Highly Stable 72-Nuclearity Nanocages for Efficient Synthesis of Aryl Nitriles via Ni/Cu Synergistic Catalysis.

Seeking noble-metal-free catalysts for efficient synthesis of aryl nitriles under mild conditions poses a significant challenge due to the use of hypertoxic cyanides or high-pressure/temperature NH3/O2 in conventional synthesis processes. Herein, we developed a novel framework 1 assembled by [Ni72] nanocages with excellent solvents/pH stability. To investigate the structure-activity relationship of catalytic performance, several isostructural MOFs with different molar ratios of Ni/Cu by doping Cu2+ into framework 1 (Ni0.59Cu0.41 (2), Ni0.81Cu0.19 (3), Ni0.88Cu0.12 (4), and Ni0.92Cu0.08 (5)) were prepared. Catalytic studies revealed that catalyst 3 exhibited remarkable performance in the synthesis of aryl nitriles, utilizing a formamide alternative to hypertoxic NaCN/KCN. Notably, catalyst 3 achieved an excellent TOF value of 9.8 h-1. Furthermore, catalyst 3 demonstrated its applicability in a gram-scale experiment and maintained its catalytic performance even after six recycling cycles, owing to its high stability resulting from significant electrostatic and orbital interactions between the Ni center and ligands as well as a large SOMO-LUMO energy gap supported by DFT calculations. Control experiments and DFT calculations further revealed that the excellent catalytic performance of catalyst 3 originated from the synergistic effect of Ni/Cu. Importantly, this work not only provides a highly feasible method to construct highly stable MOFs containing multinuclear nanocages with exceptional catalytic performance but also represents the first example of a heterogeneous catalyst for the synthesis of aryl nitriles using formamide as the cyanide source.

Soil phosphorus availability alters the correlations between root phosphorus-uptake rates and net photosynthesis of dominant C3 and C4 species in a typical temperate grassland of Northern China.

Phosphorus (P) fertilization can alleviate a soil P deficiency in grassland ecosystems. Understanding plant functional traits that enhance P uptake can improve grassland management. We measured impacts of P addition on soil chemical and microbial properties, net photosynthetic rate (Pn ) and nonstructural carbohydrate concentrations ([NSC]), and root P-uptake rate (PUR), morphology, anatomy, and exudation of two dominant grass species: Leymus chinensis (C3 ) and Cleistogenes squarrosa (C4 ). For L. chinensis, PUR and Pn showed a nonlinear correlation. Growing more adventitious roots compensated for the decrease in P transport per unit root length, so that it maintained a high PUR. For C. squarrosa, PUR and Pn presented a linear correlation. Increased Pn was associated with modifications in root morphology, which further enhanced its PUR and a greater surplus of photosynthate and significantly stimulated root exudation (proxied by leaf [Mn]), which had a greater impact on rhizosheath micro-environment and microbial PLFAs. Our results present correlations between the PUR and the Pn of L. chinensis and C. squarrosa and reveal that NSC appeared to drive the modifications of root morphology and exudation; they provide more objective basis for more efficient P-input in grasslands to address the urgent problem of P deficiency.

EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation.

BACKGROUND: The echinoderm microtubule-associated protein-like-4 anaplastic lymphoma kinase (EML4-ALK) fusion gene was identified in a subset of non-small cell lung cancer (NSCLC) patients. They responded positively to ALK inhibitors. This study aimed to characterize the mechanisms triggered by EML4-ALK to induce NSCLC transformation. METHODS: HEK293 and NIH3T3 cells were transfected with EML4-ALK variant 3 or pcDNA3.1-NC. H2228 cells were transfected with siRNA-EML4-ALK or siRNA-NC. Cell viability and proliferation were measured by the CCK-8 and EdU methods, respectively. Flow cytometry revealed apoptosis. Gene expression profiles were generated from a signaling pathway screen in EML4-ALK-regulated lung cancer cells and verified by qPCR and Western blotting. The co-immunoprecipitation and immunohistochemistry/ immunofluorescence determined the interaction and colocalization of JAK2-STAT pathway components with EML4-ALK. RESULTS: Microarray identified several genes involved in the JAK2-STAT pathway. JAK2 and STAT6 were constitutively phosphorylated in H2228 cells. EML4-ALK silencing downregulated phosphorylation of STAT6. Expression of EML4-ALK in HEK293 and NIH3T3 cells activated JAK2, STAT1, STAT3, STAT5, and STAT6. In EML4-ALK-transfected HEK293 cells and EML4-ALK-positive H2228 cells, activated STAT6 and JAK2 colocalized with ALK. STAT3 and STAT6 were phosphorylated and translocated to the nucleus of H2228 cells following IL4 or IL6 treatment. Apoptosis increased, while cell proliferation and DNA replication decreased in H2228 cells following EML4-ALK knockdown. In contrast, HEK293 cell viability increased following EML4-ALK overexpression, while H2228 cell viability significantly decreased after treatment with ALK or JAK-STAT pathway inhibitors. CONCLUSIONS: Our data suggest that the aberrant expression of EML4-ALK leads to JAK2-STAT signaling pathway activation, which is essential for the development of non-small cell lung cancer.

Underlying mechanism on source-sink carbon balance of grazed perennial grass during regrowth: Insights into optimal grazing regimes of restoration of degraded grasslands in a temperate steppe.

Overgrazing is the main driver of grassland degradation and productivity reduction in northern China. The restoration of degraded grasslands depends on optimal grazing regimes that modify the source-sink balance to promote best carbon (C) assimilation and allocation, thereby promoting rapid compensatory growth of the grazed plants. We used in situ13CO2 labeling and field regrowth studies of Stipa grandis P.A. Smirn.to examine the effects of different grazing intensities (light, medium, heavy, and grazing exclusion) on photosynthetic C assimilation and partitioning, on reallocation of non-structural carbohydrates during regrowth, and on the underlying regulatory mechanisms. Light grazing increased the sink demand of newly expanded leaves and significantly promoted 13C fixation by increasing the photosynthetic capacity of the leaves and accelerating fructose transfer from the stem. Although C assimilation decreased under medium and heavy grazing, S. grandis exhibited a tolerance strategy that preferentially allocated more starch and 13C to the roots for storage to balance sink competition between newly expanded leaves and the roots. Sucrose phosphate synthase (SPS), sucrose synthase (SS), and other plant hormones regulated source-sink imbalances during regrowth. Abscisic acid promoted accumulation of aboveground biomass by stimulating stem SPS activity, whereas jasmonate increased root starch synthesis, thereby increasing belowground biomass. Overall, S. grandis could optimize source-sink relationships and above- and belowground C allocation to support regrowth after grazing by the regulating activities of SPS, SS and other hormones. These results provide new insights into C budgets under grazing and guidance for sustainable grazing management in semi-arid grasslands.

EZH2 inhibitors reverse resistance to gefitinib in primary EGFR wild-type lung cancer cells.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. In traditional anti-cancer therapy, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) have been proven to be beneficial for patients with EGFR mutations. However, patients with EGFR wild-type NSCLC were usually not respond to EGFR-TKIs. Enhancer of zeste homolog 2 (EZH2) is a key molecular in the PRC2 complex and plays an important role in epigenetic regulation and is overexpressed in variant tumors. EZH2 inhibitors have been reported to sensitize variant tumor cells to anticancer drugs. This study aimed to investigate whether the EZH2 inhibitors, GSK343 and DZNep when combined with gefitinib can reverse EGFR-TKIs resistance in EGFR wild-type NSCLC cells. METHODS: The RNA-sequencing data of patients with NSCLC [502 patients with lung squamous cell carcinoma, including 49 paracancerous lung tissues and 513 patients with lung adenocarcinoma (LUAD), including 59 paracancerous lung tissues] from the Cancer Genome Atlas (TCGA), were analyzed for EZH2 expression. EZH2 expression was verified in 40 NSCLC tissue cancer samples and their corresponding paracancerous tissues from our institute (TJMUGH) via RT-PCR. A549 and H1299 cells treated with siRNA or EZH2 inhibitors were subjected to cell viability and apoptosis analyses as well to EGFR pathway proteins expression analyses via western blotting. RESULTS: EZH2 was upregulated in human NSCLC tissues and correlated with poor prognosis in patients with LUAD based on data from both TCGA and TJMUGH. Both GSK343 and DZNep sensitized EGFR wild-type LUAD cells (A549 and H1299) to gefitinib and suppressed cell viability and proliferation in vitro by downregulating the phosphorylation of EGFR and AKT and by inducing cell apoptosis. Co-administration of EZH2 inhibitors (GSK343 or DZNep) with gefitinib exerted a stronger inhibitory effect on tumor activity, cell proliferation and cell migration than single drug administration in vitro and in vivo. CONCLUSIONS: These data suggest that the combination of EZH2 inhibitors with EGFR-TKIs may be an effective method for treating NSCLC-patients with EGFR-wild type, who do not want to undergo traditional treatment with chemotherapy.

Regrowth strategies of Leymus chinensis in response to different grazing intensities.

In temperate grassland ecosystems, grazing can affect plant growth by foraging, trampling, and excretion. The ability of dominant plant species to regrow after grazing is critical, since it allows the regeneration of photosynthetic tissues to support growth. We conducted a field experiment to evaluate the effects of different grazing intensities (control, light, medium, and heavy) on the physiological and biochemical responses of Leymus chinensis and the carbon (C) sources utilized during regrowth. Light grazing promoted regrowth and photoassimilate storage of L. chinensis, by increasing the net photosynthetic rate (Pn ), photosynthetic quenching, light interception, sugar accumulation, sucrose synthase activities, and fructose supply from stems. At medium grazing intensity, L. chinensis had low Pn , light interception, and sugar accumulation, but higher expression of a sucrose transporter gene (LcSUT1) and water-use efficiency, which reflected a tendency to store C in belowground to promote survival. This strategy was associated with regulation by abscisic acid (ABA), jasmonate, and salicylic acid (SA) signaling. However, L. chinensis tolerated heavy grazing by increased ABA and jasmonate-induced promotion of C assimilation and osmotic adjustment, combined with photoprotection against photo-oxidation, suggesting a strategy based on regrowth. In addition, stems were the main C source organs and energy supply rather than roots. Simultaneously, SA represented a weaker defense than ABA and jasmonate. Therefore, L. chinensis adopted different strategies for regrowth under different grazing intensities, and light grazing promoted regrowth the most. Our results demonstrate the regulation of C reserves utilization by phytohormones, and this regulation provides an explanation for recent results about grazing responses.

Landslide Susceptibility Prediction Modeling Based on Remote Sensing and a Novel Deep Learning Algorithm of a Cascade-Parallel Recurrent Neural Network.

Landslide susceptibility prediction (LSP) modeling is an important and challenging problem. Landslide features are generally uncorrelated or nonlinearly correlated, resulting in limited LSP performance when leveraging conventional machine learning models. In this study, a deep-learning-based model using the long short-term memory (LSTM) recurrent neural network and conditional random field (CRF) in cascade-parallel form was proposed for making LSPs based on remote sensing (RS) images and a geographic information system (GIS). The RS images are the main data sources of landslide-related environmental factors, and a GIS is used to analyze, store, and display spatial big data. The cascade-parallel LSTM-CRF consists of frequency ratio values of environmental factors in the input layers, cascade-parallel LSTM for feature extraction in the hidden layers, and cascade-parallel full connection for classification and CRF for landslide/non-landslide state modeling in the output layers. The cascade-parallel form of LSTM can extract features from different layers and merge them into concrete features. The CRF is used to calculate the energy relationship between two grid points, and the extracted features are further smoothed and optimized. As a case study, the cascade-parallel LSTM-CRF was applied to Shicheng County of Jiangxi Province in China. A total of 2709 landslide grid cells were recorded and 2709 non-landslide grid cells were randomly selected from the study area. The results show that, compared with existing main traditional machine learning algorithms, such as multilayer perception, logistic regression, and decision tree, the proposed cascade-parallel LSTM-CRF had a higher landslide prediction rate (positive predictive rate: 72.44%, negative predictive rate: 80%, total predictive rate: 75.67%). In conclusion, the proposed cascade-parallel LSTM-CRF is a novel data-driven deep learning model that overcomes the limitations of traditional machine learning algorithms and achieves promising results for making LSPs.

Physiology of Leymus chinensis under seasonal grazing: Implications for the development of sustainable grazing in a temperate grassland of Inner Mongolia.

Plants have different physiological characteristics as the season changes, grazing management in compliance with plant growth and development characteristics may provide new ideas for sustainable livestock development. However, there has been little research on seasonal grazing and plants physiological responses under it. Here, we studied a typical steppe ecosystem of Inner Mongolia, with Leymus chinensis as the dominant species, in five grazing treatments: continuous grazing, seasonal grazing (which started in spring or in early and late summer), and no grazing (the control). We analyzed growth and resistance of L. chinensis in the five treatments by measuring annual primary productivity, morphological traits and various physiological processes. Compared with continuous grazing, seasonal grazing significantly alleviated grassland degradation. The plants were less affected by stress under spring grazing, with net photosynthesis and non-photochemical quenching closer to the control values and with a lower malondialdehyde content. The annual primary production of plants under grazing started in the early and late summer were 3-4 times the value under continuous grazing. Regrowth under early-summer grazing was greatly improved, and stress resistance was stronger with a higher proline content and high antioxidant enzyme activity. And nutrient accumulation at the end of the growing season such as abundant soluble sugars were transferred from aboveground tissue to the roots in September under late-summer grazing, which benefited regrowth the next year. All these physiological processes were regulated by hormonal changes. Our results highlight how plants response grazing stress in different growing seasons and suggest that seasonal grazing can improve the stress resistance and regrowth capacity of forage vegetation, and applying this knowledge can promote more sustainable grazing practices.

Enzyme-Inspired Room-Temperature Lithium-Oxygen Chemistry via Reversible Cleavage and Formation of Dioxygen Bonds.

Li-O2 batteries are promising energy storage systems due to their ultra-high theoretical capacity. However, most Li-O2 batteries are based on the reduction/oxidation of Li2 O2 and involve highly reactive superoxide and peroxide species that would cause serious degradation of cathodes, especially carbon-based materials. It is important to explore lithium-oxygen reactions and find new Li-O2 chemistry which can restrict or even avoid the negative influence of superoxide/peroxide species. Here, inspired by enzyme-catalyzed oxygen reduction/oxidation reactions, we introduce a copper(I) complex 3 N-CuI (3 N=1,4,7-trimethyl-1,4,7-triazacyclononane) to Li-O2 batteries and successfully modulate the reaction pathway to a moderate one on reversible cleavage/formation of O-O bonds. This work demonstrates that the reaction pathways of Li-O2 batteries could be modulated by introducing an appropriate soluble catalyst, which is another powerful choice to construct better Li-O2 batteries.

Differences in the photosynthetic and physiological responses of Leymus chinensis to different levels of grazing intensity.

BACKGROUND: Grazing is an important land use in northern China. In general, different grazing intensities had a different impact on the morphological and physiological traits of plants, and especially their photosynthetic capacity. We investigated the responses of Leymus chinensis to light, medium, and heavy grazing intensities in comparison with a grazing exclusion control. RESULTS: With light grazing, L. chinensis showed decreased photosynthetic capacity. The low chlorophyll and carotenoid contents constrained light energy transformation and dissipation, and Rubisco activity was also low, restricting the carboxylation efficiency. In addition, the damaged photosynthetic apparatus accumulated reactive oxygen species (ROS). With medium grazing, more energy was used for thermal dissipation, with high carotene content and high non-photochemical quenching, whereas photosynthetic electron transport was lowest. Significantly decreased photosynthesis decreased leaf C contents. Plants decreased the risk caused by ROS through increased energy dissipation. With high grazing intensity, plants changed their strategy to improve survival through photosynthetic compensation. More energy was allocated to photosynthetic electron transport. Though heavy grazing damaged the chloroplast ultrastructure, adjustment of internal mechanisms increased compensatory photosynthesis, and an increased tiller number facilitated regrowth after grazing. CONCLUSIONS: Overall, the plants adopted different strategies by adjusting their metabolism and growth in response to their changing environment.

Growth-defense trade-off regulated by hormones in grass plants growing under different grazing intensities.

Herbivory creates conflicts between a plant's need to allocate resources for growth and defense. It is not yet clear how plants rebalance resource utilization between growth and defense in response to increasing grazing intensity. We measured characteristics of the primary and secondary metabolism of Leymus chinensis at five levels of grazing intensity (control, light, moderate, heavy and extremely heavy). Furthermore, we evaluated hormone signaling by quantifying the impact of key hormones on plant growth and defense. Under light grazing intensity, indole-3-acetic acid and jasmonates appeared to promote the growth of L. chinensis through a high photosynthetic rate, high water-use efficiency and high soluble protein contents, whereas abscisic acid decreased these properties. Under moderate grazing intensity, L. chinensis had a low photosynthetic capacity but greater production of secondary metabolites (tannins, total flavonoids and total phenols), possibly induced by salicylic acid. When the grazing pressure further intensified, L. chinensis translocated more carbohydrates to its roots in order to survive and regrow. Leymus chinensis therefore exhibited a trade-off between growth and defense in order to survive and reproduce under herbivory. Plants developed different mechanisms to enhance their grazing tolerance by means of hormonal regulation.

Dietary fresh fish and processed fish intake and the risk of glioma: A meta-analysis of observational studies.

The current study was to evaluate the predicted role of dietary fresh fish and processed fish intake for risk of glioma. Databases of Web of Science, PubMed, and Wan Fang Med Online were retrieved up to Jan 31th, 2018. Eligible studies were identified based on defined inclusion criteria. Summarized results of relative risk (RR) with corresponding 95% confidence intervals (CI) were calculated using a random effects model. Sensitivity analysis and publication bias were also performed. The final analysis in this report included a total of 9 articles. The summarized RR and 95%CI from 8 studies for dietary fresh fish intake and glioma risk was 0.823 (95%CI= 0.698-0.970), with no evidence of significant between-study heterogeneity (I2=43.6%, P=0.088). Moreover, positive associations were also found both in Caucasian populations and Asia populations. Seven studies were used to assess the relationship between dietary processed fish intake and the risk of glioma. Significantly increased risk of glioma was found for the highest category of dietary processed fish intake [summarized RR= 1.554, 95%CI= 1.169-2.066, I2= 72.1%, P= 0.001], especially among Caucasian populations. No publication bias was found. In summary, findings from this meta-analysis concluded that dietary fresh fish intake could reduce the risk of glioma. However, very high processed fish intake had a significant association with increased glioma risk.

Nationwide cross-sectional adherence to mammography screening guidelines: national behavioral risk factor surveillance system survey results.

PURPOSE: Varying recommendations about breast cancer screening have generated much confusion about when and how often to undergo mammography screening, yet there is limited population-based data about the extent to which patients adhere to various mammographic screening guidelines in practice. Our purpose was to evaluate population-based adherence to mammographic screening using criteria from major guideline-producing organizations. METHODS: Women aged 40-74 in the 2014 Behavioral Risk Factor Surveillance System survey were included. Self-reported mammographic screening within 1 or 2 years, according to major guideline-producing organizations (American Cancer Society [ACS], US Preventative Services Task Force [USPSTF], American College of Radiology [ACR], American College of Obstetricians and Gynecologists [ACOG]) was calculated with logistic regression, adjusting for demographics and indices of access to health care. RESULTS: 159,123 women were included. By age category, cross-sectional adherence to USPSTF guidelines ranged from 76 to 81%, ACS (55-81%) and ACR/ACOG (45-64%) with increasing age being associated improved adherence. The highest proportions of women undergoing mammographic screening were seen in women ages 65-69 (66% within last year, 81% within last 2 years). Statistically significant predictors of adherence to mammography screening included increased income category (OR 1.08, 1.07-1.09), higher education category (OR 1.13, 1.11-1.16), and increased access to health care (OR 2.25, 1.94-2.60), adjusted for age categories. CONCLUSIONS: Adherence to mammography screening was closest to USPSTF guidelines with 76-81% cross-sectional adherence. Frequency of screening increases with age with highest screening proportions in women ages 65-69 (66% within last year, 81% within last 2 years). For all screening guidelines, adherence to mammography screening remains poor in women with limited access to health insurance with less than half of women obtaining recommended screening.

Immune status of children with obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: We aimed to evaluate the immune status of children with obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: Fifty children with OSAHS having the symptoms of "snoring, mouth breathing and suffocating during sleep", who were admitted in our hospital from May 2014 to May 2016, were randomly selected. Another 52 healthy, age- and gender-matched children were enrolled as control subjects after taking informed consent. After admission, the peripheral venous blood was collected. T cell subsets and cytokines were analyzed by flow cytometry. Immunoglobulin and complement levels were detected by immunoassay analyzer. RESULTS: The percentage of CD8+ T lymphocytes in children with OSAHS was (26.47 ± 1.52)% which was significantly higher than that of control group ((21.94 ± 1.92)%) (P<0.05). OSAHS group had a significantly lower CD4+/CD8+ ratio (1.24 ± 0.12) than that of control group (1.45 ± 0.11) (P<0.05). The two groups had similar percentages of CD3+ and CD4+ T lymphocytes (P>0.05). OSAHS group had significantly higher serum levels of IL-4, IL-6, IL-10 and IFN-γ than those of control group (P<0.05), but their IL-2 and TNF-α levels were similar (P>0.05). The serum IgA and C3 levels of OSAHS group significantly exceeded those of control group (P<0.05), but their IgG, IgM and C4 levels were similar (P>0.05). CONCLUSION: Children with OSAHS had increased percentage of CD8+ T lymphocytes and decreased CD4+/CD8+ ratio, suggesting this group had poor immune function. Increase in humoral immune-related indices IL-4, IL-6, IL-10 and IFN-γ indicated the occurrence of oxidative stress and systemic inflammatory status.

Can energy internet improve corporate ESG performance? -- Evidence from Chinese high energy-consuming companies.

Under the challenges of global crises such as climate warming, ESG performance, which represents sustainable development, has received widespread attention at home and abroad. Using the panel data from 2011 to 2020, comprising 726 high energy-consuming companies listed on the Shanghai and Shenzhen A-shares, this paper takes Energy Internet demonstration project in 2016 as a quasi-natural experiment and builds a difference-in-difference model to study its microscopic policy effects. The study found that, firstly, Energy Internet can markedly enhance ESG performance of high energy-consuming companies. Secondly, the mechanism test finds that Energy Internet can facilitate high energy-consuming enterprises to enhance their ESG performance through three mechanisms: increasing government subsidies for enterprises in energy conservation and environmental protection, absorbing talent employment and improving information environment within the enterprises. Finally, the heterogeneity analysis proves that Energy Internet's policy effects are more pronounced in regions with higher financial expenditures on local science undertakings and among state-owned enterprises. China ought to persist in advancing the development of Energy Internet and provide companies with adequate support on finance, talent and technology. Meanwhile, during the construction of Energy Internet, attention should be paid to adapting to local conditions and enterprises.

Exploring spatial heterogeneity in factors associated with injury severity in speeding-related crashes: An integrated machine learning and spatial modeling approach.

Speeding, a risky act of driving a vehicle at a speed exceeding the posted limit, has consistently emerged as a leading contributor to traffic fatalities. Identifying the risk factors associated with injury severity in speeding-related crashes is essential for implementing countermeasures aimed at preventing severe injury incidents and achieving Vision Zero goals. With the wealth of traffic crash data collected by various agencies, researchers have a valuable opportunity to conduct data-driven studies and employ various modeling methods to gain insights into the correlated factors affecting injury severity in traffic crashes. Machine learning models, owing to their superior predictive power compared to statistical models, are increasingly being adopted by researchers. These models, in conjunction with interpretation techniques, can reveal potential relationships between crash injury severity and contributing factors. Traffic crashes are inherently tied to geographic locations, distributed across road networks influenced by diverse socioeconomic and geographical factors. Recognizing spatial heterogeneity in traffic safety is crucial for tailored safety measures to address speeding-related crashes, as a one-size-fits-all approach may not work effectively everywhere. However, most existing machine learning models are unable to incorporate the spatial dependency among observations, such as traffic crashes, which hinders their ability to uncover spatial heterogeneity in traffic safety. To address this gap, this study introduces the Geographically Weighted Neural Network (GWNN) model, a spatial machine-learning model that integrates neural network (NN) and geographically weighted modeling approaches to investigate spatial heterogeneity in speeding-related crashes. Unlike the traditional NN model, which trains a single set of model parameters for all observations, the GWNN trains a local NN model for each crash location using a spatially weighted subsample of nearby crashes, allowing for the quantification of corresponding local effects of features through calculating local marginal effects. To understand the spatial heterogeneity in speeding-related crashes, this study extracted two years (2020 and 2021) of speeding-related crash data from Alabama for the development of the GWNN local models. The modeling results show significant spatial variability among several factors contributing to injury severity in speeding-related crashes. These factors include driver condition, vehicle type, crash type, speed limit, weather, crash time and location, roadway alignment, and traffic volume. Based on the GWNN modeling results, this study identified three types of spatial variations in relationships between contributing factors and crash injury severity: consistent positive associations, consistent negative associations, and inverse associations (i.e., marginal effects can vary between positive and negative depending on the location). This study contributes by integrating advanced machine learning and spatial modeling approaches to uncover intricate spatial patterns and factors influencing injury severity in speeding-related crashes, thereby facilitating the development of targeted policy implementations and safety interventions.

"Being a Good Parent" During Times of Illness as Defined by Chinese Children With Cancer, Their Parents, and Providers.

BACKGROUND: Identifying the definition of "being a good parent" facilitates the understanding of parents' personal beliefs and deeds regarding their ill child. OBJECTIVE: The aim of this study was to explore the concept of "being a good parent to my ill child" during pediatric cancer treatment from the perspective of Chinese children, parents, and providers. METHODS: A descriptive qualitative study was conducted with 6 children, 18 parents, 5 doctors, 19 nurses, and 3 social workers by semistructured interviews at 3 Chinese hospitals. RESULTS: Except for "letting the Lord lead," 7 themes from the original conceptual model were validated, for example, "being there for my child" (n = 51, 100.0%); "doing right by my child" (n = 38, 74.5%), "being an advocate for my child" (n = 27, 52.9%), "conveying love to my child" (n = 26, 51.0%), "making my child healthy" (n = 18, 35.3%), "being a good life example" (n = 13, 25.5%), and "not allowing suffering" (n = 13, 25.5%). A new theme, "rebuilding myself" (n = 39, 76.5%), emerged in the Chinese context. "Being a good parent to my ill child" is perceived differently among stakeholders. Healthcare professionals' facilitation to fulfill the concept included "recognizing the individualized good-parent definition," "providing best available care" and "establishing a supportive environment." CONCLUSION: "Being a good parent to my ill child" is meaningfully expressed by Chinese parents and recognized by children and providers during pediatric cancer treatment. IMPLICATIONS FOR PRACTICE: It is important to support parents in conveying their internal good parent definition and sharing it with stakeholders. Attention should be paid to related cultural influencers, a supportive family-friendly environment, and shared decision making involving the child's voice.

A novel low-background nitroreductase fluorescent probe for real-time fluorescence imaging and surgical guidance of thyroid cancer resection.

Thyroid cancer always appears insidiously with few noticeable clinical symptoms. Due to its limitations, conventional ultrasound imaging can lead to missed or misdiagnosed cases. Surgery is still the primary treatment method of thyroid cancer, but removal of surrounding healthy tissues to minimize recurrence leads to overtreatment and added patient suffering. To address this challenge, herein, a nitroreductase (NTR) fluorescent probe, Ox-NTR, has been developed for detecting thyroid cancer and tracking the surgical removal of thyroid tumors by fluorescence imaging. The conjugated structure of oxazine 1 was disrupted, significantly reducing the issue of high background signals, thus effectively achieving low background fluorescence. Under hypoxic conditions, the nitro group of Ox-NTR can be reduced to an amine and subsequently decomposed into oxazine 1, emitting intense red fluorescence. Ox-NTR has a low detection limit of 0.09 µg/mL for NTR with excellent photostability and selectivity. Cellular studies show that Ox-NTR can effectively detect NTR levels in hypoxic thyroid cancer cells. Moreover, the ability of Ox-NTR of rapid response to thyroid cancer in vivo is confirmed by fluorescence imaging in mice, distinguishing tumors from normal tissues due to its superior low background fluorescence. Utilizing this fluorescence imaging method during surgical resection can guide the removal of tumors, preventing both missed tumor tissues and accidental removal of healthy tissue. In summary, the novel Ox-NTR offers precise detection capabilities that provide significant advantages over traditional imaging methods for thyroid cancer diagnosis and treatment, making it a valuable tool to guide tumor removal in surgical procedures.

Correlations between root phosphorus acquisition and foliar phosphorus allocation reveal how grazing promotes plant phosphorus utilization.

Overgrazing and phosphorus (P) deficiency are two major factors limiting the sustainable development of grassland ecosystems. Exploring plant P utilization and acquisition strategies under grazing can provide a solid basis for determining a reasonable grazing intensity. Both foliar P allocation and root P acquisition are crucial mechanisms for plants to adapt to environmental P availability; however, their changing characteristics and correlation under grazing remain unknown. Here, we investigated foliar P fractions, root P-acquisition traits and gene expression, as well as rhizosphere and bulk soil properties of two dominant plant species, Leymus chinensis (a rhizomatous grass) and Stipa grandis (a bunchgrass), in a field grazing intensity gradient site in Inner Mongolia. Grazing induced different degrees of compensatory growth in the two dominant plant species, increased rhizosphere P availability, and alleviated plant P limitation. Under grazing, the foliar metabolite P of L. chinensis increased, whereas the nucleic acid P of S. grandis increased. Increased P fractions in L. chinensis were positively correlated with increased root exudates and rapid inorganic P absorption. For S. grandis, increased foliar P fractions were positively correlated with more fine roots, more root exudates, and up-regulated expression of genes involved in defense and P metabolism. Overall, efficient root P mobilization and uptake traits, as well as increases in leaf metabolic activity-related P fractions, supported plant compensatory growth under grazing, a process that differed between tiller types. The highest plant productivity and leaf metabolic activity-related P concentrations under medium grazing intensity clarify the underlying basis for sustainable livestock production.

Nerve injury disrupts temporal processing in the spinal cord dorsal horn through alterations in PV+ interneurons.

How mechanical allodynia following nerve injury is encoded in patterns of neural activity in the spinal cord dorsal horn (DH) remains incompletely understood. We address this in mice using the spared nerve injury model of neuropathic pain and in vivo electrophysiological recordings. Surprisingly, despite dramatic behavioral over-reactivity to mechanical stimuli following nerve injury, an overall increase in sensitivity or reactivity of DH neurons is not observed. We do, however, observe a marked decrease in correlated neural firing patterns, including the synchrony of mechanical stimulus-evoked firing, across the DH. Alterations in DH temporal firing patterns are recapitulated by silencing DH parvalbumin+ (PV+) interneurons, previously implicated in mechanical allodynia, as are allodynic pain-like behaviors. These findings reveal decorrelated DH network activity, driven by alterations in PV+ interneurons, as a prominent feature of neuropathic pain and suggest restoration of proper temporal activity as a potential therapeutic strategy to treat chronic neuropathic pain.