHOR]