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Abstract Green finance (GF) is recognized as a key driver of sustainable development. While existing studies have extensively discussed the relationship between GF and the Sustainable Development Goals (SDGs), few have explored the coupling coordination relationship between GF and SDGs. In this paper, we use data from thirty Chinese provinces (municipalities and autonomous regions) from 2008–2021 to examine the degree of coupling coordination development (CCD) between GF and the SDGs systems using the CCD model. We find that most SDGs and their sub-goals exhibit a significant upward trend, except for SDG8, 14–16. GF presents a fluctuating upward trend, with a significant decline in 2010 and 2019. The CCDs between GF and SDGs and their sub-goals generally show an M-shaped upward trend in most regions, with most of them experiencing a synchronous decline in 2011–2012 and 2019. In the analysis of regional heterogeneity, the eastern region performs better in SDG8–9, the central region performs better in SDG3, 14–15, while the western region performs better in SDG7. This paper provides empirical evidence for a further in-depth understanding of the relationship between GF and SDGs, which can contribute to advancing GF development and the SDG process.

Purpose: As the most common subset of breast cancer (BC), estrogen receptor positive (ER+) BC accounting for 80% of cases, has become a global public health concern. The female hormone estrogen (E2) unequivocally drives ER + breast malignancies. The reasons that estrogen affects BC development has long been considered, yet further study remains to be conducted of the molecular events in the E2-estrogen receptor α (ERα) signaling pathway in ER + BC progression, especially lipid metabolism, so providing more options for tailored and individualized therapy. Our aim is to find out new targets and clinical biomarkers for ER + breast cancer treatment from the perspective of lipid metabolism. Methods: Lipid metabolomics profiling was used to examine the membrane phospholipid stimulated by E2. Clinical BC samples were used to assess the association of CYP4F2, CYP4F11 expression with clinicopathological characteristics and patient outcomes. Some inhibitors of main enzymes in AA metabolism were used combined with E2 to assess roles of CYP4F2/CYP4F11 in the progression of ER + BC. CYP4F2, CYP4F11 overexpression and knockdown BC cell lines were employed to examine the effects of CYP4F2, CYP4F11 on cellular proliferation, apoptosis and tumor growth. Western blotting, qPCR, Immunohistochemical staining and flow cytometry were also conducted to determine the underlying mechanisms related to CYP4F2, CYP4F11 function. Results: The activation of the CYP450 signaling pathway in arachidonic acid metabolism contributed to ER + BC tumorigenesis. In ER + BC, CYP4F2 and CYP4F11 overexpression induced by E2 could promote cancer cell proliferation and resistance to apoptosis by producing the metabolite 20-HETE and activating the antiapoptotic protein Bcl-2. CYP4F2 and CYP4F11 elevation correlates with poorer overall survival and disease-free survival in ER + BC patients. Conclusion: CYP4F2, CYP4F11 and their metabolite 20-HETE could serve as effective prognostic markers and attractive therapeutic targets for novel anticancer drug development about ER + BC.

Abstract China’s Belt and Road Initiative (BRI) aims to strengthen regional economic and policy cooperation and achieve the rapid development among the participating countries. While the impact on the financial development of the economic growth and energy environment of BRI participating countries has garnered close attention among scholars, few studies focus on the impact of financial development on the sustainable development goals (SDGs) of the BRI participating countries. To address this gap, we utilized panel regression models to quantitatively assess the impact of China’s financial development scale, structure, and efficiency on the SDGs of the BRI participating countries, and adopted Geographically and Temporally Weighted Regression (GTWR) model to explore the spatial-temporal effects of China’s financial development scale, structure, and efficiency on the SDGs of the BRI participating countries. Our findings indicate that China’s financial development has significantly promoted the SDGs of the BRI participating countries. This study further reveals that the scale and efficiency of China’s financial development have had a more pronounced impact on the SDGs of Asian countries, low- and middle-income countries, and the Land Silk Road participating countries, compared to those of European countries, high-income countries, and the Maritime Silk Road participating countries, respectively. In contrast, the structure of financial development primarily promotes the SDGs of European and high-income BRI participating countries in the land silk belt. The role of China’s financial development in promoting the SDGs of most BRI participating countries has gradually increased over time. This study provides valuable insights for decision-makers in China to facilitate the sustainable development of BRI participating countries and foster a shared community within the BRI framework.

Abstract Emission Trading System (ETS) is an innovative practice under the progress of green development in China. It is also an important method for China to achieve market-oriented environmental governance in ecological civilization construction. The ETS pilot policy has implemented for more than 10 years. However, the co-benefits of ETS pilot policy by the integration of energy consumption, carbon and sulfur dioxide emissions, and wastewater has not been evaluated. In order to fill this gap, we use the 2003–2017 annual data of 30 China’s provinces (municipalities and autonomous regions), and utilize the Difference-in-Differences (DID) model and Propensity Score Matching (PSM-DID) methodology to evaluate the co-benefits of ETS pilot policy on energy conservation and emission reduction. We find that the ETS pilot policy significantly promote energy conservation and emission reduction. Eastern and central China have significantly benefited from the policy, while the western China has not due to the limited technology and innovation as well as an imbalance of the industrial structure. The results provide the policy reference for China’s government and institutions as well as the governments and institutions around the world to fulfill their commitments to save energy and reduce emissions, and early achieve the carbon peaking and carbon neutralization.

Pepper anthracnose caused by Colletotrichum gloeosporioides infection is an important fungal disease and represents a serious threat to pepper yield and quality. At present, the pathogenic molecular mechanism of C. gloeosporioides is not very clear. In our study, we characterized the function of C. gloeosporioides CgNis1, a homolog of Magnaporthe oryzae MoNis1. We found that the ∆Cgnis1 mutant reduced the growth rate and was defective in conidiation. Although the rate of appressorium formation was unaffected, the germ tube was found to be abnormal. CgNis1 was shown to be involved in the H2O2 stress response and maintaining cell membrane permeability. The pathogenicity assays performed in this study indicated that the deletion of CgNIS1 is associated with virulence. Our results indicate that CgNis1 is necessary for the growth, development, and pathogenicity of the fungus. This work provides an in-depth analysis of the Nis1 protein, helps to enhance studies on pathogen-related molecular mechanisms, and provides a theoretical basis for the prevention and control of C. gloeosporioides in peppers.

Gold nanoparticle (AuNPs) influence the biomedical sciences owing to different potential characteristics and potential features. To date, the bioinspired fabrication of AuNPs is further recognized due to their safety and efficacy. In this study, we synthesized AuNPs using leaf extract of Citrus medica (C. medica) and well-characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and UV–visible analyses. Afterward the selective anticancer effects of biosynthesized AuNPs against HepG2 cells were evaluated by different techniques including MTT, oxidative markers, qPCR, and western blot assays.The results showed that the polyphenols of the C. medica leaf extract was responsible for the bioinspired reduction and stability of the AuNPs with a powder size in the range of 20–50 nm. Additionally, it was seen that biosynthesized AuNPs show selective inhibition on the proliferation of HepG2 (human liver cancer cell line) relative to THLE3 (normal adult liver epithelial cells) via generation of ROS and MDA, reduction of GSH level and SOD activity, and over expression of Bax/Bcl-2 and Caspase-3 mRNA. It was also shown that biosynthesized AuNPs regulate the Wnt signaling pathway through upregulation of phosphorylated GSK-3β known as the inactivated form of GSK-3β and downregulation of β-catenin and Cyclin-D1 at protein level. This study may hold great promise for development of NP-based anticancer agents, although it needs further investigations in vivo.

Abstract Background Lymphangioleiomyomatosis (LAM) is a female‐predominant interstitial lung disease, characterized by progressive cyst formation and respiratory failure. Clinical treatment with the mTORC1 inhibitor rapamycin could relieve partially the respiratory symptoms, but not curative. It is urgent to illustrate the fundamental mechanisms of TSC2 deficiency to the development of LAM, especially mTORC1‐independent mechanisms. Glutaredoxin‐1 (Glrx), an essential glutathione (GSH)‐dependent thiol‐oxidoreductase, maintains redox homeostasis and participates in various processes via controlling protein GSH adducts. Redox signalling through protein GSH adducts in LAM remains largely elusive. Here, we demonstrate the underlying mechanism of Glrx in the pathogenesis of LAM. Methods 1. Abnormal Glrx expression in various kinds of human malignancies was identified by the GEPIA tumour database, and the expression of Glrx in LAM‐derived cells was detected by real‐time quantitative reverse transcription (RT‐qPCR) and immunoblot. 2. Stable Glrx knockdown cell line was established to evaluate cellular impact. 3. Cell viability was determined by CCK8 assay. 4. Apoptotic cell number and intracellular reactive oxygen species (ROS) level were quantified by flow cytometry. 5. Cox2 expression and PGE2 production were detected to clarify the mechanism of Bim expression modulated by Glrx. 6. S‐glutathionylated p65 was enriched and detected by immunoprecipitation and the direct regulation of Glrx on p65 was determined. 7. The xenograft animal model was established and photon flux was analyzed using IVIS Spectrum. Results In LAM, TSC2 negatively regulated abnormal Glrx expression and activation in a mTORC1‐independent manner. Knockdown of Glrx increased the expression of Bim and the accumulation of ROS, together with elevated S‐glutathionylated proteins, contributing to the induction of apoptotic cell death and inhibited cell proliferation. Knockdown of Glrx in TSC2‐deficient LAM cells increased GSH adducts on nuclear factor‐kappa B p65, which contributed to a decrease in the expression of Cox2 and the biosynthesis of PGE2. Inhibition of PGE2 metabolism attenuated phosphorylation of ERK, which led to the accumulation of Bim, due to the imbalance of its phosphorylation and proteasome degradation. In xenograft tumour models, knockdown of Glrx in TSC2‐deficient LAM cells inhibited tumour growth and increased tumour cell apoptosis. Conclusions Collectively, we provide a novel redox‐dependent mechanism in the pathogenesis of LAM and propose that Glrx may be a beneficial strategy for the treatment of LAM or other TSC‐related diseases.

Abstract Lymphangioleiomyomatosis (LAM), a progressive pulmonary disease exclusively affecting females, is caused by defects or mutations in the coding gene tuberous sclerosis complex 1 (TSC1) or TSC2, causing the mammalian target of rapamycin complex 1 (mTORC1) activation and autophagy inhibition. Clinically, rapamycin shows limited cytocidal effects, and LAM recurs after drug withdrawal. In this study, we demonstrated that TSC2 negatively regulated the sphingolipid metabolism pathway and the expressions of sphingosine kinase 1 (SPHK1) and sphingosine-1-phosphate receptor 3 (S1PR3) were significantly elevated in LAM patient-derived TSC2-deficient cells compared to TSC2-addback cells, insensitive to rapamycin treatment and estrogen stimulation. Knockdown of SPHK1 showed reduced viability, migration and invasion in TSC2-deficient cells. Selective SPHK1 antagonist PF543 potently suppressed the viability of TSC2-deficient cells and induced autophagy-mediated cell death. Meanwhile, the cognate receptor S1PR3 was identified to mediating the tumorigenic effects of sphingosine-1-phosphate (S1P). Treatment with TY52156, a selective antagonist for S1PR3, or genetic silencing using S1PR3-siRNA suppressed the viability of TSC2-deficient cells. Both SPHK1 and S1PR3 inhibitors markedly exhibited antitumor effect in a xenograft model of TSC2-null cells, restored autophagy level, and triggered cell death. Together, we identified novel rapamycin-insensitive sphingosine metabolic signatures in TSC2-null LAM cells. Therapeutic targeting of aberrant SPHK1/S1P/S1PR3 signaling may have potent therapeutic benefit for patients with TSC/LAM or other hyperactive mTOR neoplasms with autophagy inhibition.

Abstract Pancreatic cancer has an extremely terrible prognosis and is a common cause of cancer death. In this study, the clinic value, biological function and underlying mechanisms of Zinc finger protein 655 (ZNF655) in human pancreatic cancer were evaluated. The expression level of ZNF655 in pancreatic cancer was determined by immunohistochemistry (IHC) staining. The biological effects of ZNF655 in pancreatic cancer cells was investigated by loss/gain-of-function assays in vitro and in vivo. The downstream molecular mechanism of ZNF655 was explored using co-immunoprecipitation (Co-IP), dual-luciferase reporter and chromatin immunoprecipitation (Ch-IP). ZNF655 expression was significantly elevated in human pancreatic cancer and possessed clinical value in predicting poor prognosis. Functionally, ZNF655 knockdown inhibited the biological progression of pancreatic cancer cells, which was characterized by weaken proliferation, enhanced apoptosis, arrested cell cycle in G2, impeded migration, and suppressed tumor growth. Mechanistically, ZNF655 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the cyclin-dependent kinase 1 (CDK1) promoter. Furthermore, knockdown of CDK1 alleviated the promoting effects of ZNF655 overexpression in pancreatic cancer cells. The promotive role of ZNF655 in pancreatic cancer via CDK1 was determined, which drew further interest regarding its clinical application as a promising therapeutic target.

Tuberous sclerosis complex (TSC) is characterized by multisystem, low-grade neoplasia involving the lung, kidneys, brain, and heart. Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease affecting almost exclusively women. TSC and LAM are both caused by mutations in TSC1 and TSC2 that result in mTORC1 hyperactivation. Here, we report that single-cell RNA sequencing of LAM lungs identified activation of genes in the sphingolipid biosynthesis pathway. Accordingly, the expression of acid ceramidase (ASAH1) and dihydroceramide desaturase (DEGS1), key enzymes controlling sphingolipid and ceramide metabolism, was significantly increased in TSC2-null cells. TSC2 negatively regulated the biosynthesis of tumorigenic sphingolipids, and suppression of ASAH1 by shRNA or the inhibitor ARN14976 (17a) resulted in markedly decreased TSC2-null cell viability. In vivo, 17a significantly decreased the growth of TSC2-null cell–derived mouse xenografts and short-term lung colonization by TSC2-null cells. Combined rapamycin and 17a treatment synergistically inhibited renal cystadenoma growth in Tsc2+/– mice, consistent with increased ASAH1 expression and activity being rapamycin insensitive. Collectively, the present study identifies rapamycin-insensitive ASAH1 upregulation in TSC2-null cells and tumors and provides evidence that targeting aberrant sphingolipid biosynthesis pathways has potential therapeutic value in mechanistic target of rapamycin complex 1–hyperactive neoplasms, including TSC and LAM.

Information is a critical element of capital markets, and liquidity is the lifeblood of capital markets. Relative to historical information, forward-looking information is of significant value to investors. Based on textual analysis calculations, we selected Chinese A-share listed companies as a research sample to explore the impact of forward-looking information disclosure level on stock liquidity. It is found that the higher the level of forward-looking information disclosure, the better the stock liquidity. Investor sentiment is the transmission mechanism through which the forward looking statement disclosure level affects stock liquidity. The heterogeneity analysis shows that the level of forward-Looking statement disclosure has a more significant effect on stock liquidity improvement for state-owned enterprises and enterprises in low-market regions than those in regions with high marketization levels. The article expands and enriches the research on forward-looking information disclosure, and also has some reference value for regulators to formulate laws and regulations and regulate forward-looking information disclosure.

Lakes play a crucial role in the global water cycle and significantly contribute to enhancing regional ecological environments and simulating economic growth. In this study, based on the data from the Landsat TM 4-5, Landsat 7 ETM SLC-off, and Landsat 8-9 OLI/TIRS C2 L2 satellites, the surface area of Qinghai Lake is obtained by using the Normalized Difference Water Index (NDWI) method. Additionally, leveraging the European Centre for Medium-Range Weather Forecasts (ECMWF) fifth-generation land surface reanalysis dataset (ERA5-Land), we analyzed the interplay between lake area and related climate factors by using the Noise Assisted–Multivariate Empirical Mode Decomposition (NA-MEMD) and wavelet coherence analysis method. The surface area of Qinghai Lake showed an overall expansion trend from 1986 to 2022, with an expansion rate of 2.89 km2/a. Precipitation, temperature, and evapotranspiration (ET) also showed an increasing trend, with the largest increasing trend in autumn, summer, and summer, respectively. The area of Qinghai Lake did not demonstrate distinct periodic patterns from 1986 to 2022, in contrast to the marked 8–16 month oscillations observed in precipitation, temperature, and ET. In the phase of lake area expansion between 2008 and 2016, changes in the lake’s surface area were observed to trail behind variations in precipitation and temperature by approximately three months. Furthermore, the shift in ET was found to lag behind alterations in the lake area, displaying a delay of 3–6 months.

Measurement(s) Metagenome Technology Type(s) Illumina Sequencing Factor Type(s) Genotype Sample Characteristic - Organism Oryza sativa Sample Characteristic - Environment agricultural field Sample Characteristic - Location China

The extreme marine weather is a very vital factor and has important implications for of marine economic development. However, there is a lack of systematic and quantitative analyses of its impact on the marine economic development. Here, we study the impacts of extreme marine weather on marine economic development of 11 coastal regions in China, using the dynamic panel model. We found that extreme marine weather exerts a significant negative impact on the marine economic development. The marine scientific and technological innovation promotes marine economic development in a prominent manner. The marine scientific and technological innovation slows down the unfavorable impact of extreme marine weather on the marine economy. After considering different industries for marine economic development and heterogeneity, we found that extreme marine weather and marine scientific and technological innovation have a great impact on marine economic development in the tertiary industry and the areas with high development concerning marine economy level, while deliver a small impact on the marine economic development in the primary industry and the areas low development level. This paper empirically studies the relationship between the two variables of marine extreme weather and marine science and technology innovation and its impact on marine economic development, enriches the research perspective of extreme weather on marine economic development, and provides new method evidence for improving the level of marine scientific and technological innovation and promoting the development of marine economy.

We have simulated BiCoO3 films epitaxially grown along (001) direction with density functional theory computations. Leading candidates for the lowest-energy phases have been identified. The tensile strains induce magnetic phase transition in the ground state (P4mm symmetry) from a C-type antiferromagnetic order to a G-type order for the in-plane lattice parameter above 3.922 Å. The G-type antiferromagnetic order will be maintained with larger tensile strains; however, a continuous structural phase transition will occur, combining the ferroelectric and antiferrodistortive modes. In particular, the larger tensile strain allows an isostructural transition, the so-called Cowley’s ‘‘Type Zero’’ phase transitions, from Cc-(I) to Cc-(II), with a slight volume collapse. The orientation of ferroelectric polarization changes from the out-of-plane direction in the P4mm to the in-plane direction in the Pmc21 state under epitaxial tensile strain; meanwhile, the magnetic ordering temperature TN can be strikingly affected by the variation of misfit strain.

This paper proposes an adaptive threshold segmentation algorithm for the magnesium ingot stack based on image overexposure area correction (ATSIOAC), which solves the problem of mirror reflection on the surface of magnesium alloy ingots caused by external ambient light and auxiliary light sources. Firstly, considering the brightness and chromaticity information of the mapped image, we divide the exposure probability threshold into weak exposure and strong exposure regions. Secondly, the saturation difference between the magnesium ingot region and the background region is used to obtain a mask for the magnesium ingot region to eliminate interference from the image background. Then, the RGB average of adjacent pixels in the overexposed area is used as a reference to correct the colors of the strongly exposed and weakly exposed areas, respectively. Furthermore, in order to smoothly fuse the two corrected images, pixel weighted average (WA) is applied. Finally, the magnesium ingot sorting experimental device was constructed and the corrected top surface image of the ingot pile was segmented through ATSIOAC. The experimental results show that the overexposed area detection and correction algorithm proposed in this paper can effectively correct the color information in the overexposed area, and when segmenting ingot images, complete segmentation results of the top surface of the ingot pile can be obtained, effectively improving the accuracy of magnesium alloy ingot segmentation. The segmentation algorithm achieves a segmentation accuracy of 94.38%.

Abstract Cold tolerance at the bud burst stage (CTB) is a key trait for direct-seeded rice. Although quantitative trait loci (QTL) affecting CTB in rice have been mapped using traditional linkage mapping and genome-wide association study (GWAS) methods, the underlying genes remain unknown. In this study, we evaluated the CTB phenotype of 339 cultivars in the Rice Diversity Panel II (RDP II) collection. GWAS identified four QTLs associated with CTB (qCTBs), distributed on chromosomes 1–3. Among them, qCTB-1-1 overlaps with Osa-miR319b, a known cold tolerance micro RNA gene. The other three qCTBs have not been reported. In addition, we characterised the candidate gene OsRab11C1 for qCTB-1-2 that encodes a Rab protein belonging to the small GTP-binding protein family. Overexpression of OsRab11C1 significantly reduced CTB, while gene knockout elevated CTB as well as cold tolerance at the seedling stage, suggesting that OsRab11C1 negatively regulates rice cold tolerance. Molecular analysis revealed that OsRab11C1 modulates cold tolerance by suppressing the abscisic acid signalling pathway and proline biosynthesis. Using RDP II and GWAS, we identified four qCTBs that are involved in CTB and determined the function of the candidate gene OsRab11C1 in cold tolerance. Our results demonstrate that OsRab11C1 is a negative regulator of cold tolerance and knocking out of the gene by genome-editing may provide enhanced cold tolerance in rice.

The rice blast disease caused by Magnaporthe oryzae threatens global rice production yields. Tricyclazole and isoprothiolane are widely used fungicides with high activity against rice blast, and our previous study indicated the photosynthetic bacterium Rhodopseudomonas palustris PSB-06 significantly antagonizes rice blast. However the effect of combining these two chemical fungicides with PSB-06 on rice blast control is unclear. Here we test the control effect of photosynthetic bacteria PSB-06 combined with isoprothiolane and tricyclazole on rice blast. The growth of PSB-06 was unaffected by up to 1.25 mg/L of tricyclazole and 0.3 mg/L of isoprothiolane in the photosynthetic medium, indicated the two fungicides have no inhibition on PSB-06. The control efficiency in the field test reached 76.06% when PSB-06 was combined with isoprothiolane. This value was significantly higher than the individual efficiency of PSB-06 (67.99%) and tricyclazole (65.46%) and the combined control efficiency (72.20%) of those two antifungal agents. Our current findings highlighted the potential of combining R. palustris strain PSB-06 with isoprothiolane to control rice blast, providing environmental protection and reducing the use of fungicides.

Green finance is an important practice of China’s high-quality economic development in the new era, which is closely related to economic development, environment, and energy conditions. However, few studies systematically analyze the impact of green finance on economic development, environmental pollution, and energy consumption, especially on China which is turning to high-quality economic development. In order to fill the gap, based on the annual data on 30 provinces (autonomous regions and municipalities) in China from 2008 to 2018, we construct a comparatively comprehensive green finance index system and use a panel regression model to explore the impacts of green finance on high-quality economic development, environmental pollution, and energy consumption. We find that green finance can significantly promote high-quality economic development, mitigate environmental pollution, and reduce energy consumption. There is spatial and temporal heterogeneity in the impact of green finance on China’s economic quality, environmental pollution, and energy consumption. In the eastern region, green finance has a remarkable positive impact on high-quality economic development and a significant negative impact on energy consumption, but the impact on environmental pollution is inconspicuous. In the central region, green finance has a prominent effect on reducing environmental pollution, but the impact on high-quality economic development and energy consumption is not significant. In the western region, green finance has not been able to significantly promote high-quality economic development, mitigate environmental pollution, and reduce energy consumption. After the clear proposal of green finance, the role of green finance in promoting a high-quality economy has enhanced, and the role of green finance in reducing environmental pollution and energy consumption has decreased. This study can provide a useful decision-making reference for promoting high-quality economic development, reducing environmental pollution and energy consumption, and spurring sustainable development.

Microglia are the resident macrophages in the brain, which play a critical role in post-stroke neuroinflammation. Accordingly, targeting neuroinflammation could be a promising strategy to improve ischemic stroke outcomes. Ethyl ferulate (EF) has been confirmed to possess anti-inflammatory properties in several disease models, including acute lung injury, retinal damage and diabetes-associated renal injury. However, the effects of EF on microglial activation and the resolution of post-stroke neuroinflammation remains unknown. Here, we found that EF suppressed pro-inflammatory response triggered by lipopolysaccharide (LPS) stimulation in primary microglia and BV2 cell lines, as well as post-stroke neuroinflammation in an in vivo transient middle cerebral artery occlusion (tMCAO) stroke model in C57BL/6 mice, consequently ameliorating ischemic brain injury. Furthermore, EF could directly bind and inhibit the activity of monoamine oxidase B (MAO-B) to reduce pro-inflammatory response. Taken together, our study identified a MAO-B inhibitor, Ethyl ferulate, as an active compound with promising potentials for suppressing post-stroke neuroinflammation.

With the aggravation of air pollution, the impact of air pollution on the stock market, especially from the perspective of investor sentiment, has been of great concern and widely discussed. Based on data from China's A-share listed firms from January 1, 2016, to December 31, 2020, the relationship between urban air pollution and stock liquidity of listed firms and the internal mechanism is examined. Firstly, based on local preference theory, we start by predicting the impact of air pollution on stock liquidity. We, then, build a regression model for air pollution and stock liquidity, introducing the intermediary effect model to detect the relationship between the two and its mechanism. Finally, by subdividing the samples, we discuss the differential impact of air pollution on stock liquidity under different circumstances. We found that when air pollution worsens it reduces stock liquidity. The results of the mechanism analysis show that investor sentiment plays an intermediary role in the process of air pollution affecting stock liquidity, and pessimism induced by air pollution can reduce stock liquidity. Heterogeneity test results show that there are differences in the impact of air pollution on stock liquidity between heavily polluting firms and non-heavily polluting firms, different industries, different city sizes, and different levels of air pollution, has a greater effect in non-heavily polluting enterprises, manufacturing and other industries, medium sized cities and light pollution. The results of this research have important reference value for environmental protection departments to establish and improve air pollution monitoring systems and for listed firms to improve stock liquidity and deal with the environmental financial risks appropriately.

Right ventricular outflow tract (RVOT) reconstruction is a common surgical method to treat congenital cardiac lesions, and bovine jugular vein conduit (BJVC) has become a prevalent candidate of prosthetic material for this procedure since 1999. Although many clinical studies have shown encouraging results on BJVCs, complications such as stenosis, aneurysmal dilatation, valve insufficiency, and infective endocarditis revealed in other clinical outcomes still remain problematic. This review describes the underlying mechanisms causing respective complications, and summarizes the current technological development that may address those causative factors. Novel crosslinking agents, decellularization techniques, conduit coatings, and physical reinforcement materials have improved the performances of BJVCs. The authors expect that the breakthroughs in the clinical application of BJVC may come from new genetic research findings and advanced characterization apparatuses and bioreactors, and are optimistic that the BJVC will in the future provide sophisticated therapies for next-generation RVOT reconstruction.

Glycosylphosphatidylinositol (GPI) anchoring the protein GPI modification post-transcriptionally is commonly seen. In our previous study, MoPer1, a GPI anchoring essential factor, has a critical effect on Magnaporthe oryzae growth, pathogenicity, and conidiogenesis, but its molecular mechanism is not clear. Here, we extracted the glycoproteins from the ΔMoper1 mutant and wild-type Guy11 to analyze their differential levels by quantitative proteomic analysis of TMT markers. After background subtraction, a total of 431 proteins, with significant changes in expression, were successfully identified, and these differential proteins were involved in biological regulation, as well as cellular process and metabolic process, binding, catalytic activity, and other aspects. Moreover, we found that MoPer1 regulates the expression of 14 proteins involved in growth, development, and pathogenicity of M. oryzae. The above findings shed light on MoPer1’s underlying mechanism in regulating growth, development, and pathogenicity of M. oryzae.

BackgroundThe prognostic and clinical value of tumor-associated macrophages (TAMs) in patients with breast cancer (BCa) remains unclear. We conducted the current meta-analysis to systematically evaluate the association of CD68+ and CD163+ TAM density with the prognosis and clinicopathologic features of BCa patients.MethodsSearches of Web of Science, PubMed, and EMBASE databases were performed up to January 31, 2022. The meta-analysis was conducted using hazard risks (HRs) and 95% confidence intervals (CIs) for survival data including overall survival (OS), disease-free survival (DFS), and BCa specific survival. Sensitivity and meta-regression analyses were also conducted to identify the robustness of the pooled estimates.ResultsOur literature search identified relevant articles involving a total of 8,496 patients from 32 included studies. Our analysis indicates that a high CD68+ TAM density in the tumor stoma was significantly linked with poor OS (HR 2.46, 95% CI, 1.83–3.31, P

IntroductionAcquired resistance to endocrine therapy (ET) remains a big challenge in the management of metastatic breast cancer (MBC). A novel therapeutic agent, histone deacetylase inhibitors (HDACi), targets the abnormal epigenetic modification and may overcome acquired resistance. However, HDACi efficacy and the safety profile for hormone receptor (HoR)-positive/human epidermal growth factor receptor 2 (HER2)-negative MBC remain controversial.MethodsTwo independent reviewers searched PubMed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies on HDACi and HoR+/HER2- MBC. Demographic and clinicopathological parameters were extracted and presented as means and proportions, and between-group differences were assessed by Pearson chi-square test. Fixed- or random-effects models were used for meta-analysis based on inter-study heterogeneity. Pooled results were presented as L’Abbé plot and forest plot. Funnel plot and Egger’s test were employed for evaluation of publication bias.ResultsFour studies with 1,457 patients were included for meta-analysis. The overall objective response rates (ORRs) of HDACi + ET (HE) and placebo + ET (PE) groups were 11.52% and 6.67%, respectively. The HE regimen significantly increased ORR (odds ratio [OR] 1.633, 95% confidence interval [CI] = 1.103–2.418, p < 0.05) and showed higher clinical benefit rate (CBR) than the PE regimen (HE vs. PE groups: 38.82% vs. 30.58%, OR 1.378, 95% CI = 1.020–1.861, p < 0.05). Additionally, the HE regimen was associated with prolonged progression-free survival (PFS) (hazard ratio [HR] 0.761, 95% CI = 0.650–0.872, p < 0.001) and overall survival (OS) (HR 0.849, 95% CI = 0.702–0.996, p < 0.001). Regarding safety profile, the HE regimen had increasing toxicity in terms of higher overall adverse event (AE), Grade ≥3 AE, dose modification, and discontinuation rate.ConclusionsThis meta-analysis validated that the HE regimen had superior efficacy over control in terms of ORR, CBR, PFS, and OS, but was accompanied with increasing toxicity. HDACi plus ET could serve as an important option in managing HoR+/HER2- MBC. Future studies may focus on the clinical difference among different HDACi and AE managements to enhance tolerability.

Abstract Objective The aim of this study is to investigate the effect of irisin on leukemia inhibitory factor (LIF) and integrin αvβ3 in implantation failure uterus. Methods Early pregnant rats were randomly divided into normal group (N), mifepristone treated group (M), irisin group (I) and progestin group (P). The implantation failure model was established using mifepristone. Second, we evaluated the average number of embryos and detected the expression of LIF and integrin αvβ3 protein and mRNA in endometrium. Results Compared with group M, the average number of embryos was significantly higher in group N, P and I, the expression of LIF and integrin αvβ3 in endometrium was significantly higher in group N, P and I. Conclusion Irisin could improve the poor receptive state of endometrium by promoting LIF and integrin αvβ3 secretion to improve blastocyst implantation in rats of implantation failure.

Breast cancer is one of the most prevalent types of cancers worldwide, especially for females. Surgery is the preferred treatment for breast cancer, and various postoperative adjuvant therapies can be reasonably used according to different pathological characteristics, especially traditional radiotherapy, chemotherapy, and endocrine therapy. In recent years, targeting agent therapy has also become one of the selective breast cancer treatment strategies, including anti-HER-2 drugs, CDK4/6 inhibitor, poly ADP-ribose polymerase inhibitor, PI3K/AKT/mTOR pathway inhibitor, ER targeting drugs, and aromatase inhibitor. Because of the different pathologic mechanisms of these adjuvant therapies, each of the strategies may cause cardiotoxicity in clinic. The cardiac adverse events of traditional endocrine therapy, radiotherapy, and chemotherapy for breast cancer have been widely detected in clinic; however, the targeting therapy agents have been paid more attention with the extension of application. This review will summarize the cardiac toxicity of various adjuvant therapies for breast cancer, especially for targeting drug therapy.

To assess the high-pressure production characteristics of double-vug reservoirs with bottom water in the Tahe Oilfield, in this study, a high-pressure physical simulation experiment apparatus is built for double-vug reservoirs with bottom water. The high-pressure production characteristics of “vug-fracture-vug” reservoirs under different bottom water characteristics are studied experimentally, and fracture-vug relationship and oil recovery rates are explored. According to the findings, the oil recovery rate significantly affects the development effect of double-vug reservoirs with bottom water, and bottom water provides sufficient energy for reservoir development. Furthermore, considering the possible occurrence of water invasions, the production rate control must receive close attention in the development process to avoid strong water channeling. Constant-pressure bottom water has sufficient energy and can quickly replenish vug energy. Therefore, the recovery percentage and bottom water invasion and retention volume of fractured-vuggy reservoirs with constant-pressure bottom water are higher than those of fractured-vuggy reservoirs with constant-volume bottom water. Under the appropriate control of production factors, the presence of bottom water can noticeably improve the development effect of fractured-vuggy reservoirs.

Abstract Background To evaluate the clinical efficacy of robotic, laparoscopic, and open hemihepatectomy for giant liver haemangiomas. Methods From April 2011 to April 2017, consecutive patients who underwent hemihepatectomy for giant liver haemangiomas were included in this study. According to the type of operation, these patients were divided into the robotic hemihepatectomy (RH) group, the laparoscopic hemihepatectomy (LH) group, and the open hemihepatectomy (OH) group. The perioperative and short-term postoperative outcomes were compared among the three groups. The study was reported following the STROCSS criteria. Results There were no significant differences in age, sex, tumour location, body surface area (BSA), future liver remnant volume (FLR), standard liver volume (SLV), liver haemangioma volume, FLR/SLV, resected normal liver volume/resected volume, hepatic disease, rates of blood transfusion, liver function after 24 h of surgery, operative morbidity and mortality among the three groups. Compared with patients in the RH group (n = 19) and the LH group (n = 13), patients in the OH group (n = 25) had a significantly longer postoperative hospital stay (P 0.05) between the RH group and the LH group. When the setup time in the RH group was excluded, the operative time in the RH group was significantly shorter than that in the LH group (P0.05). The amount of intraoperative blood loss in the RH group was the lowest among the three groups (P

Summary Although many biocontrol bacteria can be used to improve plant tolerance to stresses and to promote plant growth, the hostile environmental conditions on plant phyllosphere and the limited knowledge on bacterial colonization on plant phyllosphere minimized the beneficial effects produced by the biocontrol bacteria. Rhodopseudomonas palustris strain GJ‐22 is known as a phyllosphere biocontrol agent. In this paper, we described detailed processes of strain GJ‐22 colony establishment at various colonization stages. Four different types of bacterial colonies, Type 1, scattered single cells; Type 2, small cell clusters; Type 3, small cell aggregates; and Type 4, large cell aggregates, were observed in the course of bacterial colonization. We categorized bacterial colonization into four phases, which were, Phase I: bacterial colony exists as Type 1 and cell population reduced quickly; Phase II: Type 1 evolved into Type 2 and cell population remained steady; Phase III: Type 3 arose and replaced Type 2, and cell population expanded slowly; and Phase IV: Type 3 matured into Type 4 and cell population increased quickly. We have shown that the preferable location sites of bacterial aggregates on leaf phyllosphere are grooves between plant epidermal cells. Analyses of expressions of plant defence‐related genes showed that, starting from Phase III, bacterial cells in the Type 3 and Type 4 colonies produced unidentified signals to induce host defence against Tobacco mosaic virus infection. In addition, we determined the crucial role of aggregates formation of GJ‐22 cell on plant phyllosphere in terms of bacterial cell stress tolerance and ISR (induced systemic resistance) priming. To our knowledge, this is the first report focused on the colonization process of a phyllosphere biocontrol agent and gave a clear description on the morphological shift of bacterial colony on phyllosphere.

Non-small cell lung cancer (NSCLC) accounts for 85~90% of lung cancer cases, with a poor prognosis and a low 5-year survival rate. Sphingosine kinase-1 (SPHK1), a key enzyme in regulating sphingolipid metabolism, has been reported to be involved in the development of NSCLC, although the underlying mechanism remains unclear. In the present study, we demonstrated the abnormal signature of SPHK1 in NSCLC lesions and cell lines of lung cancers with a potential tumorigenic role in cell cycle regulation. Functionally, ectopic Pre-B cell leukemia homeobox-1 (PBX1) was capable of restoring the arrested G1 phase induced by SPHK1 knockdown. However, exogenous sphingosine-1-phosphate (S1P) supply had little impact on the cell cycle arrest by PBX1 silence. Furthermore, S1P receptor S1PR3 was revealed as a specific switch to transport the extracellular S1P signal into cells, and subsequently activated PBX1 to regulate cell cycle progression. In addition, Akt signaling partially participated in the SPHK1/S1PR3/PBX1 axis to regulate the cell cycle, and the Akt inhibitor significantly decreased PBX1 expression and induced G1 arrest. Targeting SPHK1 with PF-543 significantly inhibited the cell cycle and tumor growth in preclinical xenograft tumor models of NSCLC. Taken together, our findings exhibit the vital role of the SPHK1/S1PR3/PBX1 axis in regulating the cell cycle of NSCLC, and targeting SPHK1 may develop a therapeutic effect in tumor treatment.

BackgroundVarious lymph node staging strategies were reported to be significantly correlated with perihilar cholangiocarcinoma(pCCA) prognosis. This study aimed to evaluate their predictive abilities and construct an optimal model predicting overall survival (OS).MethodsPatients with pCCA were collected as the training cohort from the Surveillance, Epidemiology, and End Results (SEER) database. Four models were constructed, involving four LNs staging strategies. The optimal model for predicting OS was evaluated by calculation of the concordance index (C-index) and Akaike information criterion (AIC), and validated by using the area under curve (AUC) and calibration curves. The clinical benefits of nomogram were evaluated by decision curve analysis (DCA). A Chinese cohort was collected to be an external validation cohort.ResultsThere were 319 patients and 109 patients in the SEER database and Chinese cohort respectively. We developed an optimal model involving age, T stage, tumor size, LODDS, which showed better predictive accuracy than others. The C-index of the nomogram was 0.695, the time-dependent AUC exceeded 0.7 within 36 months which was significantly higher than that of the American Joint Committee on Cancer (AJCC) stage. The calibration curves for survival probability showed the nomogram prediction had good uniformity of the practical survival. The DCA curves exhibited our nomogram with higher clinical utility compared with the AJCC stage and single LOODS.ConclusionsLODDS is a strong independent prognostic factor, and the nomogram has a great ability to predict OS, which helps assist clinicians to conduct personalized clinical practice.

Pyrotinib is an irreversible pan-ErbB receptor tyrosine kinase inhibitor, designed for the therapy of HER2-positive breast cancers. Inhibition of the epidermal growth factor receptor (EGFR, HER family) efficiently and selectively suppresses the proliferation of human TSC2-deficient smooth muscle cells and reverses lung changes in LAM/TSC. Our pilot study indicated that pyrotinib dramatically restrained the vitality of TSC2-deficient cells compared to its limited impact on TSC2-expression cells. Pyrotinib induced G1-phase arrest and triggered apoptosis by blocking abnormally activated CD24 in TSC2-deficient cells. CD24 is not only an important immune checkpoint, but is also involved in the regulation of signaling pathways. Pyrotinib inhibited the nuclear import of pEGFR and restrained the pEGFR/pSTAT3 signals, which directly boosted the transcriptional expression of CD24 by binding to its promoter region. In reverse, CD24 enhanced pEGFR function by directly binding. Pyrotinib specifically targeted TSC2-deficient cells, inhibited tumor cell viability and induced apoptosis through EGFR-STAT3/CD24 Loop in vivo and in vitro. Thus, pyrotinib may be a promising new therapeutic drug for TSC treatment.

C-terminal peptidase (Ctp) cleaves the C-terminal extension of the D1 precursor (pD1) to form mature D1. Among the three homologs CtpA, CtpB, and CtpC in photosynthetic organisms only the first is capable of processing pD1 while the roles of CtpB and CtpC remain elusive. Phylogenetic analysis of Ctps from photosynthetic organisms revealed that CtpA has diverged early from CtpB and CtpC during evolution implying distinct roles for the Ctps. Analysis of Arabidopsis Ctp-deficient mutants revealed that pD1 processing was not affected in atctpb, atctpc, or atctpbatctpc mutants, demonstrating that AtCtpA, not AtCtpB or AtCtpC, is responsible for cleaving the pD1 C-terminal extension. Ectopic expression of CtpAs from Synechococcus elongatus, Chlamydomonas reinhardtii, and Physcomitrella patens in atctpa rescued the lethal phenotype of the mutant indicating that SeCtpA, CrCtpA, and PpCtpA could process pD1 in Arabidopsis. Enzyme activity assays showed that PpCtpA and CrCtpA could convert pD1 into mature D1 in vitro. In contrast, expressing CtpB or CtpC from Arabidopsis, C. reinhardtii, or P. patens in atctpa did not rescue its D1 maturation deficiency, and enzyme activity assays also showed that neither CtpB nor CtpC could process pD1 in vitro. Taken together, we conclude that the function of pD1 processing by CtpA is conserved in photosynthetic organisms. It is possible that among other factors CtpA developed this function to initiate the formation of the oxygenic D1/D2 type PSII complex during evolution whereas CtpB or CtpC have other roles that are still unclear.

Abstract Background Effective management of rice blast, caused by the fungus Magnaporthe oryzae, requires an understanding of the genetic architecture of the resistance to the disease in rice. Rice resistance varies with M. oryzae strains, and many quantitative trait loci (QTLs) affecting rice blast resistance have been mapped using different strains of M. oryzae from different areas. However, little is known about the genetic architecture of rice resistance against the M. oryzae population in Hunan Province, which is a main rice production area in South China. Results In this study, we used three isolates from Hunan Province and the rice diversity panel 1 to perform a genome-wide association study (GWAS) of blast resistance in rice. A total of 56 QTLs were identified. One of the QTLs is localized with the resistance gene Pik locus which confers resistance to all three isolates. Genomic sequence analysis of the resistant cultivars led to the identification of a new Pik allele, which we named Pikx. Yeast two-hybrid and co-immunoprecipitation assays between AvrPiks and Pikx confirmed that Pikx is a new allele at the Pik locus. Conclusions Our GWAS has identified many new blast resistance QTLs. The identified new Pik allele Pikx will be useful for breeding cultivars with high resistance to blast in Hunan and other South China provinces. Further research on the relationship between AvrPiks and Pikx will provide new insights into the molecular mechanism of rice resistance to M. oryzae.

Abstract Background Purpose of this study was to analyze whether preoperative maximum standardized uptake value (SUVmax) and carbohydrate antigen 19–9 (CA19–9) levels might provide prognostic information in Chinese patients with pancreatic duct adenocarcinoma (PDAC) after pancreaticoduodenectomy (PD). Methods Standard PD was performed on 109 patients with PDAC by the same operative team, and all patients received preoperative positron emission tomography/computed tomography examination and blood test. Results Patients had a mean age of 59 ± 9.35 years. Females accounted for 38.5%. Mean levels of SUVmax, carcino-embryonic antigen (CEA) and CA19–9 were 5.70 ± 2.76, 3.95 ± 4.16ng/mL and 321.62 ± 780.71kU/L. In univariate Logistic regression analysis, preoperative SUVmax, CEA and CA19–9 levels (p 0.05 for all) were significantly related to AJCC stages. Multivariate Logistic regression analysis showed that preoperative SUVmax and CA19–9 levels (p 0.05 for all) were significantly associated with AJCC stages. Mean overall survival (OS) was 21 ± 14.50 months. In univariate Cox regression analysis, age, SUVmax, CEA and CA19–9 levels before operation (p 0.05 for all) were significantly related to OS. Multivariate Cox regression analysis showed that age, SUVmax and CA19–9 levels before operation (p 0.05 for all) were significantly associated with OS. Conclusions This study demonstrated that preoperative SUVmax and CA19–9 levels independently predicted pathological stages and OS of patients with PDAC after PD. These preoperative variables might have significant prognostic implication in patients with PDAC after PD. Patients with abnormal SUVmax and CA19–9 levels should be paid special attention to in operative strategy and perioperative management.

This study empirically analyzes factors influencing the coupling and coordinated development of rural urbanization and rural finance. For this purpose, the study employs the coupling degree model and develops a panel quantile model to estimate the coupling degree and coupling coordination degree of rural urbanization and rural finance. Accordingly, the study presents panel data comprising 31 provinces, municipalities, and autonomous regions in China from 2010 to 2019. The empirical results reveal that the coupling degree of rural urbanization and rural finance is relatively low in most study areas. This result suggests that rural urbanization and rural financial development in most provinces in China have not exhibited coordinated development. Further, the results reveal that urban population density negatively affects the coupling and coordination degree of rural urbanization and rural finance. Moreover, the effects of urban population density are more significant in areas with a low coupling coordination degree compared with those with a higher coupling coordination degree. An increase in the quantile gradually decreases the effect of the proportion of educational expenditure to GDP on the degree of rural urbanization and rural financial coupling coordination. However, the effect of financial development efficiency increases accordingly. The per capita GDP, per capita fiscal expenditure, and per capita built-up area significantly affect all the quantiles, indicating a positive correlation. This correlation can promote the coupling and coordinated development of rural urbanization and rural finance. In areas with a low coupling coordination degree, the financial development scale significantly positively affects the coupling coordination degree of rural urbanization and rural finance. In areas with a high coupling coordination degree, the financial development scale significantly negatively correlates with the coupling coordination degree. In addition, a positive correlation exists between the financial development structure and the coupling coordination degree of rural urbanization and rural finance.

Here, by utilizing crystal structure analysis through the particle swarm optimization (CALYPSO) structural searching method with density functional theory (DFT), we investigate the systemic structures and electronic properties of Ca2Mgn (n = 1–15) clusters. Structural searches found that two Ca atoms prefer to occupy the external position of magnesium-doped systems at n = 2–14. Afterward, one Ca atom begins to move from the surface into the internal of the caged skeleton at n = 15. Calculations of the average binding energy, second-order difference of energies, and HOMO–LUMO gaps indicated that the pagoda construction Ca2Mg8 (as the magic cluster) has higher stability. In addition, the simulated IR and Raman spectra can provide theoretical guidance for future experimental and theoretical investigation. Last, further electronic properties were determined, including the charge transfer, density of states (DOS) and bonding characteristics. We hope that our work will provide theoretical and experimental guidance for developing magnesium-based nanomaterials in the future.

Abstract Background GPI-anchoring is a prevalent Glycosylphosphatidylinositol modification process of posttranslational protein and is necessary for cell wall integrity in eukaryotes. To date, the function of GPI anchored-related protein remains unknown in phytopathogenic fungi. Results We here characterized the functions of MoPer1, a homolog of Saccharomyces cerevisiae ScPer1, from the rice blast fungus Magnaporthe oryzae. Transcriptional analysis demonstrated that MoPER1 was significantly upregulated during conidiation and infection. We found that the ∆Moper1 mutant was defective in conidiation and appressoria formation, and MoPer1 was involved in osmotic stress response and maintaining the cell wall integrity. Pathogenicity assays indicated that deletion of MoPEP1 significant reduction in virulence. Microscopic examination of the lesions revealed that the invasive hyphae of ∆Moper1 mutants were mostly restricted to the primary infected leaf sheath cells. Conclusions Our results indicated that MoPer1 is necessary for growth, conidiogenesis, and pathogenicity of the fungus. Our study facilitated to deep elucidate the pathogenic molecular mechanism of M. oryzae, and also provided a very helpful reference value for developing effective fungicide pointed at as the gene for target.

The low-cost, highly efficient online finance credit provides underfunded individuals and small and medium enterprises (SMEs) with an indispensable credit channel. Most of the previous studies focus on the client crediting and screening of online finance. Few have studied the risk rating under a complete credit risk management system. This paper introduces the improved neural network technology to the credit risk rating of online finance. Firstly, the study period was divided into the early phase and late phase after the launch of an online finance credit product. In the early phase, there are few manually labeled samples and many unlabeled samples. Therefore, a cold start method was designed for the credit risk rating of online finance, and the similarity and abnormality of credit default were calculated. In the late phase, there are few unlabeled samples. Hence, the backpropagation neural network (BPNN) was improved for online finance credit risk rating. Our strategy was proved valid through experiments.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-β1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-β1-induced epithelial–mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.

Lymphangioleiomyomatosis (LAM) is a devastating lung disease caused by inactivating gene mutations in either TSC1 or TSC2 that result in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). As LAM occurs predominantly in women during their reproductive age and is exacerbated by pregnancy, the female hormonal environment, and in particular estrogen, is implicated in LAM pathogenesis and progression. However, detailed underlying molecular mechanisms are not well understood. In this study, utilizing human pulmonary LAM specimens and cell culture models of TSC2-deficient LAM patient-derived and rat uterine leiomyoma-derived cells, we tested the hypothesis that estrogen promotes the growth of mTORC1-hyperactive cells through pyruvate kinase M2 (PKM2). Estrogen increased the phosphorylation of PKM2 at Ser37 and induced the nuclear translocation of phospho-PKM2. The estrogen receptor antagonist Faslodex reversed these effects. Restoration of TSC2 inhibited the phosphorylation of PKM2 in an mTORC1 inhibitor-insensitive manner. Finally, accumulation of phosphorylated PKM2 was evident in pulmonary nodule from LAM patients. Together, our data suggest that female predominance of LAM might be at least in part attributed to estrogen stimulation of PKM2-mediated cellular metabolic alterations. Targeting metabolic regulators of PKM2 might have therapeutic benefits for women with LAM and other female-specific neoplasms.

The development of renewable clean energy such as hydropower can not only ensure energy security, but also help achieve the United Nation’s Sustainable Development Goals. This paper uses the annual data of 30 provinces in China from 2000 to 2017, and constructs a dynamic spatial Durbin model and a geographically weighted regression model to empirically test the dynamic impact of hydropower on haze pollution and economic growth at the national and provincial levels. The empirical results show that the promoting effect of hydropower on economic growth in Western China is less than that in Eastern China, which further aggravates the economic development gap between the eastern and western regions. In addition, the suppression effect of hydropower on the haze pollution in the western region is greater than that in the eastern region, where the haze pollution is serious. From the national level, hydropower can promote regional economic growth and inhibit haze pollution, and the spatial spillover effects of these two effects are greater than the local effects, and the long-term impact is greater than the short-term impact. The research conclusions of this paper will help China realize the sustainable development goals of energy saving and emission reduction.

The solution of the dynamic equations of the six-axis accelerometer is a prerequisite for sensor calibration, structural optimization, and practical application. However, the forward dynamic equations (FDEs) and inverse dynamic equations (IDEs) of this type of system have not been completely solved due to the strongly nonlinear coupling relationship between the inputs and outputs. This article presents a comprehensive study of the FDEs and IDEs of the six-axis accelerometer based on a parallel mechanism. Firstly, two sets of dynamic equations of the sensor are constructed based on the Newton–Euler method in the configuration space. Secondly, based on the analytical solution of the sensor branch chain length, the coordination equation between the output signals of the branch chain is constructed. The FDEs of the sensor are established by combining the coordination equations and two sets of dynamic equations. Furthermore, by introducing generalized momentum and Hamiltonian function and using Legendre transformation, the vibration differential equations (VDEs) of the sensor are derived. The VDEs and Newton–Euler equations constitute the IDEs of the system. Finally, the explicit recursive algorithm for solving the quaternion in the equation is given in the phase space. Then the IDEs are solved by substituting the quaternion into the dynamic equations in the configuration space. The predicted numerical results of the established FDEs and IDEs are verified by comparing with virtual and actual experimental data. The actual experiment shows that the relative errors of the FDEs and the IDEs constructed in this article are 2.21% and 7.65%, respectively. This research provides a new strategy for further improving the practicability of the six-axis accelerometer.

This study aims to examine the impact of organizational cultural difference and mutual trust on the contract management of nonequity project alliances in the construction industry. A questionnaire survey was conducted to collect the quantitative data for this study. The relationships between the variables were analyzed using hierarchical regression analysis. It was found that the contractual complexity of nonequity project alliances was impacted by the differences in management style, differences in organizational responsiveness, mutual goodwill trust, and mutual competence trust. It was also found that the relationship between differences in organizational responsiveness and contractual complexity was moderated by mutual goodwill trust. The research may provide theoretical basis for the management when making decisions on the selection of project alliance partners and contracts. The findings imply that when the firms seek to form project alliances, they need to recognize the level of organizational cultural differences and then determine the proper contractual complexity of the project alliance. In addition, the establishment of mutual goodwill trust between alliance partners will not only reduce the costs of making contracts but also the costs of implementing the contracts.

Low solubility, tissue accumulation, and toxicity are chief obstacles to developing triptolide derivatives, so a better understanding of the pharmacokinetics and toxicity of triptolide derivatives will help with these limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative immunosuppressant in a conditional knockout (KO) mouse model with liver-specific deletion of CYP450 reductase. Compared to wild type (WT) mice, after LLDT-8 treatment, KO mice suffered severe testicular toxicity (decreased testicular weight, spermatocytes apoptosis) unlike WT mice. Moreover, KO mice had greater LLDT-8 exposure as confirmed with elevated AUC and Cmax, increased drug half-life, and greater tissue distribution. γ-H2AX, a marker of meiosis process, its localization and protein level in testis showed a distinct meiosis block induced by LLDT-8. RNA polymerase II (Pol II), an essential factor for RNA storage and synapsis in spermatogenesis, decreased in testes of KO mice after LLDT-8 treatment. Germ-cell line based assays confirmed that LLDT-8 selectively inhibited Pol II in spermatocyte-like cells. Importantly, the analysis of androgen receptor (AR) related genes showed that LLDT-8 did not change AR-related signaling in testes. Thus, hepatic CYP450s were responsible for in vivo metabolism and clearance of LLDT-8 and aggravated testicular injury may be due to increased LLDT-8 exposure in testis and subsequent Pol II reduction.

Exposure to aristolochic acid I (AAI) can lead to aristolochic acid nephropathy (AAN), Balkan endemic nephropathy (BEN) and urothelial cancer. The induction of hepatic CYP1A, especially CYP1A2, was considered to detoxify AAI so as to reduce its nephrotoxicity. We previously found that baicalin had the strong ability to induce CYP1A2 expression; therefore in this study, we examined the effects of baicalin on AAI toxicity, metabolism and disposition, as well as investigated the underlying mechanisms. Our toxicological studies showed that baicalin reduced the levels of blood urea nitrogen (BUN) and creatinine (CRE) in AAI-treated mice and attenuated renal injury induced by AAI. Pharmacokinetic analysis demonstrated that baicalin markedly decreased AUC of AAI in plasma and the content of AAI in liver and kidney. CYP1A induction assays showed that baicalin exposure significantly increased the hepatic expression of CYP1A1/2, which was completely abolished by inhibitors of the Aromatic hydrocarbon receptor (AhR), 3ʹ,4ʹ-dimethoxyflavone and resveratrol, in vitro and in vivo, respectively. Moreover, the luciferase assays revealed that baicalin significantly increased the luciferase activity of the reporter gene incorporated with the Xenobiotic response elements recognized by AhR. In summary, baicalin significantly reduced the disposition of AAI and ameliorated AAI-induced kidney toxicity through AhR-dependent CYP1A1/2 induction in the liver.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which direct post-transcriptional gene silencing (PTGS) and function in a vast range of biological events including cancer development. Most miRNAs pair to the target sites through seed region near the 5' end, leading to mRNA cleavage and/or translation repression. Here, we demonstrated a miRNA-induced dual regulation of heme oxygenase-1 (HO-1) via seed region and non-seed region, consequently inhibited tumor growth of NSCLC. We identified miR-1254 as a negative regulator inhibiting HO-1 translation by directly targeting HO-1 3'UTR via its seed region, and suppressing HO-1 transcription via non-seed region-dependent inhibition of transcriptional factor AP-2 alpha (TFAP2A), a transcriptional activator of HO-1. MiR-1254 induced cell apoptosis and cell cycle arrest in human non-small cell lung carcinoma (NSCLC) cells by inhibiting the expression of HO-1, consequently suppressed NSCLC cell growth. Consistently with the in vitro studies, mouse xenograft studies validated that miR-1254 suppressed NSCLC tumor growth in vivo. Moreover, we found that HO-1 expression was inversely correlated with miR-1254 level in human NSCLC tumor samples and cell lines. Overall, these findings identify the dual inhibition of HO-1 by miR-1254 as a novel functional mechanism of miRNA, which results in a more effective inhibition of oncogenic mRNA, and leads to a tumor suppressive effect.

Monometallic Ru catalysts with different particle size were prepared via a precipitation method and reduced at different temperatures. In addition, their catalytic activity towards cyclohexene formation from selective hydrogenation of benzene was investigated. With the utilization of ZnO and ZnSO4 as reaction additives, (Zn(OH)2)3(ZnSO4)(H2O)3 could be generated and chemisorbed on the Ru surface, which played a crucial role on increasing the selectivity to cyclohexene and retarding the catalytic activity towards benzene conversion. Interestingly, without addition of ZnO and ZnSO4, no cyclohexene was observed over all tested Ru catalysts with different particle sizes. This suggested that particle size plays no role in cyclohexene synthesis from selective hydrogenation of benzene over the pure monometallic Ru catalysts in the absence of ZnO and ZnSO4. On the other hand, when both ZnO and ZnSO4 were applied, surface n(Zn2+)/n(Ru) molar ratio increased with increasing particle size of the monometallic Ru catalysts after catalytic experiments, demonstrating that the content of chemisorbed (Zn(OH)2)3(ZnSO4)(H2O)3 on Ru catalysts surface is enhanced under such a circumstance. More importantly, the maximum cyclohexene yield obtained over monometallic Ru catalysts showed a volcanic-type variation with increasing particle size of Ru from 3.6 nm to 5.6 nm. When the particle size of the monometallic Ru catalyst was 4.7 nm, the highest cyclohexene yield of 60.4% was achieved with an optimum n(ZnO)/n(Ru) ratio of 0.19:1 in the presence of 0.62 mol·dm−3 ZnSO4 within 25 min of catalytic experiments at 423 K under 5.0 MPa of H2. In addition, no decrease of catalytic activity towards cyclohexene generation was observed over this catalyst after 10 catalytic experiments without any regeneration.