Palladium-Catalyzed Sequential Cross-Coupling/Annulation of ortho-Vinyl Bromobenzene with Aryl Bromide: Bimetallic Pathway versus Pd(II)-Pd(IV) Pathway: A DFT Investigation.

The palladium-catalyzed sequential cross-coupling/annulation of ortho-vinyl bromobenzenes with aryl bromides generating phenanthrenes was characterized by density functional theory (DFT). The Pd(II)-Pd(IV) pathway (Path V) is shown to be less probable than the bimetallic pathway (Path I), the latter proceeding via the following six steps: oxidative addition, vinyl-C(sp2)-H activation, Pd(II)-Pd(II) transmetalation, C-C coupling, aryl-C(sp2)-H activation, and reductive elimination. The aryl-C(sp2)-H activation process acts as the rate-determining step (RDS) of the entire chemical transformation, with an activation free energy barrier of ca. 27.4-28.8 kcal·mol-1, in good agreement with the corresponding experimental data (phenanthrenes' yields of ca. 65-90% at 130 °C after 5 h of reaction). The K2CO3 additive effectively reduces the activation free energy barrier of the RDS through direct participation in the reaction while preferentially modulating the charge distributions and increasing the stability of corresponding intermediates and complexes along the reaction path. Furthermore, bonding and electronic structure analyses of the key structures indicate that the chemo- and regioselectivities of the reaction are strongly influenced by both electronic effects and steric hindrance.

Metal-Centered Boron-Wheel Cluster of Y©B112- with Rare D11h Symmetry.

Molecules with high point-group symmetry are interesting prototype species in the textbook. As transition metal-centered boron clusters tend to have highly symmetric structures to fulfill multicenter bonding and high stability, new boron clusters with rare point-group symmetry may be viable. Through in-depth scrutiny over the structures of experimentally already observed transition metal-centered boron-wheel complexes, geometric and electronic design principles are summarized, based on which we studied M©B11k- (M = Y, La; Zr, Hf; k = 1, 2) clusters and found that a Y©B112- boron-wheel complex has an unprecedented D11h point-group symmetry. The remarkable stability of the planar Y©B112- complex is illustrated via extensive global-minimum structural search as well as comprehensive chemical bonding analyses. Similar to other boron-wheel complexes, the Y©B112- complex is shown to possess σ and π double aromaticity, indeed following the electronic design principle previously summarized. This new compound is expected to be experimentally identified, which will extend the currently known largest possible planar molecular symmetry and enrich the metal-centered boron-wheel class.

Nickel-Catalyzed Three-Component Unsymmetrical Bis-Allylation of Alkynes with Alkenes: A Density Functional Theory Study.

Density functional theory (DFT) characterizations were employed to resolve the structural and energetic aspects and product selectivities along the mechanistic reaction paths of the nickel-catalyzed three-component unsymmetrical bis-allylation of alkynes with alkenes. Our putative mechanism initiated with the in situ generation of the active catalytic species [Ni(0)L2] (L = NHC) from its precursors [Ni(COD)2, NHC·HCl] to activate the alkyne and alkene substrates to form the final skipped trienes. This proceeds via the following five sequential steps: oxidative addition (OA), ß-F elimination, ring-opening complexation, C-B cleavage and reductive elimination (RE). Both the OA and RE steps (with respective free energy barriers of 24.2 and 24.8 kcal·mol-1) contribute to the observed reaction rates, with the former being the selectivity-controlling step of the entire chemical transformation. Electrophilic/nucleophilic properties of selected substrates were accurately predicted through dual descriptors (based on Hirshfeld charges), with the chemo- and regio-selectivities being reasonably predicted and explained. Further distortion/interaction and interaction region indicator (IRI) analyses for key stationary points along reaction profiles indicate that the participation of the third component olefin (allylboronate) and tBuOK additive played a crucial role in facilitating the reaction and regenerating the active catalyst, ensuring smooth formation of the skipped triene product under a favorably low dosage of the Ni(COD)2 catalyst (5 mol%).

Decent work, work engagement, and turnover intention among registered nurses: a cross-sectional study.

BACKGROUND: Nurses face substantial career challenges arising from global pandemics, economic crises, and their roles in conflict-ridden areas. In this context, the rights of nurses pertaining to decent work, such as freedom, fairness, safety, and dignity, are not adequately safeguarded. This study examines decent work status among Chinese nurses and its links to demographics, work engagement, and turnover intention. METHODS: A cross-sectional study design was used following STROBE guidelines. Through a convenient sampling method, a total of 476 nurses were surveyed. These participants were drawn from three esteemed tertiary Grade A hospitals in Hangzhou, with data collection spanning from June to August in 2023. We used a comprehensive set of assessment instruments, encompassing an evaluation of demographic characteristics, the Decent Work Perceptions Scale (DWPS), the Utrecht Work Engagement Scale (UEWS), and turnover intention questionnaire. Bootstrapping procedures were used to ensure the robustness and reliability of the model. RESULTS: The study revealed that nurses' perceptions of decent work significantly impacted work engagement (ß = 0.603, p < 0.001) and turnover intention (ß = -0.275, p < 0.001). Work engagement operated as a mediator between decent work and turnover intention, decreasing the likelihood of nurses leaving their positions (ß = -0.062, p < 0.001). Factors such as age, years of working experience, professional title, job category, and attendance at professional conferences significantly influenced nurses' perceptions of decent work (all p < 0.05). CONCLUSIONS: This study examines factors affecting decent work among nurses and explores its connection with work engagement and the intention to leave. Despite limitations (sample, social desirability bias), the study offers valuable insights for nursing practice. This suggests managers improve decent work for young nurses through rational shift schedules and continuous education. Policymakers should consider adjusting nursing policies for better employment conditions.

Assessing the mediation pathways: How decent work affects turnover intention through job satisfaction and burnout in nursing.

AIM: This study aimed to assess the potential mediating roles of nurses' job satisfaction and burnout in the association between decent work and turnover intention. BACKGROUND: There is a global challenge of nursing shortages in healthcare systems worldwide. Decent work is crucial for safeguarding the rights and professional development outcomes of nurses. However, there is currently limited research on decent work among nurses, and there is a lack of studies exploring the relationships between nurses' decent work, job satisfaction, burnout, and turnover intention. METHODS: A cross-sectional survey design was employed with a sample of 460 nurses from three hospitals: The Affiliated Hospital of Hangzhou Normal University, Hangzhou Third People's Hospital, and Hangzhou Red Cross Hospital. The STROBE checklist was used. Mediation analysis using the PROCESS Macro was used to examine the relationships between decent work, job satisfaction, burnout, and turnover intention. RESULTS: The results showed that nurses' perception of decent work directly influences their turnover intention. Additionally, these findings strongly support the role of job satisfaction and burnout as mediating factors in the relationship between decent work and turnover intention. CONCLUSIONS: Decent work reduces nurse burnout and turnover intention of enhancing their job satisfaction. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study's findings have important implications for healthcare organizations and policymakers. Recognizing the pivotal role of decent work in nurses' job satisfaction and well-being can guide the development of strategies to improve working conditions and reduce turnover rates. It is imperative for healthcare institutions to prioritize creating safe, supportive, and equitable work conditions for nurses, as this can contribute to higher job satisfaction and, subsequently, lower turnover rates.

Enzymatic Synthesis of Noncanonical α-Amino Acids Containing γ-Tertiary Alcohols.

Noncanonical amino acids (ncAAs) containing tertiary alcohols are valuable as precursors of natural products and active pharmaceutical ingredients. However, the assembly of such ncAA scaffolds from simple material by C-C bond formation remains a challenging task due to the presence of multiple stereocenters and large steric hindrance. In this study, we present a novel solution to this problem through highly selective enzymatic decarboxylative aldol addition. This method allows for the streamlined assembly of multifunctionalized ncAAs with γ-tertiary alcohols from readily available materials, such as L -aspartatic acid and isatins, vicinal diones and keto esters. The modularity of electrophiles furnished four classes of ncAAs with decent efficiency as well as excellent site and stereocontrol. Computational modeling was employed to gain detailed insight into the catalytic mechanism and to provide a rationale for the observed selectivities. The method offers a single-step approach to producing multifunctionalized ncAAs, which can be directly utilized in peptide synthesis and bioactivity assessment.

The spatiotemporal matching pattern of Ezrin/Periaxin involved in myoblast differentiation and fusion and Charcot-Marie-Tooth disease-associated muscle atrophy.

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.

Ultra-stable cryogenic sapphire cavity laser with an instability reaching 2 × 10-16 based on a low vibration level cryostat.

Cryogenic ultra-stable lasers have extremely low thermal noise limits and frequency drifts, but they are more seriously affected by vibration noise from cryostats. Main material candidates for cryogenic ultra-stable cavities include silicon and sapphire. Although sapphire has many excellent properties at low temperature, the development of sapphire-based cavities is less advanced than that of silicon-based. Using a homemade cryogenic sapphire cavity, we develop an ultra-stable laser source with a frequency instability of 2(1) × 10-16. This is the best frequency instability level among similar systems using cryogenic sapphire cavities reported so far. Low vibration performance of the cryostat is demonstrated with a two-stage vibration isolation, and the vibration suppression is optimized by tuning the mixing ratio of the gas-liquid-helium. With this technique, the linear power spectral densities of vibrations at certain frequencies higher than tens of hertz are suppressed by two orders of magnitude in all directions.

Visible-Light-Promoted α-Benzylation of N-Phenyl α-Amino Acids to α-Amino Phenylpropanoids.

A new method for the synthesis of α-amino phenylpropanoids under blue light-emitting diode irradiation has been developed through α-C-H benzylation of readily available N-phenyl glycine ester with benzyl oxalates as a coupling partner under mild conditions. A range of N-phenyl glycine esters were successfully converted to α-amino phenylpropanoid products in moderate to good yields. The utility of this methodology is underlined by its application to the late-state modification of natural products.

Effect of acceptance and commitment therapy for depressive disorders: a meta-analysis.

OBJECTIVE: To systematically evaluate the effect of Acceptance and Commitment Therapy (ACT) on depressive disorders. METHODS: The electronic databases of Web of Science Core Collection, Pubmed, EMBASE, Cochrane Library, PsycInfo, CNKI, Wanfang and Weipu were used to select relevant publications. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. RevMan5.4 was used for meta-analysis. RESULTS: 11 studies with a total of 962 patients were included. Random-effects model analysis showed that ACT could effectively reduce the level of depressive symptoms in patients with depressive disorders (SMD = - 1.05, 95% CI: - 1.43-- 0.66, P < 0.00001), improve psychological flexibility (MD = 4.84, 95% CI: 2.70-6.97, P < 0.00001), and have good maintenance effect (SMD = - 0.70, 95% CI: - 1.15-- 0.25, P = 0.002). All differences were statistically significant. CONCLUSIONS: ACT not only improves depressive symptoms and psychological flexibility, but also has a good maintenance effect, and it is particularly effective in Chinese patients. Large randomized controlled trials are needed to validate the findings from this meta-analysis.

The relationship of superoxide dismutase and malondialdehyde levels with left ventricular geometry and function in patients with primary hypertension.

INTRODUCTION: To investigate the relationship of superoxide dismutase (SOD) and malondialdehyde (MDA) levels with left ventricular geometry (LVG) and function in patients with primary hypertension (PH). METHODS: A total of 222 PH patients and 25 healthy control (HC)s were enrolled in this study. All subjects underwent echocardiography and blood biochemical examination. PH patients were divided into four groups based on Ganau classification: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group, and concentric hypertrophy (CH) group. Pearson correlation analysis and logistic regression analysis were used to analyze the relationship between SOD and MDA with left ventricular structure and function. RESULTS: Compared to the HC, NG and CR groups, MDA level was higher while SOD level was lower in the EH and CH groups (all P < 0.001). SOD level was negatively correlated with IVSd, LVDd, LVPW, and global longitudinal strain (GLS), but positively correlated with LVEF. MDA level was positively correlated with IVSd, LVPW, and GLS, while negatively correlated with e'/a' and LVEF. SOD and MDA were independently associated with CR (OR = 0.970, P = 0.003; OR = 1.204, P = 0.043), EH (OR = 0.879, P < 0.001; OR = 2.197, P = 0.001) and CH (OR = 0.796, P < 0.001; OR = 3.669, P < 0.001). CONCLUSION: The SOD and MDA levels were correlated with LVG and function in PH patients. SOD and MDA may be important influencing factors of LVG change.

A study on dynamic simulation and improvement strategies of flood resilience for urban road system.

As one of the most important and directly affected infrastructure by flood disasters in urban areas, the road system plays a crucial role in maintaining the order of human production and life, as well as providing a foundation for the implementation of emergency response work in disaster scenarios. The existing flood resilience quantification methods based on maximum inundation depths of each individual road unit neglects the influences on flood resilience caused by the connectivity of road system. Therefore, this paper focuses on the road system, simulates the flood resilience of the road system in multiple disaster scenarios based on the functionality curve of road system under rainfall-inundation processes, then quantifies the improvement effect of Low Impact Development (LID) measures on flood resilience. A case study is conducted in Yunmen community, Jingdezhen city in China. The results indicate that: (1) The flood resilience of the road system decreases with the increase of rainfall intensity under different scenarios, and the magnitude of the decrease reduces. (2) The road system exhibits strong adaptability during the early stages of rainfall; The duration of functionality loss increases with increasing of rainfall intensity in different scenarios. (3) Implementation of LID measures can significantly improve system robustness by enhancing the reliability of the roads around critical nodes, thereby effectively enhancing flood resilience. The conclusions can provide a theoretical basis for decision-makers to develop urban flood mitigation engineering plans and resilience strategies tailored to local conditions.

Exploring interactions in water-related ecosystem services nexus in Loess Plateau.

Scientific understanding of the driving relationship between water-related ecosystem services (WESs) and influencing factors, as well as the trade-off and synergy relationship between WESs and WESs, is the premise of reasonably bringing them into management decisions. However, the existing research often separates the above-mentioned two relationships and conducts independent research, which leads to the conflict of research conclusions and cannot be well adopted by managers. Therefore, based on the panel data of Loess Plateau in 2000-2019, this paper uses the simultaneous equation model to combine the two kinds of relationships existing between WESs and influencing factors, establish a feedback loop, and reveal the interactions mechanism of WESs nexus. The results show that: (1) The fragmentation of land use leads to the uneven spatial-temporal distribution of WESs. (2) Vegetation factors and land factors are the main driving factors that affect WESs, and the impact of climate factors on WESs is decreasing year by year. (3) The increase of water yield ecosystem services will lead to the obvious increase in soil export ecosystem services, and there is a synergistic relationship between soil export ecosystem services and nitrogen export ecosystem services. The conclusion can provide an important reference for implementing the strategy of ecological protection and high-quality development.

Asymmetric C1 Extension of Aldehydes through Biocatalytic Cascades for Stereodivergent Synthesis of Mandelic Acids.

The development of mild, efficient, and enantioselective methods for preparing chiral building blocks from simple, renewable carbon units has been a long-term goal of the sustainable chemical industry. Mandelate derivatives are valuable pharmaceutical intermediates and chiral resolving agents, but their manufacture relies heavily on highly toxic cyanide. Herein, we report (S)-4-hydroxymandelate synthase (HmaS)-centered biocatalytic cascades for the synthesis of mandelates from benzaldehydes and glycine. We show that HmaS can be engineered to perform R-selective hydroxylation by single-point mutation, empowering the stereodivergent synthesis of both (S)- and (R)-mandelate derivatives. These biocatalytic cascades enabled the production of various mandelate derivatives with high atom economy as well as excellent yields (up to 98 %) and ee values (up to >99 %). This methodology offers an effective cyanide-free technology for greener and sustainable production of mandelate derivatives.

Bonding Nature of "Ionic Carbenes" in [M3(µ3-CH2)]-Containing Compounds: The Covalent Interaction.

While a series of trinuclear rare-earth metal methylene (divalent >CH2) complexes with the so-called "ionic carbene" have been known for decades, the nature of metal-carbene interactions in this class of compounds remains elusive. Herein, a quantum chemical investigation has been performed to reveal the bonding nature in typical trimetallic "ionic carbene" species with the [M3(µ3-CH2)] (M = Sc, Y, La, and Ac) cluster core. Through various chemical bonding analyses, we have demonstrated that there exists a non-negligible covalent interaction between µ3-CH2 and M3 moieties, and the chemical bonding can be accounted for with two three-center two-electron (3c-2e) bonds. The chemical bonding analyses reveal that the metal d-electron configuration plays an important role in stabilizing various µ3-coordinated carbene complexes. The late transition metals do not favor such a µ3-coordination geometry, thus explaining why ionic carbene complexes are usually found for rare-earth and early transition metals. A series of ionic carbene complexes with early transition metals, lanthanides, and actinides are predicted to be stable as well. These reactive ionic carbene complexes may have characteristic properties for organic synthesis and catalysis.

Determinants of never-treated status in rural versus urban contexts for individuals with schizophrenia in a population-based study in China.

BACKGROUND: A goal of China's 2012 National Mental Health Law is to improve access to services and decrease urban versus rural disparities in services. However, pre-reform data is needed for objective evaluation of these reforms' effectiveness. Accordingly, this study compares the pre-reform utilization of medical services for the treatment of schizophrenia in rural and urban communities in China. METHODS: In a large community-based study in four provinces representing 12% of China's population conducted from 2001 to 2005, we identified 326 individuals with schizophrenia (78 never treated). Comparing those living in urban (n = 86) versus rural (n = 240) contexts, we used adjusted Poisson regression models to assess the relationship of 'never treated' status with family-level factors (marital status, family income, and number of co-resident family members) and illness severity factors (age of onset, symptom severity and functional impairment). RESULTS: Despite similar impairments due to symptoms, rural patients were less likely to have received intensive mental health services (i.e., use psychiatric inpatient services), and appeared more likely to be 'never treated' or to only have received outpatient care. Among rural patients, only having more than four co-resident family members was independently associated with 'never-treated' status (RR = 0.34; 95% CI, 0.12-0.94; p = 0.039). Among urban patients, only older age of onset was independently associated with 'never-treated' status (RR = 1.06; 95% CI 1.02-1.10, p = 0.003). CONCLUSIONS: Identifying differential drivers of service utilization in urban and rural communities is needed before implementing policies to improve the utilization and equity of services and to define metrics of program success.

Life events and depression among children and adolescents in southwest China: a two-stage moderated mediation model of social support and cognitive styles.

BACKGROUND: According to data from the National Health Commission in 2018, more than 30 million children and adolescents in China suffered from mental health problems of varying degrees, with depression accounting for the largest proportion. Life events occur at every stage of child and adolescent development. Many studies have found a relationship between life events and depression in children and adolescents, but few studies have further explored the mediating and moderating variables that influence this relationship. Based on theoretical and empirical research on social support and cognitive styles, this study established a two-stage moderated mediating model to test whether social support mediates life events to depression, and cognitive style moderates the two mediating pathways. METHODS: We recruited 3540 participants from primary and secondary schools in Chongqing and collected 2814 valid data. All the participants completed self-report measures of life events, depression, social support and cognitive styles. The moderated mediation model was examined using SPSS PROCESS model 58. RESULTS: (1) There were significant positive correlations between life events and depression. (2) Social support mediates the relationship between life events and depression in children and adolescents. (3) Cognitive style moderates life events to social support and social support to depression. LIMITATIONS: This is a cross-sectional study and the questionnaire is self-reported. CONCLUSIONS: In children and adolescents, life events can influence depression through the mediating role of social support and cognitive styles could moderate its two mediating pathways.

Electrocatalytic NiCo2O4 Nanofiber Arrays on Carbon Cloth for Flexible and High-Loading Lithium-Sulfur Batteries.

Lithium-sulfur batteries have ultrahigh theoretical energy densities, which makes them one of the most promising next-generation energy storage systems. However, it is still difficult to achieve large-scale commercialization because of the severe lithium polysulfide (LiPS) shuttle effect and low sulfur loading. Here, we report a flexible lithium-sulfur battery of a high sulfur loading with the assistance of NiCo2O4 nanofiber array grown carbon cloth. The NiCo2O4 nanofibers are ideal electrocatalysts for accelerating LiPS conversion kinetics through strong chemical interactions. Therefore, the composite cathode delivers a high specific capacity of 1280 mAh g-1 at 0.2 C with a sulfur loading of 3.5 mg cm-2, and it can maintain a high specific capacity of 660 mAh g-1 after 200 cycles, showing a good cycle stability. The "layer-by-layer" stacking strategy enables the Li-S battery with a high S loading of ∼9.0 mg cm-2 to deliver a high areal capacity of 8.9 mAh cm-2.

Factors driving water yield ecosystem services in the Yellow River Economic Belt, China: Spatial heterogeneity and spatial spillover perspectives.

The stable supply of water resources is an important foundation for maintaining human production and life. With the development of economy and society, climate, socioeconomic and land factors directly or indirectly affect surface Water yield ecosystem services (WY). The driving factors of WY in the Yellow River Economic Belt (YREB) show the spatial spillover effect, which has been neglected in previous related studies. The results show that: (1) From 2000 to 2015, WY in YREB showed an obvious downward trend, with Henan and Shandong having the largest declines; (2) The decrease of WY is positively correlated with climate factors and negatively correlated with socioeconomic and land factors. (3) WY of YREB presents is characterized by obvious spatial heterogeneity characteristics of uneven distribution in the north and south, which is mainly due to the spatial spillover effect caused by climate and socioeconomic factors. Scientifically identifying the spatial heterogeneity of WY and the spatial spillover effect of the driving factors can help managers better understand the spatial driving mechanism of the driving factors on WY. This conclusion provides support for the ecological protection and high-quality development strategy of YREB.

Assessing potential liver injury induced by Polygonum multiflorum using potential biomarkers via targeted sphingolipidomics.

CONTEXT: Polygonum multiflorum Thunb. (Polygonaceae) (PM) can cause potential liver injury which is typical in traditional Chinese medicines (TCMs)-induced hepatotoxicity. The mechanism involved are unclear and there are no sensitive evaluation indicators. OBJECTIVE: To assess PM-induced liver injury, identify sensitive assessment indicators, and screen for new biomarkers using sphingolipidomics. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were randomly divided into four groups (control, model with low-, middle- and high-dose groups, n = 6 each). Rats in the three model groups were given different doses of PM (i.g., low/middle/high dose, 2.7/8.1/16.2 g/kg) for four months. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and liver were quantitatively analyzed. Fixed liver tissue sections were stained with haematoxylin and eosin and examined under a light microscope. The targeted sphingolipidomic analysis of plasma was performed using high-performance liquid chromatography tandem mass spectrometry. RESULTS: The maximal tolerable dose (MTD) of PM administered intragastrically to mice was 51 g/kg. Sphingolipid profiling of normal and PM-induced liver injury SD rats revealed three potential biomarkers: ceramide (Cer) (d18:1/24:1), dihydroceramide (d18:1/18:0)-1-phosphate (dhCer (d18:1/18:0)-1P) and Cer (d18:1/26:1), at 867.3-1349, 383.4-1527, and 540.5-658.7 ng/mL, respectively. A criterion for the ratio of Cer (d18:1/24:1) and Cer (d18:1/26:1) was suggested and verified, with a normal range of 1.343-2.368 (with 95% confidence interval) in plasma. CONCLUSIONS: Three potential biomarkers and one criterion for potential liver injury caused by PM that may be more sensitive than ALT and AST were found.