Nitric oxide nano-reactor DNMF/PLGA enables tumor vascular microenvironment and chemo-hyperthermia synergetic therapy.

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.

A wheat WRKY transcription factor TaWRKY17 enhances tolerance to salt stress in transgenic Arabidopsis and wheat plant.

WRKY transcription factors are essential to plant growth, development, resistance, and the regulation of metabolic pathways. In this study, we characterized TaWRKY17, a WRKY transcription factor from wheat, which was differentially expressed in various wheat organs and was up-regulated by salt, drought, hydrogen peroxide (H2O2) and abscisic acid (ABA) treatment. To analyze TaWRKY17 function under salt stress, we obtained stable T3 generation transgenic Arabidopsis and wheat TaWRKY17 overexpression plants. TaWRKY17 overexpression in Arabidopsis and wheat caused a significant plant salt-stress tolerance enhancement. Under salt stress, superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities were elevated in transgenic Arabidopsis and wheat plants compared with the wild type (WT), whereas H2O2 and malondialdehyde (MDA) accumulation was reduced in the transgenic lines. Moreover, ABA/reactive oxygen species (ROS)-related, and stress-response genes were regulated in the transgenic wheat plants, increasing tolerance to salt stress. The transgenic wheat plants were highly sensitive to ABA during seed germination and early seedling growth. In addition, TaWRKY17 virus-induced gene silencing (VIGS) decreased salt tolerance. These results showed that TaWRKY17 enhances salt tolerance by regulating ABA/ROS-related, and stress-response genes and increasing anti-oxidative stress capabilities. Therefore, this gene could be a target for the genetic modification of wheat.

Factors influencing mosaicism: a retrospective analysis.

RESEARCH QUESTION: What factors affect the incidence of mosaic embryos resulting from assisted reproductive technology? DESIGN: A retrospective analysis of data from preimplantation genetic testing for aneuploidies in 544 couples was conducted using data from an electronic medical record database. RESULTS: Of 1910 embryos studied, 127 (6.6%) were mosaic. In multivariable logistic regression analysis, mosaicism incidence increased in embryos from IVF versus intracytoplasmic sperm injection (ICSI) (odds ratio [OR] 4.560, 95% confidence interval [CI] 2.800-7.424, P < 0.001), and in embryos from abnormal versus normal semen (OR 3.496, 95% CI 2.455-4.979, P < 0.001). Embryos tested using SurePlex 24Sure had lower mosaicism percentages than those tested using MALBAC-NGS and PicoPLEX GenetiSure (OR 2.726, 95% CI 1.532-4.852, P = 0.001; OR 2.389, 95% CI 1.537-3.711, P < 0.001, respectively). CONCLUSIONS: Semen quality, fertilization method and detection system are independent factors associated with embryonic mosaicism.

A novel targeted multifunctional nanoplatform for visual chemo-hyperthermia synergy therapy on metastatic lymph nodes via lymphatic delivery.

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.

[Application of mapping allele with resolved carrier status technique for preimplantation genetic testing in carriers with balanced chromosomal translocations].

OBJECTIVE: To assess the application value of mapping allele with resolved carrier status (MaReCs) technique for preimplantation genetic testing (PGT). METHODS: The characteristics of MaReCs for PGT and outcome of patients were retrospectively analyzed. RESULTS: Compared with those who could not use the technique, carriers who have used the MaReCs technique were younger, had significantly higher level of anti-Mullerian hormone, more antral follicles, occytes, mature occytes, biopsied embryos and euploid embryos, and lower risks for de novo chromosomal abnormality (P<0.05). It was necessary for couples with fewer oocytes, mature oocytes and balstocyst to preserve discarded embryos to facilitate the test. Carriers who have used the MaReCs technique had higher clinical pregnancy rate and abortion rate compared with those undergoing routine PGT, albeit no significant difference was found between the two groups (P> 0.05). Carriers undergoing MaReCs test could preferentially select embryos with normal chromosome structures for the transfer. CONCLUSION: Application of MaReCs has a prerequisite for having a minimum number of occytes and biopsied embryos and using discarded embryos sometimes. MaReCs is efficient for the detection of carrier status of embryos and attaining higher rate of pregnancy and live birth, which can significantly improve the outcome for couples carrying chromosomal translocations.

Dietary protein intake affects expression of genes for lipid metabolism in porcine skeletal muscle in a genotype-dependent manner.

Skeletal muscle is a major site for the oxidation of fatty acids (FA) in mammals, including humans. Using a swine model, we tested the hypothesis that dietary protein intake regulates the expression of key genes for lipid metabolism in skeletal muscle. A total of ninety-six barrows (forty-eight pure-bred Bama mini-pigs (fatty genotype) and forty-eight Landrace pigs (lean genotype)) were fed from 5 weeks of age to market weight. Pigs of fatty or lean genotype were randomly assigned to one of two dietary treatments (low- or adequate-protein diet), with twenty-four individually fed pigs per treatment. Our data showed that dietary protein levels affected the expression of genes involved in the anabolism and catabolism of lipids in the longissimus dorsi and biceps femoris muscles in a genotype-dependent manner. Specifically, Bama mini-pigs had more intramuscular fat, SFA and MUFA, as well as elevated mRNA expression levels of lipogenic genes, compared with Landrace pigs. In contrast, Bama mini-pigs had lower mRNA expression levels of lipolytic genes than Landrace pigs fed an adequate-protein diet in the growing phase. These data are consistent with higher white-fat deposition in Bama mini-pigs than in Landrace pigs. In conclusion, adequate provision of dietary protein (amino acids) plays an important role in regulating the expression of key lipogenic genes, and the growth of white adipose tissue, in a genotype- and tissue-specific manner. These findings have important implications for developing novel dietary strategies in pig production.

Intracellular detection of ATP using an aptamer beacon covalently linked to graphene oxide resisting nonspecific probe displacement.

Fluorescent aptamer probes physisorbed on graphene oxide (GO) have recently emerged as a useful sensing platform. A signal is generated by analyte-induced probe desorption. To address nonspecific probe displacement and the false positive signal, we herein report a covalently linked aptamer probe for adenosine triphosphate (ATP) detection. A fluorophore and amino dual modified aptamer was linked to the carboxyl group on GO with a coupling efficiency of ∼50%. The linearity, specificity, stability, and regeneration of the covalent sensor were systematically studied and compared to the physisorbed probe. Both sensors have similar sensitivity, but the covalent one is more resistant to nonspecific probe displacement by proteins. The covalent sensor has a dynamic range from 0.125 to 2 mM ATP in buffer at room temperature and is resistance to DNase I. Intracellular ATP imaging was demonstrated using the covalent sensor, which generated a higher fluorescence signal than the physisorbed sensor. After the cells were stimulated with 5 mM Ca(2+) for ATP production, the intracellular signal enhanced by 31.8%. This work highlights the advantages of covalent aptamer sensors using GO as both a quencher and a delivery vehicle for intracellular metabolite detection.

Nitrogen-fixing and non-nitrogen-fixing legume plants differ in leaf nutrient concentrations and relationships between photosynthetic and hydraulic traits.

Legumes account for a significant proportion of plants in the terrestrial ecosystems. Nitrogen (N)-fixing capability of certain legumes is a pivotal trait that contributes to their ecological dominance. Yet, the functional traits and trait relationships between N-fixer and non-N-fixer legumes are poorly understood. Here, we investigated 27 functional traits associated with morphology, nutrients, hydraulic conductance and photosynthesis in 42 woody legumes (19 N-fixers and 23 non-N-fixers) in a common garden. Our results showed that N-fixers had higher specific leaf area, photosynthetic phosphorus (P)-use efficiency, leaf N, and iron concentrations on both area and mass basis, N/P ratio, and carbon (C) to P ratio, but lower wood density, area-based maximum photosynthetic rate (Aa), photosynthetic N-use efficiency, leaf mass- and area-based P and molybdenum and area-based boron concentrations, and C/N ratio, compared with non-N-fixers. The mass-based maximum photosynthetic rate (Am), stomatal conductance (gs), intrinsic water-use efficiency (WUEi), mass- and area-based leaf potassium and mass-based boron concentrations, leaf hydraulic conductance (Kleaf), and whole-shoot hydraulic conductance (Kshoot) showed no difference between N-fixers and non-N-fixers. Significant positive associations between all hydraulic and photosynthetic trait pairs were found in N-fixers, but only one pair (Kshoot-Aa) in non-N-fixers, suggesting that hydraulic conductance plays a more important role in mediating photosynthetic capacity in N-fixers compared with non-N-fixers. Higher mass-based leaf N was linked to lower time-integrated gs and higher WUEi among non-N-fixer legumes or all legumes pooled after phylogeny was considered. Moreover, mass-based P concentration was positively related to Am and gs in N-fixers, but not in non-N-fixers, indicating that the photosynthetic capacity and stomatal conductance in N-fixers were more dependent on leaf P status than in non-N-fixers. These findings expand our understanding of the trait-based ecology within and across N-fixer and non-N-fixer legumes in tropics.

Wheat WRKY transcription factor TaWRKY24 confers drought and salt tolerance in transgenic plants.

Drought and salt stress are major environmental conditions that severely limit plant growth and productivity. WRKY transcription factors play a vital role in the responses against biotic or abiotic stress. In this study, TaWRKY24, a gene of the IIe WRKY family identified in wheat, was cloned and characterized. TaWRKY24 was mainly expressed in wheat leaf and stem and induced by treatment with PEG6000, salt, H2O2, ABA, MeJA, and ethrel. TaWRKY24 transient expression in onion epidermal cells suggested its nuclear localization and its transcriptional activation capability characteristics. Overexpression of TaWRKY24 in tobacco improved the seed germination rate and root growth of seedlings in transgenic lines when subjected to higher mannitol and NaCl concentrations. Further research showed that transgenic lines had higher proline and soluble sugars and lower levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, compared to normal and negative control plants, TaWRKY24 silenced wheat seedlings had reduced growth under salt and drought stress. This study shows that wheat TaWRKY24 is crucial to plant stress, providing an excellent candidate gene for wheat resistance breeding.

Genome-wide identification of ETHYLENE INSENSITIVE 2 in Triticeae species reveals that TaEIN2-4D.1 regulates cadmium tolerance in Triticum aestivum.

ETHYLENE INSENSITIVE 2 (EIN2), as the core component of the ethylene signaling pathway, can widely regulate plant growth, development, and stress responses. However, the comprehensive study and function of EIN2 in wheat Cadmium (Cd) stress remain largely unexplored. Here, we identified 33 EIN2 genes and designated as TaEIN2-2B to TaEIN2-Un.3 in Triticum aestivum. The analysis of cis-regulatory elements in promoter regions and RNA-Seq showed that TaEIN2s were functionally related to plant growth and development, as well as the response to biotic and abiotic stress. qRT-PCR analysis of TaEIN2s indicated their sensitivity to Cd stress. Compared with WT plants, TaEIN2-4D.1-RNAi transgenic wheat lines showed enhanced shoot and root elongation, dry weight and chlorophyll accumulation, together with a reduced accumulation of Cd in wheat grain. In addition, TaEIN2-4D.1-RNAi transgenic wheat lines showed enhanced Reactive Oxygen Species (ROS) scavenging capacity compared with WT plants. In conclusion, our research indicates that TaEIN2 plays a key role in response to cadmium stress in wheat, which provides valuable information for crop improvement.

Has China's carbon market stress released? Measurement and comparison of national and pilot carbon markets' stress.

This paper constructs a novel stress measurement system of carbon market from the perspective of trading, emission reduction, and external shocks and simulates the stress indices of national and pilot carbon markets of China with the methods of functional data analysis and criteria importance through intercriteria correlation. It concludes that the overall carbon market stress is in the shape of "W" and still at a high level, with frequent fluctuations and an upward trend. In addition, the stress of Hubei, Beijing, and Shanghai carbon market fluctuates and rises, while the stress of Guangdong carbon market decreases. Moreover, carbon market stress mainly comes from trading and emission reduction. Furthermore, stress fluctuation of Guangdong and Beijing carbon market is more prone to "big waves," indicating that the two markets are sensitive to big events. Finally, the pilot carbon markets are divided into stress-driven and stress-release market and the type of which keeps change in different period.

Three-dimensional core-shell alginate microsphere for cancer hypoxia simulation in vitro.

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.

Analysis of Nucleoporin 107 Overexpression and Its Association with Prognosis and Immune Infiltration in Lung Adenocarcinoma by Bioinformatics Methods.

Background: Lung adenocarcinoma (LUAD) has high morbidity and mortality. Current studies indicate nucleoporin 107 (NUP107) is involved in the construction of nuclear pore complex, and NUP107 overexpression contributes to the growth and development in most types of cancers, but its effect in LUAD has not been elucidated. Methods: Differences in NUP107 expression were investigated using the Cancer Genome Atlas (TCGA) and multiple Gene Expression Omnibus (GEO) data sets. Enrichment analysis were implemented to probe the NUP107 function. The association of NUP107 with the degree of immune cell infiltration was investigated by the TIMER database, single-sample gene set enrichment analysis (ssGSEA), and ESTIMATE. The association of NUP107 expression with tumor mutation burden (TMB), TP53, and immune checkpoint was analyzed. Single-cell RNA sequencing data were used to detect NUP107 expression in different cell clusters. Finally, we performed real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) to prove the difference of NUP107 expression. Results: NUP107 was overexpressed in LUAD and mainly expressed in cancer stem cell (CSC). Overexpression of NUP107 in LUAD suggested a poorer prognosis. Functional enrichment analysis pointed out that NUP107 was mainly linked to the regulation of cell cycle. Both immune cell infiltration and TMB were found to be in connection with NUP107. Cases in the group with high NUP107 expression had poorer immune infiltration, but had higher expression of immune checkpoints, TMB, and proportion of TP53 mutations. Conclusion: NUP107 is a sensitive diagnostic and prognostic factor for LUAD and may be involved in tumor progression through its effects on cell cycle and immune infiltration.

Does technology innovation reduce haze pollution? An empirical study based on urban innovation index in China.

Haze pollution is one of the most concerning environmental issues, and controlling haze pollution without affecting economic development is of immense significance. Using the panel data composed of PM2.5 concentration and other data from 278 cities in China between 2003 and 2016, this paper empirically investigates the impact of urban innovation on haze pollution and its transmission mechanism. Based on the fixed effect model, the research finds that increasing urban innovation significantly reduces haze pollution. Even after dealing with possible endogenous problems, the result still holds. Energy consumption and industrial agglomeration are two important transmission channels through which urban innovation affects haze pollution. Furthermore, time heterogeneity analysis shows that the negative effect of urban innovation on haze pollution increases with time. Spatial heterogeneity analysis shows that urban innovation has a more significant mitigation effect on haze pollution in eastern cities than in central and western cities in China. This paper indicates that technological innovation, as the main driving force for development, can provide vital support to China to improve the ecological environment.

Nomogram models for stratified prediction of axillary lymph node metastasis in breast cancer patients (cN0).

Objectives: To 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. Methods: From 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. Results: Univariate 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. Conclusion: We 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.

Growth performance, fatty acid composition, and lipid metabolism are altered in groupers (Epinephelus coioides) by dietary fish oil replacement with palm oil.

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 < 0.05) the FA profile in the liver and flesh of the fish species in comparison with the control diet. Furthermore, the mRNA levels of FAS, G6PD, LPL, PPARΑ, and Δ6FAD genes in the liver had positive linear and/or quadratic responses, but the SCD, HSL, ATGL, FABP, SREBP-1C and ELOVL5 had the opposite trend, with increasing dietary PO inclusion levels, whereas the mRNA level of ACC was not affected by dietary treatments. The optimal level of PO substitution for FO was estimated to be 47.1% of the feed, based on the regression analysis of percent weight gains against dietary PO inclusion levels; however, it might affect the FA profile in the liver and flesh of the fish species, and further study is required to investigate whether the changes in tissue FA composition will affect the welfare and market value over a production cycle of grouper.

3d oxidized alginate-porcine liver acellular collagen droplets for tumor microenvironment mimicking.

The traditional 2d culture has been proved inferior to reproduce the subtle interaction between cell-to-cell and cell-to-extracellular matrix (ECM) in tumor microenvironment (TME) and collagen in ECM contributes to various malignancies of tumors. Hence, the 3d model contained with collagen may overcome the shortcomings of 2d culture. In this study, the in vitro TME mimicking matrix was prepared by coupling porcine liver-derived collagen (COL) and the dialdehyde group of partially oxidized alginate (OA), namely OA-COL, and the 3d OA-COL droplets were polymerized by divalent calcium ions. In the 3d OA-COL droplets, cancer cells displayed vigorous proliferation, and the cells grew in clusters and formed a unique spindle like clone. Quantitative analysis proved that various gene transcription and protein expression were up-regulated for the cells in the 3d OA-COL droplets, including F-actin reassembling, focal adhesion, pseudopodia formation, and the proteins involved in epithelial-to-mesenchymal transition (EMT). The 3d OA-COL droplets induced the cells with strengthened polarity, invasiveness, higher IC50, and manifested stronger tumorigenicity in vivo. The fabricated 3d OA-COL droplets reproduced a variety of TME parameters, constructed an in vitro model similar to the TME in vivo, and it may facilitate many investigations in cell biology and tumor biology.

Abnormal expression of uncoupling protein-2 correlates with CYP11A1 expression in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) may result from hypersensitivity to insulin, which is negatively regulated by uncoupling protein (UCP)-2. Because cholesterol side-chain cleavage enzyme (CYP11A1) is closely linked to PCOS, the expression of UCP-2 and CYP11A1 in ovarian tissues from PCOS patients was examined in the present study. Twelve PCOS patients with hyperandrogenaemia who underwent laparoscopic ovarian wedge resection and 12 age-matched control patients who underwent contralateral ovarian biopsy were enrolled in the study. UCP-2 expression in early stage (primordial, primary and secondary) and late stage (sinus and mature) follicles was examined using immunohistochemistry, whereas UCP-2 and CYP11A1 mRNA and protein levels in ovarian tissue were determined using quantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively. UCP-2 expression increased significantly with follicular development in both control and PCOS tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls. In addition, both UCP-2 and CYP11A1mRNA and protein levels, mean fasting blood glucose concentrations and fasting serum insulin levels were significantly higher in PCOS patients compared with the control group. Finally, a significant correlation between UCP-2 and CYP11A1 expression was found in PCOS but not control patients. In conclusion, in PCOS patients, there was a correlation between UCP-2 and CYP11A1 expression, which was significantly higher than in the control group. These changes in UCP-2 and CYP11A1 expression may mediate follicle development in PCOS.

Have China's Pilot Free Trade Zones Improved Green Total Factor Productivity?

Free trade zones (FTZ) are designated areas for promoting trade openness and investment facilitation. In China, FTZs are also regarded as "green areas" in which planning actions and institutional innovations are implemented, and there is a commitment to promoting urban green and healthy development. Given that green total factor productivity (GTFP) is an important measure of a city's health and green performance, this study exploits the difference-in-differences method to explore the impact of pilot FTZs on urban GTFP in 280 cities in China for the period between 2005 and 2017. The results show that the green areas positively contributed to the growth of GTFP. Moreover, the outcome holds with robustness tests. Statistically, the positive effect emerged in cities during the first three years after introducing the initiative, with the effect disappearing afterward. It also had a strong positive impact in the central and western regions and in large and medium-sized cities, while the influence remained insignificant in the remaining areas in China. Furthermore, the paper also reveals that the promotion of foreign direct investment and industrial structure upgrading are the primary channels through which the positive relationship between pilot FTZs and GTFP is established.

Resource Misallocation and Energy-Related Pollution.

Developing countries face the conflict between economic development and environmental protection. Resource misallocation will not only affect the effectiveness of economic development, but also have environmental impacts. Based on two large-scale enterprise databases in China, this paper measured the level of enterprise resource allocation, and further used empirical research methods to investigate the environmental impact of enterprise resource misallocation and specific mechanisms. The results show that the low efficiency of resource allocation will harm the quality of China's environment. Further investigation, resource misallocation is accompanied by an increase in total energy input, a decrease in the labor-to-energy ratio and the capital-to-energy ratio, and a loss of energy efficiency, which in turn affects the environmental performance of enterprises. China is the largest developing country in the world, and research on China's environmental and economic issues is important. The conclusions of this paper can provide experience and suggestions for other developing countries to improve environmental quality and promote sustainable development from the perspective of resource misallocation.