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This study investigates whether green bonds (GBs) can hedge against geopolitical risk (GPR). This study extends the booming literature on GPR and GBs, develops a modified connectedness network model to measure the connectedness between GPR and GBs, confirms the hedging property of GBs against GPR, and becomes the first to discuss alternative hedging properties of GBs against GPR. We find evidence of market-, time-, and quantile-varying linkage between GPR and GB markets based on the time-varying Granger causality test and quantile extended joint spillover index model. We confirm via a regression model that only the GB markets in China and Japan can hedge against GPR. At the same time, GB in China remains a weak hedging and safety-haven asset simultaneously. The results remain robust for alternative proxy variables, data frequency, and model specification. Finally, the MVP approach provides superior performance while maintaining weak hedging and safety-haven properties against GPR. This study has considerable portfolio-related implications: (1) it offers an efficient hedge (i.e., GB) against GPR, (2) the heterogeneous performance of regional GB markets reminds investors to be cautious when selecting GBs assets, and (3) it encourages reasonable investment allocations on GBs to achieve a balance between profit and risk. First published online 24 September 2024

Abstract Background Breast cancer ranks first among malignant tumors, of which triple-negative breast cancer (TNBC) is characterized by its highly invasive behavior and the worst prognosis. Timely diagnosis and precise treatment of TNBC are substantially challenging. Abnormal tumor vessels play a crucial role in TNBC progression and treatment. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis, while effective NO delivery can normalize the tumor vasculature. Accordingly, we have proposed here a tumor vascular microenvironment remodeling strategy based on NO-induced vessel normalization and extracellular matrix collagen degradation with multimodality imaging-guided nanoparticles against TNBC called DNMF/PLGA. Results Nanoparticles were synthesized using a chemotherapeutic agent doxorubicin (DOX), a NO donor L-arginine (L-Arg), ultrasmall spinel ferrites (MnFe2O4), and a poly (lactic-co-glycolic acid) (PLGA) shell. Nanoparticle distribution in the tumor was accurately monitored in real-time through highly enhanced magnetic resonance imaging and photoacoustic imaging. Near-infrared irradiation of tumor cells revealed that MnFe2O4 catalyzes the production of a large amount of reactive oxygen species (ROS) from H2O2, resulting in a cascade catalysis of L-Arg to trigger NO production in the presence of ROS. In addition, DOX activates niacinamide adenine dinucleotide phosphate oxidase to generate and supply H2O2. The generated NO improves the vascular endothelial cell integrity and pericellular contractility to promote vessel normalization and induces the activation of endogenous matrix metalloproteinases (mainly MMP-1 and MMP-2) so as to promote extravascular collagen degradation, thereby providing an auxiliary mechanism for efficient nanoparticle delivery and DOX penetration. Moreover, the chemotherapeutic effect of DOX and the photothermal effect of MnFe2O4 served as a chemo-hyperthermia synergistic therapy against TNBC. Conclusion The two therapeutic mechanisms, along with an auxiliary mechanism, were perfectly combined to enhance the therapeutic effects. Briefly, multimodality image-guided nanoparticles provide a reliable strategy for the potential application in the fight against TNBC. Graphical Abstract

n-Type silicon (n-Si), with surface easily oxidized and passivated in an aqueous electrolyte, has suffered from sluggish oxygen evolution reaction (OER) kinetics for photoelectrochemical (PEC) water splitting. Herein, a trimetallic Ni0.9Fe0.05Co0.05 protective layer is successfully electrodeposited on a p+n-Si substrate by underpotential deposition. The prepared Ni0.9Fe0.05Co0.05/p+n-Si photoanode exhibits excellent stability and activity for PEC water oxidation, with a low onset potential of 0.938 V versus a reversible hydrogen electrode (RHE) and a remarkable photocurrent density of about 33.1 mA∙cm−2 at 1.23 V versus RHE, which significantly outperforms the Ni/p+n-Si photoanode as a reference. It is revealed that the incorporation of Fe into the Ni layer creates a large band bending at the Ni0.9Fe0.05Co0.05/p+n-Si interface, promoting interfacial charge separation. Moreover, the incorporation of Co produces abundant Ni3+ and oxygen vacancies (Ov) that act as active sites to accelerate the OER kinetics, synergistically contributing to a major enhancement of PEC water oxidation activity. Encouragingly, by connecting the Ni0.9Fe0.05Co0.05/p+n-Si photoanode to an inexpensive Si solar cell, an integrated photovoltaic/PEC (PV/PEC) device achieved a solar-to-hydrogen conversion efficiency of as high as 12.0% without bias. This work provides a facile approach to design efficient and stable n-Si-based photoanodes with a deep understanding of the structure–activity relationship, which exhibits great potential for the integration of low-cost PV/PEC devices for unassisted solar-driven water splitting.

Objective: To study the protective effect of broad bean seedling extract (BSE) on Parkinson’s disease. Methods: PC-12 and SH-SY5Y cell injury were induced by 50 μmol/L 6-OHDA. The effects of BSE on the proliferation of neuro cells were determined by MTT method. The effects of BSE on reactive oxygen species (ROS), mitochondrial membrane potential and apoptosis in neuro cells were measured. The mouse model of Parkinson’s disease was established by intraperitoneal injection of MPTP, and the mice were divided into blank control group, model control group, 500 mg/kg BSE group, 300 mg/kg BSE group and 25 mg/kg L-dopa group with 6 rats in each group. The effects of BSE on the behavioral function of mice were studied via pole climbing test, rotation test and grip test, and the effects of BSE on the contents of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the brain of mice were determined by the test kit. Results: After PC-12 and SH-SY5Y neuro cells were treated by 6-OHDA, the cell proliferation was inhibited, the level of reactive oxygen species increased, the mitochondrial membrane potential decreased and the apoptosis increased. After pretreatment with BSE, the inhibition rate of cell proliferation and the level of reactive oxygen species were significantly decreased, the mitochondrial membrane potential was increased and the apoptosis was inhibited (P

Hypoxia is one of the major causes of cancer resistance and metastasis. Currently, it is still lack of convenient ways to simulate the in vivo hypoxic tumor microenvironment (TME) under normoxia in vitro. In this study, based on multi-polymerized alginate, we established a three-dimensional culture system with a core-shell structure (3d-ACS), which prevents oxygen diffusion to a certain extent, thereby simulating the hypoxic TME in vivo. The cell activity, hypoxia inducible factor (HIF) expression, drug resistance, and the related gene and protein changes of the gastric cancer (GC) cells were investigated in vitro and in vivo. The results demonstrated that the GC cells formed organoid-like structures in the 3d-ACS and manifested more aggressive growth and decreased drug responses. Our study provides an accessible hypoxia platform in the laboratory with moderate configuration and it may be applied in studies of the hypoxia-induced drug resistances and other preclinical fields.

In this study, we conducted a 56-d feeding trial to investigate the effects of replacing the fish oil (FO) with palm oil (PO) on the performance, tissue fatty acid (FA) composition, and mRNA levels of genes related to hepatic lipid metabolism in grouper (Epinephelus coioides). Five isolipidic (13% crude lipid) and isonitrogenous (48% CP) diets were formulated by incrementally adding PO to the control diet (25% fish meal and 9% added FO) to replace FO in the control diets. Triplicate groups of 30 groupers (initial weight: 12.6 ± 0.1 g) were fed one of the diets twice daily, to apparent satiety. The replacement of FO with 50% PO revealed maximum growth without affecting the performance and whole-body proximate compositions, and replacing FO with 100% PO revealed a comparable (P > 0.05) growth with that of the control diet, suggesting PO as a suitable alternative to FO. The analysis of FA profiles in the dorsal muscle and liver though reflected the FA profile of the diet, PO substitutions above 50% could compromise (P

Abstract Background Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy. Results Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy. Conclusions The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation. Graphical Abstract

ObjectivesTo determine the predictors of axillary lymph node metastasis (ALNM), two nomogram models were constructed to accurately predict the status of axillary lymph nodes (ALNs), mainly high nodal tumour burden (HNTB, > 2 positive lymph nodes), low nodal tumour burden (LNTB, 1-2 positive lymph nodes) and negative ALNM (N0). Accordingly, more appropriate treatment strategies for breast cancer patients without clinical ALNM (cN0) could be selected.MethodsFrom 2010 to 2015, a total of 6314 patients with invasive breast cancer (cN0) were diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and internal validation groups at a ratio of 3:1. As the external validation group, data from 503 breast cancer patients (cN0) who underwent axillary lymph node dissection (ALND) at the Second Affiliated Hospital of Chongqing Medical University between January 2011 and December 2020 were collected. The predictive factors determined by univariate and multivariate logistic regression analyses were used to construct the nomograms. Receiver operating characteristic (ROC) curves and calibration plots were used to assess the prediction models’ discrimination and calibration.ResultsUnivariate analysis and multivariate logistic regression analyses showed that tumour size, primary site, molecular subtype and grade were independent predictors of both ALNM and HNTB. Moreover, histologic type and age were independent predictors of ALNM and HNTB, respectively. Integrating these independent predictors, two nomograms were successfully developed to accurately predict the status of ALN. For nomogram 1 (prediction of ALNM), the areas under the receiver operating characteristic (ROC) curve in the training, internal validation and external validation groups were 0.715, 0.688 and 0.876, respectively. For nomogram 2 (prediction of HNTB), the areas under the ROC curve in the training, internal validation and external validation groups were 0.842, 0.823 and 0.862. The above results showed a satisfactory performance.ConclusionWe established two nomogram models to predict the status of ALNs (N0, 1-2 positive ALNs or >2 positive ALNs) for breast cancer patients (cN0). They were well verified in further internal and external groups. The nomograms can help doctors make more accurate treatment plans, and avoid unnecessary surgical trauma.

Credit scoring, which is typically transformed into a classification problem, is a powerful tool to manage credit risk since it forecasts the probability of default (PD) of a loan application. However, there is a growing trend of integrating survival analysis into credit scoring to provide a dynamic prediction on PD over time and a clear explanation on censoring. A novel dynamic credit scoring model (i.e., SurvXGBoost) is proposed based on survival gradient boosting decision tree (GBDT) approach. Our proposal, which combines survival analysis and GBDT approach, is expected to enhance predictability relative to statistical survival models. The proposed method is compared with several common benchmark models on a real-world consumer loan dataset. The results of out-of-sample and out-of-time validation indicate that SurvXGBoost outperform the benchmarks in terms of predictability and misclassification cost. The incorporation of macroeconomic variables can further enhance performance of survival models. The proposed SurvXGBoost meanwhile maintains some interpretability since it provides information on feature importance. First published online 14 December 2020

ObjectivesTo screen out the predictors of central cervical lymph node metastasis (CLNM) for papillary thyroid carcinoma (PTC) and establish a prediction model to guide the operation of PTC patients (cN0).MethodsData from 296 PTC patients (cN0) who underwent thyroid operation at the Second Affiliated Hospital of Chongqing Medical University were collected and retrospectively analyzed. They were divided into two groups in accordance with central CLNM or not. Their information, including ultrasound (US) features, BRAFV600E status, and other characteristics of the two groups, was analyzed and compared using univariate and multivariate logistic regression analyses, and the independent predictors were selected to construct a nomogram. The calibration plot, C-index, and decision curve analysis were used to assess the prediction model’s calibration, discrimination, and clinical usefulness.ResultsA total of 37.8% (112/296) of PTC patients had central CLNM, and 62.2% (184/296) did not. The two groups were compared using a univariate logistic regression analysis, and there were no significant differences between the two groups in sex, aspect ratio, boundary, morphology, hypoechoic nodule, thyroid peroxidase antibody, or tumor location (P>0.05), and there were significant differences between age, tumor size, capsule contact, microcalcifications, blood flow signal, thyroglobulin antibodies (TgAb), and BRAF gene status (P 1.0 cm), US features (microcalcifications), and TgAb (positive), were screened out. A visualized nomogram model was established based on the three predictors in this study, which could be used as a basis of central cervical lymph node dissection (CLND) for PTC patients (cN0).

This paper constructs an enterprise green development performance system by integrating green development concept and enterprise performance measurement. Based on the panel data of 458 industrial listed enterprises in China from 2011 to 2018, this paper simulates the green development performance index of industrial enterprises by using the functional data analysis method and functional entropy weight method. There are four main conclusions. First, the change in the green development performance index of industrial enterprises is U-shaped, which shows an upward trend overall. Within a range of [0.006–0.05], the minimum value is 0.006, and considering the strength and trend of future policies there is no maximum value. The higher the value is, the higher the level of green development of industrial enterprises. Second, according to the weight and fitting curves, we can find that the importance and development level of social performance are at the highest, and the importance level basically floats around 0.5, far higher than the average level. The importance of economic performance and the development level of innovation performance are at the lowest respectively, and there is a big gap with the average level. Third, the shape and trend of the index generated by the average weight and the subjective weight of social performance are basically consistent with the index generated by the objective weight. This shows that the index is not sensitive to the weight and has certain robustness and representativeness. Finally, according to the location of enterprises, they were divided into three categories: middle, east and west. The boost Trap method was used to conduct FANOVA (Functional ANOVA) with the P value of 0.314. The results showed that the index did not differ significantly between regions at the significance level of 0.05.

The present study investigated the effects of ferulic acid (FA) on the growth performance, serum cytokine profile, intestinal morphology, and intestinal microbiota in ducks at the growing stage. 300 female Linwu ducks at 28 days of age with similar body weights were randomly divided into five groups. Each group contained six replicates of 10 birds. The dietary treatments were corn-soybean-based diet supplemented with FA at the concentrations of 0 (control), 100, 200, 400, and 800 mg/kg diet. The results demonstrated that dietary FA at the levels of 200, 400, and 800 mg/kg increased the average daily gain (P = 0.01), 400 and 800 mg/kg FA increased the final body weight (P = 0.02), 100, 200, and 800 mg/kg FA increased the serum glutathione (P = 0.01), and 100, 400, and 800 mg/kg FA increased the glutathione peroxidase activities in birds (P < 0.01). Additionally, 200, 400, and 800 mg/kg dietary FA lowered the serum levels of interleukin-2 (P = 0.02) and interleukin-6 (P = 0.04). Moreover, the morphometric study of the intestines indicated that 400 mg/kg FA decreased the crypt depth in jejunum (P = 0.01) and caecum (P = 0.04), and increased the ratio of villus height to crypt depth in jejunum (P = 0.02). Significant linear and/or quadratic relationships were found between FA concentration and the measured parameters. 16S rRNA sequencing revealed that dietary FA increased the populations of genera Faecalibacterium, Paludicola, RF39, and Faecalicoccus in the cecum (P < 0.05), whereas decreased the populations of Anaerofilum and UCG-002 (P < 0.05). The Spearman correlation analysis indicated that phylum Proteobacteria were negatively, but order Oscillospirales, and family Ruminococcaceae were positively related to the parameters of the growth performance. Phylum Bacteroidetes, class Negativicutes and family Rikenellaceae were negatively associated with the parameters of the antioxidative capability. And phylum Cyanobacteria, Elusimicrobia, and Bacteroidetes, class Bacilli, family Rikenellaceae, and genus Prevotella were positively associated with the parameters of the immunological capability. Thus, it was concluded that the supplementations of 400 mg/kg FA in diet was able to improve the growth performance, antioxidative and immunological capabilities, intestinal morphology, and modulated the gut microbial construction of Linwu ducks at the growing stage.

The mutations of polyglutamine binding protein 1 gene (PQBP1) can lead to the rare inherited X-linked Renpenning syndrome (X-RSY). Here, an induced pluripotent stem cell (iPSC) line WMUi017-A was generated through reprogramming the urine cells of a 5-year-old male X-RSY patient with the hemizygous PQBP1 gene mutation p.P609A (c.1825C>G) using the commercial Sendai virus reprogramming system. The established iPSCs can stably express pluripotent stem cell markers OCT4 and NANOG, and can be induced into three germ layers and maintain a normal karyotype (46, XY) in vitro.

An adaptive projected affine scaling algorithm of cubic regularization method using a filter technique for solving box constrained optimization without derivatives is put forward in the passage. The affine scaling interior-point cubic model is based on the quadratic probabilistic interpolation approach on the objective function. The new iterations are obtained by the solutions of the projected adaptive cubic regularization algorithm with filter technique. We prove the convergence of the proposed algorithm under some assumptions. Finally, experiments results showed that the presented algorithm is effective in detail.

Ecosystem services are directly related to human well-being. Previous studies showed that management policies and human activities alter the trade-offs and synergies of ecosystem services. Taking effective measures to manage the trade-offs and synergies of ecosystem services is essential to sustain ecological security and achieve a “win-win” situation between society and ecosystems. This study investigated the spatiotemporal changes of water yield, soil conservation, and carbon sequestration in the Jiulianshan National Nature Reserve from 2000 to 2020 based on the InVEST model. We distinguished spatial patterns of trade-offs and synergies between ecosystem services using the correlation relationship analysis. Then we analyzed the response of ecosystem services relationships among different vegetation types and elevation bands. The results showed that water yield and carbon sequestration presented an overall upward trend, while soil conservation remained a marginal degradation. Rising ecosystem services were mainly in the central, western, and southeastern regions, and declining areas were mainly distributed in the midwestern and northeastern fringes. Synergies spatially dominated the interactions among water yield, soil conservation, and carbon sequestration, and the trade-offs were primarily concentrated in the northern, southern, and southwestern fringes. Among the different vegetation types, synergies dominated ecosystem services in broad-leaved forests, coniferous forests, mixed forests, and Moso bamboo forests and in grass. The trade-offs were gradually reduced with elevation. This study highlighted that trade-off of ecosystem services should be incorporated into ecological management policies, strengthening the effectiveness of nature reserves in protecting and improving China’s ecosystem services.

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Among studies of the factors that influence carbon emissions and related regulations, economic aggregates, industrial structures, energy structures, population levels, and energy prices have been extensively explored, whereas studies from the perspective of fiscal leverage, particularly of local government investment (LGI), are rare. Of the limited number of studies on the effect of LGI on carbon emissions, most focus on its direct effect. Few studies consider regulatory effects, and there is a lack of emphasis on local areas. Using a cointegration test, a panel data model and clustering analysis based on Chinese data between 2000 and 2013, this study measures the direct role of LGI in carbon dioxide (CO2) emissions reduction. First, overall, within the sample time period, a 1% increase in LGI inhibits carbon emissions by 0.8906% and 0.5851% through its influence on the industrial structure and energy efficiency, respectively, with the industrial structure path playing a greater role than the efficiency path. Second, carbon emissions to some extent exhibit inertia. The previous year's carbon emissions impact the following year's carbon emissions by 0.5375%. Thus, if a reduction in carbon emissions in the previous year has a positive effect, then the carbon emissions reduction effect generated by LGI in the following year will be magnified. Third, LGI can effectively reduce carbon emissions, but there are significant regional differences in its impact. For example, in some provinces, such as Sichuan and Anhui, economic growth has not been decoupled from carbon emissions. Fourth, the carbon emissions reduction effect in the 30 provinces and municipalities sampled in this study can be classified into five categories-strong, relatively strong, medium, relatively weak and weak-based on the degree of local governments' regulation of carbon emissions. The carbon emissions reduction effect of LGI is significant in the western and central regions of China but not in the eastern and northeast regions. This study helps overcome the limitations of previous studies on the regulatory effects of LGI on carbon emissions, and the constructed model may more closely reflect actual economic conditions. Moreover, the current study can benefit countries similar to China that aim to objectively identify the impacts of their LGI on carbon emissions, and such countries can use it as a reference in the formulation of investment policies based on their economic and industrial characteristics.